Sen_E_ID	External factors	Category	Cell name	Tissue type	Phenotype	Aging type	Experiment	Description	Target gene	Regulatory type of target gene	Target gene experiment	Target gene description	Regulatory pathway 	Regulatory type of pathway	Pathway experiment	Pathway description	Experimental category	Aging characteristic	PMID
Sen_E_001	lipopolysaccharide	Chemical compounds	DPSC	Human impacted third molar	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay//Cell morphological analysis	"A senescence-like morphology was observed after repeated stimulation with LPS for 3 or 6 times. The morphology of DPSCs was characterized by a flat shape and increased size.Flow cytometry showed that more DPSCs were restricted to the G1 phase harvested from DPSCs treated with LPS 3 times and 6 times (3 times: 62.46 %±4.6 %, 6 times:66.80 %±4.8 %) than in the DPSCs from the control group or DPSCs treated with LPS only once (control: 45.09 %±3.6 %,once: 46.23 %±3.9 %;).After treatment with LPS, the number of SA-β-gal–positive cells clearly increased in LPS-treated DPSCs, with the strongest staining being seen in DPSCs receiving LPS stimulation 6 times."	γ-H2A.X//p16	Upregulation//Upregulation	Western blot//RT-PCR//qRT-PCR	"The result suggested that the stimulation of LPS 3 or 6 times markedly increased γ-H2A.X protein expression. Analysis by reverse transcription plus PCR (RT-PCR) showed that levels of γ-H2A.X were up-regulated after exposure to LPS 3 or 6 times.After stimulation with LPS, the expression level of p16INK4A was up-regulated in a manner dependent on the number of repeated treatments."	TLR4	Upregulation	Western blot	"After stimulation with LPS, the expression level of TLR4 was upregulated in a manner dependent on the number of repeated treatments ."	L	cellular senescence	24676500
Sen_E_002	Resveratrol	Chemical compounds	MSC	Bone marrow	Aging	Prevent	SA-β-gal activity assay//Colony formation assay	SA-β-gal activity significantly increased in LP-MSCs compared with that in EP-MSCs(SIRT1 expression) treated with either EtOH or with resveratrol.The CFU-F assay was performed. The results showed that resveratrol enhanced the colony-forming ability of EP-MSCs.	β-catenin	Downregulation	Western blot	"Western blot results showed that in EP-MSCs, ERK phosphorylation was reduced by resveratrol, resulting in a decrease of Activate β-catenin (non-phosphorylated)."	ERK	Downregulation	Western blot	"Western blot results showed that in EP-MSCs, ERK phosphorylation was reduced by resveratro."	L	delay aging	26456654
Sen_E_003	Acrolein	Chemical compounds	HFL-1	--	Aging	Accelerate	SA-β-gal activity assay//Cell counting//Cell viability assay	"Repetitive acrolein exposure reduced cell viability in a dose-dependent manner.During that time period, cell growth was significantly reduced in cells previously exposed to acrolein Cells previously exposed to acrolein exhibited a significant increase in SA β-gal activity compared with control cells."	WRN	Downregulation	Western blot	"In HFL-1 cells exposed to 25 μM acrolein, steadystate levels of WRN were reduced at 48 hr (p = 0.07) and significantly reduced at 72 hr ."	p53-p21	Activation	Western blot//SA-β-gal activity assay//Cell counting	"Although both p53 and p21 levels were higher in acrolein-exposed cells than in controls during the period, they appeared to be slightly lower on day 3. In addition, both p53 and p21 levels did increase in control cells over the 3-day period . Suppression of p53 prevented acrolein-induced growth inhibition. Consistent with the cell growth data, p53 knockdown significantly attenuated SA β-gal activity in acrolein-exposed cells."	L	cellular senescence	24747221
Sen_E_004	Ang II	Chemical compounds	BVSMC	--	Cerebrovascular aging	Accelerate	SA-β-gal activity assay//Western blot	"Two different concentrations of AngII (10-7 M and 10-6 M) incubation for 5 days caused significant positive β-gal staining (blue) in cultured hBVSMCs,Two concentrations of AngII incubation also triggered NBS1 protein(molecular marker of senescence)level in hBVSMCs."	TRF2	Downregulation	Western blot	AngII caused significant downregulation of TRF2.	p53//Siah-1	Upregulation//Upregulation	Western blot	AngII treatment for 5 days enhanced total p53 protein expression by ~4.5 folds in hBVSMCs as well as the phospho-p53 expression.FGF21 inhibited Siah-1 expression induced by AngII.	L	delay aging	27364911
Sen_E_005	Morin	Chemical compounds	Human interfollicular epidermal stem cell	Foreskin	Aging	Prevent	SA-β-gal activity assay	Morin significantly inhibited UVB-induced accumulation of SA-β -gal in KSC.	TNF-α//IL-1 β//IL-6	Downregulation//Downregulation//Downregulation	ELISA	"However, morin led to a significant decrease in the production of TNF- α , IL-1 β , and IL-6 in the UVB-irradiated KSC."	ATM	--	Flow cytometry//Western blot	"Flow cytometric result showed that fl uorescence intensity of ATM phosphorylation was 74.7% value in the morin-treated KSC compared with 86.1% value in UVB-irradiated KSC. As a result, ATM-related signaling pathway molecules (Chk2, p53, and H2A.X), MAPK family members (JNK/SAPK and p38/MAPK), and S6RP were rapidly phosphorylated in response to UVB irradiation in KSC ."	L	cellular senescence	23952478
Sen_E_006	As2O3	Chemical compounds	"U87,U251,SHG44,C6"	Glioma	Glioblastoma	Accelerate	Immunostaining//SA-β-gal activity assay//Telomere length assay//Flow cytometry//Western blot	"Immunofluorescent labeling showed that ATR, 53BP1, γ-H2 AX and Mer11 accumulated in the nucleus of cells exposed to 4 μM As2 O3 for 48h .In addition,obvious dose-related increases in p-ATM, ATR, γ-H2 AX,53BP1, Mer11, and p21 were detected by immunoblotting. As2O3 significantly reduced the telomeric G-overhang length after 48 h of treatment (P < 0.01), though the total telomere length did not change. Most of the cells in the control group are in G0-G1 phase. By contrast, As2O3 induced G2-M phase arrest, which is in agreement with the reported effect of As2O3 on Burkitt’s lymphoma cells .Using aging staining we also observed that As2O3 treatment for 2 weeks increased the incidence of cellular senescence marked by cell swelling and blue staining. Dose-related effects were seen with all of four cell types tested ."	p53//p21	Upregulation//Upregulation	Western blot	"In addition, obvious dose-related increases in p-A TM, A TR, γ-H2AX, 53BP1, Mer11, and p21 were detected by immunoblotting . Moreover, immunoblotting revealed dose- and time-dependent up-regulation of the pro-apoptotic proteins p53, p-p53 and Bax and down-regulation of anti-apoptotic protein Bcl-2 in U87 cells. We also observed elevation of PARP and Caspase-3 cleavage, which is consistent with increased incidence of apoptosis."	--	--	--	--	L	telomere attrition	26871293
Sen_E_007	Telomestatin	Chemical compounds	HT-1080	--	Fibrosarcoma	Accelerate	Immunostaining	"Treatment of HT1080 cells with 1, 2, and 5μM telomestatin for 48 h induces a dose-dependent decrease of the G-overhang signal, which represents 32, 15, and 10% of the untreated control, respectively.Telomestatin treatment induces a marked DNA damage response evidenced by a strong increase in theγH2AX foci.Interestingly, the exposure of HT1080 cells to telomestatin (2μM)induces a rapid telomere shortening detectable after short term treatment."	POT1//TRF2	Downregulation//Downregulation	Immunostaining	"Telomestatin treatment of HT1080 cells(2μM,48 h) induced a noticeable decrease of the TRF2 signal at telomeres .Telomestatin strongly reduced the GFP-POT1 punctated signal associated with telomeres to nearly undetectable levels, as compared with untreated controls.The dose-dependent effect of telomestatin was also studied in HT1080GFP-POT1 cells after 48 h of treatment."	--	--	--	--	L	telomere attrition	17050546
Sen_E_008	Tamoxifen	Chemical compounds	MCF-7	--	Breast cancer	Accelerate	SA-β-gal activity assay	"Similarly, there was a 35% induction of cellular senescence in tamoxifen-treated shLacZ cells that was not observed in either pool of MCF-7 cells expressing shYPEL3."	YPEL3	Upregulation	RT-PCR	There was a 2.3-fold induction of YPEL3 mRNA expression in control cells (shLacZ) treated with tamoxifen verses vehicle control.	--	--	--	--	L	cellular senescence	21671470
Sen_E_009	RTI	Chemical compounds	"MCAS,HEC-1"	--	Gynaecological Cancer	Accelerate	MTT assay//TRAP assay	Cell proliferation after 72 h of incubation was assessed by the MTT assay. Both the cell lines demonstrated reduced proliferation with increasing concentrations of RTI.	p53//p21	Upregulation//Upregulation	RT-PCR	"In HEC-1 cells, the expression of TP53 increased with ddI (P< 0.001).The expression of p21 increased with ddI (P< 0.001)."	--	--	--	--	L	telomere attrition	10533489
Sen_E_010	E235	Chemical compounds	"HT-1080,B16F10"	--	Cancer	Accelerate	SA-β-gal activity assay//Western blot//Cell morphological analysis	"While assaying the antiproliferative effects of E235 on transformed cells, we observed that cells treated for at least 48h with lower doses of E235 (0.25-1μM) increased in size and displayed characteristics consistent with a senescent phenotype. Both  15 HT1080 and B16F10 cells exhibited a dramatic increase in perinuclear SA-β-gal staining after 48h of treatment with lower doses of E235, with almost all of the cells treated with 1μM E235 being positive for β-gal expression.Both HT1080 and B16F10 cells displayed elevated levels of p21 with 1μM E235 at 8 and 16h."	ATF4	Upregulation	Luciferase reporter assay//Western blot	"E235 caused a dose-dependent increase in luciferase activity from a reporter plasmid containing the 5 UTR of the ATF4 mRNA fused to the luciferase gene .A dose-dependent increase in ATF4 protein levels was seen only in the HT1080 and B16F10 cells. There was no appreciable induction of ATF4 protein in the normal diploid AG1522 human fibroblasts in response to E235, whereas thapsigargin induced a potent upregulation of ATF4 levels , suggesting that this effect is restricted to transformed cells."	--	--	--	--	L	cellular senescence	23229510
Sen_E_011	AngII	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"Ang II induced a dose-dependent increase in the fraction of cells staining positive for β-galactosidase, indicating an increased fraction of senescent cells."	TERT//UCP2//p-Akt//c-Myc//p53	Upregulation//Upregulation//Upregulation//Upregulation//Upregulation	Western blot	"Incubation with Ang II further elevated TERT protein levels from 0.006±0.041 at baseline, to 0.480±00.031 in the presence of 10 lM Ang II, UCP2 protein levels from 0.297±0.051 to 2.512±0.024, p-Akt protein levels from 0.012± 0.024 to 0.874± 0.015, c-myc protein levels from 0.521 ±0.015 to 1.064± 0.025, and p53 protein levels from 0.035± 0.047 to 1.195 ±0.029 but Akt levels were not significantly affected by incubation with even 10 lM Ang II."	PI3K-Akt	--	SA-β-gal activity assay	β-Galactosidase staining indicated a decline in the fraction of senescent cells with increasing LY concentration.	L	cellular senescence	25078983
Sen_E_012	Triptonide	Chemical compounds	"U937,HL60"	--	Acute leukemia	Accelerate	Flow cytometry//Cell morphological analysis//SA-β-gal activity assay	"Cell cycle assay showed that the cell populations at G0/G1 phases were significantly increased for 40.6% at the dose of 10 nM, but those at G2/M phases were significantly decreased for 38% after 3 days of triptonide treatment, suggesting that triptonide increases leukemia cell arrest at G0/G1.In particular, cell size was enlarged, and cells profoundly changed shape from rounded to an irregular form, with budding evident on the plasma membrane surface, and an enlarged nucleus containing big vacuoles.The results showed that β-Gal-positive HL60 and U937 cells were significantly increased after 6 days of triptonide treatment by 21.3% and 25%, respectively , compared to that in the control cells."	TERT//c-Myc//p16//p21//DDIT3	Downregulation//Downregulation//Upregulation//Upregulation//Upregulation	RT-PCR//Western blot	"QT -PCR analysis indicated that TERT expression in HL60 cells was reduced for 6.7 and 11.4 times at triptonide doses of 10 and 15 nM, respectively. In addition, western blotting analysis showed that TERT protein levels were also significantly diminished .RT -PCR analysis showed that the mRNA levels of p16 were significantly increased, while p21 in the cells were notably elevated, and QT-PCR analysis indicated that the expression levels of p16 and p21 were increased by 9- and 24.7-fold, respectively , after 3 days of treatment with 15 nM triptonide, respectively.The results showed that c-Myc gene expression was signif icantly reduced in the presence of 15 nM triptonide, whereas, triptonide at doses of 10 nM and less did not significantly promote c-Myc expression, RT -PCR analysis showed that triptonide treatment markedly elevated DDIT3 mRNA levels.Western blotting indicated that DDIT3 protein levels were significantly elevated in HL-60 cells after triptonide treatment."	MKK3-p38//ERK	Upregulation//Downregulation	Western blot	"Western blotting indicated that the level of phsphorylated p38 was significantly increased, whereas the level of p-ERK was obviously diminished ."	L	apoptosis	27908660
Sen_E_013	Resveratrol	Chemical compounds	EPC	--	Aging	Prevent	SA-β-gal activity assay	"Resveratrol influenced EPCs senescence dose dependently, with a maximal inhibitory effect achieved at 50mM."	Telomerase	Activation	Western blot	"Resveratrol dose dependently increased telomerase activity, with a maximal increase at 50mM."	PI3K-Akt	--	Western blot	"Stimulation with resveratrol led to dose-dependent phosphorylation of Akt, although it did not affect the total amount of Akt."	L	delay aging	18587418
Sen_E_014	Carbocysteine	Chemical compounds	Endothelial cell	--	Chronic obstructive pulmonary disease	Prevent	Flow cytometry//Colony formation assay//SA-β-gal activity assay//Western blot	Incubation with CARB significantly counteracted this phenomenon in cells exposed to CSE; CSE increased beta galactosidase staining and incubation with CARB completely reverted this phenomenon;CSE increased p21 expression and CARB counteracted this phenomenon.	Survivin	Downregulation	Flow cytometry	"A dose dependent manner, survivin expression and the costimulation with CARB significantly counteracted this phenomenon (reduction versus CSE 10% =17 ± 13; p b 0.02 reduction versus CSE 20% = 16 ± 11; p b 0.007)."	SIRT1-FOXO3	Upregulation	Western blot	"CSE in a dose dependent manner reduced nuclear expression of SIRT1; CSE reduced nuclear expression of FoxO3, in a dose dependent manner."	L	delay aging	27237816
Sen_E_015	Cigarette smoke extract	Other	Endothelial cell	--	Chronic obstructive pulmonary disease	Accelerate	Flow cytometry//Colony formation assay//SA-β-gal activity assay//Western blot	"CSE reduced, in a dose dependent manner, short-term cell proliferation;CSE increased beta galactosidase staining;CSE increased p21 expression."	Survivin	Upregulation	Flow cytometry	"CSE increased, in a dose dependent manner, survivin expression (increase versus baseline of CSE 10% = 13 ± 10; p b 0.01; increase versus baseline of CSE 20% = 26 ± 16; p=0.002)."	SIRT1-FOXO3	Downregulation	Western blot	"CSE in a dose dependent manner reduced nuclear expression of SIRT1; CSE reduced nuclear expression of FoxO3, in a dose dependent manner."	L	delay aging	27237816
Sen_E_016	Catalpol	Chemical compounds	THP-1	--	Atherosclerosis	Prevent	TRAP assay//SA-β-gal activity assay	Catalpol could obviously increase the telomerase activities in a concentration-dependent manner.Ctalpol partly inhibited the macrophage senescence compared to the oxLDL group.	--	--	--	--	--	--	--	--	L	telomere attrition	30046372
Sen_E_017	G-quadruplex interActivate agent S2T1-6OTD	Chemical compounds	"D341,D425,Daoy ,BT-12,BT-16"	--	Tumor	Accelerate	Telomere length assay//SA-β-gal activity assay//Cell morphological analysis	Treatment with S2T1-6OTD at 0.04 μmol/L resulted in telomere shortening in all MB and AT/RT cells tested.The morphologic examination of the 0.04 μmol/L S2T1- 6OTD–treated cells at the plateau phase showed an increased proportion of flat and giant cells with phenotypic characteristics of senescence and positive for senescence-associated β-galactosidase.	c-Myc//hTERT	Downregulation//Downregulation	qRT-RCR//ELISA	"Treatment with S2T1-6OTD resulted in significant reductions of c-Myc mRNA and protein expression in all other MB and AT/RT cell lines tested .it was found that S2T1-6OTD could indeed reduce hTERT mRNA expression in BT-12, BT-16, DAOY ,and D341 cells.S2T1-6OTD reduced telomerase activity in all cell lines tested, with maximum inhibition in D341 (64%) and a minimum 17% in D425."	--	--	--	--	L	telomere attrition	20053783
Sen_E_018	CRT0063465	Chemical compounds	HCT116	--	Hypoglycemia	Prevent	Southern blot	"Strikingly, however, despite the lack of effects observed on total cellular telomerase activity by CRT0063465, hypoglycemic erosion of telomeres was blocked in the presence of the compound at both 100 nM and 10 nM."	PGK1//DJ1	--//--	Co-IP	"For PGK1, 10 nM CRT0063465 increased telomere association under physiological glucose conditions.For DJ1, compound treatment did not significantly affect telomere association under physiological conditions."	--	--	--	--	L	telomere attrition	31401411
Sen_E_019	Paclitaxel	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Treatment with paclitaxel, sirolimus, and everolimus significantly induced a senescent phenotype as judged by SA-βgal and an enlarged, flattened cell morphological appearance at 10 days."	PAI-1//eNOS//SIRT1	Upregulation//Downregulation//Downregulation	Western blot	"In parallel with SA-βgal, expression of PAI-1 was increased by treatment with paclitaxel, sirolimus, and everolimus .Paclitaxel, sirolimus, and everolimus decreased the expression of eNOS and Sirt1."	--	--	--	--	L	cellular senescence	19520256
Sen_E_020	Sirolimus	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Treatment with paclitaxel, sirolimus, and everolimus significantly induced a senescent phenotype as judged by SA-βgal and an enlarged, flattened cell morphological appearance at 10 days."	PAI-1//eNOS//SIRT1	Upregulation//Downregulation//Downregulation	Western blot	"In parallel with SA-βgal, expression of PAI-1 was increased by treatment with paclitaxel, sirolimus, and everolimus .Paclitaxel, sirolimus, and everolimus decreased the expression of eNOS and Sirt1."	--	--	--	--	L	cellular senescence	19520256
Sen_E_021	LG2055	Chemical compounds	--	Worm	Aging	Prevent	SA-β-gal activity assay//Immunostaining	"We observed that feeding with LG2055 delayed aging, with intestinal lipofuscin( a marker of cellular damage during aging) levels being 12% lower in LG2055-fed worms than in OP50-fed worms. However, the ratio of stained area in the whole body was decreased in LG2055-fed worms compared with that in OP50-fed worms."	SKN-1	Upregulation	GFP localization assay	We observed that extrachromosomal and integrated transgenes driving skn-1c–gfp expression from ges-1 promoter 16 induced stronger fluorescence in LG2055-fed worms than in OP50-fed worms.	p38 MAPK	Activation	Western blot	"We observed that feeding with LG2055 altered the expression of genes involved in p38 MAPK signaling ；In addition, levels of phosphorylated p38 were increased in LG2055-fed worms ."	L	delay aging	26710940
Sen_E_022	Vitamin D3	Chemical compounds	--	Worm	Aging	Prevent	SDS-PAGE//GO analysis	"We found that in aged worms, D3 treatment significantly decreased the number of detectable and identified SDS-insoluble proteins compared to control samples .Previous work found that reducing expression of several genes encoding proteins suppressed by D3 treatment in aged worms by RNAi resulted in significant lifespan extension."	SKN-1	--	Lifespan assay	"We observed no lifespan extension by D3 for skn-1(zu135) mutant worms, demonstrating that SKN-1 is requiredfor the effects of D3 feeding."	IRE-1-XBP-1	--	Lifespan assay	"We found that the D3-induced increase on survival was dependent on IRE-1/XBP-1 signaling. Worms carrying the loss-of-function allele,ire-1(v33), showed significantly reduced lifespan with D3 feeding compared to vehicle-treated worms . Lifespan of worms maintaining the loss-of-function allele, xbp-1(zc12), showed no significant change with D3 feeding compared to vehicle-treated worms. Interestingly, ire-1(v33) mutant worms exhibited a shortened lifespan upon D3 feeding."	HL	delay aging	27783938
Sen_E_023	Calorie restriction	Other	--	Kidney	Aging	Prevent	SA-β-gal activity assay//ELISA	"SA-β-gal assay is an effective method to measure cell senescence21and significantly fewer SA-β-gal positive cells were observed in CR conditions.Compared with AL group, reduced production of renal TNF-a and IL-1β were observed in mice subjected to CR ,indicated that CR can reduce renal inflammatory activity effectively."	SIRT6	Upregulation	Immunostaining//Western blot//SA-β-gal activity assay	"Immunohistochemistry and Western blot analysis of SIRT6 indicated enhanced SIRT6 expression in CR condition. Our results strongly supports the evidence that CR can effectively prevent age-dependent renal failure and promotes in vivo SIRT6 expression.Using SA-β-gal staining, reduced number of SA-β-gal positive cells were observed in WI38 with SIRT6-WT overexpression, but not in cells with SIRT6-HY overexpression."	NF-κB	Downregulation	DAPI staining	"SIRT6 knockdown induced the translocation of NF-kB p65 into the nucleus along with enlarged cell bodies, indicated an activation of the NF-kB signaling and accelerated cell senescence ."	L	delay aging	26940461
Sen_E_024	Carbamide peroxide	Chemical compounds	RPMI8226	--	Myeloma	Accelerate	SA-β-gal activity assay//Western blot	"In the myeloma cell KM-HM_(31), CP treated cell and increased levels of aging proteins P53 and P16, indicating the establishment of a successful aging model for further studies."	SIRT6	Upregulation	Western blot	"We further observed that in cell aging model, Sirtuin 6 level was apparently increased, indicating the possible role of Sirtuin 6 to CP-induced myeloma cell KM-HM_(31) aging."	Hippo	Downregulation	Western blot	"Also, the evident reduction of Hippo was found in myeloma cell aging model compared to normal control."	L	cellular senescence	30402853
Sen_E_025	PQQ	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay	"The results showed that the percentage of cells stained by X?gal following 9 J/cm2 UVA irradiation was markedly increased compared with that in the control group (53 and 8%, respectively;  P<0.05), while 50 ng/ml PQQ attenuated the ratio of positive staining compared with that of the UVA-only cells (29 vs. 53%, respectively; P<0.01) ."	SIRT1//SIRT6	Upregulation//Upregulation	Western blot//qRT-PCR	"At 72 h following the addition of 50 ng/ml PQQ to the culture media of UVA-irradiated HDFs, mRNA and protein expression levels of SIRT1 and SIRT6 were found to be increased ."	Nrf2-HO-1	Activation	Western blot//qRT-PCR	"As SIRT1/Nrf2/HO?1 is a classical anti?apoptotic pathway, the present study investigated whether this pathway was involved in UVA-induced cell apoptosis. Altered expression levels of Nrf2 and HO?1 mRNA expression levels were not found to be significant in HDFs pre-treated with 50 ng/ml PQQ without UVA irradiation. However, following UVA irradiation, PQQ was shown to alter the mRNA and protein expression of Nrf2 and HO?1."	L	apoptosis	26126510
Sen_E_026	Everolimus	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Treatment with paclitaxel, sirolimus, and everolimus significantly induced a senescent phenotype as judged by SA-βgal and an enlarged, flattened cell morphological appearance at 10 days."	PAI-1//eNOS//SIRT1	Upregulation//Downregulation//Downregulation	Western blot	"In parallel with SA-βgal, expression of PAI-1 was increased by treatment with paclitaxel, sirolimus, and everolimus .Paclitaxel, sirolimus, and everolimus decreased the expression of eNOS and Sirt1."	--	--	--	--	L	cellular senescence	19520256
Sen_E_027	Aspirin	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay	"Treatment with aspirin decreased SA-β gal–positive cells and expression of PAI-1, but treatment with ticlopidine or clopidogrel did not have any effect on them."	PAI-1	Downregulation	Western blot	"Treatment with aspirin decreased SA-β gal–positive cells and expression of PAI-1, but treatment with ticlopidine or clopidogrel did not have any effect on them."	--	--	--	--	L	cellular senescence	19520256
Sen_E_028	Metformin	Chemical compounds	MEF	Embryo	Aging	Accelerate	SA-β-gal activity assay	Exposure of MEFs to metformin as a single agent augmented baseline senescence measured as the percentage of cells that have SA-β-gal activity between approximately 3 4-fold.	miR-200a	Upregulation	qRT-PCR	"When a 2-fold or greater difference in miRNA expression levels was used as the cut-off to determine significant regulatory effects on miRNAs involved in the EMT/ MET genetic program, we found that miR-200a (more than 20-fold), miR-141 and miR-429, three members of the miRNA200 family, were markedly upregulated in HDFs that have undergone SIS in response to metformin compared with young and old BJ-1 untreated fibroblasts ."	--	--	--	--	L	cellular senescence	22356767
Sen_E_029	PD-0332991	Chemical compounds	"EC109,EC9706"	--	Esophageal cancer	Accelerate	SA-β-gal activity assay	"Treatment with PD-0332991 drastically increased the activity of SA-β-gal, a marker for senescent cells in EC109 and EC9706 cells."	FOXM1	Downregulation	Western blot//SA-β-gal activity assay	"Western blotting analysis revealed that the protein level of FOXM1 was decreased by PD-0332991 in a concentration-dependent manner. Importantly, compared with si-control transfection, knockdown of FOXM1 obviously potentiated the PD-0332991-induced cellular senescence, as indicated by a significant increase in the percentage of SA-β-gal positive cells."	--	--	--	--	L	cellular senescence	28444744
Sen_E_030	5-AZA	Chemical compounds	ASC	Adipose	Aging	Prevent	Cell proliferation assay//SA-β-gal activity assay//Flow cytometry//qRT-PCR	"Cell activity in control culture declined after 24 hrs and began to increase after 48 hr till the last day of the experiment. Proliferation of cells cultured with 5-AZA was characterized by exponential cell growth during the whole experiment.we observed that 5-AZA treatment reduced the amount of enlarged cells in culture.Obtained results showed that the percentage of dead cells was decreased in 5-AZA treated cells (P < 0.01). Senescence associated accumulation of βgalactosidase (β-gal) was stained blue on histology samples. Number of positive stained cells was decreased in 5-AZA in comparison to control group.Quantitative analysis of transcripts revealed that expression of and p53 mRNA was significantly decreased in 5-AZA cultures . Similarly, the level of p21 transcript was also decreased in experimental cultures. The ratio of Bcl-2/BAX mRNA was increased (P < 0.01) after 5-AZA treatment. GAPDH was used as an endogenous control."	--	--	--	--	--	--	--	--	L	deregulated nutrient sensing	27998022
Sen_E_031	Doxorubicin	Chemical compounds	BJ	--	Aging	Accelerate	SA-β-gal activity assay	"Thus in order to induce senescence we treated BJ cells with 50 and 100 ng/ml of doxorubicin for 5 days as suggested in literature [38]. Induction of senescence was evident with increased SA-β-gal activity, increased levels of p53 and p21CIP1 and γ-H2A.X foci formation."	SIRT1//SIRT3	Downregulation//Downregulation	Western blot	Remarkably WB analysis showed that expressions of SIRT1/2 were also slightly reduced during doxorubicin induced senescence.	p53-p21	Activation	SA-β-gal activity assay//Western blot	"Additionally, when we tested p16 INK4A levels we found rather minor increase in p16INK4A levels suggesting doxorubicin induced senescence is mediated mainly by activation of p53-p21 pathway ."	L	apoptosis	25924011
Sen_E_032	Resveratrol	Chemical compounds	BJ	--	Aging	Accelerate	SA-β-gal activity assay//Immunofluorescence	"The number of SA-β-gal positive senescent cells was significantly increased in resveratrol-treated cells compared to control or DMSO treated cells. Furthermore, the percentage of SA-β-gal positive cells increased with the concentrations of resveratrol indicates that resveratrol induces premature senescence in a dose-dependent manner.Results showed that H3K9-me3 positive stained cells were also increased in BJ cells treated with the increasing concentrations of resveratrol."	SIRT1//SIRT2//p16	Downregulation//Downregulation//Activation	Western blot//qRT-PCR	"Interestingly, Western blotting analysis showed that expression of SIRT1 and SIRT2 proteins were significantly decreased upon 10 μM resveratrol treatment and also continued at higher concentrations (25, 50 and 100 μM). We confirmed these data by RT-qPCR analysis and showed that mRNA level of SIRT1 and SIRT2 was also significantly decreased starting with 10μM resveratrol treatment in BJ fibroblasts.As shown by Western blotting the expression levels of p53, p21CIP1 and p16INK4A were significantly increased upon 10 μM of resveratrol treatment in BJ cells, compared to control or DMSO."	p53-p21	Activation	Western blot	"As shown by Western blotting the expression levels of p53, p21CIP1 and p16INK4A were significantly increased upon 10 μM of resveratrol treatment in BJ cells, compared to control or DMSO ."	L	apoptosis	25924011
Sen_E_033	Baker ethanol extract	Chemical compounds	Hs68	--	Aging	Prevent	MTT assay//SA-β-gal activity assay//RT-PCR//Western blot	"H2O2 exposure reduced cell proliferation compared to the normal cells;however,KPE treatment significantly reinstated the proliferative activity of Hs68 cells to almost the normal level .H2O2 exposure caused almost a 1.39-fold increase in the SA-β-gal activity in Hs68 cells, but this activity was dose-dependently decreased by KPE. The mRNA levels of cell-cycle inhibitors were significantly reduced by KPE treatment. The protein expression of cell-cycle inhibitors was dosedependently reduced upon KPE treatment .H2O2-induced senescent Hs68 cells exhibited higher IL-6 and IL-8 mRNA levels than that in normal cells; however, KPE treatment markedly reduced these mRNA levels.The protein expression of other inflammatory markers, NF-kB and COX-2, was also decreased by KPE treatment as compared to that in the H2O2 control ."	SIRT1//PGC-1α	Upregulation//Upregulation	RT-PCR//Western blot	"SIRT1 mRNA expression was significantly upregulated by KPE compared to that in the H2O2 control. The protein level of SIRT1 was also increased in KPE treated Hs68 cells. Reduced expression of PGC-1α, which is responsible for mitochondrial function and biogenesis, was recovered by KPE treatment."	PI3K-Akt//p53-p21//p16-pRb	Downregulation//Downregulation//Downregulation	RT-PCR//Western blot	"The H2O2-induced expression of PI3K and phospho-AKT was decreased by KPE without any visible changes in the total AKT level compared to that in the H2O2 control.Compared to young mice intrin- sically MA mice showed increased mRNA and protein levels of cell-cycle inhibitors, including p53, p21,p16, and pRb. In the KPE administered group, the p53, p21,p16, and pRb levels exhibited 33.1%, 44.4%, 40.8%, and 37 .4% reduction, respectively, compared to those in the intrinsically MA group. The protein levels of cell-cycle inhibi- tors were also attenuated by KPE treatment."	L	delay aging	28831286
Sen_E_034	HIV Tat	Other	PT-ECFC	--	Aging	Accelerate	Western blot	Expression levels of GFAP(astrocyte activation as an indicator of aging) were significantly increased with aging in the both the WT and Tg rats.	SIRT1//miR-34a//miR-138	Downregulation//Upregulation//Upregulation	Western blot//qRT-PCR	"A significant decrease in SIRT1 protein content was detected in both A172 and human primary astrocytes following stimulation with HIV Tat;And in keeping with the in vivo data, there was increased expression of miRs-34a & -138 in the both cell line and primary astrocytes treated with HIV Tat compared with untreated control cells."	NF-κB	Upregulation	Western blot	Pretreatment of A172 cells with Ikk-2 inhibitor SC514 (5 μM) significantly decreased HIV Tat-mediated induction of GFAP.This was further confirmed by the fact that transfection of A172 cells with mutant IκB  resulted in amelioration of HIV Tat-mediated induction of GFAP .	L	delay aging	28236278
Sen_E_035	Atorvastatin	Chemical compounds	Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay//BrdU assay	"Treatment with atorvastatin, pravastatin, or pitavastatin inhibited the senescent phenotype at 10 days.In parallel with this, an increased rate of 5-bromodeoxyuridine (BrdU) (index of proliferation) incorporation and telomerase activity were restored by treatment with atorvastatin, pravastatin, and pitavastatin."	SIRT1//eNOS	Upregulation//Activation	Western blot	"In the presence of H2O2, treatment with atorvastatin, pravastatin, and pitavastatin increased eNOS expression dose dependently. In parallel with eNOS expression, activity of eNOS was increased by treatment with atorvastatin,We found that atorvastatin, pravastatin, and pitavastatin significantly increased SIRT1 expression in a concentration-dependent manner for 10 days after treatment with H2O2."	Akt	--	Western blot	"Treatment with atorvastatin, pravastatin, or pitavastatin increased the phosphorylation of Akt at Ser473."	L	delay aging	20705918
Sen_E_036	Regulatory T cells	Other	"CD4+CD25?T,CD8+T,B,NK"	Blood	Aging	Accelerate	TRAP assay//Flow cytometry//SA-β-gal activity assay	"Using the TRAP assay, we found that both nTregs and iTregs could induce the inhibition of telomerase activity in all the target cells.Upon co-cultivation with Tregs, we observed a significant decrease in the number of target cells in the S and G2/M phases and a reliable increase in the number of cells in the G0/G1 phases 30 days after transfection. β–Gal expression levels remained stably high over the days 60. β–Gal enzymatic activity also increased 45 days after transfection and remained high on day 60."	α+β+hTERT	Upregulation	Western blot//RT-PCR	"Western blotting results showed a significant decrease in full-length α+ β+ hTERT and an increase in α+β– hTERT and EndoG in the target cells co-cultured with nTregs or iTregs Real-time RT-PCR revealed that cultivation of the target cells in the absence of iTregs resulted in a gradual increase in α+ β+ hTERT expression, decrease in α+ β– hTERT expression and decrease in EndoG expression to the levels of the control target cells over 48 h."	--	--	--	--	L	apoptosis	30025223
Sen_E_037	Lipodystrophy	Other	VSMC	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//Cell morphological analysis	"We tested senescence markers in LMNA-mutated and observed that SA-β-galactosidase activity was increased by 2.2- to 2.5-fold in LMNA mutant versus WT.The protein expression of the senescence markers, p16INK4, p21WAF, p53 and phospho-p53 was also altered. LMNA mutant harbored the typical morphology of senescent cells, with an increased number of prelamin A-stained nuclei showing dysmorphies, and of foci containing phosphorylated histone γ-H2AX indicating DNA damages."	ZMPSTE24	Downregulation	Western blot	"We first evaluated the expression of miR-141-3p, which was shown by Yu et al. to regulate ZMPSTE24 protein expression during cellular senescence [40]. The level of miR-141-3p was increased by 1.5-fold in VSMCs expressing D47Y and R482W LMNA mutant and by 2-fold in LPV/r-treated cells, as compared to control cells."	--	--	--	--	L	cellular senescence	26724531
Sen_E_038	HIV protease inhibitors	Other	VSMC	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//Cell morphological analysis	"We tested senescence markers in PI-treated VSMCs and observed that SA-β-galactosidase activity was increased by 3- to 4-fold in LPV/r- and ATV/r-treated cells versus DMSO .The protein expression of the senescence markers, p16INK4, p21WAF, p53 and phospho-p53 was also altered .LPV/r-treated VSMCs harbored the typical morphology of senescent cells, with an increased number of prelamin A-stained nuclei showing dysmorphies, and of foci containing phosphorylated histone γ-H2AX indicating DNA damages."	ZMPSTE24	Downregulation	Western blot	"We first evaluated the expression of miR-141-3p, which was shown by Yu et al. to regulate ZMPSTE24 protein expression during cellular senescence [40]. The level of miR-141-3p was increased by 1.5-fold in VSMCs expressing D47Y and R482W LMNA mutant and by 2-fold in LPV/r-treated cells, as compared to control cells."	--	--	--	--	L	cellular senescence	26724531
Sen_E_039	Estrogen	Chemical compounds	MCF-7	--	Breast cancer	Prevent	SA-β-gal activity assay	The addition of 1 nM beta-estradiol to MCF-7 cells grown in charcoal-stripped serum brought the level of cellular senescence down to 35% β-galactosidase positive cells.	YPEL3	Downregulation	SA-β-gal activity assay//RT-PCR//Knockdown	"In contrast, shLacZ expressing MCF-7 cells did show the expected induction of cellular senescence when grown in charcoal-stripped serum. Knockdown of YPEL3 expression was confirmed with relative mRNA expression."	--	--	--	--	L	cellular senescence	21671470
Sen_E_040	Estrogen	Chemical compounds	A549	--	Werner syndrome	Prevent	SA-β-gal activity assay//Western blot	"Estrogen was able to block the adriamycin-induced DcR2 and p16/INK4A, molecular markers of senescence. SA-β-Gal staining also showed a similar pattern so that estrogen was able to block the adriamycin-induced senescence ."	WRN	Upregulation	Western blot	"The transcript of WRN was induced by estrogen treatment in a time-dependent manner. In the same cell line, we could also observe the induction of WRN protein expression."	--	--	--	--	L	delay aging	20395656
Sen_E_041	Pravastatin	Chemical compounds	Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay//BrdU assay	"Treatment with atorvastatin, pravastatin, or pitavastatin inhibited the senescent phenotype at 10 days.In parallel with this, an increased rate of 5-bromodeoxyuridine (BrdU) (index of proliferation) incorporation and telomerase activity were restored by treatment with atorvastatin, pravastatin, and pitavastatin."	SIRT1//eNOS	Upregulation//Activation	Western blot	"In the presence of H2O2, treatment with atorvastatin, pravastatin, and pitavastatin increased eNOS expression dose dependently. In parallel with eNOS expression, activity of eNOS was increased by treatment with atorvastatin,We found that atorvastatin, pravastatin, and pitavastatin significantly increased SIRT1 expression in a concentration-dependent manner for 10 days after treatment with H2O2."	Akt	--	Western blot	"Treatment with atorvastatin, pravastatin, or pitavastatin increased the phosphorylation of Akt at Ser473."	L	delay aging	20705918
Sen_E_042	Pitavastatin	Chemical compounds	Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay//BrdU assay	"Treatment with atorvastatin, pravastatin, or pitavastatin inhibited the senescent phenotype at 10 days.In parallel with this, an increased rate of 5-bromodeoxyuridine (BrdU) (index of proliferation) incorporation and telomerase activity were restored by treatment with atorvastatin, pravastatin, and pitavastatin."	SIRT1//eNOS	Upregulation//Activation	Western blot	"In the presence of H2O2, treatment with atorvastatin, pravastatin, and pitavastatin increased eNOS expression dose dependently. In parallel with eNOS expression, activity of eNOS was increased by treatment with atorvastatin,We found that atorvastatin, pravastatin, and pitavastatin significantly increased SIRT1 expression in a concentration-dependent manner for 10 days after treatment with H2O2."	Akt	--	Western blot	"Treatment with atorvastatin, pravastatin, or pitavastatin increased the phosphorylation of Akt at Ser473."	L	delay aging	20705918
Sen_E_043	Ionizing radiation	Other	Rabbit Articular Chondrocyte	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//Cell morphological analysis//Cell counting	"The cytosol stained positive for senescent cells (blue), and 60 and 90% of cells displayed SA-β-gal activity at 48 and 72 h, respectively.p53 accumulation and phosphorylation at Ser-15 peaked 3 h after IR, and p21 was activated by a p53-dependent pathway. IR treatment resulted in induction of p16, a positive regulator of pRb, and thus caused hypophosphorylation and activation of pRb. Consistent with SA-β-gal activity, characteristics of senescence, such as large and flat morphology, were identified in cells treated with IR in a dose-dependent manner. Various doses of IR ranging from 0 to 10 Gy additionally caused a decrease in number of chondrocytes in a concentration-dependent manner at 48 h after irradiation , and this phenomenon was also dependent upon the time after irradiation with 10 Gy."	SIRT1	Downregulation	Western blot	"IR treatment with 10 Gy resulted in a time-dependent reduction in the SIRT1 protein level after irradiation and increased acetylation level of histone H3, a major deacetylation substrate of SIRT1 ."	ROS-p38//ERK	--//--	Flow cytometry//SA-β-gal activity assay//Western blot	"Consistent with these findings, at 6 and 12 h after irradiation, ROS levels increased significantly with the radiation dose in primary cultured articular chondrocytes. ROS production was continuously accumulated up to 8 h and then slightly reduced at 12 h after IR treatment. Conversely, phosphorylation of p38 kinase was continuous and lasted up to 12 h after IR treatment.To establish the feedback linkage between elevation of the intracellular ROS level and MAPK activation in IRtreated articular chondrocytes, cells were preincubated with specific MAPK inhibitors.Pretreatment of cells with the p38 kinase-specific inhibitor, SB203580, did not affect IR-induced ROS generation at the early time point (90 min; top) but led to the complete inhibition of ROS production at a later time point (12 h; middle) with concomitant suppression of SA-β-gal activity after IR treatment (48 h; bottom). The results support the formation of a ROS-p38 positive feedback loop to sustain down-stream signaling. In contrast, the ERK inhibitor, PD98059, significantly suppressed IR-induced ROS generation at the early and late time points (top and middle) as well as SA-β-gal activity (bottom), indicating that the ERK pathway acts upstream of ROS generation."	L	cellular senescence	19887452
Sen_E_044	Sirtinol	Chemical compounds	"MCF-7,H1299"	--	Cancer	Accelerate	BrdU assay//SA-β-gal activity assay//Western blot//Colony formation assay	"Treatment with Sirtinol inhibited cell growth in both MCF-7 and H1299 cells；This was supported by reduced incorporation of BrdU in Sirtinol-treated MCF-7 and H1299 cells at 10 days after the addition of Sirtinol, as compared with untreated cells；Sirtinol treatment increased SA-β-gal-positive cells in a dose-dependent manner 10 days after the addition of Sirtinol in both MCF-7 and H1299 cells；Sirtinol treatment also resulted in increased expression of PAI-1 in both MCF-7 and H1299 cells.Colony formation assay also revealed that both Sirtinol and Splitomicin elicited antiproliferative effects in MCF-7 and H1299 cells in a dose-dependent manner."	SIRT1	Downregulation	Cell morphological analysis//SA-β-gal activity assay	"Sirt1 inhibition by Sirtinol, Splitomicin or siRNA also induced senescence-like phenotype in human diploid fibroblasts, WI-38 and IMR-90 cells, reflected by induction of SA-β-gal staining, and enlarged and flattened cell morphology."	Ras-MAPK	--	Western blot	"By contrast, in Sirtinol-treated senescent MCF-7 and H1299 cells at 10 days after the addition of Sirtinol (100mM), basal (unstimu-lated) phosphorylation of ERK, JNK/SAPK and p38 MAPK was reduced compared with untreated cells."	L	cellular senescence	16170353
Sen_E_045	Trimethylamine-N-oxide	Chemical compounds	--	Aorta	Cardiovascular disease	Accelerate	SA-β-gal activity assay//Western blot//Cell viability assay//Flow cytometry//Wound healing assay	"After TMAO treatment, the SA-β-gal activity was slightly increased in the SAMR1 group and further elevated in the SAMP8 mice.HUVECs treated with 200 mM and 500 mM TMAO showed a decrease in the cell proliferation rates in a time-dependent manner.Then, SA-β-gal staining and western blot analyses were performed.Gradual increases in the percentage of SA-β-gal positive cells and the slight upregulation of p53, p21, and plasminogen activator inhibitor-1 (PAI-1) were observed in TMAO-treated HUVECs.TMAO treatment resulted in G0/G1 cell cycle arrest. Moreover, TMAO treatment decreased cell migration in HUVECs measured using a wound-healing assay."	SIRT1	Downregulation	Western blot//RT-PCR	The NO concentration and the expression of eNOS and SIRT1 decreased in SAMP8 mice compared with SAMR1 mice.	p53-p21-Rb	Activation	Western blot//qRT-PCR	"TMAO treatment could increase the expression of p53 and p21, induce acetylation of p53, decrease the expression of CDK2 and cyclinE1, and reduce the phosphorylation of Rb. Quantitative PCR analysis showed comparable results."	L	cellular senescence	29325896
Sen_E_046	Bood flow	Other	HUVEC	Aorta	Atherosclerosis	Accelerate	SA-β-gal activity assay	"Studies using porcine aortae ( 6 months old) revealed SA-β-gal positive staining at sites of disturbed flow including the origin of the left subclavian artery and brachiocephalic trunk and along the inner curvature of the aortic arch. The percentage of large, SA-β-gal positive (senescent) cells was significantly higher at the disturbed flow region compared with the undisturbed flow region or compared with static cultures in both venous and arterial ECs. Similarly, studies using syringe-pump flow bioreactor systems revealed that oscillatory flow induced cells that were SA-β-gal positive, large, and multinucleated, whereas undisturbed flow did not."	SIRT1	--	SA-β-gal activity assay//Immunofluorescence	"Pretreatment of ECs using resveratrol (100 μmol/L) reduced the subsequent induction of senescent ECs by disturbed flow. Suppression of sirtuin 1 by treatment with sirtinol or by gene silencing restored the induction of EC senescence by disturbed flow in resveratrol-treated cells, indicating that resveratrol protects ECs via sirtuin 1.  Similarly, it was concluded that SRT1720 can protect ECs from senescence because treatment using this compound significantly reduced the induction of p21 and activation of SA-β-gal in response to disturbed flow."	p53-p21	--	SA-β-gal activity assay//Immunofluorescence	"Single-cell analysis of proteins levels by immunofluorescent staining revealed that p53 and p21 expression was strikingly elevated in senescent ECs compared with nonsenescent cells, and costaining revealed that p53 and p21 were coexpressed in senescent ECs.In cultures exposed to disturbed flow, silencing of p53 or p21 significantly reduced the incidence of senescent cells."	L	cellular senescence	24651677
Sen_E_047	Glucocorticoid	Chemical compounds	Tenocyte	--	Aging	Accelerate	SA-β-gal activity assay	"By 48 and 72 h post-treatment, a significant increase in the percentage of SA-β-gal-positive cells was observed."	SIRT1	Downregulation	qRT-PCR//Western blot	"We found a small but significant reduction in RNA levels of sirt1, but a marked reduction in protein levels in glucocorticoid-treated cells compared with carrier-treated controls."	p53	Activation	Western blot	"In contrast, levels of acetylated p53 (but not phosphorylated p53) were higher in glucocorticoid-treated tenocytes compared with controls. While there were no significant differences in p53 RNA levels, RNA levels of p21cip/waf1, a pro-senescence modulator of p53 activity, were markedly elevated post-glucocorticoid treatment ."	L	delay aging	23727633
Sen_E_048	Inauhzin	Chemical compounds	H460	--	Lung cancer	Accelerate	SA-β-gal activity assay//Knockdown	"INZ induced senescence in H460 or HCT116p53+/+, but not in HCT116p53?/?, cells, though to a much less degree than did Nutlin-3."	SIRT1	Downregulation	Western blot	"INZ inhibited SIRT1 deacetylase activity in a dose‐dependent fashion and effectively inhibited this activity at 3?μM. This inhibition was specific to INZ and its chemical analogue INZ1 (methyl substituted R1), which activated p53 and decreased SIRT1 activity in a dose‐dependent fashion."	p53	Upregulation	Western blot	We found that INZ induced p53 level in a time-dependent manner as early as 6 h post-treatment in both p53-containing H460 and HCT116 cells.	L	delay aging	22331558
Sen_E_049	Vitamin D	Chemical compounds	HUVEC	--	Aging	Prevent	Flow cytometry//Western blot//SA-β-gal activity assay	"In quiescent HUVEC, 24 h of Vit.D pre-treatment reduced ROS generation induced by increasing doses of IR (p < 0.05), achieving the maximum efficacy at 75 nmol/l. Vit.D at this concentration reduced the ROS production by 33.3 % (RT 2 Gy), 46.1 % (RT 4 Gy), 63 % (RT 6 Gy), 54.1 % (RT 8 Gy). On quiescent HUVEC treated with IR, Vit.D pre-treatment, compared to non-Vit.D pre-treatment, reduced by 46.3 % and increased by 65 % the cells in G0 or G1cell cycle phase, respectively, reduced over 45.7 % the β-galactosidase content compared to cells non Vit.D pretreated and prevented the p53 phosphorylation and both p21Cip1/Waf1 and p16INK4a proteins up-regulation, all marker of cellular senescence."	SIRT1	Upregulation	Western blot	"In proliferating HUVEC, Vit.D pre-treatment counteracted SirT1 protein expression downregulation mediated by IR and this action was annulled by U0126-mediated MEKs/ERKs inhibition."	p38	Downregulation	Western blot//MTT assay//TUNEL assay	MKK6 over-expression activated basal levels of p38 that were further increased by RT and slightly reduced by Vit.D treatment.	L	apoptosis	26335302
Sen_E_050	Glucose Restriction	Other	Fibroblast	--	Aging	Prevent	SA-β-gal activity assay//Cell proliferation assay	"The lifespan of all three human fibroblasts cell lines grown in GR medium was extended by an additional 2–4 weeks accompanied by an additional 5–10 PDs, which constituted a 23–67 prolongation of lifespan depending on different types of cells in GR medium.We found a low proportion of senescent cells in all three types of fibroblasts at the early stage of cell proliferation both in NG and GR medium-treated cells. Further, no prominen differences in SA-β-gal activity were observed between fibroblast cells with the treatment of NG and GR medium at early passage. However, successive subculture resulted in significantly increased senescent cells accumulation in NG medium versus GR medium at late passage."	SIRT1	Upregulation	Western blot//qRT-PCR	"We discovered that GR significantly increased SIRT1 mRNA and protein levels expression, most notably in late passage of cell growth and that this applied to all of the cell lines we examined."	p16-Rb//Akt-p70S6K1	Downregulation//Activation	Western blot	"Our results revealed a gradually increased p16 expression was accompanied by reduced expression of phosphorylated Rb (Ser-795) in NG medium during the cellular passaging . However,in GR medium, p16 protein signals were barely detected and expression of phosphorylated Rb was increased accordingly.Phosphorylated Akt and Akt protein kinase showed an increased expression trend during increased PDs in response to GR.p70S6K1 is a downstream target of Ak,GR caused a decreased expression of mTOR and its dependent protein kinases, phosphorylated p70S6K1 (Thr-389, Thr-421/Ser-424), whereas it did not affect the expression of p70S6K1 total protein, compared with the protein expression in NG."	L	delay aging	21390332
Sen_E_051	Amyloid beta oligomer	Other	HBMEC	--	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay	"S1A and S1B, HBMECs exposed to Aβ1–42 oligomers showed increased senescence-associated β-galactosidase staining (> 60% compared to ~23% in controls), confirming a senescent phenotype.Using optical microscopy, we observed that the morphology of β-galactosidase positive Aβ1–42 oligomer treated HBMECs displayed a mixed population of normal appearing cells as well as enlarged cells with a flatter and spread-out nucleus, the latter being a characteristic feature of senescent cells."	VEGFR-1//Rac1	Upregulation//Downregulation	Western blot	"Furthermore, we showed that VEGFR-1 was highly upregulated in HBMECs following treatment with Aβ1 42 oligomers and knockdown of VEGFR-1 significantly reduced Aβ1 42 oligomerinduced senescence in the HBMECs, suggesting a key role of VEGRF-1 expression and signaling in this paradigm.Quantification of the western blot showed a significant reduction in Rac 1 protein levels in the senescent HBMECs (~40 50% reduction compared to untreated controls."	--	--	--	--	L	cellular senescence	31513781
Sen_E_052	Resveratrol	Chemical compounds	"U87 MG,U-118 MG"	--	Glioma	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Resveratrol induced dramatic changes in cell volume and cell morphology in both U87 and U118 cells. Specifically, resveratrol transformed spindle-shaped glioma cells to enlarged and irregular flattenshaped ones.SA-β-gal was detected in these hypertrophic cells."	uH2B	Downregulation	Western blot	Resveratrol inhibited uH2B within 4 h in a dose-dependent manner.	--	--	--	--	L	delay aging	21481687
Sen_E_053	4-hydroxynonenal	Chemical compounds	VEC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Treatment with 10 lM 4-HNE increased the proportion of senescent cells, demonstrated by cellular enlargement and positive staining for SA-β-gal ."	TXNIP//PPARd	Upregulation//Activation	Western blot	We found increased TXNIP expression in VEC incubated with 10 lM 4-HNE for 7 days.TXNIP expression was increased in VEC co-cultured with foam-cells. The 4-HNE scavenger FL926-A16 decreased TXNIP expression in VEC co-cultured with foam cells.The selective PPARd antagonist GSK0660 abolished 4-HNE effects on the expression of the different senescence markers and prevented the upregulation of TXNIP.	--	--	--	--	L	cellular senescence	25754218
Sen_E_054	Sulforaphane	Chemical compounds	Chondrocyte	--	Aging	Prevent	SA-β-gal activity assay	There was also a decrease in net L-lactate formation and onset of increased cell senescence - as indicated by decreased cell staining for β-galactosidase activity with SFN treatment.	TXNIP//HK2	Upregulation//Downregulation	RT-PCR//Western blot	"The most profound effect of senescence on the gene expression of MRC-5 cells was the 8-fold increase in the expression of TXNIP. This was increased further to 21- fold by treatment with SFN .HK1 and HK2 mRNA levels were increased in senescent MRC-5 fibroblasts, and this was not corrected by SFN, although there was a time treatment effect where SFN decreased mRNA of HK1 and HK2 in senescence. In BJ fibroblasts, SFN treatment increased HK1 mRNA modestly in both early and late passages whereas for HK2 it was decreased in senescence. A similar effect was found in BJ fibroblasts where SFN decreased HK2 protein in senescence ."	--	--	--	--	HL	cellular senescence	30595796
Sen_E_055	Harmine	Chemical compounds	"A549,H460,H358"	--	Lung cancer	Accelerate	SA-β-gal activity assay//Western blot	"Similar to silencing of TWIST1, treatment of the KRAS mutant NSCLC lines A549, H460, and H358 with harmine-induced changes characteristic of OIS, including positive Senescence-Associated β-galactosidase (SA-β-Gal) staining and induction of p21 and p27. We also found that harmine treatment induced OIS in NSCLC cell lines with EGFR and MET mutations ."	TWIST1//E3A	Downregulation//Downregulation	Western blot	"Harmine treatment reduced the levels of TWIST1 protein in a dose- and time-dependent manner as shown by Western blotting. Remarkably, treatment with harmine resulted in a dose-dependent decrease of E2A protein expression in both KRAS-mutant and MET-mutant/amplified NSCLC cell lines."	--	--	--	--	L	apoptosis	28851812
Sen_E_056	BTM-0512	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay	"A trend for increased senescence, although non-significant, could be observed at 24 h after treating the endothelial cells with D-glucose (30 mmol ? L), which reached the significant level at 48 h after the treatment. The high glucose-induced senescence was significantly reduced in the presence of BTM-0512 at a concentration of more than 3 lmol ? L. L-glucose (30 mmol ? L) and the vehicle (0.1% alcohol) had no effect on cell senescence."	SIRT1	Activation	RT-PCR	"Moreover, BTM-0512 also reversed the high glucose-induced downregulation of SIRT1 mRNA expression."	DDAH-ADMA	--	qPCR//Western blot	"Administration of BTM-0512 alone dramatically upregulated DDAH2 mRNA expression and DDAH activity .Transfection of HUVEC with PGCsi-DDAH2-shRNA successfully knocked down the DDAH2 mRNA expression, reduced the DDAH activity and increased the level of ADMA in the cultured medium ."	L	cellular senescence	20132235
Sen_E_057	Bradykinin	Other	EPC	--	Diabetes	Prevent	SA-β-gal activity assay	Furthermore both 0.1 nM and 1.0 nM BK dramatically inhibited H2O2-induced hEPC senescence compared to cells treated with H2O2 alone.	Rb	Downregulation	PCR	"Notably, RB gene expression was down-regulated 176.15-fold after BK treatment."	B2R-Akt-cyclin D1-Rb//B2R-EGFR-cyclin D1-Rb	--//--	Western blot	"P-Ser473AKT expression was down-regulated following treatment with 300 μM H2 O2 compared to control cells. Furthermore, BK increased P-Ser473AKT expression in H2 O2 -treated hEPCs, while B2R blockade and siRNA knockdown, along with PI3K antagonist treatment, reduced P-Ser473AKT expression in H2 O2 -treated hEPCs compared to treatment with BK and H2 O2 alone. However, the addition of AG1478 had no impact on P-Ser473AKT expression compared with BK treatment alone. Furthermore, there were no differences found in total AKT expression between groups, indicating that these results were due to changes in protein phosphorylation and not expression. Cyclin D1 expression was elevated in controls but reduced dramatically following H2O2 -induced senescence. Also, while BK treatment up-regulated cyclin D1 expression, treatment with either a B2R antagonist or siRNA along with PI3K antagonist treatment reduced cyclin D1 and P-Ser473AKT expression compared with BK and H2 O2 treatment alone. Treatment with AG1478 also reduced cyclin D1 expression. Additionally, we found that changes in the expression of P-Ser249 and Thr252RB paralleled those of cyclin D1."	HL	cellular senescence	26360782
Sen_E_058	Temsirolimus	Chemical compounds	Fibroblast	--	Hutchinson-Gilford progeria syndrome	Prevent	Immunocytochemistry//SA-β-gal activity assay//Cell viability assay	"Immunocytochemistry:temsirolimus significantly stimulated autophagy in both normal and HGPS fibroblasts.viability assays:viability assays confirmed that temsirolimus increased the number of viable cells in HGPS culturesSA-β-gal activity assay:In the presence of temsirolimus, the number of β-Gal-positive cells was decreased in both control (2.0%) and HGPS (5.9%) cultures.Immunocytochemistry:Temsirolimus treatment induced a decreased number of γH2A.X-positive HGPS nuclei (36.1%) signifying a reduction in DNA damage."	Progerin	Downregulation	Western blot	Western blot analyses of long-term cultures showed reduced levels of progerin in HGPS cells treated for 85 days.	mTOR	Downregulation	Western blot	"As expected, temsirolimus lowered the phosphorylated 4E-BP1 and S6RP protein levels, indicating that the mTOR-signaling pathway was inhibited."	L	cellular senescence	28033363
Sen_E_059	ZnPyr	Chemical compounds	Dermal Fibroblast	Skin	Aging	Accelerate	SA-β-gal activity assay	ZnPyr at the concentration of 125 nM markedly increased the expression of the aforementioned marker with the first significant changes occurring as early as at 6 h of treatment and with the maximum expression observed at 24 h of treatment.	p53//p38//NAC	--//--//--	SA-β-gal activity assay//Knockdown	"The results suggested that both oxidative stress and p53 play an important role in ZnPyr induced apoptosis. Similarly, 125 nM ZnPyr-stimulated premature senescence was targeted using the above mentioned manipulations. The rate of premature senescence in thus treated cells was slightly reduced in the presence of NAC. Conversely, both p38 and p53 knockdown significantly decreased the number of cells with premature senescence phenotype and this decrease was even more marked when both targets were inhibited simultaneously."	mTOR	--	SA-β-gal activity assay//Western blot	"Finally, mTOR pathway which is known to influence proliferation-senescence axis in cells was investigated in ZnPyr-treated fibroblasts. The results indicated its inhibition upon 500 nM ZnPyr treatment while 125 nM ZnPyr exposure had an opposite effect .mTOR-specific inhibitor had a significant effect on ZnPyrinduced premature senescence too."	L	apoptosis	21557991
Sen_E_060	G-quadruplex ligand 12459	Chemical compounds	A549	--	Aging	Accelerate	Western blot//Immunostaining	"Prolongation of 12459 treatment to 8 days provokes a cell growth arrest where P21 expression became readily detectable, suggesting the onset of cell senescence. Results showed that DNA damage foci induced by 12459 co-localized with TRF1 and corresponded to TIFs (Telomere-dysfunction Induced Foci)."	p53//Chk1	Upregulation//Activation	Western blot	"Results indicate that 12459 treatment of A549 cells(0.5–2mM) induces a transient overexpression of p53 after 4 days.In contrast, a significant activation of Chk1(Ser317) was found at the onset of senescence after 8 days that coincides with the expression of p21."	PPM1D-WIP	Activation	Western blot	The expression of PPM1D/WIP1 was thus analyzed by western blot during the time-course induction of p53 by 12459 . Results show that PPM1D/WIP1 expression is activated by 12459 treatment and starts after 2 h. An increased level of PPM1D/WIP1 is maintained up to 48h.	L	telomere attrition	23396447
Sen_E_061	HU	Chemical compounds	MEF	Embryo	Aging	Accelerate	SA-β-gal activity assay//qRT-PCR//Western blot	"The mRNA and protein levels of each MCM declined as a function of time in culture.However, HU treatment triggered more severe senescence-associated phenotypes in M2 than WT primary MEFs, both in terms of markedly higher p16Ink4a/p19ARF induction and a ~2 fold increase in cells positive for SA-β-gal."	trp53	Upregulation	qRT-PCR	"We confirmed the sequencing results using miRNA qRT-PCR. Interestingly, Trp53 deletion abolished the HU induced miRNA upregulation in the WT primary MEFs, confirming these candidate miRNAs are Trp53-dependent."	--	--	--	--	HL	genomic instability	26765334
Sen_E_062	HCV infection	Other	CD4+T	Blood	Aging	Accelerate	Flow cytometry//qRT-PCR//Western blot// FISH	"Remarkably, at day 3 of TCR stimulation,CD57 expression on CD4+CD45RA+na?ve T cells was significantly increased in HCV patients compared with HS .HCV na?ve T cells exhibited higher mRNA levels of CDKN1A (encodes p21cip1), CDKN2A (encodes p16ink4a), and p53, as determined by real-time RT-PCR. However, we observed increases in p53 protein expression and cleaved poly ADP-ribose polymerase 1 (PARP-1) in unstimulated memory CD4 T cells,as well as increases in p21 and γH2AX levels in TCR-stimulated memory CD4 T cells derived from HCV patients. Telomere length was significantly shortened in HCV-derived total CD4 T cells,as well as in na?ve and memory CD4 T cells compared with HS."	TRF2	Downregulation	Western blot	The TRF2 protein level was significantly downregulated in na?ve CD4 T cells isolated from HCV patients.	--	--	--	--	L	telomere attrition	30185784
Sen_E_063	Cigarette smoke	Other	HFL-1	Lung	Chronic obstructive pulmonary disease	Accelerate	SA-β-gal activity assay//Western blot	"As expected, we found that CSE (0.5%) treatment for both 15 days and 30 days induced cellular senescence, which is characterized by increased senescence-associated β-galactosidase (SA-β-gal) activity, p16 (CDKN2A or INK4A) and p21 (CDKN1A) protein abundance."	TPP1//SIRT1	Downregulation//--	Western blot//Immunofluorescence	"Nuclear abundance of TPP1 and TIN2 was reduced with CSE .We performed coimmunoprecipitation of TPP1 with or without CSE (0.5% for 15 days) in HFL1 cells, and probed with acetyl lysine and the Sirt1 antibody. Similarly, Sirt1 pull-down was performed and the lysate was probed for the TPP1 antibody. This was further confirmed by co-immunofluorescence for Sirt1 and TPP1 in HFL1 cells."	--	--	--	--	L	cellular senescence	27559927
Sen_E_064	γ-irradiation	Other	HCT116	--	Aging	Accelerate	SA-β-gal activity assay	"The senescence-associated β-galactosidase (SA-β-gal)staining showed that p73 knockdown significantly increased the proportion of positive cells (~89.1% in p73i-1 and 79.7% in p73i-2 transfected cells) at 5 dpi, compared to the irradiated controls (~41.2%)."	TP73	Activation	Flow cytometry	"The proportion of cells in the G2 phase increased significantly in irradiated p73-knockdown cells(30.2% in p73i-1 and 27.2% in p73i-2 transfected cells),compared to that in irradiated control cells (17.8%)."	--	--	--	--	L	cellular senescence	29511339
Sen_E_065	Areca nut alkaloids	Chemical compounds	"NHOF-1,NHOF-5"	--	Oral submucous fibrosis	Accelerate	SA-β-gal activity assay//Immunofluorescence//Cell morphological analysis	"Using these doses, the oral fibroblasts adopted a flattened and enlarged morphology but did not display obvious signs of cell death.Permanent cell cycle exit is a hallmark of cellular senescence and, therefore, we performed immunofluorescence staining of oral fibroblasts to detect the cell cycle antigen Ki67. We then proceeded to test the effect of the alkaloids on the histochemical marker of senescence, SA-β-Gal. We showed that the fraction of positive cells increased after exposure to both alkaloids in a dose-dependent manner;All doses of ARC and ARD, the fraction of cells positive for  p16INK4A increases."	TGF-β//MMP2	Upregulation//Upregulation	ELISA	"ARC did not induce increased TGF-β accumulation in the CM at 100 lM, but that at 300 lM, there was ~threefold increase that approached statistical significance (P = 0.07). ARD induced ~ threefold increase at 30 lM that approached significance (P = 0.09) and ~ fivefold increase at 100 lM, which was highly significant (P < 0.02). Both doses of both alkaloids showed a small but insignificant increase in MMP-2 that showed a strong trend for significance at 100 lM ARD (P = 0.075) and at 100 lM ARC (P = 0.07) but slightly less so at 300 lM ARC and at 30 lM ARD (P = 0.1)."	--	--	--	--	L	cellular senescence	26414019
Sen_E_066	Metformin	Chemical compounds	HepG2	--	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay//Western blot//BrdU assay//Flow cytometry	"Low concentration of metformin induced HepG2 cell senescence in a dose-dependent manner, as evident by increased SA-β-gal activity, a universal marker of cellular senescence .Protein expression level of Dec1, one of he established markers for senescence (18) was enhanced in response to metformin compared with controls.HepG2 cells treated with 1 mM metformin exhibited a marked decrease in BrdU incorporation, a marker of cell proliferation.The results indicated that the percentage of G0/G1 phase cells was significantly increased in metformin treated cells and correspondingly, the cell population of G2/M was declined  compared with the controls."	p53	--	Western blot	The acetylation of p53 (Ac-p53) and p21 were increased in metformin-treated HepG2 cells.	AMPK	Activation	Western blot	"In metformin-treated senescent HepG2 cells, robust phosphorylation of AMPK and ACC was observed compared with untreated cells, indicating that activation of AMPK signaling cascade are relevant to the senescence in HepG2 cells."	L	cellular senescence	23982736
Sen_E_067	BI+PAC	Chemical compounds	"MCF-7,T47D"	--	Breast cancer	Prevent	SA-β-gal activity assay	"Our results showed that β-galactosidase staining was more prominent in untreated resistant controls in MCF 7/TAM and T-47D/TAM cells. However, on either drug treatments staining of these cells were decreased. Moreover, the numbers of stained cells in BI-PAC treatment are sparsely visible in both cells with respect to other treatments and controls."	p38	Downregulation	Western blot	In specific we also found that the activated p38 levels in BI-PAC treatments were drastically reduced in comparison to either drug.	NF-κB	Downregulation	Western blot	"In order to further ratify these results we carried immunoblot studies of downstream molecules of NF kb signaling such as IL6, XIAP, MMP2, MMP9 and cleaved caspase 9. We found that considerable decreased expression of IL6, XIAP, MMP2, and MMP9 were observed in combination treatments in comparison to other individual drug treatments and controls while contrastingly apparent increase of caspase 9 was observed in treatments."	L	apoptosis	26349973
Sen_E_068	Matrine	Chemical compounds	GBM	--	Aging	Accelerate	SA-β-gal activity assay//Immunofluorescence staining//Flow cytometry	"Flow cytometric analysis revealed that a greater percentage of U251, U87, and P3 cells were arrested in G1/G0 (~ 60% vs ~ 80% and 100%, control vs U251, U87, and P3 under 0.2 mmol/L matrine for 3 days;Matrine treatment for 3 days also led to increased γH2AX‐positive nuclei indicative of DNA double‐strand breaks , and accumulation of SA‐β‐gal‐positive cells ."	p27	Upregulation	Western blot	Matrine treatment induced a marked increase in p27 protein expression in both U251 and U87 cells within 24 hours.	IGF1-PI3K-Akt-p27	Downregulation	Western blot//SA-β-gal activity assay	"Matrine treatment led to decreased expression of two proteins associated with cycling cells, PI3K and pAKT . Activation of the pathway was partially restored when cells were treated simultaneously with SC79; pAKT was partially increased while p27 was decreased to control levels. exogenous IGF1 partially reversed the expression of PI3K, pAKT, and p27 .Anti‐IGF1 with matrine was more effective at inducing cellular senescence in both U251 and U87 cells than treatment with matrine alone ."	HL	cellular senescence	30079478
Sen_E_069	TMZ	Chemical compounds	"LN-229-MGMT,U87,LN-229"	--	Glioblastoma	Accelerate	Flow cytometry//PI staining//SA-β-gal activity assay	"The data revealed that repeated low-dose TMZ exposure is highly efficient in inducing senescence in p53 proficient U87 (up to 60%) and LN229 (up to 80%) cells .Compared to the high level of senescence, apoptosis and necrosis were induced at low levels (up to 20%) upon repeated treatment of U87 and up to 10% necrosis and 25% apoptosis upon single exposure. Also in LN229 cells repeated treatment induced up to 20% apoptosis and necrosis and single exposure induced up to 15% apoptosis and necrosis ."	p21//NF-κB	--//--	SA-β-gal activity assay//Flow cytometry	"In line with this, knockdown of p21 completely abrogated the induction of senescence , The results showed a dramatic reduction in temozolomide-induced senescence following NF-κB inhibition ."	MRN-ATR	--	SA-β-gal activity assay	"To analyze whether this is also true for the activation of senescence, the DDR factors ATM, ATR, MRN, and DNA-PKcs were pharmacologically inhibited and the frequency of senescence was measured in LN229 cells (proficient for p53 and deficient for MGMT) by scoring senescence-associated β-galactosidase (β-Gal)–positive cells. To identify the senescence-inducing DNA lesions, activation of senescence was also measured in LN229 cells that express MGMT following transfection with MGMT cDNA (LN229-MGMT). The data show that senescence was induced only in MGMT-deficient LN229 glioma cells, but not in the MGMT-proficient LN229-MGMT isogenic cell line."	L	apoptosis	30361254
Sen_E_070	The BET bromodomain inhibitor JQ1	Other	SW 13 53	--	Chondrosarcoma	Accelerate	Flow cytometry//BrdU assay	"Treatment of JQ1 significantly induced G0/G1 cell cycle arrest, and retarded S phase entering,consistent with the results from EdU incorporation assay.We investigated whether JQ1 induces senescence of SW 1353 cells.JQ1 did significantly increase senescence of SW 1353 cells."	p21	Upregulation	Western blot	"Knockdown of p21 induced by JQ1 decreased the expression of c-Myc and Bcl-xL, indicating that p21 is indeed an upstream regulator of c-Myc/Bcl-xL axis in the presence of JQ1."	YAP-p21-c-Myc	Activation	Western blot//Knockdown	"Consistent with this, JQ1 did significantly attenuate the c-Myc expression in both SW 1353 and Hs 819.T cells, as evidence by immunoblotting, suggesting that c-Myc is a direct target of JQ1 in these cells.Knockdown of p21 induced by JQ1 decreased the expression of c-Myc and Bcl-xL, indicating that p21 is indeed an upstream regulator of c-Myc/Bcl-xL axis in the presence of JQ1.We also demonstrated that knockdown of YAP up-regulated the expression of p21,suggesting that p21 is a downstream target of YAP in chondrosarcoma SW 1353 cells."	L	cellular senescence	28059436
Sen_E_071	TSY-1	Chemical compounds	"HL60,PBMV,HSC"	--	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay//Telomerase activity assay	"Under the microscope field,we found that the total number of healthy HL60 cells significantly decreased after TSY -1 treatment.After treatment,the dark blue staining became larger and denser,and the percentage of labeling cells also increased in HL60 cells.With the treatment of TSY -1, the Telomerase activity decreased significantly in HL60 cells."	TERT	Downregulation	Western blot	Western blot combined with immunoprecipitation showed that TERT protein level in HL60 cells decreased significantly after TSY-1 treatment by a dose-dependent manner .	--	--	--	--	HL	delay aging	28002788
Sen_E_072	GAPDH	Chemical compounds	MCF-7	--	Breast cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	Cells expressing exogenous GAPDH exhibited an enlarged and flattened morphology characteristic of typical stress-induced premature senescence cells.Further staining of cells expressing elevated GAPDH for senescence-associated β-galactosidase (SA-β-Gal) activity confirmed the cellular senescence phenotype. Approximately 91% of cells with enlarged flattened morphology showed SA-β-Gal positivity vs.less than 10% in the controls.	TERC	Binding	RT-PCR//Western blot	Purified human GAPDH bound full-length hTERC (1 451) in a concentration-dependent manner.	--	--	--	--	L	cellular senescence	22847419
Sen_E_073	F14512	Chemical compounds	P388	--	Cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"Cell cycle analysis revealed that the treatment of P388 cells with F14512 or etoposide resulted in S-phase accumulation at 4–8 h of treatment whereas the proportion of cells in G1 phase decreased.P388 cells positive for SA-β-gal demonstrated enlarged morphology.Using this flow cytometric method for quantitative analysis of senescent cells, we observed that F14512 was more successful in inducing premature senescence of P388 cells than etoposide."	Survivin	Upregulation	Western blot//Immunofluorescence	Immunofluorescence experiments revealed a pronounced increase of survivin level in the nucleus and to a lesser extent in the cytoplasm of F14512 or etoposide treated cells .Exposure of cancer cells to F14512 or etoposide resulted in a striking increase in survivin expression by western blotting.	--	--	--	--	L	apoptosis	22127645
Sen_E_074	Losartan	Chemical compounds	Human mesangial cell	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry	"Pretreatment with losartan decreased the percentage of SA-β-gal positive cells, reversed the distribution of cells at each phase."	STAT1	Downregulation	Western blot	"Pretreatment with losartan reduced the expression of STAT1, phosphorylation of STAT1, and phosphorylation of p53, p53, and p21Cip1."	--	--	--	--	L	cellular senescence	22217266
Sen_E_075	AngⅡ	Chemical compounds	Human mesangial cell	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"SA-β-gal positive cells were significantly increased in Ang II-stimulated cells, in contrast to the control cells (79.79% ± 5.44%; 7.09% ± 2.48%, p < 0.01).Cell morphology was enlarged and flattened after treatment with Ang II. Flow cytometry was used to characterize the nature of cell-cycle arrest. The cell cycle was arrested at the G0/G1 phase in the Ang II-stimulated group (87.98% ±1.83%), compared with the control cells (54.09% ± 1.22%,p < 0.05)."	STAT1	Activation	Western blot	"Ang II induced STAT1 activation during HMC senescence,as manifested by an increase in STAT1 phosphorylation."	--	--	--	--	L	cellular senescence	22217266
Sen_E_076	Low-power laser irradiation	Other	NIH-3T3	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//Western blot	"Both overexpression of HA-FOXM1c and LPLI treatment alone inhibited UVB-induced cell senescence by SA-β-Gal staining assay. More importantly, overexpression of HA-FOXM1c with LPLI further suppressed the cell senescence.We found that LPLI inhibited the expression of p21 about 20% changes compared to UVBtreated cells at 24 h.The p21 expression decreased at 36 h was almost the same as control cells, ultimately inhibited UVB-induced cell senescence.We found that overexpression of HA-FOXM1c with/without LPLI treatment significantly decreased the percentage of cells at the G0/G1 phase, suggesting that the protective function was due to an indirect effect of a perturbation in cell cycle progression."	p21	Downregulation	Western blot//Knockdown	"Overexpression of HA-FOXM1c promoted the expression of c-Myc with or without LPLI and inhibited the expression of p21, while adding PD98059 or knockdown of FOXM1 decreased c-Myc expression, and enhanced p21 expression even under LPLI."	ERK-FOXM1	Activation	Western blot//RT-PCR	"ERK translocation from cytoplasm to nucleus indicated that ERK was activated by LPLI, which was associated with phosphorylation as detected with Western blotting .Results show that LPLI increased the expression of FOXM1 at both protein and transcript levels, while PD98059 inhibited the effect of LPLI."	L	cellular senescence	23804320
Sen_E_077	Palbociclib	Chemical compounds	MPM	--	Malignant pleural mesothelioma	Accelerate	Cell cycle analysis//Cell morphological analysis//SA-β-gal activity assay//Western blot	"Palbociclib induced a significant blockade of the progression from G1 to S phase of the cell cycle in all MPM sensitive cells; Interestingly, treatment with palbociclib induced an accumulation of senescent-like cells, characterized by the production of the Senescent-Associated β-galactosidase enzyme (SA-β-Gal) and by flat and enlarged cell morphology;In addition, the level of cyclin D1 was increased, confirming cyclin D1 induction as a marker associated to cellular senescence."	p21	Upregulation	Western blot	"We observed a great increase in p21 expression,that might be ascribed to the release of p21 gene negative regulation exerted by myc, or to AKT/mTOR signaling activation, which has been shown to initiate p21-dependent senescence in particular conditions."	Akt-mTOR	Activation	Western blot	"The additive/synergistic inhibitory effects of the drug combination on cell proliferation were associated with a significant downregulation of p-CDK6, p-Rb, Rb levels, as well as with the inhibition of the AKT/mTOR pathway in both MSTO and ZS-LP cells."	L	cellular senescence	28704762
Sen_E_078	PM2.5	Other	Keratinocyte	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//Cell morphological analysis//Colony formation assay//DAPI staining	"PM2.5-treated cells exhibited β-galactosidase activity in the cytosol, a characteristic of cellular senescence, as evidenced by higher levels of green signal in PM2.5-treated cells than in untreated cells. Moreover, the expression of p16INK4A, a CDK inhibitor and senescence inducer, was considerably higher in PM2.5-treated cells than in the corresponding untreated cells . Furthermore, PM2.5-treated cells showed characteristics of cellular senescence, including an enlarged and flattened cell shape and irregular size, low proliferation, and decreased colony-forming ability. Chromatin in senescent cells undergoes large-scale rearrangement, forming dense nuclear domains called SAHF26. PM2.5-treated cells displayed significantly more SAHF-like chromatin foci in the nuclei than the controls."	p16INK5a//TET//DNMT	Upregulation//Upregulation//Downregulation	RT-PCR//Western blot//Immunofluorescence	"The mRNA expression of p16INK4A, a senescence inducer, was upregulated in PM2.5-treated cells from 3?h onwards, continuing up to 72?h. In agreement with the RT-PCR results, western blotting also revealed strong induction of the p16INK4A protein.DNMT1 and DNMT3B expression decreased 3–12?h after PM2.5 treatment, whereas TET1 expression increased transiently at 3–12?h after PM2.5 treatment. The decrease in the expression of DNMT1 and DNMT3B and the increase in TET1 observed at 3?h after treatment by western blot analysis was also confirmed by immunofluorescence."	AhR-ROS	Activation	Western blot//Immunofluorescence	"Immunoblotting data showed that the nuclear accumulation of AhR in PM2.5-treated cells occurred at 0.5?h and continued until 24?h. The nuclear accumulation of AhR was confirmed by immunofluorescence at 0.5?h . In response to PM2.5, the ROS level increased from 0.5?h, and the increase continued until 24?h in HaCaT cells and NHEKs, concomitant with AhR expression."	HL	delay aging	31551408
Sen_E_079	Angelica sinensis Polysaccharides	Chemical compounds	CD34+CD38-	--	Acute Leukemia	Accelerate	SA-β-gal activity assay//Southern blot	"After 40 μg/ml ASP treatment for 48h, the staining positive cells are much more than CD34+CD38? cells absence of ASP performed by SA-β-Gal staining assay.The telomere lengths of AML CD34+CD38? cells chromosome ends have been sharply shortened after ASP treatment presented by Southern Blotting."	p16//p21//Cyclin E//CDK4	Upregulation//Upregulation//Downregulation//Downregulation	Western blot	"As a result, increased level expression of P16INK4a and P21 but decreased level of CDK4 and CyclinE were observed after 40 μg/ml ASP treatment for 48 h ."	p53-p21//p16-pRb	Upregulation//Upregulation	qRT-PCR	"The expressions of these genes have remarkably been enhanced due to ASP treatment, indicating that p53/p21 and p16INK4a/pRb pathways play an important role in the process of ASP-induced AML CD34+CD38? cells senescence."	L	cellular senescence	24377566
Sen_E_080	IL-6/sIL-6R	Chemical compounds	TIG-3	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"We assessed two biomarkers characteristic of most senescent cells, morphological changes and SA-β-Gal activity.13 TIG3 cells treated with IL-6/sIL-6R for 8 d showed both an enlarged and flattened morphology and increased SA-β-Gal activity, indicating that IL-6/sIL-6R stimulation can cause premature senescence in young TIG3 fibroblasts in the culture conditions used here."	p15INK4b (CDKN2B)//STAT3//IGFBP5	Upregulation//--//--	Western blot//qRT-PCR	"This IL-6-induced premature senescence was accompanied by increased levels of the cyclin-dependent kinase inhibitor p15INK4b (CDKN2B).The mRNA levels for all four factors increased on days 4 and 5 after IL-6/sIL-6R stimulation, and rapidly decreased thereafter. The levels were markedly reduced in TIG3 cells expressing HA-STAT3F.Consistent with this, TIG3/IGFBP5KD cells showed a much poorercellular senescence response to IL-6/sIL-6R compared with control TIG3 cells , indicating that IGFBP5 induction is important for the IL-6/sIL-6R-induced premature senescence."	p53	--	Knockdown//SA-β-gal activity assay	Knocking down p53 markedly decreased the SA-β-Gal activity in TIG3 cells stimulated with IL-6/sIL-6R and caused continuous proliferation (data not shown). This indicates that p53 is essential for the IL6/sIL-6R-induced premature senescence.	L	cellular senescence	22374671
Sen_E_081	AngII	Chemical compounds	HMC	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"SA-β-gal activity was significantly increased in Ang II and H2O2 stimulated cells in contrast to the control cells (80.63 ± 2.56 and 79.84 ± 3.07% vs. 5.81 ± 0.62%, P\0.01).we used flow cytometry, the cell cycle was arrested at the G0/G1 phase in both Ang II and H2O2-stimulated groups (87.30 ± 2.59 and 82.00 ± 1.66%) as compared to the control group (52.32 ± 2.15, P\0.01)."	STAT1	Activation	SA-β-gal activity assay//Western blot	"Ang II and H2O2 induced STAT1 activation during HMCs senescence, as manifested by an increase in STAT1 phosphorylation .SA-b-gal-positive cells and the percentage of cells at G0/G1 phase was decreased after STAT1 was knocked down ."	--	--	--	--	L	cellular senescence	22193460
Sen_E_082	H2O2	Chemical compounds	HMC	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"SA-β-gal activity was significantly increased in Ang II and H2O2 stimulated cells in contrast to the control cells (80.63 ± 2.56 and 79.84 ± 3.07% vs. 5.81 ± 0.62%, P\0.01).we used flow cytometry, the cell cycle was arrested at the G0/G1 phase in both Ang II and H2O2-stimulated groups (87.30 ± 2.59 and 82.00 ± 1.66%) as compared to the control group (52.32 ± 2.15, P\0.01)."	STAT1	Activation	SA-β-gal activity assay//Western blot	"Ang II and H2O2 induced STAT1 activation during HMCs senescence, as manifested by an increase in STAT1 phosphorylation.SA-b-gal-positive cells and the percentage of cells at G0/G1 phase was decreased after STAT1 was knocked down ."	--	--	--	--	L	cellular senescence	22193460
Sen_E_083	Sodium butyrate	Chemical compounds	H1299	--	Lung cancer	Accelerate	SA-β-gal activity assay	"Incubation of H1299 cells with 2.5 mM NaBu for 5 days resulted in morphological alterations, including enlarged and flattened shape, increased cytoplasmic to nuclear ratio and decreased cell density, all these changes being consistent with cell senescence phenotypes. In agreement, almost 30% of the cells displayed intense SA-β-gal activity as compared to untreated cells."	SRSF2	Upregulation	Western blot	We observed that SRSF2 accumulated in response to NaBu in these cells.	--	--	--	--	L	delay aging	21555914
Sen_E_084	Mithramycin	Chemical compounds	"MES1,MES7"	--	Malignant pleural mesothelioma	Accelerate	MTS assay//SA-β-gal activity assay//Flow cytometry	MTS assays demonstrated that 24-hour mithramycin exposure dramatically inhibited proliferation of MES1 and MES7 cells.Mithramycin significantly diminished growth of subcutaneous MES1 and MES7 xenografts in a dose-dependent manner. Flow cytometric experiments demonstrated dose-dependent accumulation of MPM cells in G0–G1without a sub-G0 fraction consistent with a G0–G1arrest immediately following 24-hour mithramycin exposure. Histochemical experiments performed at this time point demonstrated that mithramycin mediated dose-dependent increases in β-galactosidase expression indicative of senescence in MPM cells.	SP1//p53	Downregulation//	qRT-PCR//Western blot	"qRT-PCR and immunoblot experiments demonstrated dose-dependent decreases in SP1 expression in both cell lines following mithramycin exposure.In addition, mithramycin mediated dose-dependent increases in p53, p21, PMAIP1, and PRDM1 in vitro and in vivo . Subsequent immunoblot experiments confirmed results of qRT-PCR experiments.Immunoblot experiments demonstrated dose-dependent increases in gH2AX in MES1 and MES7 cells indicative of DNA damage, which coincided with increases in total p53 as well as acetylated p53-K320, K373, K382, and phosphorylated p53-S15 levels in MES7 cells, and to a lesser extent, MES1 cells following mithramycin exposure ."	--	--	--	--	HL	apoptosis	26459178
Sen_E_085	Lactate	Chemical compounds	B2B	--	Lung cancer	Prevent	SA-β-gal activity assay//Cell cycle analysis//Immunofluorescence	"Remarkably, lactate decreased SA-β-gal activity in a dose-dependent manner.In contrast, the accumulation of γH2AX positive cells was significantly decreased upon lactate treatment.However, the majority of lactate-treated B2B/K-Ras showed a cell cycle progression though G2/M, as evident by accumulation of 4 N DNA content."	Snail//p16	Upregulation//Downregulation	qRT-PCR//Dual-Luciferase reporter assay	"Notably, lactate markedly upregulated Snail mRNA in a dose-dependent manner in both A549 and H1299 cells paralleled with obtained with Snail protein levels . Importantly, treatment with lactate attenuated p16INK4a expression activated by K-Ras oncogene. This finding is not oncogenic K-Ras specific, similar results were obtained with transfection of Activate B-Raf (V600E) and dominant negative PTEN(C124S) into B2B cells.qRT-PCR showed that lactate dose-dependently decreased p16INK4a mRNA levels in B2B cells Notably, the promoter activity of p16INK4a was significantly reduced by lactate treatment, indicating that lactate transcriptional regulate p16INK4a expression."	--	--	--	--	HL	cellular senescence	29482580
Sen_E_086	Antcin M	Chemical compounds	"HNDF,CCD966SK"	--	Aging	Prevent	SA-β-gal activity assay//Western blot//Flow cytometry//MTT assay	"We examined the protective effects of antcins on HG-induced HNDF senescence, cells were co-incubated with HG and antcins (ANA, ANH and ANM) for 72 h, senescence was measured by SA-β-gal assay. Treatment with ANM showed significant protection against HG-induced HNDF senescence as evidenced by reduction in a number of SA-β-gal positive cells from 9.59-fold to 1.51-fold, whereas ANA and ANH showed moderate inhibition as SA-β-gal positive cells were reduced to 7.46-fold and 8.13-fold, respectively. In addition, results from immunoblotting analysis confirmed that HG-induced upregulation of senescenceassociated proteins such as p16INK4A and p21CIP1 were significantly downregulated by ANM, whereas ANA and ANH showed a moderate inhibition, which is concomitant with the result of SA-β-gal assay. A two-fold increase in cell proliferation was observed in the ANM treatment group.Our results demonstrated that treatment with HG caused cell-cycle arrest in the G1-S transition phase, as the proportion of cells in the G0/G1 phase was significantly increased to 71.2% compared to 46.5% in the NG group.Treatment with ANM eliminated the effect of HG and reduced the cell population in the G0/G1  phase to 49.5%,which is similar to the control (NG) group."	Nrf2	Activation	Western blot//RT-PCR//SA-β-gal activity assay//Knockdown//Luciferase reporter assay//Immunofluorescence	"To determine whether ANM augments Nrf2 transcriptional activity, we used ARE-harboring luciferase reporter assay.a remarkable increase in luciferase activity was observed in cells that were cotreated with HG and ANM or NAC which showed 8.5-fold and 8.2-fold increase, respectively. Transcriptional activation of Nrf2 is dependent upon the rate of nuclear export followed by disassociation from cytoplasmic Keap1. Results from immunofluorescence analyses showed that Nrf2 expression in the nucleus was barely observed in the control (NG) and the HG treatment groups, whereas elevated Nrf2 expression in the nucleus was observed in the ANM or NAC treatment groups ."	SIRT1	Upregulation	Western blot//RT-PCR//SA-β-gal activity assay//Knockdown//Luciferase reporter assay	"RT-PCR analysis indicated that SIRT-1, SIRT-3 and SIRT-6 levels were significantly increased in the ANM treatment group compared to the control group.In order to ascertain whether the protective effect of ANM was SIRT-1 dependent, the effect of ANM in SIRT1 silenced HNDFs was investigated under HG conditions.In control siRNA transfected cells, treatment with ANM significantly inhibited HG-induced senescence as assessed by SA-β-gal activity. However, in SIRT-1 siRNA transfected cells, SA-β-gal activity remained partially elevated despite the presence of ANM or RES ."	L	delay aging	27542238
Sen_E_087	Paeonol	Chemical compounds	MRC-5	--	Aging	Prevent	MTT assay//SA-β-gal activity assay	"Paeonol (60–120 lM) notably increased the MRC-5 cell viability induced by 60 lM H2O2. So effective concentrations of paeonol (60, 90, 120 lM) were used in subsequent experiments. Moreover, aging MRC-5 cells was evaluated by senescence marker SA-β-gal, and paeonol treatment weakened 60 lM H2O2-induced senescence of MRC-5 cells, as indicated by reduction of the SA-β-gal activity. After the aging MRC-5 cells were treated with paeonol (60, 90, 120 lM) for 24 h, the results showed that paeonol remarkably reduced the number of blue-stained cells in a dosedependent manner."	Nrf2	Upregulation	Western blot	"To further study the suppression of ROS level and cellular senescence in H2O2- exposed MRC-5 cells by paeonol, we isolated the nuclear and cytosolic fractions to detect Nrf2 protein levels, and Lamin B was used as the loading control of nuclear Nrf2. The results showed that nuclear Nrf2 protein was increased under H2O2 exposure, but was significantly upregulated by paeonol treatment. Interestingly, cytosolic Nrf2 protein was decreased under oxidative stress, but alteration in the expression of cytosolic Nrf2 appeared to be similar to that of nuclear Nrf2 when treated with paeonol."	Id-1//p16//p53-p21	Upregulation//Downregulation//Downregulation	SA-β-gal activity assay//Western blot	"So we have decided to ascertain whether paeonol could disrupt the expression of Id-1, p16INK4a, and p53/ p21Waf1/Cip1 pathway to weaken senescence in MRC-5 cells.The expression of Id-1 in aging MRC-5 cells treated with paeonol (60, 90, 120 lM) for 24 h was gradually evaluated compared to H2O2 group; meanwhile, paeonol decreased p16INK4a, p53,and p21Waf1/Cip1 (downstream protein of p53) expression in the aging MRC-5 cells.This effect has been extensively studied that Id-1 delayed cellular senescence in human fibroblasts through suppression of p16INK4a, a known mediator of cellular senescence. Elevation of p53 and p21Waf1/Cip1 levels has been observed in aging fibroblasts, which would lead to a promotion in senescence.Our results showed that paeonol attenuated aging MRC-5 cells in part via regulation of Id-1, p16INK4a, and p53/p21Waf1/Cip1 pathways."	L	delay aging	28801702
Sen_E_088	Purple sweet potato color	Other	Endothelial cell	--	Cardiovascular disease	Prevent	Western blot//Cell cycle analysis	"Changes in the p21 level, which was increased by high glucose but decreased by PSPC, confirmed the inhibitory efficiency of PSPC on cellular senescence；We examined the distribution of cell cycle by flowcytometric analysis. In the vehicle control group, high‐glucose‐exposed HUVECs were arrested at the G1 phase of the cell cycleand this arrest was recovered by the addition of PSPC."	NLRP3 inflammasomes	Downregulation	Immunofluorescence	Colocalization of NLRP3 and LC3 was observed in endothelial cells . This phenomenon disappeared in cells treated with glucose or PSPC due to scarce LC3 conversion in the D glucose group or low levels of NLRP3 in D glucose combined PSPC treatment.	mTOR	Downregulation	Western blot	"The level of phosphorylated mTOR (p‐mTOR; ser2448) was elevated by high‐glucose administration.However, high glucose failed to increase the phosphorylation of mTOR (ser2448) in the presence of PSPC. No significant difference in p‐mTOR (ser2481) was observed after glucose or PSPC treatment."	L	cellular senescence	30585631
Sen_E_089	DNA damage	Other	FaDu	--	Aging	Accelerate	BrdU assay//SA-β-gal activity assay	"Cells were challenged in the absence or presence of 10 μM etoposide for 24 h to induce DNA damage,Brdu assay:As expected, FaDu cells displayed several markers of senescence, such as cell flattening, increase in cellular size, significantly decreased 5-bromodeoxyuridine (BrdU) incorporation.SA-β-gal activity assay:and a positive senescence-associated-β-galactosidase (SA-β-Gal) staining in response to etoposide. 66% of FaDu cells stained positive for SA-β-Gal seven days post-treatment."	MYBBP1A	Downregulation	BrdU assay//SA-β-gal activity assay//Knockdown	Knockdown//Brdu assay: it resulted in a slight but significantly decreased amount of BrdU positive cells. Knockdown//SA-β-gal activity assayand induced the relative number of senescent tumor cells at day 5 post-treatment (2–3 fold) as determined by SA-βgal-positive staining.	PI3K-Akt	--	Western blot	"A strong increase in phosphorylation of AKT (pAKT(Ser473)) was detected in response to etoposide by Western blot analysis, which was consistent with previous observation."	HL	cellular senescence	25543088
Sen_E_090	Calorie restricted	Other	Fibroblast	--	Aging	Prevent	SA-β-gal activity assay//Growth curve assay	"The growth curves under these conditions for the three cell lines tested, namely IMR-90 (I90-79) (left panel), IMR (I90-26), and WI-38 (AG06814N). Exposure of cultured IMR-90 (I90-79) and WI-38 cells to CR serum induced a significant increase in population doubling levels (PDL) and all three cell lines showed a profound delayed in the onset of senescent growth arrest.When IMR-90 cells grown in the presence of rat sera were analyzed, we found that at PDL 37, the percentage of SA β-gal-positive fibroblasts cultured in DMEM containing 10 % CR serum was reduced more than 8 folds compared to that of cells of the same passage number grown in 10% AL serum ."	MMP2	--	Gelatin zymography	"When the levels of MMP-2 activity in IMR-90 (PDL 35) fibroblasts grown in medium containing either rat AL or CR serum were analyzed, we found that CR treatment significantly reduced MMP-2 activation ."	SIRT1//p53	Upregulation//Downregulation	Western blot	"The amount of SIRT1 protein found in IMR-90 fibroblasts grown in the presence of CR serum at PDL45 was 15-20% higher than that present in IMR-90 fibroblasts grown with AL-serum at PDL32 . CR rat serum also preserved SIRT1 protein levels in WI-38 fibroblasts when compared to AL rat serum treatment at an intermediate (PDL 37) passage number.We found that CR serum treatment of IMR-90 fibroblasts at PDL43 was accompanied by a decrease in p53 protein levels when compared to AL serum treatment. Specifically, the amount of p53 present in cells cultured in medium with CR serum was 1.6-fold lower than that of the same cells cultured in medium with AL serum. Overexpression of SIRT1 in pSIRT1-transfected IMR-90 (PDL 43) fibroblasts grown in normal medium caused a significant decrease in p53 expression levels . Conversely, the knockdown of SIRT1 in early passage IMR-90 (PDL 29) fibroblasts enhanced p53 expression ."	L	cellular senescence	25855056
Sen_E_091	Butylidenephthalide	Chemical compounds	GBM8401	--	Brain tumor	Accelerate	Western blot//SA-β-gal activity assay	"We found that the senescence-associated proteins Rb, p19, and p16 were upregulated after BP treatment.Indeed, the staining intensity of GBM8401 cells was 30 % on BP 133 μM and 43 % on BP 267 μM. It showed a dose-dependent manner cellular senescence after BP treatments."	SKP2	Downregulation	Western blot//RT-PCR	"In the result, we found expression of Skp2 protein decreased in three GBM cell lines after BP treatment. In addition, GBM 8401, the highest Skp2 expression cell line, decreases in Skp2 protein expression and was dependent on both time and BP concentration.Immunohistochemical analysis indicated that tumor tissues from mice treated with BP showed downregulation of Skp2 expression and upregulation of p21 and p27."	--	--	--	--	L	apoptosis	24464249
Sen_E_092	Glucose	Chemical compounds	WI-38	--	Aging	Accelerate	SA-β-gal activity assay//DAPI staining//Western blot//Cell morphological analysis	"We discovered that the percentages of SA-βgal positive cells were decreased significantly in the LG group compared with the NG and HG groups.Senescence induced by HG conditions was characterized by pronounced punctuated DNA foci, which were visualized by DAPI staining. Moreover, high glucose leads to cell hypertrophy and nuclear volume increase. The protein levels of p16INK4A (another biomarker of cell senescence) expression in the HG group were significantly higher than in the LG and NG groups."	SIRT3	Binding	Western blot	Our experimental data showed that the levels of SIRT3 activity were decreased in the HG group compared with the LG and NG groups.	--	--	--	--	L	cellular senescence	23494737
Sen_E_093	Salidroside	Chemical compounds	"Aortic Endothelial cell,Smooth muscle cell,HUVEC"	--	Aging	Prevent	SA-β-gal activity assay//Immunostaining	"When comparing with control group, the cells of aortic endothelium and smooth muscle in mice with chronic HMD treatment showed accelerated up-regulation of p16 INK4A and p21 CIP1. However, SAL treatment abolished these changes in blood vessels. H2O2 induced the upregulation of SA-β-Gal activity, which indicated that the HUVECs were indeed undergoing senescence.SAL treatment at the concentration of 10 uM inhibited the activity of SA-β-Gal."	SIRT3	Upregulation	Western blot	"B HMD treatment significantly reduced the expression of SIRT3. However, the SAL treatment attenuated the reduced expression of SIRT3. SAL reversed the inhibitory effect of H2O2 on the expression of SIRT3 and endothelial nitric oxide synthase (eNOS)."	--	--	--	--	L	delay aging	29289557
Sen_E_094	HRW	Chemical compounds	Retinal cell	--	Aging	Prevent	Western blot//SA-β-gal activity assay	"The number of SA-β-gal-positive cells in the HRW mice were significantly reduced compared with NaIO3 mice. In addition, we further measured the expression of core proteins related to aging, such as, p53, p21 and p16, by western blot analysis. The levels of these proteins were conspicuously increased in NaIO3 mice compared with control mice. However, after HRW treatment, the expression of these proteins decreased greatly."	SIRT3	Upregulation	Western blot	"After HRW treatment, Sirt3 expression significantly increased compared with NaIO3 mice."	--	--	--	--	L	delay aging	30735837
Sen_E_095	Ubiquinol-10	Chemical compounds	HepG2	--	Aging	Prevent	--	"For middle (16kHz) and low (8kHz) frequencies, age-associated hearing losses were suppressed by ubiquinol-10 supplementation."	SIRT1//PGC-1a//SIRT3	Upregulation//Upregulation//Upregulation	Western blot//qRT-PCR	"We could show that, in agreement with the ABR test and liver results, Sirt3 and Pgc-1a mRNA and protein expression was significantly increased after ubiquinol-10 supplementation."	--	--	--	--	L	delay aging	24124769
Sen_E_096	MALAT1	Other	Fibroblast	--	Aging	Prevent	SA-β-gal activity assay	"In addition, the ratio of senescent cells was significantly lower following intervention with MALAT1 siRNA (52.1%) compared with the UVB irradiation group."	MMP1	Downregulation	ELISA	The results demonstrated that MALAT1  siRNA suppressed MALAT1 expression and inhibited 60 mJ/cm2 UVB-induced MMP-1 secretion .	MAPK	--	Western blot	"The results demonstrated that 60 mJ/cm2 UVB upregulated ERK, JNK and p38 phosphorylation levels, however MALAT1 siRNA inhibited UVB-induced ERK phosphorylation (P<0.01), with no significant influence on JNK and p38 phosphorylation levels."	L	cellular senescence	28487970
Sen_E_097	Low frequency magnetic fields	Other	"A549,LLC"	--	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//CCK-8 assay	"Flow cytometry//CCK-8 assay:In consistent with previous data, the proliferation of A549 cells and LLC cells were inhibited by exposure to LF-MF. Cell cycle progression is an essential process by which cell monitors its growth and differentiation. Compared to Sham MF, A549 cells exposed to LF-MF displayed strikingly decreased number of cells in the S and G2/M phases and increased arrest in G0/G1 phase from 53.88% to 77.90%.SA-β-gal activity assay: Staining of senescence-associated β-galactosidase (SA-β-gal) in lung cancer cells showed that LF-MF treatment up-regulate frequency of β-galactosidase (β-Gal)-positive cells."	miR-34a//p53	Upregulation//Upregulation	qRT-PCR//Flow cytometry//SA-β-gal activity assay//Western blot	"qRT-PCR:Upon checking several famous miRNAs related to cell proliferation, cell cycle and cell senescence, we found miR-34a level was up-regulated to 4.64 folds after 2 Days exposure to LF-MF.Flow cytometry//SA-β-gal activity assay:Here, LLC and A549 cells were transiently transfected with synthetic miR-34a precursor (pre-miR-34a), or antisense miR-34a inhibitor (anti-miR-34a). Compared with negative control, ectopic expression of miR-34a significantly inhibited the proliferation and induced cell G1 phase arrest in A549 cells and LLC cells .Moreover, the transfected A549 and LLC cells with pre-miR-34a appeared a senescence-like phenotype, enlarged cellular size and increased numbers of SA-β-gal positive cells . However, LF-MF treatment could up-regulate protein level of P53 in LLC cells."	E2F	--	qPCR//Western blot	"Indeed, ectopic expression of miR-34a downregulates the expressions of E2F3 and E2F1 at the translational level and protein level . Importantly, LF-MF exposure could down-regulated both E2F1 and E2F3 protein level in LLC cells."	L	cellular senescence	28389657
Sen_E_098	Kallistatin	Chemical compounds	EPC	--	Aging	Prevent	SA-β-gal activity assay//RT-PCR	"Exposure of EPCs to TNF-a for 6 days markedly increased SA-β-gal-positive cell numbers compared with the control group, whereas preincubation with purified human kallistatin significantly reduced TNF-a induced SA-β-gal-positive cells. Moreover, kallistatin markedly reduced the expression of p16INK4a, a cyclin-dependent kinase inhibitor known to be a senescence-associated inducer of cell cycle arrest."	miR-21	Downregulation	qRT-PCR	Kallistatin also antagonized TNF-a induced miR-21 synthesis.	miR-34a-SIRT1	--	Western blot//qRT-PCR	"Furthermore, STZ induced a significant increase of miR-34a and miR-21 synthesis, as well as reduced SIRT1, eNOS, and catalase mRNA levels in aortas of diabetic mice compared to control mice, while kallistatin administration reversed STZ-mediated effect.Kallistatin treatment increased SIRT1 protein levels, as determined by Western blot."	L	delay aging	28544111
Sen_E_099	High Glucose	Other	HGMC	--	Diabetes kidney disease	Accelerate	Flow cytometry	The results showed that high glucose led to the hypertrophy of HGMCs and decreased cell number. HG group of HGMCs had cell cycle arrest in G1 phase (P<0.05).	miR-126	Downregulation	Flow cytometry//qRT-PCR	"Flow cytometry was used to detect the cell cycle, and the results displayed that miR-126 transfection resulted in a decrease in the ratio of cell arrest in the G1 phase (P<0.01)The miR-126 expression in HG group (5.5±0.8) was significantly lower than that in the NG group."	Telomere-p53-p21-Rb	--//--	Southern blot//Western blot	"The osmotic pressure had no significant effect on the telomere TRF length of cells. The telomere TRF length of HGMCs in NG group and HG group was (8.97±0.35) and (6.77±0.65) kb respectively. As compared with NG group, the telomere TRF length in HG group was significantly shortened (P<0.01).The Western blotting results showed that high glucose-induced expression of p53, p21, and Rb in HGMCs was significantly higher than that in NG group ."	L	delay aging	30341510
Sen_E_100	Hypoxia	Other	HMSC	Bone marrow	Aging	Prevent	BrdU assay//SA-β-gal activity assay//Western blot//Cell morphological analysis	"Specifically, p7 hMSCs in normoxic culture displayed an enlarged flattened morphology, a characteristic of senescent cells, whereas those at the same passage maintained in hypoxic culture maintained spindle-shaped morphology. At cell passage 7, BrdU was incorporated in less than 1% hMSCs in normoxic culture, whereas BrdU was incorporated in 5.15% hMSCs in hypoxic culture.Hypoxia also reduced the number of p7 hMSCs with positive staining for the activity of senescence-associated b-galactosidase. The ratio of senescence-associated β-galactosidase-positive cells to total cells in hypoxic culture was less than that in normoxic culture . However, when comparing the cells at the same passage number between hypoxic and normoxic culture, the expression levels of p16 mRNA transcripts of p7 hMSCs in hypoxic culture were lower than those of the cells in normoxic culture."	MIF	Upregulation	Western blot	"Likewise, the expression levels of total MIF were upregulated in hypoxic culture than those in normoxic culture."	Akt	Activation	Western blot	"The results of western blotting showed that the expression levels of total AKT in hMSCs under the normoxic condition were slightly higher than those under the hypoxic condition, but the levels of pAKT were increased in hypoxic culture compared to those in normoxic culture ."	L	cellular senescence	24274936
Sen_E_101	Trans-Cinnamaldehyde	Chemical compounds	ADSC	--	Aging	Prevent	Immunostaining//SA-β-gal activity assay//ELISA	"We found that the number of Ki-67 positive cells was dramatically decreased after H2O2 induction,however, the number of Ki-67 positive cells was greatly enhanced by subsequent TC treatment;The percentage of SA-β-gal positive cells was decreased dramatically when H2O2-induced cells were treated with TC, confirming its anti-senescent effects ;The TC-treated ADSCs post H2O2 treatment showed increased telomerase activity when compared to the H2O2 group."	SIRT1//p53//p21	Upregulation//Downregulation//Downregulation	Semi-qPCR//qPCR	"Upregulation of SIRT1 in TC-treated ADSCs post H2O2 treatment is a vital indicator of antisenescence capacity of TC ;When rescued by TC treatment, the expression of p21 and p53 seemed to reduce."	--	--	--	--	HL	cellular senescence	25654692
Sen_E_102	2-O-α-glucopyranosyl-L-ascorbic acid	Chemical compounds	NHDF	--	Aging	Prevent	SA-β-gal activity assay	We investigated the effects of AA-2G on NHDF cell growth and against H2O2-induced cell damage. Pretreatment of NHDF cells with AA-2G for 72 h significantly promoted the cell growth in a dosedependent manner.Pretreatment with AA-2G for 72 h slightly but significantly decreased SA-β-gal activity in H2O2-unexposed NHDF cells.	SIRT1//p53//p21	--//Downregulation//Downregulation	Western blot//ELISA	"Neither ascorbic acid nor AA-2G alone affected SIRT1 expression when they were added to cell cultures. In contrast, when NHDF cells were exposed to H2O2, SIRT1 expression levels were significantly decreased compared to unexposed cells. Pretreatment of NHDF cells with 200 μM AA-2G for 72 h significantly inhibited the H2O2-induced decrease in SIRT1 expression. However, pretreatment with 200 μM ascorbic acid did not inhibit the H2O2-induced decrease of the SIRT1 expression. These results suggest that AA-2G prevents oxidative stress-induced cellular senescence in terms of both SA-β-gal activity and SIRT1 expression.To further clarify the anti-aging effect of AA-2G, we examined the expression levels of p53 and p21 in H2O2-exposed NHDF cells.Constitutive expression of p53 was observed in AA-2G untreated cells. Its expression level was elevated by H2O2 exposure, and reached maximum levels at 4 h postexposure. Pretreatment with 200 μM AA2G for 72 h resulted in a decrease in both constitutive and H2O2-induced expression of p53. Exposure of NHDF cells to H2O2 also resulted in increased expression of p21 in AA-2G untreated cells compared with that in H2O2-unexposed cells. The expression reached maximum levels at 4 h postexposure. These results suggest that cell cycle arrest at G1 phase is induced by H2O2-exposure. Pretreatment with 200 μM AA-2G inhibited the expression of p21 in the H2O2-exposed cells."	--	--	--	--	L	delay aging	22119379
Sen_E_103	N-acetylcysteine	Chemical compounds	γδ Treg cell	--	Chronic kidney disease	Prevent	SA-β-gal activity assay//Western blot//qRT-PCR	"NAC decreased the percentage of SA-β-Gal positive cells and C12FDG positive cells. NAC also decreased the protein levels of p53 and p21 and the mRNA levels of SASP factors (IL-6, IL-1β, and TNF-α)."	SIRT1//p53	Upregulation//Downregulation	Western blot	"NAC treatment upregulated the protein expression of SIRT1 and downregulated acetyl-p53, which is the major substrate of SIRT1."	--	--	--	--	L	cellular senescence	30447351
Sen_E_104	Curcumin	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry	"Pretreatment with curcumin at 10 and 25 μM? could? significantly? attenuate? the? H2O2-induced HUVECs? senescence? (54.40±3.40%  vs.  82.90±2.02%; 51.25±2.74% vs. 82.90±2.02%, p<0.01).Pretreatment of 10 and 25 μM?curcumin?remarkably?decreased?the?ratio of cells at G0/G1 stage (60.02±5.22% vs. 78.12±2.91% and 56.57±4.15% vs. 78.12±2.91%, p<0.05). Accordingly, the ratio of cells in S and G2/M?phases?were?increased?in?curcumin pretreated group compared to the H2O2 group (p<0.05)."	SIRT1//p21	Activation//Downregulation	Western blot	"100?μM H2O2 remarkably?decreased?the?expression?of?SIRT1?and?pretreatment with curcumin could increase the expression of SIRT1 in H2O2-treated? HUVECs?. Interestingly, treatment of curcumin alone greatly improved the enzymatic activity of SIRT1 and pretreatment of curcumin could also reverse the change of enzymatic activity of SIRT1 in H2O2-treated? HUVECs?.Meanwhile, pretreatment of 25 μM? curcumin? significantly?decreased the expression of p21 in H2O2-treated?HUVECs?."	--	--	--	--	L	cellular senescence	26235577
Sen_E_105	Red wine extract	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Comet assay//Western blot	Treatment with RWE concentration dependently decreased endothelial senescence by maximally 33+?7.1 %.RWE clearly reduced tBHP-induced DNA damage and p21 protein expression.	SIRT1//eNOS//COX-2	Activation//Upregulation//Upregulation	qRT-PCR	"RWE increased SIRT1 gene expression (by 14+?10 % at 10 min of exposure, n=8, P<0.05; results not shown).RWE up-regulated eNOS and COX-2 in HUVECs ."	--	--	--	--	L	delay aging	22563892
Sen_E_106	FL118	Chemical compounds	HCT-8	--	Colorectal cancer	Accelerate	SA-β-gal activity assay	Results from SA-β-gal activity staining indicated that 10 nmol/L FL118 treatment induced approximately 92% of SA-β-gal positivity in the surviving cells .	MdmX	Downregulation	Western blot	"Left plot, FL118 treatment induced expression of human Mdm2 (Hdm2) protein but inhibited expression of human MdmX (HdmX) protein after treatment at 10 nmol/L and 100 nmol/L for 24 hours."	p53	Activation	Western blot	p53 accumulation was induced by as low as 10 nmol/L FL118 treatment in WT p53–bearing HCT116 and HCT8 cells. Time course experiment with HCT8 cells indicated that FL118 induced evident p53 accumulation as short as 4 hours after treatment and reaching a peak after 24-hour treatment and sustained at least for 48 hours .	L	apoptosis	25512388
Sen_E_107	PD-0332991	Chemical compounds	MEF	--	Melanoma	Accelerate	SA-β-gal activity assay	"To establish senescence, presenescent MEFs (passage 4/p4) were treated with PD-0332991 (4 mmol/L for 8 days),Herein, these treated fibroblast populations are referred to as CDK4/6i.Next, we measured SA-β-gal positivity in these cells, revealing that 74% CDK4/6i treated cells were SA-β-gal positive."	MDM2//p53//p21/WAF1	Downregulation//Downregulation//Upregulation	Western blot	"We found that prolonged PD-0332991 treatment promoted a reduction in Mdm2 and p53 protein levels. However, unlike what is observed in liposarcomas, p21Cip1/Waf1 protein levels were elevated in CDK4/6i MEFs in comparison to p4 cells."	NF-κB	Activation	Western blot	"In contrast, activating phosphorylation of the NF-kB subunit, p65, was elevated in CDK4/6i, UV, and MMC fibroblasts when compared with control."	HL	cellular senescence	28039358
Sen_E_108	20(s)-Rg3	Chemical compounds	"NOZ,GBC-SD"	--	Gallbladder cancer	Accelerate	SA-β-gal activity assay//Western blot//Cell morphological analysis	"Morphological changes of NOZ and GBC-SD cells could be seen. Both cell lines became enlarged and flattened, had more cytoplasmic vacuoles in a concentration-dependent manner, representing a senescence-like state.The higher the concentration of 20(S)-Rg3, the more SA-β-gal positive cells in both cell lines was observed. Moreover, the protein amounts of p53 and p21Cip1 increased in senescent cells but not the p16 and pRB protein ."	MDM2	Downregulation	Western blot	"Western blot further showed that MDM2 protein levels were decreased by 20(S)-Rg3 treatment, in a dose- and time-dependent manner."	p53	Activation	Western blot	"We next investigated the involvement of the transcription-independent function of p53 using a protein synthesis inhibitor, (CHX), and found the suppressive effect of CHX on p53 protein accumulation was neutralized by 20(S)-Rg3 ."	L	cellular senescence	26309394
Sen_E_109	UVB irradiation	Other	Fibroblast	--	Aging	Accelerate	SA-β-gal activity assay	The ratio of senescent cells was markedly greater following UVB irradiation (74.4%) compared with cells that had not been exposed to irradiation (15.7%).	MALAT1//MMP1	Upregulation//Upregulation	RT-PCR//ELISA	Results further demonstrated that 60 mJ/cm2 UVB increased MALAT1 expression.The results demonstrated that MALAT1  siRNA suppressed MALAT1 expression and inhibited 60 mJ/cm2 UVB-induced MMP-1 secretion .	MAPK	Activation	Western blot	"The results demonstrated that 60 mJ/cm2 UVB upregulated ERK, JNK and p38 phosphorylation levels."	L	cellular senescence	28487970
Sen_E_110	CAPERα-TBX3 repressor complex	Other	"HEK293,Primary HFF,MEF"	--	Aging	Prevent	Knockdown//SA-β-gal activity assay//Immunostaining//qRT-PCR//Western blot	"Knockdown of either protein resulted in a dramatic increase in senescence associated β-galatosidase activity.This effect is specific because it occurs with two different shRNAs and is rescued by overexpression of CAPERα and Tbx3. Expression of senescence mediators was increased and conversely, expression of cell growth and cell cycle promoting genes was similarly decreased by CAPERα and TBX3 KD ."	lncRNA UCA1	Downregulation	qRT-PCR//CHIP-PCR	"We found that shRNA KD of CAPERα or TBX3 in primary HFFS recapitulated the increase in UCA1 transcripts seen in HEK293 cells.After TBX3 KD, activating chromatin marks replaced repressive ones and markedly less CAPERα was bound. CAPERα KD also led to loss of repressive marks on UCA1/A3 , although TBX3 remained bound ."	p16-Rb	Downregulation	Knockdown//SA-β-gal activity assay//qRT-PCR	"Increased expression of CDKN2A-p16INK (henceforth referred to as p16INK) and decreased PCNA, E2F1 and 2, CDK2, CDK4, CDC2 transcripts indicate that CAPERα/TBX3 represses the p16/RB pathway in proliferating HFFs.In contrast, shRNA-mediated KD of either RB  or p16 rescued these phenotypes in TBX3 and CAPERα KD cells ."	HL	delay aging	24876127
Sen_E_111	Simvastatin	Chemical compounds	Endothelial cell	--	Cardiovascular disease	Prevent	SA-β-gal activity assay	"As compared to young rats, the percentage of β-galactosidase-positive cells was significantly increased(22.00% + 2.65% vs 83.67% + 9.50%, P < .001). Administra-tion of simvastatin to aged rats significantly lowered the percentage of β-galactosidase-positive cells as compared to that seen in untreated aged rats (68.83% + 7.47% vs 83.67% + 9.50%, P ? .001)."	SIRT1	Upregulation	Western blot	Pretreatment with simvastatin also significantly inhibited OX-LDL-induced SIRT1 protein downregulation.	--	--	--	--	L	cellular senescence	22964779
Sen_E_112	Nicotinamide	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay//SAHF	"However, in the presence of NAM, the SA-β-gal positive cells’percentage significantly increased in the Y﹢N group compared with that in the young group.The expression of SAHF was significantly increased in Y+N group when compared with that in young cells."	SIRT1	Downregulation	Western blot//RT-PCR	SIRT1 expression in the Y﹢N group was significantly decreased compared with that in young group.The mRNA expression of SIRT1 in Y﹢N group was significantly decreased compared with that in the young group.	--	--	--	--	L	cellular senescence	24729176
Sen_E_113	Selaginellin	Chemical compounds	HUVEC	--	Aging	Prevent	Telomerase activity assay//SA-β-gal activity assay//Flow cytometry	"Selaginellin concentration dependently inhibited homocysteine-induced cell senescence as shown by the decreased percentages of SA-β-gal–positive cells, the increased telomerase activities, and the decrease in the percentage of cells in the G0/G1phase."	SIRT1	Upregulation	qRT-PCR	"In contrast, the decreased mRNA expression of SIRT1 was reversed by pretreatment with selaginellin in a dose-dependent manner."	--	--	--	--	L	cellular senescence	20224429
Sen_E_114	OX-LDL	Chemical compounds	Endothelial cell	--	Cardiovascular disease	Accelerate	SA-β-gal activity assay	"As the concentrations of OX-LDL increased, the number of β-galactosidase-positive cells increased significantly, reaching a maximal value at 100 mg/mL OX-LDL."	SIRT1	Downregulation	Western blot	"At this concentration of OX-LDL, the SIRT1 protein expression was significantly decreased as compared to control cells."	--	--	--	--	L	cellular senescence	22964779
Sen_E_115	NaHS	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//SAHF	"Treatment with NaHS decreased the percentage of SA-β-gal positive cells.The strongest effect was observed when NaHS was at 50 lmol/L.Treatmentwith NaHS (12.5, 25 and 50 lmol/L) decreased the expression of SAHF the strongest effect was found when NaHS was at 50 lmol/L."	SIRT1	Upregulation	Western blot//RT-PCR	"NaHS/resveratrol could increase the expression of SIRT1 compared with Y﹢N group. It was found that the mRNA expression of SIRT1 in Y﹢N group was significantly decreased compared with that in the young group, and NaHS reversed this effect."	--	--	--	--	L	cellular senescence	24729176
Sen_E_116	Kallistatin	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//qRT-PCR//Telomerase activity assay	"Representative images showed that H2O2treatment induced pronounced cellular senescence in HUVECs,while purified recombinant human kallistatin pretreatment reversed the effec.Kallistatin blocked H2O2-induced p16INK4A and PAI-1 expression,and prevented  H2O2-mediated  inhibition of telomerase activity."	Let-7g	Upregulation	qRT-PCR	"Kallistatin treatment significantly increased Let-7g synthesis, whereas genistein, a tyrosine kinase inhibitor, blocked kallistatin’s effect."	miR-34a-SIRT1-eNOS	--	qRT-PCR//Western blot	"The effects of kallistatin on the regulation of SIRT1, eNOS, catalase and SOD-2 were determined. Kallistatin treatment not only markedly enhanced SIRT1, eNOS, catalase and SOD-2 expression,but also prevented H2O2-mediated inhibition of these antioxidant genes.Let-7g inhibitor (Let-7g anti-sense RNA) blocked kallistatin’s inhibition of miR-34a synthesis .Let-7g inhibitor abolished kallistatin induced SIRT1 and eNOS mRNA levels, and blocked kallistatin-mediated elevation of SIRT1 and eNOS levels by western blot."	L	delay aging	29992759
Sen_E_117	Hyperphosphatemia	Other	HASMC	Aorta	Aging	Accelerate	Western blot//SA-β-gal activity assay	"Results showed a significant increased expression in all proteins （p53, p21 and p16）after 24 h of treatment；Senescence was also analyzed, in the same experimental conditions,by the SA-β-gal activity, using a fluorescent probe, by confocal microscopy. A strong fluorescent signal was found after 24 h of treatment which was progressively increasing until 72 h."	Integrin linked kinase (ILK)	Upregulation	Western blot	"ILK protein expression was analyzed in HASMC treated with 10 mM BGP during 24, 48 or 72 h and results showed a significant increase after 24 h of treatment, which remained until 72 h. BGP also increased ILK activity, measured as the GSK-3β phosphorylation."	IGF1-Akt-FoxO	Activation	Western blot	"We analyzed whether BGP treatment activated the IGF-1 pathway,by evaluating the IGF-1R phosphorylation,and found a sustained increase from 24 to 72h .significant increase in AKT phosphorylation at Ser473 was observed after BGP treatment.Results showed that BGP additionincreased FoxO1 phosphorylation andtotal FoxO1 expression from 24-72h after treatment ."	L	delay aging	26467393
Sen_E_118	Rapamycin	Chemical compounds	Fibroblast	--	Aging	Prevent	ELISA	"Rapamycin significantly decreased IL6 secretion by 3 strains of normal human fibroblasts, and 2 strains of immortal, but non-tumorigenic human breast epithelial cell lines (MCF-10A and 184A1)— all induced to senesce by ionizing radiation (10 Gy X-irradiation).Rapamycin also suppressed IL6 secretion by human fibroblasts induced to senesce by other stimuli."	IL1A	Downregulation	qPCR	"Rapamycin significantly decreased the translational efficiency of IL1A mRNA, and to a lesser extent IL1B, IL6 and IL8 mRNAs,in senescent cells."	mTOR//NF-κB	--//Downregulation	Knockdown//ELISA//Luciferase reporter assay	"ShRNA against raptor, but not GFP, severely blunted IL6 secretion by senescent cells. Likewise, shRNA-mediated depletion of MTOR reduced senescence-associated IL6 secretion by >90% .We infected HCA2 cells with a lentivirus carrying an NF-κB–luciferase reporter, and measured the effect of rapamycin on reporter activity. Rapamycin reduced NF-κB activity by 80%."	L	delay aging	26147250
Sen_E_119	H2O2	Chemical compounds	IMR-90	--	Aging	Accelerate	SA-β-gal activity assay	The old cells and H2O2-treated cells were higher stained with blue color than young cells.	IGFBP3	Downregulation	Western blot	The expression level of IGFBP-3 also remarkably was decreased in H2O2-induced old cells than young cells.	p53//PI3K-Akt-mTOR	Activation//--	Western blot	"The expression levels of p300, Ac-p53, p53, p-p21 and p16 also were increased in H2O2-induced old cells higher than young cells. In contrast, the expression levels of SIRT-1,SIRT-6, MDM2 and p-p53 were increased in H2O2-induced old cells in comparison with young cells;The expression level of IGFBP-3 also remarkably was decreased in H2O2-induced old cells than young cells. In contrast, the expression levels of p-PI3K, Akt-1, p-mTOR, p-FoxO1 and FoxO1 were increased in H2O2-induced old cells in comparison with young cells."	L	cellular senescence	29579543
Sen_E_120	Resveratrol	Chemical compounds	--	Kidney	Renal?injury	Prevent	Immunostaining//Western blot	"The area of tubulointerstitial fibrosis was decreased in the RSV group compared to that in the Cont group.There was no difference in the expression of BAX between the two groups, while that of BCL-2 was increased in the RSV group."	HO-1//NQO-1	Upregulation//Upregulation	Western blot	"HO-1 expression in aging kidney was decreased, and inversely increased in the RSV group .The expression of NQO-1 was significantly increased in the RSV group compared to that in the Cont group."	Nrf2//SIRT1-AMPK//PPARα	Upregulation//Upregulation//Upregulation	Western blot	"Nrf2 levels in total protein were dramatically increased in the RSV group (Cont 1 ± 0.04-fold vs. RSV 1.55 ± 0.09-fold, P<0.01;).Western blot analysis showed that SIRT1 protein levels were considerably increased in the RSV group compared to those in the Cont group.The phospho-Thr172/total-AMPK protein expression ratio was markedly increased in the RSV group compared to that in the Cont group .Also, PPARα levels were statistically increased along with PGC-1α and ERRα expressions ,which were recovered in the RSV group compared to that in the Cont group."	L	delay aging	29326403
Sen_E_121	EtOH	Chemical compounds	BM-MSC	--	Osteoporosis	Accelerate	SA-β-gal activity assay	"In untreated cells, only 13.1 4.6% cells were positive for SA-β-gal staining but, after exposure to EtOH, the percentage of SA-β-gal-positive cells increased to 17.6 6.4% at 10 mM, 36.2 3.9% at 50 mM and 56.9 6.8% at 250 mM."	SIRT1	Downregulation	qRT-PCR//Western blot	The mRNA levels of SIRT1 in BM-MSCs decreased upon treatment with EtOH and the protein levels were confirmed by western blot analysis.	--	--	--	--	L	delay aging	28339869
Sen_E_122	Trans-Resveratrol	Chemical compounds	--	Aorta	Diabetes	Prevent	SA-β-gal activity assay	The number of senescence-associated β-galactosidase (SAβgal)-stained cells in a SA-βgal assay increased significantly in the thoracic aortas of STZ-diabetic mice but decreased in the thoracic aortas of the G. gnemon extract-administered mice.	SIRT1	Upregulation	Immunofluorescence	Immunostaining of sections for SIRT1 showed that SIRT1 expression in aortic endothelial cells increased after administration of the extract to STZ-diabetic mice.	--	--	--	--	L	delay aging	23859249
Sen_E_123	Ginsenoside Rb1	Chemical compounds	HUVEC	"Umbilical cord,Aorta"	Cardiovascular disease	Prevent	SA-β-gal activity assay	"The results suggested that hyperlipidemia induced aortic endothelium senescence and that gRb1 could alleviate it.Results showed that gRb1, but not DMSO, has protective effects on ox-LDL-induced senescence and could alleviate the influence of ox-LDL on autophagy and SIRT1, while gRb1 did not influence senescence, autophagy and SIRT1 of young HUVECs."	SIRT1	Upregulation	Western blot	The western blot results suggested that both low and high dose of gRb1 could alleviate the hyperlipidemia-induced reduction in SIRT1 levels and autophagy inhibition in the aortas.	--	--	--	--	L	delay aging	31658172
Sen_E_124	17β-estradiol	Chemical compounds	HUVEC	Aorta	Cardiovascular disease	Prevent	SA-β-gal activity assay	The ratio of arterial senescence area was lower in OVX＋E2 mice than in OVX mice .The premature senescence of HUVEC treated with ox-LDL was inhibited by administration of E2.	SIRT1	Upregulation	Immunostaining	Continuous administration of E2 from an E2 pellet increased SIRT1 expression in the endothelial cells of ApoE-KO OVX mice.	--	--	--	--	L	delay aging	31105126
Sen_E_125	SERM	Chemical compounds	--	Aorta	Cardiovascular disease	Prevent	SA-β-gal activity assay	The ratio of arterial senescence area was lower in OVX＋ SERM mice than in OVX mice .	SIRT1	Upregulation	Western blot	These results suggest that SERM has an effect similar to that of E2; it increases aortic SIRT1 expression and retards arterial senescence.	--	--	--	--	L	delay aging	31105126
Sen_E_126	5-MTP	Chemical compounds	BM-MSC	--	Aging	Prevent	BrdU assay//SA-β-gal activity assay//qPCR//ELISA	"BM-MSCs cultured in HG had a lower BrdU incorporation and pretreatment with 5-MTP alleviated the reduction. HG-induced IL-6 secretion was significantly reduced by 5-MTP pretreatment. 5-MTP did not exert a significant effect on SA-β-Gal in LG-MSCs while it significantly reduced HG-induced elevation of SA-β-Gal positive cells. Pretreatment of BM-MSCs with 5-MTP attenuated p16 and p21 expression, BrdU incorporation, IL-6 secretion, SA-β-Gal and Lysotracker-positive cells. These results indicate that 5-MTP is effective in controlling oxidant-induced premature senescence."	FOXO3a	Upregulation	Western blot	5-MTP significantly increased FoxO3a proteins in HG-MSC.	mTOR	--	qPCR//SA-β-gal activity assay//ELISA	"To ascertain that 5-MTP inhibits senescence through mTOR, we treated BM-MSCs with rapamycin and analyzed senescence markers. Rapamycin did not have a significant effect on p16 expression in LG-MSC but abrogated the p16 lowering effect of 5-MTP in HG-MSC. Similarly, 5-MTP-induced reduction of p21 transcript was abrogated by rapamycin. Rapamycin did not influence HG-induced SA-β-Gal but abrogated the 5-MTP-mediated control of SA-β-Gal in HG-MSC. Rapamycin abrogated 5-MTP-mediated control of IL-6 in a manner similar to its abrogation of the rise of other senescence markers."	L	cellular senescence	28894133
Sen_E_127	zofenoprilat	Chemical compounds	"CVEC,FGF-2(-/-)"	--	Aging	Prevent	SA-β-gal activity assay	"Zofenoprilat inhibits endothelial senescence.CVEC were incubated with different concentrations of zofenoprilat (1–10uM) and FGF-2 (20 ng/ml) for 3 days. Cell senescence was evaluated by SA-β-gal staining. Representative pictures of SA-β-gal-positive cells (blue) are reported. After 3 days in culture, the number of SA-β-gal-positive cells in a total of 400 cells was counted (n=3)."	FGF-2//TERT	Activation//Upregulation	qRT-PCR//Western blot	"Zofenoprilat increased TERT mRNA (6-fold), approaching the level reached by FGF-2 (20 ng/ml).whereas that produced by FGF-2 was rapid and declined with time."	Akt//eNOS	Activation//Activation	qRT-PCR//Western blot	"Zofenoprilat (10um) enhanced the phosphorylation of Akt . This activation was slow but persistent (up to 6 h).Assessment of eNOS activation downstream of Akt, measured by phosphorylation of eNOS in Ser1177, demonstrated that zofenoprilat increased eNOS activation ."	L	apoptosis	19959747
Sen_E_128	Lidamycin	Chemical compounds	Colon cancer cell	Colon	Colorectal cancer	Accelerate	SA-β-gal activity assay	"Significant induction of senescent phenotype was observed time dependently after 0.5 nM LDM treatment for 48 120 h, with the ratio of senescent cells reaching over 60% in both cells on day 5. Lower dose (0.25 nM) LDM also caused significant senescence."	EZH2	Downregulation	Western blot//RT-PCR	"Similar reductions of EZH2, EED and SUZ12 protein levels were observed by LDM treatment at various doses for 72 h .Further RT-PCR analysis confirmed significant reduction of EZH2 mRNA upon LDM treatment time dependently."	p21	Upregulation	Western blot	"Consistent with our previous work,12 p53 is found to be increased after LDM treatment for 48 120 h in HCT116 cells harboring wild-type p53. Meanwhile, p53 downstream target p21 was increased. Although little changes of p53 expression were seen in SW620 cells carrying mutant p53, p21 level remained to be enhanced. The same tendency was also found dose dependently."	HL	cellular senescence	27882937
Sen_E_129	Low doses of ionizing radiation	Other	MCF-7	--	Aging	Prevent	SA-β-gal activity assay//Cell morphological analysis	"In comparison to cells treated with doxorubicin only, SA-β-Gal-positive cells decreased when cells were treated with both ionizing radiation and doxorubicin. Consistent with the appearance of SA-β-Gal activity,the morphological characteristics of senescent cells (such cells are typically large and flattened) decreased in cells treated with doxorubicin after low-dose ionizing radiation."	ERK//MAPK	Activation	Western blot//SA-β-gal activity assay	"ERK/MAPK was weakly induced by low-dose radiation alone, but was significantly increased in cells treated with a combination of a low dose of radiation and doxorubicin. SA-?-Gal activity also significantly increased in cells treated with PD980590. The SA-?-Gal activity of cells treated with low doses of ionizing radiation was restored to control levels by treatment with PD98059. Thus, low doses of ionizing radiation inhibited doxorubicin-induced senescence through induction of ERK/MAPK activity."	p38-p53	--	Western blot//SA-β-gal activity assay	"The phosphorylation of p38 kinase significantly increased at 4 days after doxorubicin treatment was suppressed by low doses of ionizing radiation without changing protein levels of p38 kinase.Consistently, SA-?-Gal activity was decreased in cells treated with doxorubicin following a chemical inhibitor of p38 kinase, SB203580.The phosphorylation of p53 in MCF7 cells treated with a combination of doxorubicin and a chemical inhibitor of p38 kinase, SB203580, was significantly decreased from control levels, implying that p38 kinase-dependent phosphorylation of p53 is essential for doxorubicin-induced senescence."	L	cellular senescence	20428768
Sen_E_130	"2,3,5,40-tetrahydroxystilbene-2-O-b-D-glucoside"	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Immunofluorescence	"After stimulation with H2O2 for 1 h and washing out, incubation with THSG for 4 days effectively counteracted H2O2-induced premature senescence in a dose-dependent manner.THSG inhibited vascular senescence in aortic arches .frozen section stain analysis of immunofluorescence of anti-p-gH2AX, a marker of senescence, showed that THSG treatment inhibited phosphorylation of gH2AX in SHRs, although smooth muscle a-actinin (SMA) did not exhibit any remarkable changes ."	eNOS//p53	Upregulation//Downregulation	Western blot//qRT-PCR//Luciferase reporter assay	"Using an eNOS promoter reporter luciferase, we found that THSG produced a 3-fold increase in eNOS reporter gene luciferase activity of the peaks.Results of our animal experiments also demonstrated that administration of THSG restored eNOS expression in aortas of SHRs.In aortas of rats, Western blot analysis demonstrated that THSG treatment significantly restricted expression and K373 acetylation of p53 compared with control SHRs."	SIRT1	Upregulation	Western blot	"THSG activated faintly SirT1 activity in vitro compared with resveratrol.quantitative RT-PCR revealed a pattern of decreasing expression of Sirt1, Sirt3, and Sirt6 in aortas of control SHRs compared with WKY rats, however, administration of THSG restored and elevated expression of these proteins."	L	delay aging	22981429
Sen_E_131	Testosterone	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Immunostaining	DHT-treated SAMP8 showed a reduction of SA-β-gal-stained endothelial cells and increased SIRT1 expression compared to untreated SAMP8. DHT or testosterone treatment inhibited SA-βgal activity and the morphological appearance of senescence .	SIRT1	Upregulation	Western blot//qRT-PCR	DHT treatment increased the protein and mRNA expression of SIRT1 in SAMP8 .	--	--	--	--	L	delay aging	22238626
Sen_E_132	X-radiation	Other	"BJ,MRC-5"	--	Aging	Accelerate	qRT-PCR	"Consistent with previous reports,the hTERT-mediated immortalized MRC-5 (MRC-5/TERT) and BJ (BJ/TERT) cell lines underwent senescence and the induction of IL-8 mRNA was also observed upon x-radiation. The expression of IL-8 and IL-6 mRNAs and proteins was increased after the induction of senescence."	SIRT1	Downregulation	Western blot	"In contrast, expression of the SIRT1 protein was decreased 3 days after the induction of senescence."	--	--	--	--	L	cellular senescence	25635860
Sen_E_133	OVX surgery	Other	--	Aorta	Menopause	Accelerate	SA-β-gal activity assay//Western blot	"The ratio of arterial senescence,assessed by SA-β gal,was greater in OVX mice than in sham mice.Western blot analysis revealed that the arterial expression of SIRT1 protein and the ratio of p-eNOS to eNOS were lower in OVX mice than in sham mice and the expression of Ac-p53, p21, p16, and PAI-1 was higher in OVX mice than in sham mice ."	SIRT1	Downregulation	Western blot	"Western blot analysis revealed that the arterial expression of SIRT1 protein and the ratio of p-eNOS to eNOS were lower in OVX mice than in sham mice and the expression of Ac-p53, p21, p16, and PAI-1 was higher in OVX mice than in sham mice."	--	--	--	--	L	delay aging	31105126
Sen_E_134	Resveratrol	Chemical compounds	PT-ECFC	--	Preterm	Prevent	Western blot//Immunofluorescence	RSV induced a gradual decrease in p16INK4aexpression in time-dependent manner;We found that RSV treatment of PT-ECFCs postponed the G0/G1 arrest.	SIRT	Upregulation	RT-PCR	RSV increased SIRT1 gene expression in a time-dependent manner which correlated with accumulation of Activate chromatin marks at the SIRT1 promoter.	--	--	--	--	L	delay aging	24518759
Sen_E_135	Glucose	Chemical compounds	HREC	--	Diabetes	Accelerate	SA-β-gal activity assay	"As hypothesized, HG caused notable increases in SA β-gal staining, further confirming our previous report of glucose-induced acceleration of EC senescence ."	SIRT	Downregulation	Western blot//qRT-PCR//ELISA	"HG exposure for 48?hr markedly reduced the mRNA expressions of all mitochondrial SIRTs. No such changes were seen following incubation with 25? mmol/L L-glucose (osmotic control). We further measured protein levels of these SIRTs using ELISA. In keeping with mRNA levels, protein levels of SIRTs 3, 4, and 5 were also significantly reduced under HG environments."	--	--	--	--	HL	delay aging	32026628
Sen_E_136	H2O2	Chemical compounds	RPMI8226	--	Myeloma	Accelerate	SA-β-gal activity assay//Western blot	Elevating levels of aging proteins P53 and P16 were shown in myeloma cell line RPMI8226 after being induced by H2O2.	DUSP	Upregulation	Western blot	"We further observed that in H2O2 -induced myeloma cell line RPMI8226 aging model, DUSP level was apparently increased, suggesting the possible relation of DUSP to H2O2 -induced myeloma cell aging."	TLR4	Downregulation	Western blot	"Also, the remarkable reduction of TLR4 was involved in myeloma cell aging model compared to normal control ."	L	cellular senescence	30280787
Sen_E_137	Baicalin	Chemical compounds	"HCT116,SW480 "	--	Colorectal cancer	Accelerate	CCK-8 assay//SA-β-gal activity assay//Colony formation assay	"CCK-8 assay: In CCK-8 assay, baicalin inhibited the viability of HCT116 and SW480 colon cancer cells.Treatment with baicalin at concentrations of 10–40?μM led to significant increase of the percentages of SA-β-gal-positive cells with a dose-dependent manner.SA-β-gal activity assay:Treatment with baicalin at concentrations of 10–40?μM led to significant increase of the percentages of SA-β-gal-positive cells with a dose-dependent manner.Colony formation assay:  In a colony formation assay, baicalin treatment significantly reduced the numbers of colonies in colon cancer cells at all doses tested."	DEPP	Upregulation	Western blot//qRT-PCR	"Western blot//qRT-PCR:To further explore the regulation of DEPP in a hypoxic condition of tumor cells, HCT116 cells were placed into a hypoxic incubator maintained 1% O2. Western blotting and qRT–PCR analyses showed that the expression of DEPP was significantly upregulated ."	Ras-Raf-MEK-ERK//p16-Rb	Activation//Activation	Western blot	"Western blot: In addition to the increased expression of DEPP, the phosphorylation and the activation of Raf1 and ERK were dramatically induced in the colon cancer cells in response to the hypoxic condition. Western blot: we found that the administration of baicalin in HCT116 cells only significantly affected the protein levels of p16INK4A and Rb during the induction of cellular senescence.Western blot:  Similar results of DEPP upregulation and the activation of Ras/Raf/MEK/ERK and p16INK4A/Rb pathways were also observed in A549 and Panc-1 cell lines."	HL	cellular senescence	29440765
Sen_E_138	BAPTA	Chemical compounds	HMESC	Blood	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//Colony formation assay	"BAPTA application impeded H2O2-induced increase of the cell size as well as SA-β-Gal activity, indicating some modulation of the senescence phenotype.BAPTA treatment led to marked increase in the number of proliferating cells compared to H2O2-stimulated cells, indicating that Ca2+ chelation overcame the growth arrest induced by H2O2."	DDR	Downregulation	Flow cytometry//Western?blot	"Loading of H2O2-stimulated cells with BAPTA led to a noticeable decrease in the intracellular ROS levels. Indeed, loading  with  BAPTA  dramatically  reduced phosphorylation of each DDR participant as compared to H2O2-treated cells over the entire observation period."	p53-p21-Rb	Downregulation	Western blot	"Accordingly, in H2O2-treated hMESCs, calcium chelation significantly attenuated phosphorylation of p53, prevented enhanced p21 protein expression and elevated the Rb phosphorylation levels long after senescence induction ."	L	apoptosis	27941214
Sen_E_139	SRM1649b	Chemical compounds	"HaCaT,NHDF"	--	Aging	Accelerate	CCK-8 assay//SA-β-gal activity assay//FACS analysis	"The proliferation ability of these two skin cell lines was gradually decreased when the concentration was increased;When detecting the cell cycle distributions following SRM1649b treatment, we found that cells undergone significant G1 phase arrest ;We determined the cell aging by using senescence-associated β-gal staining assay.When treated with low-dose SRM1649b, NHDF cells clearly showed elevated number and proportion of aging cells."	CYP1A1//MMP1	Upregulation//Upregulation	RT-PCR	RT-PCR data showed the level of CYP1A1 and MMP1 mRNA was dramatically increased after increasing concentrations of SRM1649b treatment for 24 h.	AhR-MAPKs	Activation	Western blot	"We found that the protein level of AhR was gradually degraded after increasing concentrations of SRM1649b treatment for 24 h. In contrast, we found that the phosphorylation level of ERK kinase was gradually increased at the same condition, which was consistent with previously reported that the activation of MAPKs pathway might be regarded for AhR degradation."	L	cellular senescence	28526404
Sen_E_140	Betaine	Chemical compounds	YPEN-1	--	Aging	Prevent	MTT assay	The result of the MTT assay showed that betaine had an ability to inhibit cytotoxicity in a dose-dependent manner.Total RS and ONOO-generation in old rats fed betaine was lower than that of the old rats not fed betaine.	COX-2	Downregulation	Western blot	"T-BHP-induced COX-2 was suppressed by betaine and kinase inhibitors, which means that betaine possibly modulates COX-2 through these kinases."	NF-κB//NIK-IKK//MAPKs	Downregulation//--//--	Western blot//Luciferase reporter assay	"Data clearly reveal that nuclear translocation of NF-kB significantly increased in aged rat, whereas old, betaine-fed rats showed lower levels of NF-kB in a dose-dependent manner compared to their old, nonbetaine-fed counterparts.The binding activity of NF-kB was upregulated during aging and that betaine suppressed up-regulation of NF-kB. NF-kB luciferase activity increased by twofold compared to transfected cell exposure of 0.25 lM t-BHP for 6 hours, and betaine showed a dose-dependent ability to decrease NF-kB luciferase activity. We tested the effects of betaine on IKKa/b, ERK1/2, p38,and JNK expression. Results showed that the addition of betaine significantly inhibited phosphorylation of IKKα/β, ERK1/2, p38, and JNK. Moreover, results showed that the addition of betaine significantly inhibited phosphorylation of NIK, MKK1/2, and MKK3/6. Finally, our data suggested that betaine prevents NF-kB nuclear translocation via NIK/IKK and MAPKs ."	L	delay aging	16282556
Sen_E_141	Melatonin	Chemical compounds	HUVEC	Umbilical cord	Systemic lupus erythematosus	Prevent	SA-β-gal activity assay//Western blot//BrdU assay	"Senescent cells were decreased in the melatonin-treated group.P53 and P21 were downregulated whereas Cyclin D1, CDK4, and CDK6 were upregulatedwhen cells were cultured with melatonin.Ten μM melatonin increased HUVEC proliferation in SLE medium."	RORα	Activation	Knockdown//SA-β-gal activity assay//Western blot//BrdU assay	"RORα-knockdown increased the percentage of senescent HUVECs, although cells were treated with melatonin. P53 and P21 were increased whereas Cyclin D1, CDK4, and CDK6 were decreased when RORα was silenced in HUVECs, although cells were protected with melatonin.However, in the RORα-silenced group, HUVEC proliferation was inhibited, although cells were treated with melatonin."	--	--	--	--	L	delay aging	32172204
Sen_E_142	Mussel oligopeptides	Other	MRC-5	--	Aging	Prevent	MTT assay//Flow cytometry//Cell morphological analysis//SA-β-gal activity assay//SAHF	"Compared with PSC, mussel oligopeptidestreated cells showed a significant dose-dependent increase in cell viability.In H2O2treated cells,pretreatment with mussel oligopeptides resulted in a significant decrease of cells in G0/G1phase (from 69.9% to 31.5%) (P < 0.05)and a concomitant increase of cells in S phase (from 27.5% to 49.1%) and G2/M phase (from 2.6% to 18.3%) (P < 0.01).When cells were pretreated with mussel oligopeptides, a significant decrease in SA-β-gal activity was observed compared with the PSC cells."	Prx1//NAMPT//SIRT1	Upregulation//Upregulation//Upregulation	qRT-PCR	"Treatment with mussel oligopeptides significantly increased the H2O2-triggered expression of Prx1, SIRT1 and NAMPT."	--	--	--	--	L	delay aging	24238886
Sen_E_143	Melatonin	Chemical compounds	CKD-mMSC	--	Chronic kidney disease	Prevent	SA-β-gal activity assay//Western blot	"Melatonin pretreatment restored cellular morphology of H2o2 -enlarged cells , with 100 μM melatonin most effectively reducing cell size. In addition, 100 μM melatonin -treated CKD -mMSCs showed a substantial reduction in the number of β-gal -positive cells. Furthermore,melatonin significantly downregulated p -P53 and p16INK4A, upregulated SMP30 reduced by H2O2 , and significantly downregulated P21."	PrPC	Upregulation	Western blot	"CKD -MCSs treated with H2O2 exhibited decreased PrPC , whereas melatonin pretreatment significantly upregulated PrPC."	--	--	--	--	L	cellular senescence	30372554
Sen_E_144	Azelaic acid	Chemical compounds	HDF	Foreskin	Aging	Prevent	SA-β-gal activity assay//Cell morphological analysis//qRT-PCR//ELISA	"AzA partly counteracted the cell shape change,AzA treatment after PUVA significantly reduced the SA-β-gal staining intensity .Supplementation with AzA significantly decreased MMP-1 protein concentrations and counteracted the PUVA-induced downmodulation of type I pro-collag."	PPARγ	Activation	Luciferase reporter assay	"Our results showed a significant induction of the PPAR-γctranscriptional activity after 24 and 48 h of AzA treatment. Interestingly, PUVA exposure decreased luciferase expression at 24 and 48 h, and AzA 2.5 mM partially counteracted this effect."	--	--	--	--	L	delay aging	23278893
Sen_E_145	PUVA	Other	HDF	Foreskin	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis//ELISA//qRT-PCR	"After 2 weeks, PUVA HDFs showed the typical enlarged and flattened senescent-like morphology and displayed de novo expression of SA-β-gal showing an expression fourfold higher than the control cells.Two weeks after PUVA,we observed a relevant decrease in type I pro-collagen expression and a significant increase in the release of MMP-1."	PPARγ	Downregulation	Luciferase reporter assay	PUVA exposure decreased luciferase expression of PPARγ at 24 and 48 h.	--	--	--	--	L	delay aging	23278893
Sen_E_146	Coumestrol	Chemical compounds	"MCF-7,HCT116"	--	Aging	Accelerate	SA-β-gal activity assay	SA-β-gal staining in cells tended to increase in a dose-dependent manner upon coumestrol treatment .	CKII	Downregulation	Western blot//SA-β-gal activity assay//Quantificationby densitometry	"Coumestrol decreased CKII activity in a dosedependent manner. Specifically, coumestrol treatment (20 lM) induced a 60% decrease in CKII phosphotransferase activity toward the synthetic peptide substrate. The inhibitory effect of coumestrol on CKII was also tested using dephosphorylated b-casein as a substrate. Quantificationby densitometry revealed that 10 lM coumestrol significantly inhibited CKII activity, based on a 70% decrease in b-casein phosphorylation.Transfection of these two cell types with CKIIa resulted in inhibition of SA-b-gal staining."	p53-p21	Activation	Western blot	Immunoblotting showed that the protein expression levels of p53 and p21Cip1/WAF1 were upregulated in coumestrol-treated cells.co-treatment of cells with CKIIa induced an apparent decrease in p53 and p21Waf-1 protein expression.	L	cellular senescence	23768371
Sen_E_147	Tamoxifen	Chemical compounds	"MCF-7,HCT116"	--	Breast cancer	Accelerate	SA-β-gal activity assay	SA-β-gal staining in both MCF-7 and HCT116 cells increased with tamoxifen treatment.	CK2	Downregulation	Western blot	Endogenous CK2 activity was reduced in MCF-7 and HCT116 cells treated with tamoxifen.	p53-p21	Upregulation	Western blot	Immunoblotting showed that the protein levels of p53 and p21Cip1/WAF1 were up-regulated in tamoxifen-treated cells.	L	cellular senescence	24361399
Sen_E_148	H2O2	Chemical compounds	Chondrocyte	--	Osteoarthritis	Accelerate	Flow cytometry//SA-β-gal activity assay//Cell morphological analysis	"When chondrocytes were incubated with 10 ng/ml IL-1β or 50 μM H2O2 for 24 hours, both treatments markedly increased the percentage of cells in the G0/G1phase and reduced the percentage in the S phase.Both stresses induced the chondrocytes to become large and flat and enhanced SA–β-gal activity in the chondrocytes."	Caveolin-1//p38MAPK//CII	Upregulation//--//Downregulation	qPCR//Western blot//qRT-PCR//ELISA	"Quantitative real-time RT-PCR analysis showed that both IL-1β and H2O2 enhanced caveolin 1 mRNA expression in a time-dependent manner, with the peak level occurring at 3 hours after stimulation(n ＝ 3).By Western blot analysis, we confirmed that both IL-1β and H2O2 also induced prolonged up-regulation of caveolin 1 protein expression. Furthermore, pretreatment with the specific p38 MAPK inhibitor SB202190 blocked the enhancement of SA–β-gal activity induced by IL-1β and H2O2.Quantitative real-time RT-PCR revealed a marked reduction in levels of expression of mRNA for CII and aggrecan in chondrocytes 3 days after stress with IL-1β or H2O2. Decreased production of CII from senescent chondrocytes after administration of either stress factor was also confirmed by ELISA (n = 4)."	p53-p21-Rb	--	Western blot//qRT-PCR	"Quantitative real time RT PCR analysis showed increased expression levels of p53 and p21 mRNA in chondrocytes 3 days after stress with IL 1β and H2O2. Western blot analysis demonstrated that caveolin 1 overexpression and both stresses (IL 1β, H2O2) up regulated p53 and p21 protein levels and down regulated phosphorylated Rb protein levels."	L	cellular senescence	16508959
Sen_E_149	Adriamycin	Chemical compounds	"A549,NCI-H460"	--	Lung cancer	Accelerate	MTT assay//SA-β-gal activity assay//Cell morphological analysis	"MTT assays showed that adriamycin was able to decrease the proliferation indices of NCI-H460 and A549 cells at 500 nM and 2 M, respectively. We then found that NCIH460 and A549 cells treated with adriamycin exhibited phenotypic changes that resembled those observed in cells undergoing senescence,including theintensified SA-β- gal staining, flattened cell morphology, and enlarged cell size, in just 1 week.We next examined the endogenous SA-β-gal (pH 6.0) activity.A great increase in SA-β-gal activity was seen 6 days after adriamycin treatment,in comparison with untreated cells."	BMP4	Upregulation	SA-β-gal activity assay//Knockdown//Western blot//qRT-PCR	"We then showed that suppression of endogenous BMP4 expression restrained the adriamycin-induced senescence ,eliciting the critical role of BMP4 in thisprocess. Representative results show that induction of the BMP4 expression by DOX was both doseand time-dependent. Moreover, Western blots revealed that the induction of BMP4 expression by DOX was well equivalent to the extent of BMP4 up-regulation by adriamycin.RT-PCR and quantitative real-time PCR data demonstrated that the BMP4 mRNA level was greatly up-regulated when NCI-H460 and A549 cells were treated with adriamycin at 500 nM and 2 M, respectively."	BMP-Smad	Activation	SA-β-gal activity assay//Knockdown//Western blot	"The ectopic expression of Smad6- myc was first confirmed by Western blot analysis . We then showed that suppression of the BMP-Smad pathway by Smad6 did interfere with the BMP4-induced premature senescence, as revealed by SA-β-gal activity assay, SA-β-gal staining, and cellular immunofluorescence."	L	cellular senescence	19269967
Sen_E_150	IRGs	Other	IMR-90	--	Aging	Accelerate	Western blot//BrdU assay//Colony formation assay//Cell morphological analysis//SA-β-gal activity assay//SAHF	"IRGs induced a stable cell cycle arrest, as determined by a reduction in cyclin A, the phosphorylation status of RB, and 5-bromo-2′-deoxyuridine (BrdU) inco -rporation.The number of colony-forming cells after 2-wk incubation with compound-free medium was strongly reduced if they were pretreated with IRGs.Cells pretreated with the IRGs typically showed an enlarged cellular morphology with increased SA-β-gal activity. p53 and its target p21  were stably upregulated in IRG-treated cells. the levels of HMGA2(a senescence marker) were increased only at the later time point. SAHF formation was also more evident at d9."	AURKA//AURKB	Downregulation//Downregulation	Western blot	"All five IRGs exhibited a substantial inhibitory effect against AURKA and AURKB, with stronger effects on AURKB."	p53	Upregulation	Western blot	"Of interest, we found that the p53-p21 pathway and HMGA2 were up-regulated, particularly at d9 ."	L	cellular senescence	26133385
Sen_E_151	T-oligo	Chemical compounds	LoVo	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"44.8% of cells treated with T-oligo were senescence associated β-galactosidase (SA β-gal) positive compared to only 3.9% and 4.5% of cells treated with diluent and C-oligo, respectively. T-oligo-treated cells were also larger in size, which is characteristic of cells undergoing senescence. T-oligo increased expression of senescent markers p53 (2.0-fold), p27 (1.8-fold), and p21 (2.0-fold)."	POT1//TRF2	Downregulation//Downregulation	Western blot//Immunfluorescence	"We demonstrated that T-oligo treatment downregulated TRF2 in LoVo (2.4-fold, p<0.01) and HT-29 (1.8-fold (p<0.02) cells compared to C-oligo treatment as assessed by immunfluorescence. Additionally, T-oligo treatment downregulates POT1 in both HT-29 (2-fold) and LoVo (3-fold) cells at 48 h and 72 h, respectively as seen by immunoblotting."	--	--	--	--	L	apoptosis	24632202
Sen_E_152	Gamma irradiation	Other	"MSC,Fibroblast"	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"We observed a dose-dependent decrease in proliferation that leveled around 5Gy.SABG activity was detected in damaged MSC or fibroblasts 9 days following irradiation while no detectable SABG expression was found baseline (0 Gy). This was confirmed by a significant increase in cell size 8 days after irradiation as measured by flow cytometry.Overall, irradiated MSC display all the critical hallmarks associated with the presence of a senescence-associated persistent DDR."	PML	Upregulation	Immunoflurescence	"Immunoflurescence targeting PML revealed a strong increase of the protein in MSC, 10 days after 5Gy irradiation."	--	--	--	--	L	cellular senescence	26934440
Sen_E_153	GSK461364	Chemical compounds	"U2OS,MG-63,SJSA"	--	Osteosarcoma	Accelerate	Flow cytometry//MTT assay//Trypan blue staining//SA-β-gal activity assay//qRT-PCR	"Flow cytometric analysis of DNA content in cells treated with GSK461364 for 24 h demonstrated marked accumulation, GSK461364 displayed cytotoxicity against all the three OS cell lines when assessed using either an MTT assay, or a trypan blue exclusion assay cells at G2/M DNA content in all 3 OS cell lines.A significant increase in SA-β-gal activity in the U2OS cells was revealed following GSK461364 treatment.Furthermore, the expression of IL-1α, a cytokine associated with the senescence-associated secretory phenotype (SASP) (34,36), was upregulated in the U2OS cells treated with GSK461364, as measured through qRT-PCR."	PLK1	Downregulation	Western blot	Decreased level of PLK1 and pCDC25C were noted in all three GSK461364-treated OS cell lines.	--	--	--	--	HL	apoptosis	26794530
Sen_E_154	12-O-tetradecanoylphorbol-13-acetate	Chemical compounds	HDF	--	Aging	Prevent	RNA-seq//Cell morphological analysis	"All data strongly supported the occurrence of cell cycle progression, along with the morphological and cytoskeletal changes in senescent cells linked with reduced focal adhesion to extracellular matrix."	PKCα//PERK1/2	Downregulation//--	Knockdown//Immunocytochemistry	"Indeed, the knockdown of PKCα expression significantly reduced pErk1/2 translocation after TPA treatment.The loss of PKCα expression was much faster after TPA treatment than after siPKCα transfection."	--	--	--	--	HL	delay aging	26912086
Sen_E_155	Glucagon‐like peptide 1	Chemical compounds	EA.hy926	--	Aging	Prevent	SA-β-gal activity assay	"Pre‐incubation with GLP‐1 significantly reduced 5FU‐elicited senescence of EA.hy926 cells. This effect occurred through GLP‐1 receptor, as it was attenuated by the GLP‐1 receptor antagonist, E9. GLP‐1 prevented endothelial cells senescence initiated by sera from patients taking capecitabine."	PKA//ERK1/2//PI3K//NOS	Downregulation//Downregulation//Downregulation//Downregulation	Western blot//Densitometry analysis	"GLP‐1 prevented endothelial cells senescence initiated by sera from patients taking capecitabine, with this effect being eliminated by antagonism of GLP‐1 receptors or inhibition of PKA, ERK1/2, PI3K and NOS."	--	--	--	--	L	delay aging	28127745
Sen_E_156	ABT-737	Chemical compounds	"PV-10,22RV1"	--	Prostate cancer	Accelerate	MTT assay//BrdU assay//Colony formation assay	MTT assay: Long-term exposure of PV-10 cells to ABT-737 induced significant growth inhibition and a G1/S cell cycle blockade. Brdu assay//Colony formation assay: a dose-dependent inhibition of colony formation and an inhibition of BrdU incorporation was seen after the addition of ABT-737 to both PV-10 and 22Rv1 cells.	AMT	Activation	Western blot//SA-β-gal activity assay	"Western blot:  In a pool of PV-10 cells ATM levels were decreased by shRNA, we found that a marked reduction in ATM levels prevented ABT-737 from inducing γ-H2AX.SA-β-gal activity assay: ABT-737 treatment of cells with lower levels of ATM protein kinase caused a markedly reduced level of SA-β-Gal and senescence-like morphologic changes .we measured levels of IL-6 and IL-8 mRNA in PV-10-shRNAmir-ATM and PV-10-shRNAmir-control cells. QT-PCR analysis showed that ATM knockdown prevented the ABT-737–mediated induction of IL-6 and IL-8 mRNA."	p53-p21	Activation	Western blot//SA-β-gal activity assay	Western blot: Both PV-10 and 22Rv1 cells when treated with ABT-737 show increased levels of both wild-type p53 and p21 protein levels. We find that ABT-737 treatment inhibits Cdk2 activity in a dose-dependent fashion in both PV-10 and 22Rv1 cells. Western blot//SA-β-gal activity assay: Western blot analysis confirmed that after ABT-737 treatment overexpression of DN p53 caused a substantial reduction in p21 and inhibited the ability of ABT-737 to induce SA-β-Gal.	HL	cellular senescence	21084274
Sen_E_157	Icariin	Chemical compounds	HUVEC	Coronary artery	Aging	Prevent	SA-β-gal activity assay//Western blot	"When HUVECs under 400 μM homocysteine stimulation were treated by ICA (0.1 5 μM), the percentage of SA-β-gal-positive cells were reduced significantly in a dose-dependent manner."	Akt//ERK//eNOS	--//--//--	Western blot	" As shown ICA induced rapid AKT phosporylation after 30-min incubation in HUVECs, maximum effects were achieved at ~60min. ERK1/2 phosphorylation was stimulated 10min later, the maximum effects were achieved at 30 60min. Both in HUVECs and in homocysteine-stimulated HUVECs, ICA increased the protein expression of phosphorylated eNOS."	PI3K-Akt-eNOS	--	Measurement of nitrite	"The presence of PI3K inhibitor wortmannin abolished most effects of ICA on NO production, while the MEK inhibitor PD98059 did not show this ability . These results suggested that effects of ICA on NO production mainly involved PI3K/AKT-eNOS signaling pathways."	L	cellular senescence	23336586
Sen_E_158	HIV	Other	HIVBaL	--	Aging	Accelerate	Western blot//SA-β-gal activity assay	Infection of VSVG-HIV also caused a 1.8-fold increase in p16INK4Alevels .Transfection of HFAs with HIVBal plasmid induced SA‐β-Gal+ cells from 8% in pcDNA3 control plasmid to 20% in HIV‐transfected cells.	--	--	--	--	β-catenin	Downregulation	Western blot//SA-β-gal activity assay	"HIV also inhibited β-catenin signaling in HFA, as demonstrated by inhibition of Activate β-catenin expression post-VSVG-HIV infection to 30% at 48 h and 22% at 72 h of the VSVG control."	L	cellular senescence	28612507
Sen_E_159	Drug abuse	Other	HFA	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis//Western blot	"Meth significantly induced SA-β-Gal expression even at the lower meth dose of 10 lM ；Meth-treated HFAs demonstrated a classical flat morphology of senescent astrocytes ;Meth also increased the expression of another marker of cell senescence, p161NK4A, as evaluated by Meth also increased the expression of another marker of cell senescence, p161NK4A, as evaluated by Western blot."	--	--	--	--	β-catenin	Downregulation	SA-β-gal activity assay	Meth at 300 lM inhibited TOPflash activities by approximately 45%.	L	cellular senescence	28612507
Sen_E_160	Norcantharidin	Chemical compounds	A549	Lung	Lung cancer	Accelerate	SA-β-gal activity assay	SA-β-Gal assay showing that NCTD at 15 μM significantly increased cell senescence phenotype in A549 cells for 72 h.	--	--	--	--	YAP	Downregulation	RT-PCR//Western blot	NCTD time-dependently reduced Yap mRNA(E) and protein level (F) in A549 cells at 15 μΜ.	L	apoptosis	27903989
Sen_E_161	TCDD	Chemical compounds	Astrocyte	Brain	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry //Western blot	"After treatment with different doses of TCDD  for 96 h, and the rate of SA-β-Gal positive astrocytes was significantly elevated in a dose-dependent manner.Flow cytometry showed that there were more astrocytes restricted in the G1 phase harvested from the TCDD-treated group 74.64 ± 2.9%(P <0.01) than the control group 63.49 ± 3.3%, and cell populations in the S phase decreased in the TCDD-treated group 23.39 ± 3.29% (P <0.01) compared with the control group 15.63 ± 2.05%. The protein levels of p16 and p21 were evidently increased in astrocytes treated with different doses of TCDD for 96 h in a dose-dependent manner."	--	--	--	--	WNT-β-catenin	Upregulation	Western blot	"β-catenin was significantly up-regulated by TCDD in a dose-dependent manner, and peaked at 100 nm TCDD exposure."	L	delay aging	25382668
Sen_E_162	Aβ1-42 oligomers	Chemical compounds	HBMEC	--	Alzheimer's disease	Accelerate	SA-β-gal activity assay// Western blot	"HBMECs exposed to Aβ1-42 oligomers appeared flattened and enlarged and showed increased senescence-associated β-galactosidase staining, exhibiting hallmark features of a senescent phenotype.Western blot analysis showed significantly increased p21 protein levels in the Aβ1-42 oligomer-treated HBMECs compared with control group."	--	--	--	--	VEGFR//p21-p53	Upregulation//Upregulation	Western blot//qRT-PCR	"Upon Aβ1-42 oligomer treatment, we observed a significant increase in VEGFR-1 protein levels, whereas protein levels of VEGFR-2 were not significantly altered.Western blot analysis showed significantly increased VEGFR-1 protein levels only in the Aβ1-42 oligomer-treated HBMECs but not in either Aβ1-42 monomers or Aβ1-42 fibrils-treated HBMECs .Western blotting analysis from chimeric receptor EGLT-transfected lysates confirmed the increased expression of the VEGFR-1 protein and increased p21 proteins levels and decreased expression of VEGFR-2 levels. qRT-PCR analysis showed increased mRNA levels of VEGFR-1, p21,and p53. There was a decrease in the p53 isoform Δ133p53 mRNA levels and no significant changes in p53b or VEGFR-2 mRNA levels.Western blot analysis showed increased levels of VEGFR-1 and p21 protein expression following Aβ1-42 oligomer treatment compared with control groups as previously shown."	L	delay aging	30576228
Sen_E_163	"1,25(OH)2D3"	Chemical compounds	BM-MSC	--	Osteoporosis	Prevent	SA-β-gal activity assay//Western blot	"Serum calcium and phosphorus levels were increased significantly in exogenous 1,25(OH)2D3-supplemented 18-month-old mice compared with vehicle-treated mice. In addition, BMD, trabecular bone volume, trabecular number and thickness, osteoblast number, MAR, and BFR were increased significantly ,whereas TRAP-positive osteoclastic number, the percentages of β-gal+, p16+, and IL-6+ osteocytes, and the mRNA levels of TNFα,IL-1α, IL-1β, IL-6, Mmp3, and p16 were all significantly decreased in exogenous 1,25(OH)2D3-supplemented 18-month-old mice compared with vehicle-treated mice."	--	--	--	--	VDR-Ezh2-p16	--	Western blot//qRT-PCR//CHIP//Luciferase reporter assay	"We found that 1,25(OH)2D3 increased the mRNA level of Ezh2 and down-regulated p16 and p19 expression at both protein and mRNA levels .The results of a ChIP-PCR assay demonstrated that the VDR could directly bind to the Ezh2 promoter at the predicted binding site. Luciferase reporter assays demonstrated that treatment of 1,25-(OH)2-D3 increased luciferase activity significantly in BM-MSCs transfected with an Ezh2-Luc plasmid, but failed to activate the mutant Luc reporter."	L	delay aging	31880094
Sen_E_164	Tumor-derived γδTreg cells	Other	γδ Treg cell	--	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay//Western blot	"85% of naive CD4+T cells treated with γδ Treg cells remained in G0/G1, indicating that γδ Treg cell treatment promotes the accumulation of naive T cells in cell cycle arrest ;As expected, significantly increased p53, p21, and p16 expressions were observed in naive CD4+T cells after treatment with γδ Treg cells ;Naive CD4+ and CD8+T cells treated with γδ Treg cells significantly induced cell senescence, resulting in SA-β-Gal expression."	--	--	--	--	TLR8	--	SA-β-gal activity assay	Pretreatment of γδ Treg cells with poly-G3 significantly blocked the induction of senescence in the transferred CD4+T cells.	L	cellular senescence	23355732
Sen_E_165	Ultraviolet radiation	Other	HDF	--	Aging	Accelerate	SA-β-gal activity assay	"When cells were exposed to UVA (7.5 J/cm2) or UVB (0.25 J/cm2) for 24 h, S HDFs showed an increased number of SA-β-gal positive cells as compared to control-treated cells, whereas NS HDFs showed negative staining for SA-β-gal activity."	--	--	--	--	TLR4-ERK	--	Mitochondrial flux analysis	"Furthermore, ERK or TLR4 inhibitor-treated senescent HDFs had strikingly decreased OCR than control-treated cells, suggesting that TLR4-ERK signaling pathways can lead to control of mitochondrial metabolic profilings in senescent HDFs."	HL	cellular senescence	30118525
Sen_E_166	Chitosan	Chemical compounds	Fibroblast	Foreskin	Aging	Prevent	SA-β-gal activity assay	"SA-β-gal activity assay:cellCompared to fibroblasts always on TCPS without culturing on chitosan (w/o treatment), cells after chitosan treatment for 3 days significantly decreased the percentage of SA β-gal-positive cells from about 20% to less than 10%  cultured on chitosan for 5 DIV increased the percentage of SA β-gal-positive cells."	--	--	--	--	TGF-β	Downregulation	SA-β-gal activity assay//Western blot	"SA-β-gal activity assay:The tendency of cell senescence increased with increasing the TGF-b concentration. Therefore, we assumed chitosan could suppress TGF-β signaling to delay the progress of fibroblast senescence.Western blot:compared to cells cultured on TCPS, only cells treated by chitosan showed significantly lower expression of TGF-b, Smad2/3 and pSmad2/3 ."	L	cellular senescence	29081244
Sen_E_167	MHY2233	Chemical compounds	EPC	--	Aging	Prevent	SA-β-gal activity assay//IP//qRT-PCR//western blot//Annexin V binding assay	"The results show that MHY2233 treatment significantly decreased the percentage of SA-β-gal-positive cells concentration-dependently. The results show that MHY2233 and resveratrol significantly reduced the percentage of apoptotic cells, whereas the percentage was increased by EX527 .MHY2233 treatment also decreased the mRNA levels of various SASPs, namely, IL-6, IL-8, IL-1α, and IL-1β. MHY2233 also increased the phosphorylation of eNOS on serine 1177 .treatment with MHY2233 decreased the mRNA levels of p16, p53, and p21."	--	--	--	--	STAT1	Upregulation	Western blot//qRT-PCR	"SIRT1 protein and mRNA levels were assessed in EPCs after concentration-dependent treatment with MHY2233. SIRT1 protein and mRNA levels both were upregulated with increasing concentrations of MHY2233 .The mRNA and protein levels of SIRT1 were increased by MHY2233 and resveratrol, but were decreased by EX527. "	L	cellular senescence	31223423
Sen_E_168	Atraric acid	Chemical compounds	LNCaP	--	Aging	Accelerate	SA-β-gal activity assay//SAHF//FACS analysis	"Treatment with AA leads to the induction of SA-β-gal activity, indicating the induction of cellular senescence. These findings are further confirmed by the occurrence of SAHF . Quantitative analyses revealed that AA induces cellular senescence in LNCaP cells in a concentration-dependent manner, reaching a maximum at 30uM . Interestingly, treatment of the cells for 3 days was sufficient for the induction of cellular senescence; a longer incubation with AA did not increase the percentage of SA-β-gal-positive cells.FACS analysis revealed an increase of the number of cells in the G1 phase of the cell cycle after AA treatment. allow the regrowth of cells."	--	--	--	--	Src-Akt//Id-1-p16-pRb	--//Activation	SA-β-gal activity assay//qRT-PCR	"Inhibitors of Src and Akt were used to analyze whether these factors are involved in AA-induced cellular senescence in LNCaP cells. Interestingly, cotreatment of the Src inhibitor PP2 with AA reduces the level of cellular senescence relative to single treatment with AA. Similarly, cotreatment of the Akt inhibitor with AA also reduces the level of cellular senescence, indicating that this nongenomic pathway is involved in the AA-mediated induction of cellular senescence.On the other hand a dephosphorylation of pRb was detected. Reduced phosphorylation of pRb leads to its activation and hence down-regulation of the transcription factor E2F1 (23). In line with this, a down-regulation of the pRB target E2F1 associated with the up-regulation of p16 are observed at protein level by AA treatment.An inhibitor of p16 gene expression is the cell cycle regulator Id1 via the repression of transcription factors of the E-twenty six family (26). In line with this, a reduction of Id1 gene expression after AA administration was observed . Additionally, a down-regulation of Id1 expression in LNCaP cells leads to an increase of SA -β-gal-positive cells, suggesting that Id1 inhibition is required for the activation of p16 and subsequent induction of cellular senescence triggered by AA treatment."	L	cellular senescence	25203674
Sen_E_169	Sjp40	Chemical compounds	LX-2	--	Aging	Accelerate	Western blot	"Western blot: To further confirm the role of Sjp40 on cellular senescence, phosphorylation of Rb, which has been viewed as the crucial step in the progression of G1-S phase transition, was measured by Western blot. We observed obvious dephosphorylation of Rb in Sjp40-treated cells."	--	--	--	--	SKP2-p27	--	Western blot//SA-β-gal activity assay//Knockdown	"Western blot:Since Sjp40 treatment markedly increased the protein level of P27。SA-β-gal activity assay//Knockdown:SA-β-Gal positive percent mediated by Sjp40 in LX-2 cells obviously reduced via knockdown of P27, which confirmed the crucial role of P27 in regulating cellular aging induced by Sjp40。Western blot：SKP2 over-expression reversed P27 protein level induced by Sjp40, indicating that P27 expression induced by Sjp40 is dependent on SKP2 in LX-2 cells.SA-β-gal activity assay：Over-expression of SKP2 rescued the Sjp40-induced senescence analyzed by SA-β-Gal assay."	HL	cellular senescence	28325896
Sen_E_170	Melatonin	Chemical compounds	--	Aorta	Aging	Prevent	Histological staining	"In control mice not treated and treated with FAST or RETARD melatonin and in APOE-treated mice with both formulations of melatonin,the vessels showed a normal morphology."	--	--	--	--	SIRT1-p53-eNOS	--	Immunostaining	"SIRT1 was expressed in cytoplasm and nuclei of tunica intima cells of APOE FAST-and RETARD-treated mice.On the contrary, intima, media, and adventitial cells were negative in the vessels of control mice and in those given either APOE FAST or RETARD melatonin .Melatonin treatments restored significantly the expression of this protein after either in APOE FAST or RETARD melatonin treatment. This positivity was moderate in ECs of APOE FAST-treated animals and strong in APOE RETARD-treated mice."	L	delay aging	22109832
Sen_E_171	Montelukast	Chemical compounds	Chondrocyte	--	Osteoarthritis	Prevent	SA-β-gal activity assay//Immunostaining//Flow cytometry	"However,treatment with the specific cysLTR1 antagonist montelukast (10 and 20μM) ameliorated TNF-α-induced elevation of SA-β-Gal activity.Treatment with TNF-α (10 ng/ml) significantly increased γ-H2AX foci formation, which was prevented by montelukast in a dose-dependent manner. However, treatment with montelukast (10 and 20 μM)reduced the proportion of cells in the G0/G1 phase to 55.6% and 52.1%, respectively."	--	--	--	--	SIRT1-p53	--	IP//Western blot	"Immunoprecipitation assay results indicate that TNF-α significantly enhanced p53 K382 acetylation, which was inhibited by montelukast.The results indicate that TNF-α significantly reduced expression of SIRT1, which was prevented by montelukast in a concentration-dependent manner.Silencing of SIRT1 blocked the inhibitory effects of montelukast on p53 K382 acetylation."	L	delay aging	29331588
Sen_E_172	High glucose	Other	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"Compared with NG, both HG and HN significantly increased the percentage of SA β-Gal staining cells by more than 2 fold."	--	--	--	--	SIRT1-p300-p53-p21	--	SA-β-gal activity assay//Western blot	"Compare to either NG or MN treated cells, exposure to HG resulted in a significant decrease in SIRT1 protein expression and its deacetylase activity .After transfection of pSIRT1, the protein expression and deacetylase activity of SIRT1 was significantly increased, while the protein expression of Ac-p53 and p21 were markedly decreased. In a similar manner, p300 siRNA transfection reduced the protein levels of p300, Ac-p53, and p21. It is interesting that SIRT1 over-expression suppressed the expression of p300 by nearly 50%, and p300 knock-down reciprocally increased the expression and activity of SIRT1."	L	delay aging	26629991
Sen_E_173	Genistein	Chemical compounds	HUVEC	Umbilical cord	Aging	Prevent	SA-β-gal activity assay//Western blot	"Pretreatment with genistein (1000?nM) inhibited the protein levels of P16 and P21, and decreased the activity of SA-β-gal."	--	--	--	--	SIRT1-LKB1-AMPK	Activation	SA-β-gal activity assay//Western blot//Knockdown	"The effect of genistein on senescence and was restrained by SIRT1 siRNA, LKB1 siRNA, and AMPK siRNA.Ox-LDL ameliorated the phosphorylation of AMPK (Thr-172), and pretreatment with genistein elevated the phosphorylation of AMPK (Thr-172); meanwhile, the effect of genistein was abolished by SIRT1 siRNA or LKB1 siRNA. Compared with SIRT1 siRNA and LKB1 siRNA, control siRNA had no effect. These data ascertained that the effect of genistein could be associated with activating SIRT1/LKB1/AMPK pathway."	L	delay aging	30443855
Sen_E_174	Aspirin	Chemical compounds	"SW620,HCT116"	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//MTT assay	"Indeed, we found that aspirin induced cellular senescence, with maximum senescence-inducing effects observed at a concentration of 500 M in SW620 cells. We found that aspirin concentration-dependently reduced cell viability in both SW620 human metastatic colorectal carcinoma cells (p53 mutant-type) and HCT116 human primary colorectal carcinoma cells (p53 wild-type), and that it highly inhibited cell proliferation at concentrations greater than 1 mM ."	--	--	--	--	SIRT1-AMPK	--	Western blot	"Aspirin treatment was found to dose- and time-dependently increase the protein levels of SIRT1, phospho-AMPK (p-AMPK T172), and p-ACC S79. Interestingly, the increase in SIRT1 protein expression was followed by AMPK activation."	L	cellular senescence	26219912
Sen_E_175	Ergothioneine	Chemical compounds	Endothelial cell	--	Type 2 diabetes mellitus	Prevent	Cell morphological analysis	The Egt treatment in the presence of hGluc (EgtthGluc) resulted in a morphological adjustment to the control cell-like small spindle shape.	--	--	--	--	SIRT1//SIRT6//NF-κB	Upregulation//Upregulation//Downregulation	Confocal microscopy//Immunofluorescence//Western blot	"Specifically, SIRT1 arbitrary fluorescence units (AFU) were significantly decreased by 48 h treatment with hGluc whereas EgtthGluc cells showed a SIRT1 fluorescence intensity significantly higher than that observed in hGluc cells.These effects were blocked by Egt and, more in details, SIRT6 expression in EgtthGluc cells was 78.373.1 AFU vs 49.273.1 AFU in hGluc cells, whereas NF-κB expression was 48.971.8 AFU vs. 12473.3 AFU in hGluc cells . Moreover, a reduced SIRT6 downregulation and a reduced NF-κB upregulation were observed during hGluc treatment in the presence of Egt (EgtthGluc)."	L	delay aging	27101740
Sen_E_176	Metformin	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay	"In accordance to these changes, RSV or MET treatment also significantly increased the expression of SMP-30 and decreased the percentage of SA β-Gal staining in HN-treated HUVECs."	--	--	--	--	SIRT1	Upregulation	Western blot	"When cells were treated with RSV or MET during the incubation in HG for 3 days followed by NG for another 3 days, the expression and deacetylase activity of SIRT1 were significantly increased and the expression of p300, Ac-p53, and p21 was significantly decreased ."	L	delay aging	26629991
Sen_E_177	Resveratrol	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay	"In accordance to these changes, RSV or MET treatment also significantly increased the expression of SMP-30 and decreased the percentage of SA β-Gal staining in HN-treated HUVECs."	--	--	--	--	SIRT1	Upregulation	Western blot	"When cells were treated with RSV or MET during the incubation in HG for 3 days followed by NG for another 3 days, the expression and deacetylase activity of SIRT1 were significantly increased and the expression of p300, Ac-p53, and p21 was significantly decreased ."	L	delay aging	26629991
Sen_E_178	Melatonin	Chemical compounds	SH-SY5Y	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//Immunofluorescence	"After treatment with 100 μM H2O2 and incubation for 24 h,cells were stained with SA-βgal staining solution.We found that the number of SA-βgal-positive cells increased significantly compared to the untreated-control cells. Furthermore, the number of SA-βgal-positive cells treated with both 100 μM H2O2 and 1 μM melatonin was significantly lower than the H2O2-treated group .To confirm aging, a cell cycle assay and flow cytometry analysis were performed and revealed that treatment with H2O2 caused a change in the cell cycle phase distribution,representing cell cycle arrest. Cells treated with H2O2 showed a significantly higher percentage of cells in the subG1 phase and a lower proportion in the S phase compared to untreated-control cells. In addition, H2O2-melatonin-treated cells demonstrated significantly decreased subG1 phase, which represented the cell cycle arrest state, compared with H2O2-treated cells.Ki67 expression was used to detect alterations in proliferation.Melatonin increased Ki67 expression, whereas cells preincubated with H2O2 demonstrated decreased Ki67 expression. Treatment with H2O2 and melatonin resulted in an increase in the number of Ki67-positive cells compared to cells treated with H2O2 alone."	--	--	--	--	SIRT1	Upregulation	Western blot	"These results showed that SIRT1 levels of cells treated with 100 μM H2O2 alone were significantly decreased compared to untreated-control cells. In cells co-treated with 1 μM melatonin, SIRT1 levels were rescued to 91.3 ± 3.1% (p < 0.01) of control levels compared to the H2O2-treated group and increased in melatonin-treated alone cells.In control cells, there was moderate SIRT1 immunoreactivity (A). Confocal analysis revealed the formation of SIRT1-positive aggregates in melatonin-treated cells (B)."	L	delay aging	28295567
Sen_E_179	Donepezil	Chemical compounds	HUVEC	--	Alzheimer’s disease	Prevent	MTT assay//Western blot//qRT-PCR//SA-β-gal activity assay//Flow cytometry	"The rate of SA-?-gal-positive cells was significantly higher in the HG (30 mmol/L) group compared with the NG (5.6 mmol/L) group, and this increase was suppressed by treatment with donepezil in a concentrationdependent manner from 10 to 50 μM. Our results demonstrated that treatment with 30 mmol/L glucose arrested HUVECs in the G0/G1 phase as the proportion of cells in the G0/G1 phase was~69.9 % compared to 53.3 % in the NG (5.6 mmol/L) group. Donepezil (20 μM) pretreatment eliminated the effects of HG and reduced the proportion of cells in the G0/ G1 phase to 55.3 % . Next, we examined the impact of donepezil on cell viability. Treatment with HG (30 mmol/L) significantly suppressed endothelial cell viability, which was reversed by treatment with donepezil in a concentration dependent manner from 10 to 50 μM.HG treatment drastically increased the expression of PAI-1 and p21, which was markedly suppressed by donepezil treatment . This result was confirmed by Western blot analysis at protein levels."	--	--	--	--	SIRT1	Activation	Western blot	"Immunoblot analyses indicated that SIRT1 levels were decreased in response to treatment with HG (30 mmol/L), which was partially rescued by treatment with donepezil. SIRT1 deacetylase activity was reduced by treatment with HG. However, donepezil restored the deacetylase activity of SIRT1, indicating a direct effect on SIRT1-mediated pathways."	L	delay aging	26194321
Sen_E_180	Melatonin	Chemical compounds	BM-MSC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry	"The percentage of SA-β-gal-positive cells showed a declining dose-dependent tendency in response to melatonin, in which the ratio decreased to 64.7 ± 3.2% at 10 nM, 54.4 ± 2.3% at 1 μM, and 24.3 ± 5.7% at 100 μM . The cell cycle distribution results showed that melatonin-treated BM-MSCs exhibited a significantly increased proportion in the S phase ."	--	--	--	--	SIRT1	Upregulation	qRT-PCR//Immunofluorescence//Western blot	"On the other hand, treatment with 100 μM melatonin increased the SIRT1 mRNA level by 1.8 ± 0.2-fold higher than the H2O2 group.exposure to H2O2 inhibited SIRT1 protein expression but treatment with melatonin recovered it. Further experiments revealed that the protein level of SIRT1 in H2O2-treated BM-MSCs was significantly down-regulated to 42.8 ± 6.3% compared with the control, but treatment with melatonin upregulated the level of SIRT1."	L	delay aging	25975679
Sen_E_181	Hydrogen sulfide	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//MTT assay	"Examination of SA-β-gal activity in HUVECs treated with H2O2 (25 μM) revealed a significant increase in SA-β-galpositive cells, which reached 11.2±1.06%. However, increases in SA-β-gal-positive cells were significantly attenuated in the NaHS (60 μM) group.Our results demonstrated that treatment with 25 μM H2O2 arrested HUVECs in the G0/G1 phase as the proportion of cells in the G0/G1 phase was ~70.2% compared to 54.4% in the control group. NaHS (60 μM) pretreatment eliminate Our study indicated that NaHS (60 μM) improved H2O2-induced decreases in HUVEC proliferation. d the effects of H2O2 and reduced the proportion of cells in the G0/G1 phase to 58.1%. These results indicate that H2S protects against HUVEC senescence."	--	--	--	--	SIRT1	Activation	Western blot	"Immunoblot analyses indicated that SIRT1 levels were decreased in the H2O2 (25 μM) treatment group compared to the control, and NaHS (60 μM) treatment did not rescue SIRT1 expression. In contrast to its effect on protein expression, NaHS enhanced SIRT1 deacetylase activity in vitro, indicating a direct effect on SIRT1-mediated pathways."	L	delay aging	23588928
Sen_E_182	CSE	Other	16HBE	--	Aging	Accelerate	MTT assay//SA-β-gal activity assay	"To detect the appropriate dose and action time of CSE, the cell survival rate was observed by MTT assays. 16HBE cells were treated with CSE at different doses and time points. The relative cell number was detected to evaluate cell growth. Cell survival rate was inhibited by CSE in a time- and dose-dependent manner. According to the survival curve , considering IC50 and the obvious downward trend, stimulation by 2% CSE for 24 hours could be used in the follow-up experiments.We found SA-β-gal positive cells ratio was obviously increased by CSE stimulation. After adding C. sinensis, the ratio was able to be decreased compared to CSE group. These data indicated that CSE stimulation could induce cellular senescence in human bronchial epithelial cells, and C. sinensis can inhibit the senescence induced by CSE."	--	--	--	--	ROS-PI3K-Akt-mTOR	Activation	Western blot	"The expressions of p-AKT and p-mTOR were promoted by CSE in a time- and dose-dependent manner.mTOR signaling pathway was increased in the CSE group, and decreased when C. sinensis was added.We inhibited ROS with N-acetylcysteine, and ROS generation and cellular senescence induced by CSE was weakened. Activation of mTOR signaling pathway was decreased."	L	cellular senescence	27555762
Sen_E_183	Cardiac glycoside	Chemical compounds	HeLa	--	Aging	Accelerate	SA-β-gal activity assay	"The  number of SA-β-Gal positive cells increased after the treatment of all cardiac glycosides for 72 h, significantly indicating the cardiac glycoside-induced senescence in HeLa cells."	--	--	--	--	Rho-Rho	--	Cell morphological analysis	"The measurements demonstrated that cardiac glycosides increased the cell areas in HeLa cells comparing to the control group. Pretreatment of Rock inhibitor, Y-27632, significantly reduced the increased cell area induced by cardiac glycosides."	L	cellular senescence	30369081
Sen_E_184	Arctigenin	Chemical compounds	GBC	Cholecyst	Gallbladder cancer	Accelerate	Flow cytometry//SA-β-gal activity assay	"We also evaluated whether ATG was responsible for cellular senescence in GBC cells. Flow cytometric analysis of the cell cycle distribution indicated that the ATGtreated GBC cells were primarily arrested in the G1/G0 phase. SA-β-gal staining revealed that ATG treatment significantly increased the percentage of SA-βgal-positive cells, starting at 24 h after treatment with ATG.Apparently, cellular senescence occurs before cell apoptosis in ATG-treated cells, which is consistent with the cell cycle distribution analysis."	--	--	--	--	Raf-MEK-ERK	Downregulation	Western blot//qRT-PCR//Immunofluorescence	"Immunofluorescence staining and western blot showed that the EGFR protein level significantly decreased in the ATG-treated group compared with the control group. Moreover, we observed a significant reduction in the level of the phosphorylated form of Raf (c-Raf and b-Raf), MEK, and ERK. The in vivo assay showed that the gene expression of EGFR was remarkably diminished by ATG treatment in ATG-treated subcutaneous mouse tumors."	L	cellular senescence	28459363
Sen_E_185	CSE	Other	HBEC	--	Aging	Accelerate	Western blot	We performed western blotting of CDKN2A/p16 and CDKN1A/p21 (senescence-associated cyclin dependent kinase inhibitors). Increased CDKN2A and CDKN1A expression levels indicated acceleration of cellular senescence.	--	--	--	--	PINK1-PARK2	--	Knockdown//SA-β-gal activity assay//Immunofluorescence//Western blot	"PINK1 knockdown also enhanced CSE-induced mitochondrial ROS production and HBEC senescence . PINK1 knockdown noticeably reduced PARK2-HA levels in the mitochondrial fraction, while increased PARK2-HA levels were observed in the cytosolic fraction in PARK2-HA-transfected HBEC, supporting the notion that PINK1 is responsible for translocation of PARK2 from the cytoplasm to the mitochondria ."	L	cellular senescence	25714760
Sen_E_186	EGCG	Chemical compounds	3T3-L0	--	Aging	Prevent	SA-β-gal activity assay	"SA-β-gal activity significantly(p＜0.05) enhanced in H2O2treated cells with over 60% cells appearing senescent as compared to control group, which was significantly (p＜0.05) abrogated on treatment with EGCG."	--	--	--	--	PI3K-Akt-mTOR	Downregulation	Western blot	EGCG treatment significantly (p＜0.05) downregulated expression of both PI3K and Akt as well as p-mTOR(albeit at 100 lM only) suggesting its role in modulation of stress-induced mTOR signaling pathway. A suppression in the gene expression of translation initiation factors (4E-BP1 and eIF4E) downstream of mTOR pathway was also observed that further indicated the inactivation of mTOR pathway in the presence of EGCG.	L	apoptosis	30456590
Sen_E_187	High glucose	Other	ARPE?19	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"We found that the number of SA-β-Gal-positive cells significantly increased in a time-dependent manner, indicating that ARPE-19 might be senescent when treated with 25 mM glucose for 48 h. High glucose also triggered  the cell cycle arrest in ARPE-19, and the cells in G0/G1 phase gradually increased from 63.91% to 78.42% after incubation of ARPE-19 with 25 mM high glucose for 48 h."	--	--	--	--	PI3K-Akt-mTOR	Activation	Western blot	"We found the up-regulated expression of PI3K, p-AKT and p-mTOR in ARPE-19 treated with 25 mM glucose ."	L	apoptosis	30339883
Sen_E_188	Leptin/NAP-2	Chemical compounds	MSC	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"When cultured with UC‐MSCs, both leptin and NAP‐2 increased the percentage of SA β‐gal–positive cells and up‐regulated expression of p53 and p21 in a dose‐dependent manner. Strikingly, concomitant stimulation of UC‐MSCs with leptin and NAP‐2 further increased the frequency of SA β‐gal–positive cells (38.2?±?1.4% versus 24.3?±?0.6% with leptin stimulation alone and 26.0?±?2.0% with NAP‐2 stimulation alone) and increased expression of p53 and p21 compared with stimulation of cells with leptin or NAP‐2 alone, which suggests that these 2 factors act synergistically to affect MSC senescence."	--	--	--	--	PI3K-Akt	Activation	SA-β-gal activity assay//Western blot	"We indeed demonstrated a substantial, dose‐dependent elevation of phospho‐Akt expression in UC‐MSCs treated with leptin or NAP‐2 . Consistent with this, the senescence induced by leptin and/or NAP‐2 was almost completely reversed after LY294002 treatment, which was demonstrated by a decreased number of SA β‐gal–positive cells and by diminished levels of p53 and p21."	HL	cellular senescence	25989537
Sen_E_189	mTORC1	Chemical compounds	BJ-T	--	Aging	Prevent	SA-β-gal activity assay//Cell morphological analysis//RT-PCR	"Upon treatment with rapamycin,the percentage of AKT cells positive for SA-β-GAL was significantly reduced. Rapamycin treatment also dramatically reduced AKT-induced effects on cell size, and the SASP."	--	--	--	--	PI3K-Akt	Activation	SA-β-gal activity assay//Cell morphological analysis//RT-PCR	"To determine the contribution of enhanced mTORC1 signalling to AKT-induced senescence, BJ-T cells transduced with myr-AKT or control pBABE were treated with the mTORC1-selective inhibitor, rapamycin and markers of senescence analysed. Upon treatment with rapamycin,the percentage of AKT cells positive for SAbGAL was significantly reduced . Rapamycin treatment also dramatically reduced AKT-induced effects on cell size , and the SASP ,indicating that mTORC1 activity is critical for PI3K/AKT-driven senescence."	L	cellular senescence	21909130
Sen_E_190	17β-Estradiol	Chemical compounds	EPC	--	Aging	Prevent	SA-β-gal activity assay	Co-incubation with 17b-estradiol significantly inhibited the increase in SA-β-gal-positive cells.17b-estradiol dose-dependently increased telomerase activity.	--	--	--	--	PI3K-Akt	Activation	Western blot	"Interestingly, pretreatment with phosphatidylinositol 3-kinase (PI3-K) blockers,either wortmannin or LY294002, significantly attenuated the increase inhTERT mRNA induced by 17β-estradiol.We examined the effect of 17β-estradiol on Akt activity in EPCs. EPCs were stimulated with several different doses of 17β-estradiol for 1 h and immunoblots were performed with a phosphospecific Akt antibody directed at the Ser473 phosphorylation site. Stimulation with 17β-estradiol led to a dose-dependent phosphorylation of Akt."	L	delay aging	16093915
Sen_E_191	High glucose	Other	EPC	Blood	Type 2 diabetes mellitus	Accelerate	SA-β-gal activity assay	"Exposure of EPCs with either 25 mM glucose or 200 uM FFA for 3 days significantly increased the percentage of SA-β-gal EPCs compared with control group. Furthermore, EPCs incubation to combined stimuli displayed much higher percentage of senescent cells."	--	--	--	--	PGC-1α-SIRT1//SIRT1-p53-p21//p38	--//Activation//--	Western blot//qRT-PCR//RT-PCR	"EPCs exposed to 48 h of combined stimuli exhibited significant increase in PGC-1α mRNA and protein levels.SIRT1 mRNA and protein levels in EPCs were significantly decreased after 2 days incubation with combined stimuli relative to control cells. SIRT1 mRNA and protein levels in EPCs were significantly decreased after 2 days incubation with combined stimuli relative to control cells. We also found that mRNA and protein levels of P53 and P21 increased significantly when compared to control cells.The effect of high glucose and FFA induced protein expression of PGC-1α were compromised by P38 MAPK inhibitor SB230580 significantly, while ERK MAPK inhibitor U0126 and JNK MAPK inhibitor SP600125 didn t have the same effects ."	L	cellular senescence	28786152
Sen_E_192	Free fatty acids	Other	EPC	Blood	Type 2 diabetes mellitus	Accelerate	SA-β-gal activity assay	"Exposure of EPCs with either 25 mM glucose or 200 uM FFA for 3 days significantly increased the percentage of SA-β-gal EPCs compared with control group. Furthermore, EPCs incubation to combined stimuli displayed much higher percentage of senescent cells."	--	--	--	--	PGC-1α-SIRT1//SIRT1-p53-p21//p38	--//Activation//--	Western blot//qRT-PCR//RT-PCR	"EPCs exposed to 48 h of combined stimuli exhibited significant increase in PGC-1α mRNA and protein levels.SIRT1 mRNA and protein levels in EPCs were significantly decreased after 2 days incubation with combined stimuli relative to control cells. SIRT1 mRNA and protein levels in EPCs were significantly decreased after 2 days incubation with combined stimuli relative to control cells. We also found that mRNA and protein levels of P53 and P21 increased significantly when compared to control cells.The effect of high glucose and FFA induced protein expression of PGC-1α were compromised by P38 MAPK inhibitor SB230580 significantly, while ERK MAPK inhibitor U0126 and JNK MAPK inhibitor SP600125 didn t have the same effects ."	L	cellular senescence	28786152
Sen_E_193	Curcumin	Chemical compounds	VMSC	--	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay	Cell cycle arrest in the G1 and G2 phase was observed already 24 h after treatment and lasted for several days. The activity of senescence associated-β galacto -sidase increased already on day 3 and after 7 days almost all cells were SA-β-gal positive.	--	--	--	--	p53-p21//Rb	Activation//Downregulation	Western blot	We observed quite rapid (several hours after curcumin treatment) activation of the p53/p21 signaling pathway and a decrease in Rb. The latter protein almost completely disappeared after 7 days of treatment).	L	delay aging	31372798
Sen_E_194	"4,5-diphenyl-2-methyl picolinate"	Chemical compounds	MKN28	--	Gastric cancer	Accelerate	SA-β-gal activity assay//SAHF//Western blot	"DMP treatment resulted in significantly enhanced number of SA-β-gal positive cells and SAHF positive cells when compared with untreated ones. H3K9me3 protein, a core element of SAHF, was accumulated in nuclear and co-localized with SAHF. Western blot results suggested that expression levels of H3K9me3, as well as another SAHF protein marker HP1γ, were dramatically increased after DMP treatment."	--	--	--	--	p53-p21//p16-Rb	Activation//Activation	Western blot	"Furthermore, some key proteins in p53/p21 and p16/Rb signaling pathways were greatly changed in DMP-treated gastric cancer cells. Compared with vehicle-treated cells, expression levels of p-AKT were dramatically reduced; expression levels of p-p38, p-p53, p21, and p16 were greatly increased; while expression levels of p27 remained unchanged, indicating that DMP induced gastric cancer cell senescence by activating p53/p21 and p16 signaling pathways."	L	cellular senescence	31639393
Sen_E_195	Hyperoxia	Other	PHLF	--	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay	"Unlike PHLFs grown in 21% O2, those cultured in 70% O2 displayed a marked growth arrest, as indicated by reduced number of cells seen per field, and enlarged, flattened phenotype associated with senescence.Approximately 10% of untreated cells stained blue, while 80% stained blue in the PHLF population exposed to 70% O2."	--	--	--	--	p53-p21//p16-pRb	--//--	Western blot//SA-β-gal activity assay	"We suppressed p53 function by overexpressing a dominant negative p53 (DN-p53) in a retroviral vector, which resulted in effective suppression of p21 expression .PHLFs overexpressing DN-p53 showed a significant decrease in the number of β-galactosidase-positive cells after 70% O2 exposure compared to PHLFs expressing empty vector. To test for the requirement of both the p53/p21 and p16/pRb pathways under hyperoxia, we overexpressed the HPV proteins E6 (which suppresses p53 function;ref. 42)and E7 together in the same cells. While ～70% of the PHLFs expressing vector controls senesced under 70% O2, only 20% of E6/E7 expressing PHLFs underwent senescence."	L	delay aging	18948382
Sen_E_196	TPL	Chemical compounds	HepG2	Liver	Aging	Accelerate	Cell cycle analysis	"TPL accelerated cellular senescence in a dose-dependent manner. Compared with control group, HepG2 cells treated with TPL had an increased percentage of cells at G0/G1 phase and decreased percentage of cells at G2/M phase."	--	--	--	--	p53-p21//Akt//hTERT	Upregulation//Activation//Downregulation	Western blot//RT-PCR	"The p53/p21 signaling pathway is the key regulatory pathway of the  cell cycle. Treatment of HepG2 cells with  TPL significantly increased the expression levels of p53 and  p21 and decreased the cyclin D1 expression, suggesting that TPL arrests cells at G0/G1 phase by regulating  the p53/p21 pathway.Treatment of HepG2 cells with TPL significantly increased phosphorylated AKT level while phosphorylated AKT level reduced after treatment with TPL and MK2206 (AKT inhibitor), indicating that TPL could enhance phosphorylated AKT level and activated the AKT pathway.TPL inhibited telomerase activity and hTERT expression in a time-dependent manner."	L	cellular senescence	27878302
Sen_E_197	Ginsenoside Rg3	Chemical compounds	U87	--	Glioma	Accelerate	SA-β-gal activity assay	~67% of U87 cells after chronic 20(S)-Rg3 treatment at a 20 M concentration were stained positively compared with only ~5% cells with positive staining in the DMSO control group.	--	--	--	--	p53-p21//Akt	Upregulation//Activation	Western blot	The treatment of U87 cells with 20(S)-Rg3 significantly increased the expression levels of p53 and p21.U87 cells treated with 20 M 20(S)-Rg3 were characterized by increases in phosphoAkt.	L	delay aging	22922739
Sen_E_198	Dexamethasone	Chemical compounds	"A549,NCI-H292"	Tumor tissue	Lung cancer	Prevent	CCK-8 assay//SA-β-gal activity assay//Cell morphological analysis//SAHF	"First, we noted that DDP caused remarkable and characteristic morphological alterations, including enlarged cellular size and a flattened shape in A549 cells and H292 cells, and DEX co-treatment attenuated these morphological alterations. DEX co-treatment also significantly affect the growth of A549 and H292 cell lines. DDP significantly induced increased SA-β-gal activity, and interestingly, DEX cotreatment decreased SA-β-gal activity compared with that of DDP treatment alone. DEX co-treatment could decrease the percentage of SAHFpositive cells compared with that of DDP treatment alone."	--	--	--	--	p53-p21	--	Western blot//qPCR//Luciferase reporter assay//SA-β-gal activity assay	"After DDP treatment, p53 protein gradually accumulated, and effect was strikingly weakened in the presence of DEX. The same trend was also detected about the protein expression of p21CIP1, a well-established transcriptional target and downstream effector of p53 with functions in cell cycle arrest, senescence induction and apoptosis . Similarly, p53 mRNA level was also increased after DDP treatment, and DEX co-treatment attenuated this increase. Furthermore, we also used luciferase reporter assays to detect p53 promoter activity, and the analysis showed DEX co-treatment could also attenuate p53 promoter activity compared with that of DDP treated group.After 2 days of DDP treatment with or without pcDNA3.1-/p53, we investigated that overexpression of p53 could prevent the decrease of SA-β-Gal activity in DEX co-treatment group."	L	cellular senescence	23272171
Sen_E_199	Cisplatin	Chemical compounds	A375	--	Melanoma	Accelerate	SA-β-gal activity assay	"4 days after the CDDP treatment, the β-gal-positive (blue-stained) cells were observed when CDDP was greater than 2 μM."	--	--	--	--	p53-p21	Upregulation	Western blot//qRT-PCR	"The results showed that the increase of γ-H2AX occurred first, followed by DDB2 (a key protein involved in DDR), p-P53 and P53, and then by P21. The upregulation of P21 was maintained up to7 days .Quantitative reverse transcription PCR (qRT–PCR) showed that, CDDP significantly increased the mRNA expression of P21 but not that of P53 or P16. At 7 days after the CDDP treatment, immunofluorescence revealed the obvious accumulation of P21 in the cell nuclei, with the strongest fluorescence located in the huge, malformed nuclei,a typical characteristic of cell senescence."	L	cellular senescence	29449532
Sen_E_200	Dehydroleucodine	Chemical compounds	"HeLa S3,MCF-7"	--	Cancer	Accelerate	MTT assay//Cell Cell proliferation assays//Western blot//SA-β-gal activity assay//Flow cytometry	"HeLa and MCF-7 cells were treated with various concentrations of DhL for 72 h, and the effect on cell growth was evaluated by cell counting. The half maximal inhibitory concentration (IC50) of DhL at 72 h culture for HeLa cells was 10 mM. The cell number further decreased to 80% when 20 mM DhL was used. The IC50 of DhL at 72 h culture for MCF-7 cells was 5 mM. Similar effects were observed when DhL was added to synchronized HeLa cells and cell proliferation was assessed by cell count or by MTT assay.The time that cells spent in mitosis was also altered by DhL treatment. Control cells spent an average of 1.960.1 h in mitosis, whereas DhL-treated cells remained in mitosis an average of 4.8 h longer.The concentration of cyclin B1 was significantly lower in treated cells, consistently with the slow progression through the G2/M phase."	--	--	--	--	p53-p21	Upregulation	Western blot	"We observed increased p21 levels following DhL treatment at all times tested, consistently with our results for G1 phase accumulation. We also found a transient increase of p53 up to 16 h."	L	cellular senescence	23341930
Sen_E_201	3-deazaneplanocin A	Chemical compounds	HepG2	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Senescence-like characteristics of HepG2 cells upon 5.0?μmol/L DZNep. (a) On day 3, the cells appeared normal in morphology; on day 6, the cells displayed senescence-like morphologies and positive SA-β-gal staining in green (observed at magnification of 400×)."	--	--	--	--	p53-p21	Activation	Western blot	"p53 activation and DDR caused by 5.0?μmol/L DZNep. Expression of p53 protein elevated after 3-day treatment.(b) Doxorubicin strongly induced p53 stabilization and nuclearization after 6?h, while DZNep causes p53 accumulation gradually until 72?h.mRNA expression of checkpoint inhibitors (p16, p21) upon DZNep treatment for 8 and 72?h. (c) Protein expression of checkpoint inhibitors (p16, p21) increased upon DZNep treatment on day 3. Quantification of the protein blot was performed by Image-Pro Plus (v6.0). transient activation of p53 in G2/M phase is sufficient to induce senescence together with p21 induction."	HL	cellular senescence	28459194
Sen_E_202	"2,2'-Azobis(2-amidinopropane)dihydrochloride(AAPH)"	Chemical compounds	"A375,NIH-3T3"	--	Aging	Accelerate	SA-β-gal activity assay//SAHF//Western blot	"The results show that AAPH dramatically increased the SA β-Gal activity in A375 and NIH3T3 cells, which was significantly suppressed by NAC.AAPH caused robust SAHF formation in A375 cells, which was significantly reduced by NAC.AAPH significantly increased the protein level of p21 and elevated p53 phosphorylation in A375 cells, indicating activation of this pathway."	--	--	--	--	p53-p21	Activation	Western blot	"AAPH significantly increased the protein level of p21 and elevated p53 phosphorylation in A375 cells, indicating activation of this pathway."	L	delay aging	30555576
Sen_E_203	Bufalin	Chemical compounds	LNCaP	--	Prostate cancer	Accelerate	Flow cytometry//SA-β-gal activity assay//Cell morphological analysis	"Cell cycle distribution analyses showed increased sub G0/1 apoptotic fraction at bufalin exposure of 20 nM.We examined cellular senescence phenotype in bufalin-exposed LNCaP (PTEN-negative, high AKT activity) cells by evaluating SA-β-gal activity as a cytochemical marker and observed increased proportion of cells with blue staining and flattened morphology."	--	--	--	--	p53-p21	Upregulation	Western blot	Bufalin treatment for 48 h led to an increased total P53 protein abundance at 10-20 nM as well as that of P21CIP1 in a concentration-dependent manner.	HL	apoptosis	30166403
Sen_E_204	Centella asiatica	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay	H2O2-induced premature senescence decreased by 2.05% after treatment with C. asiatica extracts at 2 ug?ml and by 20.83% at 20 ug?ml.	--	--	--	--	p53-p21	Downregulation	Western blot	"The results of Western blotting showed that H2O2 induced a robust increase in the expression of p53, p21 and pRb and that pretreatment with C. asiatica extracts inhibited the accumulation of these proteins ."	HL	apoptosis	22092576
Sen_E_205	H2O2	Chemical compounds	HDF	--	Aging	Accelerate	SA-β-gal activity assay	"HDFs were pretreated with C. asiatica extracts or DMSO (control) for 4 h. After pretreatment, premature senescence was induced by 2-h treatment with 200 lm H2O2 and then the cells were transferred to DMEM media containing C. asiatica extracts and cultured for a further 48 h. The percentage of senescent cells increased significantly following treatment with 200 lm H2O2."	--	--	--	--	p53-p21	Upregulation	Western blot	"The results of Western blotting showed that H2O2 induced a robust increase in the expression of p53, p21 and pRb and that pretreatment with C. asiatica extracts inhibited the accumulation of these proteins ."	HL	apoptosis	22092576
Sen_E_206	Cisplatin	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis//Western blot	"We demonstrated that prolonged treatment with LA-12 or cisplatin (72-hour incubation with the drugs and subsequent 72-hour cultivation in drug-free medium) induced a strong increase in percentage of HCT116 wt cells with senescence-like phenotype, manifested by a significant increase in β-galactosidase activity and enlarged, flattened cell morphology , which was associated with increase in p53, p21, cyclin D1 level, and loss of phosphorylated Rb, cyclin B1, or survivin level compared to control ."	--	--	--	--	p53-p21	Upregulation	Western blot	"The treatment of HCT116 wt cells with LA-12/cisplatin or their combinations with SCH900776 resulted in apparent upregulation of p53 level and its augmented phosphorylation at Ser15, which was further enhanced in the absence of p21. In HCT116 wt cells, a strong p53-dependent upregulation of p21 level was also detected."	L	apoptosis	28888100
Sen_E_207	LA-12	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis//Western blot	"We demonstrated that prolonged treatment with LA-12 or cisplatin (72-hour incubation with the drugs and subsequent 72-hour cultivation in drug-free medium) induced a strong increase in percentage of HCT116 wt cells with senescence-like phenotype, manifested by a significant increase in β-galactosidase activity and enlarged, flattened cell morphology , which was associated with increase in p53, p21, cyclin D1 level, and loss of phosphorylated Rb, cyclin B1, or survivin level compared to control."	--	--	--	--	p53-p21	Upregulation	Western blot	"The treatment of HCT116 wt cells with LA-12/cisplatin or their combinations with SCH900776 resulted in apparent upregulation of p53 level and its augmented phosphorylation at Ser15, which was further enhanced in the absence of p21. In HCT116 wt cells, a strong p53-dependent upregulation of p21 level was also detected ."	L	apoptosis	28888100
Sen_E_208	SCH900776	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Western blot	"The platinum drug–induced β-galactosidase activity in wt cells was slightly enhanced by SCH900776, while we could not observe any respective differences in the level of the above-mentioned proteins."	--	--	--	--	p53-p21	Upregulation	Western blot	"The treatment of HCT116 wt cells with LA-12/cisplatin or their combinations with SCH900776 resulted in apparent upregulation of p53 level and its augmented phosphorylation at Ser15, which was further enhanced in the absence of p21. In HCT116 wt cells, a strong p53-dependent upregulation of p21 level was also detected ."	L	apoptosis	28888100
Sen_E_209	5AZA-dC	Chemical compounds	U2OS	--	Tumor	Accelerate	Western blot//Cell morphological analysis//SA-β-gal activity assay//Cell counting	"5AZA-dC-treated cells showed the expression of p16INK4A, enlarged cell size, growth arrest, and senescence associated β-gal staining."	--	--	--	--	p53-p21	Activation	Western blot	"5AZA-dC-treated cells indeed showed upregulation of p53 and its downstream effector, p21WAF1, in addition to p16INK4a, and exhibited nuclear translocation of the p53 protein. Whereas only 10% 20% of control cells showed nuclear p53, 90% of the 5AZA-dC-treated cells showed strong p53 staining in the nucleus."	L	Others	17389721
Sen_E_210	Doxorubicin	Chemical compounds	MCF 10A	--	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay	Most of them acquired enlarged flat morphology typical for senescence and developed acidic β-galactosidase activity.	--	--	--	--	p53-p21	Activation	Western blot	Doxorubicin led to a pronounced accumulation of p21 and p53 in control cells.	L	Others	18089808
Sen_E_211	Chronic low-dose rate gamma-radiation	Other	HUVEC	--	Cardiovascular disease	Accelerate	SA-β-gal activity assay	"Control cells reached replicative senescence after 20.5 ± 1.4 (mean ± SEM) cumulative population doublings. In contrast, the chronically irradiated HUVECs entered senescence after a significantly reduced number of population doublings of 7.5 ± 1.0 (mean ± SEM).At the time that irradiated cells showed an increase in SA-β-gal there was no corresponding increase in the control cells."	--	--	--	--	p53-p21	Activation	Western blot	"The cell cycle inhibitor protein p21 was gradually accumulated as the cumulative radiation dose increased.As p21 levels are regulated by tumour suppressor p53, the levels of total p53 and phospho-p53 were analysed. The expression of both forms was increased at weeks 3 and 6."	L	cellular senescence	23349028
Sen_E_212	LMWP-SOD1	Other	HDPSC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//MTT assay	"Control DPSCs (+H2 O2 ) and SOD1-treated DPSCs (+H2 O2 ) were 28.5% and 26.8% positive, respectively, for SA-β-gal staining ; however, LMWP-SOD1-treated DPSCs (+H2 O2 ) were 12.3% positive for SA-β-gal staining. LMWP-SOD1 slightly restored cell viability which had been inhibited by H2 O2. Similarly, for the control DPSCs (+H2 O2 ) and the SOD1-treated DPSCs (+H2 O2 ), the number of cells in G1 phase was increased, but the number of LMWP-SOD1-treated DPSCs (+H2 O2 ) in G1 phase slightly and significantly decreased compared with control DPSCs (+H2 O2 ) and SOD1-treated DPSCs ."	--	--	--	--	p53-p21	--	Western blot//RT-PCR	"The control DPSCs (+H2 O2 ) and SOD1-treated DPSCs (+H2 O2 ) had no influence on mRNA expression, but LMWP-SOD1- treated DPSCs (+H2 O2 ) significantly abolished the H2 Oinduced increase in p53 and p21Cip1/WAF1 mRNA expression levels to the basal state. The p53 and p21Cip1/WAF1 protein levels were also quantified by Western blot analysis. As with the mRNA levels, treatment with LMWP-SOD1 partially abolished H2 O2 -induced p53 and p21Cip1/WAF1 protein expression in human DPSCs."	L	cellular senescence	23049256
Sen_E_213	Ionizing radiation	Other	"NSCLC,H460,A549"	--	Lung cancer	Accelerate	Western blot//SA-β-gal activity assay//BrdU Assay	"The results reveal a substantial increase in SA-β-gal positive senescent cells in irradiated lung cancer cells.Similar results were also observed in A549 cells. Moreover, high levels of p16 expression, another important biomarker of senescence [25], were detected in irradiated H460 cells. In addition, BrdU incorporation assays show that the senescent lung cancer cells are unable to synthesize DNA and incorporate BrdU."	--	--	--	--	p53-p21	Activation	Western blot	Our findings here demonstrate that IR activates the p53–p21 pathway in a dose-dependent manner as evidenced by increased expression of phosphorylated p53 and p21 in irradiated H460 cells.	L	apoptosis	23683497
Sen_E_214	Cr	Other	L-02	--	Aging	Accelerate	SA-β-gal activity assay	"After stained with SA-β-Gal, Cr(VI) treatment group showed large amount of positive stained cells with blue color indicating the occurrence of premature senescence ."	--	--	--	--	p53-p21	Upregulation	Western blot//qRT-PCR	"The expression of p53 was about 9-fold higher after Cr(VI) treatment compared with control, indicating the activation of p53 in the senescent cells. Western blotting for senescence pathway analysis revealed that p53-p21WAF1/CIP1 pathway, but not Rb-p16INK4a pathway was involved in Cr(VI)-induced premature senescence. p53 and p21WAF1/CIP1 was up-regulated after Cr(VI) exposure."	L	apoptosis	27698449
Sen_E_215	Simvastatin	Chemical compounds	WM9	--	Melanoma	Accelerate	SA-β-gal activity assay//PI staining//Flow cytometry	"Our results show that simvastatin-treated WM9 cells developed some aspects of cellular senescence, including increased senescence-associated β-galactosidase activity and a G1/S cell cycle arrest."	--	--	--	--	p53//p21	Upregulation//Upregulation	Western blot//qRT-PCR	"The p53 and p21 mRNA levels were significantly increased after treatment of WM9 cells with simvastatin at the concentrations of 0.25 and 1 μmol/L .We observed an increased expression of phospho-p53 and p21 protein levels in WM9 cells treated with simvastatin , which are in agreement with RT-qPCR data ."	L	cellular senescence	23933099
Sen_E_216	Wharton’s jelly extract	Other	MSC	--	Aging	Prevent	SA-β-gal activity assay	"In the middle-phase (30 PD) of culturing, cells on uncoated plates began to change to a flattened and enlarged phenotype, while cells on the WJE-coated plates remained fibroblast-like.In the latephase (50 PD) of culturing, cells on uncoated plates exhibited a flat and hypertrophic phenotype, while most cells on WJE-coated plates remained spindle-shaped.All three samples of UC-MSCs cultured on uncoated plates showed a significant increase in the percentage of SA-β-gal-positive staining with passaging, while the proportion of senescent UC-MSCs cultured on WJE-coated plates increased slowly.Furthermore, for BMMSCs plated on WJE-coated plates, SA-b-gal positive cells were effectively reduced until 30 PD,then positive cells gradually increased  (P,0.01, n = 3)."	--	--	--	--	p53//p16-pRb	Downregulation//Downregulation	Western blot	"The expression of p53, p16INK4a, and pRb in UC-MSCs cultured on WJE-coated plates was decreased at 30 PD, 50 PD compared to cells cultured on uncoated plates.We concluded that the WJE-coated surface provides an ideal environment that efficiently suppresses p53 and p16INK4a/pRb expression in UC-MSCs to delay replicative senescence of MSCs."	L	cellular senescence	23516461
Sen_E_217	Nutlin-3a	Chemical compounds	U87 MG	Tumor tissue	Glioblastoma	Accelerate	Flow cytometry//SA-β-gal activity assay//Cell morphological analysis	"Nutlin-3a effectively arrested cell-cycle progression in U87MG cells 24 hours after treatment, depleting the S-phase compartment (from 21% to 3%) and increasing the G0/G1 (from 63% to 80%) and G2/M (from 12% to 17%) phase compartments.Cell-cycle arrest persisted 96 h after nutlin-3a incubation,suggesting that nutlin-3a might impede cell cycle progression at both the G1/S and G2/M checkpoints in wild-type p53 U87MG cell line.Nutlin-3a-treated glioma cells acquired an enlarged and flat morphology and expressed the senescence-associated SA-βGal after 4 days of nutlin-3a-incubation, which persisted upon removal the drug."	--	--	--	--	p53//mTOR	--	Flow cytometry//Western blot	"T98G mutant-p53 cells showed no significant differences regarding cell cycle profile when comparing controls (DMSO vehicle) to treated cells. In addition, nutlin-3a induced p21 expression, an important mediator of p53- dependent cell cycle arrest, 24 h after incubation, and it persisted 96 hours after treatment.Western blot analysis of S6 phosphorylation protein suggested that mTOR pathway remains Activate after nutlin-3a in glioma cells. Taken together, these results confirm that nutlin-3a induces senescence in U87MG cells and suggest that it might be dependent on mTOR pathway activity."	L	cellular senescence	21483692
Sen_E_218	Nutlin-3	Chemical compounds	WI-38	--	Aging	Prevent	SA-β-gal activity assay//Cell Cycle analysis	"All cells stained intensely for SA-β-Gal activity .Bromodeoxyuridine (BrdU) labeling revealed that less than 1% of the cell population is in S phase, indicating that they have exited the cell cycle ."	--	--	--	--	p53	--	Western blot	Treatment of early passage and senescent WI-38 cells with 10 μM nutlin-3a for 24 hours elevated p53 protein in both senescent and early passage cells .	L	cellular senescence	20157557
Sen_E_219	Nutlin-3a	Chemical compounds	H460	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"SA-β-gal activity assay markedly increased in size, acquired flat morphology, and showed intense SA-β-Gal staining typical  for senescent cells .In cubation of the lung cancer cell line H460 with 10 μmol/L nutlin-3a, the Activate enantiomer of nutlin-3, for 24 hours led to an effective cell cycle arrest primarily in G1 phase."	--	--	--	--	p53	Activation	Knockdown//BrdU assay	"Knockdown of p53 by specific siRNA that reduced p53 protein levels >85% compared with siRNA controls (data not shown) completely abolished nutlin-induced cell cycle arrest, confirming that it is driven by p53 activation."	HL	cellular senescence	19737973
Sen_E_220	DmHsp22	Chemical compounds	TIG-1	--	Aging	Prevent	SA-β-gal activity assay	"We found significant lower level of β-galactosidase expression in DmHsp22-expressing cells .Control cells entered senescence at 45 PD, as marked by their morphology and slow growth, the DmHsp22-expressing cells showed younger morphology and continued dividing until~5 PD ."	--	--	--	--	p53	Downregulation	Western blot//Immunostaining	"The intensity of nuclear p53 staining in DmHsp22-expressing cells was lower as compared with the control cells. Furthermore, inDmHsp22-expressing U2OS cells, we found that there was a significant decrease in DNA damage-induced activation of p53 pathway."	L	delay aging	19948727
Sen_E_221	Nutlin-3a	Chemical compounds	"MyLa2000,SeAx,HuT 78,Mac2a"	"Plaque,Blood,Lymphoma"	Cutaneous T-Cell Lymphoma	Accelerate	BrdU Assay//Flow cytometry//SA-β-gal activity assay	"Exposure to nutlin induced a complete inhibition of BrdU incorporation in MyLa2000, Mac1, and Mac2a within 24 hours. Flow cytometric cell-cycle profiling further demonstrated an 80% reduction in the percentageof cells in the S phase, with a concomitant increase in the G0/G1 population.MyLa2000 and Mac2a cells were clearly SA-β-gal positive after 72 hours of exposure to nutlin-3a."	--	--	--	--	p53	Activation	Western blot	The p53 protein accumulation after nutlin-3a was effectively downregulated in p53 siRNA– transfected groups compared with the scrambled siRNA– transfected ones .	L	apoptosis	22377766
Sen_E_222	Nutlin-3a	Chemical compounds	"NSCLC,H460"	--	Lung cancer	Accelerate	Clonogenic assays//SA-β-gal activity assay//BrdU Assay	"Moreover, clonogenic assays show that a combination of Nut and IR combined treatment leads to a synergistic inhibition of the clonogenic growth of H460 cells. Interestingly, the increased tumor cell killing by IR and Nut combined treatment correlates with the increased expression of senescence biomarkers(increased SA-β-gal staining and decreased BrdU incorporation) in irradiated lung cancer cells."	--	--	--	--	p53	Activation	Western blot	Our data demonstrate that Nut treatment substantially increases IR-induced p53 activation and p21 expression in H460 cells.	L	apoptosis	23683497
Sen_E_223	Nutlin-3	Chemical compounds	SKN-SH	--	Neuroblastoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"Striking morphologic alterations characteristic of senescent cells were indeed observed in SK-N-SH cells on nutlin-3 administration, including a flattened and enlarged cell shape with increased cytoplasmic granularity. Gene expression of the cell cycle inhibitor CDKN1A was increased 14-fold after 24 hours of incubation with 16 μmol/L nutlin-3, with ～70% of cells residing in G1 phase. Treatment with 16 μmol/L nutlin-3 significantly enhanced the number of SA-β-gal-expressing cells with rapid kinetics (411 per mm2 after 24 hours; 95% CI, 371-451; P < 0.0001), suggesting that nutlin-3 does not just select for SA-β-gal-expressing cells but Activately induces a senescence-like phenomenon in surviving SK-N-SH cells. After 7 days of exposure to 16 μmol/L nutlin-3, ～100% of SK-N-SH cells not subject to apoptotic cell death stained positive for SA-β-gal and had acquired a senescence-like morphology."	--	--	--	--	p53	--	Western blot	Western blot analysis of p53 and p21WAF1/CIP1 expression showed induction of a p53 response after treatment with 16 μmol/L nutlin-3 for 24 hours in all three types of control-infected SK-N-SH cells .	L	apoptosis	17018622
Sen_E_224	SAHA	Chemical compounds	U87 MG	--	Glioma	Accelerate	Colony formation assay//Flow cytometry//SA-β-gal activity assay	"As expected, SAHA was found to suppress colony formation of cells from dissociated GSCs in a dose-dependent manner. We assessed the cell cycle of GSCs by flow cytometry, and the results indicated that low doses (1 μM and 2.5 μM) of SAHA caused a decrease in the proportion of S and G2/M cells and a corresponding increase in cells with a DNA content greater than 4 N.We found that GSCs displayed high SA-β-gal activity upon SAHA treatment."	--	--	--	--	p38-p53	Activation	Western blot	"We verified that levels of p53 protein and p38 phosphorylation were up-regulated 7 days after SAHA treatment in a dose-dependent manner Low-dose SAHA-elicited phosphorylation of p38 at Thr180/Tyr182, phosphorylation of p53 at Ser33, and p53 protein levels were also significantly attenuated by SB203580 ."	L	apoptosis	27863490
Sen_E_225	Rhus coriaria ethanolic extract	Chemical compounds	MDA-MB-231	--	Breast cancer	Accelerate	SA-β-gal activity assay//Cell cycle analysis//Cell morphological analysis	"In fact, the G1 population rose from 57% ± 2 in control cells to 67% ± 4 and 71% ± 0.1 in cells treated for 48 h with 200 and 400 μ g/mL RCE, respectively.After 48 h of treating cells with 200 μ g/mL RCE, 21% of cells expressed SA-β-galctosidase; this proportion of senescent cells nearly doubled after 96 h of treatment.A subpopulation of treated cells exhibited a senescence-like phenotype characterized by cell size increase and flattening shape compared to control cells."	--	--	--	--	p38//ERK1/2	Activation//Activation	Western blot	"Interestingly, a marked induction of phosphorylation of both p38 and ERK1/2 was noted , indicating that these two pathways were activated in response to RCE.Asustained increase of phospho-p38 and phospho-ERK1/2 was observed starting 12?h after RCE treatment and lasted for more than 48?h ."	L	apoptosis	26263881
Sen_E_226	UVA	Other	Fibroblast	Koreskin	Aging	Accelerate	SA-β-gal activity assay//Western blot//Flow cytometry	"Compared with the cells in the control groups, cells in UVA-irradiated groups exhibited significantly increased β-galactosidase activity, suggesting the cells were successfully induced into the aging state (P < 0.05).Compared with the expression of SIRT1 in the control groups, there was a significant increase in the UVA-irradiated groups and combined treatment groups (P < 0.05); the combined treatment groups exhibited the highest expression. MMP-1 expression increased in the UVA-exposed groups compared with the control groups (P < 0.05). The combined treatment groups also had a higher expression of MMP-1 compared with the control groups; however, compared with the UVA groups, the expression level was slightly decreased. There was a marked enhancement in the level of p53 acetylation in the UVA-irradiated groups and the combined treatment groups compared with the control groups (P < 0.05), and the red light intervention led to attenuated p53 protein acetylation (P < 0.05). The UVA irradiation resulted in an obvious increasement of p21 and p16 (P < 0.05); and the combined treatment groups conspicuously decreased the expression level of p21 and p16 (P < 0.05).Compared with nonirradiated control groups, the scale of UVA-irradiated cells in S phase was increased, but not significantly, and the proportion in G2 phase was also increased."	--	--	--	--	p38//ERK//JNK	Upregulation//Upregulation//Upregulation	Western blot	We measured the protein expression of several molecules that are involved in MAPK signaling and found that UVA irradiation increased the expression of p38、ERK and JNK significantly . Our results showed that UVA irradiation increased the phosphorylation of p38 and ERK and JNK .	L	apoptosis	25039464
Sen_E_227	Red light	Other	Fibroblast	Koreskin	Aging	Prevent	SA-β-gal activity assay//Western blot//Flow cytometry	"Compared with the cells in the control groups, cells in UVA-irradiated groups exhibited significantly increased β-galactosidase activity, suggesting the cells were successfully induced into the aging state (P < 0.05). The UVA plus red light irradiation treatment remarkably improved the aging state of the cells, decreasing the expression of β-galactosidase (P < 0.05).Compared with the expression of SIRT1 in the control groups, there was a significant increase in the UVA-irradiated groups and combined treatment groups (P < 0.05); the combined treatment groups exhibited the highest expression. MMP-1 expression increased in the UVA-exposed groups compared with the control groups (P < 0.05). The combined treatment groups also had a higher expression of MMP-1 compared with the control groups; however, compared with the UVA groups, the expression level was slightly decreased. There was a marked enhancement in the level of p53 acetylation in the UVA-irradiated groups and the combined treatment groups compared with the control groups (P < 0.05), and the red light intervention led to attenuated p53 protein acetylation (P < 0.05). The UVA irradiation resulted in an obvious increasement of p21 and p16 (P < 0.05); and the combined treatment groups conspicuously decreased the expression level of p21 and p16 (P < 0.05).Moreover, the proportion of cells in the red light groups in S phase was also increased, whereas the proportion in G2 phase was decreased compared with the UVAirradiated group."	--	--	--	--	p38//ERK//JNK	Downregulation//Downregulation//Downregulation	Western blot	"Further results indicated that red light intervention substantially suppressed the expression of p38 and ERK (P < 0.05), whereas the expression of JNK was only slightly decreased.red light intervention significantly suppressed the phosphorylation of p38 and ERK, but had little effect on the phosphorylation of JNK."	L	apoptosis	25039464
Sen_E_228	Acidic Ph	Other	NP	Lumbar discs	Disc degenerative disease	Accelerate	Western blot//qPCR	Real-time PCR analysis showed that mRNA expression of senescence-related markers (p16 and p53) in the experimental NP cells was significantly up-regulated compared with the control NP cells. Western blot assay also showed that protein expression of p16 and p53 in the experimental NP cells was increased compared with the control NP cells.	--	--	--	--	p38 MPAK	Activation	Western blot	"Results showed that relative expression of p-p38 MAPK (p-p38/p38) in the experimental NP cells was significantly increased compared with the control NP cells. Reasonably, the inhibitor SB203580 significantly inhibited activation of the p38 MAPK pathway."	L	cellular senescence	30291218
Sen_E_229	Regulatory T(Treg)cells	Other	CD4+T	--	Aging	Accelerate	SA-β-gal activity assay	"In contrast, we found significantly increased SA-β-Gal positive T cell populations in na?ve CD4+ T cells after co-culture with CD4+ CD25hiFoxP3+ Treg cells, indicating that Treg cells can induce na?ve CD4+ T cell senescence.?We observed that the percentages of the SA-β-Gal positive cell populations in na?ve CD4+ T cells dramatically increased with longer times of co-culture with CD4+ CD25hiFoxP3+ Treg cells."	--	--	--	--	p38 MAPK//ERK1/2//TLR8	Activation//Activation//--	SA-β-gal activity assay//Western blot	"Our transcriptome analyses demonstrated that Treg-induced senescent CD8+ T cells induced significant alterations in genes involved in MAPK signaling pathways. We then confirmed the activation of MAPKs, including ERK1/2, p38 and JNK in na?ve CD4+ T cells treated with CD4+ CD25hiFoxP3+ Treg cells using Western blot analyses. We found that Treg-treated na?ve CD4+ T cells selectively activated ERK1/2 and p38, but not JNK, resulting in significantly enhanced phosphorylation of ERK1/2 and p38. We found that only the TLR8 ligands Poly-G3 and ssRNA40 significantly blocked the induction of responder T cell senescence induced by CD4+ CD25hiFoxP3+ Treg cells identified by SA-β-Gal expression ."	L	delay aging	22723548
Sen_E_230	Hepatocyte growth factor	Chemical compounds	"SKOV3,OVCAR-3,A2780"	--	Ovarian cancer	Accelerate	SA-β-gal activity assay//Cell proliferation assay	"The experiments showed that CM collected from OVCAR-3, SKOV-3, and A2780 cells inhibited proliferation of HPMCs in short-term conditions and reduced the number of divisions completed by those cells (CPD) before reaching senescence upon their prolonged exposure . These anti-proliferative effects of cancer cell-derived CM co.ncided with the induction of SA-β-Gal and the activation of DNA damage response, as evidenced according to increased incidence of DNA damage foci, i.e. γ-H2A.X and 53BP1.The study showed that HGF increased the expression of SA-β-Gal in a dosedependent manner and that the pre-incubation of CM with a specific anti-HGF antibody prevented its capability to up-regulate the enzyme."	--	--	--	--	P38 MAPK//Akt//NF-κB	Activation//Activation//Activation	ELISA	"It has been found that CM from either OVCAR-3 or SKOV-3 cells activated AKT, JNK, NF-κB, and p38 MAPK, whereas CM from A2780 cells activated NF-κB and p38 MAPK."	L	delay aging	28652056
Sen_E_231	Surfactant	Other	"TIG-7,CK,BK,FDPC"	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Various cell types were cultured in the presence of sublethal concentrations of genuine surfactants (NP-40, Triton X-100, SDS, Tween 20, etc) and commercially available products (dishwasher, shampoo, or facial cleansing foam) for 12 weeks. Normal type of cells examined, namely normal human fibroblasts (TIG-7), CK, BK, and FDPC, and all exhibited typical senescence features, flat and enlarged cell shape, and were clearly stained with the senescence-associated β-galactosidase."	--	--	--	--	p38	Activation	SA-β-gal activity assay	"Among the above inhibitors, only p38 inhibitor SB203580 clearly suppressed the senescence induced by NP-40. It suppressed the senescence induced by oleic acid or SDS as well as NP-40."	L	cellular senescence	25198914
Sen_E_232	"4-(4-fluorophenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline"	Chemical compounds	"IMR-90,A2780"	--	Ovarian cancer	Accelerate	SA-β-gal activity assay//Western blot	FPTHQ treatment dramatically increased the number of SA - β -gal positive A2780 cells.FPTHQ -treatment increased the protein levels of MMP3 and the mRNA levels of IL-6 and IL-8 in A2780 cells.	--	--	--	--	p21	Upregulation	SA-β-gal activity assay//Western blot	"In addition, we found that p21 was significantly up -regulated after FPTHQ treatment.Consistent with the observations in other two cell lines, FPTHQ also significantly increased the protein level of p21 in SKOV -3 cells."	L	cellular senescence	29143360
Sen_E_233	Doxorubicin	Chemical compounds	SKN-SH	--	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay	"Drug effect on the cell cycle was determined by flow cytometry. The population of cells in the S-phase decreased, whereas those in the G2-M increased and reached a peak at 10-7M doxorubicin.This was associated with an increased activity of the senescence-associated β galactosidase (SA-β-Gal), confirming that the cells were in senescence."	--	--	--	--	p21	Upregulation	Western blot//RT-PCR	"Expression of p21/WAF1 was maximal at 10-7M doxorubicin followed by a sharp decrease starting at 5X10-7M.However, examination of p21/WAF1 expression by RT-PCR indicated that although this may be the case at intermediate drug concentrations (such as 5X10-7M doxorubicin), high drug concentrations seemed to exert an inhibitory effect p21/WAF1expression at the message level."	HL	apoptosis	16557274
Sen_E_234	Supraphysiological and rogen	Other	"LNCaP,C4-2"	Prostate	Prostate cancer	Accelerate	SA-β-gal activity assay//SAHF//DAPI staining	"We observed that both the natural and the synthetic androgen induce cellular senescence in a concentration-dependent manner. Administration of 1 nM R1881 or 1 nM DHT indicate a strong induction of SA β-Gal activity, in contrast,lower androgen levels show the basal level of cellular senescence similar to the untreated or the solvent control.To confirm the androgen-induced cellular senescence,we examined a further marker, the formation of senescence-associated heterochromatic foci (SAHF).DAPI staining of the treated cells revealed that SAL treatment induces an accumulation of heterochromatin in LNCaP cells."	--	--	--	--	p16-pRb-E2F1//Src-Akt-Mtor	--//--	Western blot//qRT-PCR//SA-β-gal activity assay	"p16-pRb-E2F1:After administration of SAL an upregulation of p16, hypophosphorylation of pRb and down-regulation of the pRb targets Cyclin D1 as well as of E2F1 protein levels were observed indicating that the p16-pRb pathway is regulated by SAL treatment .Similar results were obtained by treating the cells for 6 days. In contrast, LAL treatment mediated no detectable changes of p16,Cyclin D1 and E2F1 expression level. In line with this,SAL treatment led to inhibition of down-stream targets of pRB, Cyclin D1 as well as E2F1 at mRNA level, whereas the p16 mRNA is upregulated by SAL doses. Accordingly, the mRNA level of ID1, an inhibitor of p16 expression, is reduced upon SAL administration . Thus, these data indicate that the p16-pRb-E2F1 pathway is associated with the androgen-mediated cellular senescence.Src-Akt-mTOR  :Notably, treatment of LNCaP cells with the Src inhibitor PP2 under SAL conditions reduces the androgen-mediated cellular senescence. In contrast, inhibition of Src without androgens or with LAL has no detectable influence on the SA β-Gal activity in LNCaP cells compared to control. Akt phosphorylation is a well-known pathway of the Src tyrosine kinase and involves signaling molecules such as the PI3K as well as the mammalian target of rapamycin (mTOR). Using inhibitors the role of these factors in androgen-mediated cellular senescence was analyzed. Inhibition of PI3K, an Akt-activating kinase,by the 3-MA inhibitor, reduced the level of androgen-induced cellular senescent cells, which confirms that the Src-Akt signaling pathway is involved in androgen-induced cellular senescence at supraphysiological levels. Similarly, using a specific Akt-kinase inhibitor(Akti) reveals a strong reduction of the SAL-mediated SAβ-Gal activity. A further downstream target of the Src- and the Akt-kinase is mTOR, which is involved in proliferation and cell cycle regulation processes [35]. Rapamycin alone mediates no detectable change in the level of cellular senescence. In contrast, rapamycin co-treated with SAL resulted in reduction of SA β-Gal positive stained cells.The data show that rapamycin reduces the androgen-mediated SA β-Gal activity and suggest that mTOR is partially involved in androgen-mediated cellular senescence. This supports the notion that the Src-Akt-mTOR signaling mediates the androgen-mediated induction of cellular senescence."	L	cellular senescence	25216853
Sen_E_235	Doxorubicin	Chemical compounds	"S3R,S4,L5"	Spleen	Nijmegen Breakage Syndrome	Accelerate	SA-β-gal activity assay	"We observed a time-dependent increase in the number of SA-β-Gal positive cells in L5 and S4, but not in S3R cell line."	--	--	--	--	p16-pRb//p53-p21	Downregulation//Activation	Western blot	"We did not observe any changes in the level of this protein in the S3R and S4 cell lines, however, a time dependent decrease in the level of p16 was observed in the L5 cell line.In the L5 and S4 cells stronger activation of the p53/ p21 pathway correlated with an increase in SA-β-Gal activity."	L	apoptosis	25119968
Sen_E_236	SDB	Chemical compounds	HFF	Skin	Aging	Accelerate	BrdU assay//SA-β-gal activity assay//Western blot	"The HFF cell population progressively and irreversibly lost the ability to divide, as assessed by reduced BrdU incorporation in 48 h and reduced cloning efficiency on removal of the SDB.When completely senescent, less than one in 105 cells in the population could form colonies, less than 5% of the cells incorporated BrdU in a 48-h period, and more than 70% expressed SA-βgal. We then proceeded to analyze the senescent-like phenotype generated by SDB at the molecular level.the accumulation of p21WAF precedes that of p16INK4A with the former declining as the latter accumulates [61]. We show that in human fibroblasts treated with SDB the pattern of expression of these two proteins is identical to that found in replicative senescence and that the upregulation of p21WAF coincides with the permanent cell cycle exit of the majority of the cells as assessed by BrdU incorporation and cloning efficiency."	--	--	--	--	P16-pRb	--	Western blot	FOO3 p16INK4A+/- fibroblasts howed a greater slowing of proliferation and an increased number of flat senescent cells in the population but surprisingly still bypassed SDB-induced stasis when compared to telomerase-expressing HFF dermal fibroblasts.	L	telomere attrition	15093749
Sen_E_237	senescence-messaging secretome factors	Other	MESC	--	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay	"Young cells incubated in CM-old for a long time gradually acquired a senescence phenotype, including a flat morphology and cell hypertrophy. Using FACS analysis, we detected the marked increase in cell size after the continuous CM-old treatment for 7 days. The CM-old evoked a significant increase in the number of SA-β-Gal positive stained cells that is typical of senescent cells."	--	--	--	--	p16-MAPKAPK2-Rb//p53-p21-Rb	Activation//Activation	Western blot	"The prolonged exposure of MESCs to CM-old resulted in long-term activation of H2A.X and ATM.Additionally, the immunoblot data were confirmed by immunofluorescence microscopy analysis for gH2A.X, pATM and p53BP1 localization. The phosphorylation levels of MAPKAPK-2 (a direct target of p38MAPK) and to a lesser degree p53 are increased in CM-treated cells with senescence progression. The senescent cells also displayed the elevated expression levels of both p21Cip1 and p16Ink4a whereas Rb phosphorylation was diminished gradually over all period of observation ."	L	cellular senescence	29397942
Sen_E_238	Cholera toxin	Other	"NHM-C,NHM-B"	--	Melanoma	Accelerate	BrdU assay	"Eventually, exposure to CT-containing medium for up to 12 weeks also resulted in senescence of the lightly pigmented NHM-C melanocytes."	--	--	--	--	p16-CDK4-pRb	--	Western blot	"pRb in NHM-C melanocytes was present in both hypo-and hyperphosphorylated forms through 3 weeks, whereas it was predominantly in the hypophosphorylated form at 6 weeks .In contrast, pRb in NHM-B melanocytes was mostly in the nonphosphorylated form by 3 weeks of CT treatment.At 6 weeks, CDK4-GST-Rb kinase activity was notably reduced in NHM-B as compared to NHM-C cells .Over a 6-week period, levels of CDK4 bound to p16 decreased dramatically in NHM-C melanocytes, whereas it remained almost unchanged in NHM-B cells."	L	delay aging	10911949
Sen_E_239	DECM	Other	UC-MSC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry	"After exposure to H2O2, the percentages of SA-β-gal-positive cells for the DECM groups remained at lower levels when compared to those in the TCPS  groups.The percentage of cells in the G0/G1 phase decreased and the percentage of cells in the G2/M phase increased in both the TCPS and DECM groups after exposure to H2O2. However, culturing on DECM increased the entry of proliferating cells into S phase even after treatment with H2O2."	--	--	--	--	P16//SIRT1//p21//p-p38//p-ERK1/2//ERK1/2	--//Upregulation//--//--//--//--	Western blot//qRT-PCR	"In agreement with the real-time reverse transcription-polymerase chain reaction (RT-PCR) data, Western blot analysis confirmed that, after exposure to H2O2, UC-MSCs on TCPS showed the highest expression of p16INK4α which was 2.7-fold of that on DECM . The levels of SIRT1 decreased in H2O2-treated cells, but DECM preserved the expression of SIRT1 .The levels of p53 showed no significant difference but, as its transcriptional target, p21 was significantly upregulated in TCPS-cultured cells .To determine the roles of p38 and Erk1/2 in H2O2-induced premature senescence, we measured the phosphorylated levels of p38 and Erk1/2. We found that treatment with H2O2 significantly enhanced phosphorylation of p38 by 6.1-fold compared with the untreated cells on TCPS, whereas DECM attenuated p-p38 by 67.8% compared with H2O2-treated cells on TCPS. However, we found that the total p38 protein expression did not vary in all the groups. The differences of phosphorylated and total levels of Erk1/2 were insignificant. Before treating with H2O2, the levels of p-Erk1/2 were higher in DECM-cultured cells than in the TCPS-cultured cells (p = 0.28) and, after exposure to H2O2, the levels of p-Erk1/2 showed an opposite tendency ."	L	delay aging	28107614
Sen_E_240	Metformin	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay	"We observed that 100?μm?metformin effectively stimulated HDF proliferation, which was characterized by the reduced percentage of senescence‐associated β‐galactosidase (SA‐β‐Gal)‐positive cells; 100?μm?metformin also increased the frequency of proliferation‐related KI67‐positive cells ."	--	--	--	--	Nrf2-GPX7//SKN-1-GPX6	--//--	Knockdown//Western blot//RNAi	"Metformin‐induced GPx7 expression was blocked after NRF2 knockdown ；The positive effect of metformin on stimulating GPx7 expression was dose‐dependent and was confirmed in two independent HDF lines. Moreover, GPx7 expression levels in HDFs were indeed increased throughout the passaging by metformin treatment .skn‐1?RNAi in?C.elegans?completely abrogated the induction of GPX‐6 by metformin, suggesting that metformin upregulates GPX‐6 expression mainly through SKN‐1 in worms."	L	cellular senescence	29659168
Sen_E_241	Terrein	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay//MTT assay//Flow cytometry	"The biological marker of senescent status was determined by in situ staining and assay of SA β-gal activity. SIPS-HDF cells displayed a markedly high level of SA β-gal activity, while terrein significantly reduced SA β-gal activity.To investigate the effects of terrein on cell survival, aged HDF cells (PD61) were treated with terrein and subjected to oxidative stress by exposure to 150-μM H2O2. Cell survival was determined at 24 and 48 h. Terrein has not shown cellular toxicity without oxidative stress. Under the oxidative stress, aged HDF cells significantly decreased cell viability at more than 20%, while terrein treatment was associated with significantly increased cell viability in time- and concentration-dependent manners."	--	--	--	--	Nrf2-ERK1/2-HO-1	--	Western blot	"In this study, Terrein decreased age-related inflammatory molecules and p-ERK1/2 signalling at the indicated time and concentration, as in young cells. Percentage bar graph shows densitometric result of western blot.To further evaluate the down-stream molecules of p-ERK1/2 signalling affected by terrein in the ageing process, the translocation of Nrf2 and NF-κB from the cytosol to the nucleus was examined, and HO-1 expression was determined as a means of gauging antioxidant status. Terrein augmented Nrf2 translocation into the nucleus in both aged-HDF cells and SIPS-HDF cells at 11th days, like PD98059.NF-κB translocation was inhibited by terrein in both aged and SIPS-HDF cells. Percentage bar graph shows densitometric result of western blot. HO-1 was overexpressed by terreintreated as well as PD98059-treated aged and SIPS-HDF cells. Percentage bar graph shows densitometric result of western blot ."	L	delay aging	26416516
Sen_E_242	Rapamycin	Chemical compounds	 Fibroblast	Skin	Aging	Prevent	SA-β-gal activity assay//qPCR	"This effect on the Nrf2 pathway correlates with inhibition of cell senescence induced by 2-h incubation with H2O2, where our results showed that 24 h of preincubation with rapamycin significantly decreased the levels of p16 and p21 molecular markers,as well as measured by the number of senescent cells measured by β-al staining."	--	--	--	--	Nrf2//STAT	Activation//--	Western blot//qPCR	"Pre-incubation of mouse skin fibroblasts with rapamycin for 24 h increased the levels of Nrf2 in a dose-dependent manner, and lowered the levels of Keap1, the cytosolic inhibitor of the Nrf2 pathway. Activation of the Nrf2 pathway is further demonstrated by the levels of Nrf2 in the nuclear localization and by the increase in mRNA levels of down target genes such GST-Ya and NQO1. Our data using lung tissue from Nrf2KO mice showed that tissue from Nrf2KO mice have increased basal levels of p-Stat3, and rapamycin treatment reduced these levels. A similar effect was observed in WI38 cells deficient in Nrf2, which showed increased basal levels of the phosphorylated form of Stat3 (p-Stat3), and rapamycin treatment was able to decrease these levels."	HL	cellular senescence	28371119
Sen_E_243	Piceatannol	Chemical compounds	"Cortex cell,Hippocampus"	"Hippocampus,Cortical tissue"	Aging	Prevent	Immunostaining//BrdU assay	"Mice with piceatannol treatment revealed a significant increase in the distance travelled and relative center distance as compared to the model group.The results demonstrated that piceatannol was able to protect the mice against learning and memory deficits, which were induced by chronic treatment with D-gal.Piceatannol reversed the decrease in the number of positive Nissl cells induced by D-gal (P < 0.01).BrdU+cells significantly increased in the piceatannol treatment group as compared to those in the model group."	--	--	--	--	Nrf2	Upregulation	Western blot	Piceatannol effectively reversed the decreased Nrf2 expression .	L	delay aging	29214257
Sen_E_244	Phenolic diterpenes carnosic acid	Chemical compounds	ASF-2	Mammary Gland	Aging	Prevent	MTT assay//SA-β-gal activity assay	The pre-incubation with CA conferred a significant protection against H2O2-induced cell growth inhibition and the appearance of SA-β-gal positive cells.	--	--	--	--	Nrf2	Upregulation	Western blot	AS increased the levels of Nrf2 in the nuclear fraction.Treatment of ASF-2 cells with CA significantly increased the transcriptional activity of Nrf2.	L	delay aging	25744415
Sen_E_245	Phenolic diterpenes carnosol	Chemical compounds	ASF-2	Mammary Gland	Aging	Prevent	MTT assay//SA-β-gal activity assay	The pre-incubation with CA conferred a significant protection against H2O2-induced cell growth inhibition and the appearance of SA-β-gal positive cells.	--	--	--	--	Nrf2	Upregulation	Western blot	CS increased the levels of Nrf2 in the nuclear fractionTreatment of ASF-2 cells with CS significantly increased the transcriptional activity of Nrf2.	L	delay aging	25744415
Sen_E_246	Molecular hydrogen	Other	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"The number of SA β-gal-positive cells was significantly higher at 24h after TCDD exposure (18.6±3.8% vs 5.5±1.4% SA β-gal-positive cells in the control). By contrast, in media with H2 and TCDD, the percentage of SA β-gal-positive cells was similar to that for the control, 5.5±1.9% . At 48 h after TCDD exposure, the percentage of SA β-galpositive cells was significantly higher than in the control (19.7±3.6% vs 5.2±1.3%), and the percentage of SA β-galpositive cells was 16.4±3.2% in TCDD-exposed cells cultured in hydrogen-rich medium, which indicates that, at 48h, H2 no longer suppressed the increase in SA β-gal-positive cells.Total p53 expression in HUVECs did not significantly differ between normal and hydrogen-rich media or between media with and without TCDD . Although acetyl-p53 expression was significantly higher at 24h after TCDD exposure than in the control, H2 significantly suppressed this increase in acetyl-p53 expression. However,at 48h after TCDD exposure, H2 did not suppress the TCDDinduced increase in acetyl-53 expression."	--	--	--	--	Nrf2	Activation	Western blot	"We therefore investigated whether the antioxidant effects of H2 might depend on activation of Nrf2, using Western blot analysis to evaluate expression of phospho-Nrf2 and its antioxidant enzymes, HO-1 and NQO-1, after exposure of HUVECs to TCDD. In the H2-enriched medium, phospho-Nrf2 expression was increased at 1h after TCDD exposure. Expression remained elevated at 24h after TCDD exposure, when H2 had returned to baseline levels. There were also significant increases in HO-1 and NQO-1 expressions . However, at 48h after TCDD exposure, both Nrf2 phosphorylation and HO-1/NQO-1 expression returned to baseline levels."	L	delay aging	27477846
Sen_E_247	Low oxygen	Other	MIAMI	Bone marrow	Aging	Prevent	SA-β-gal activity assay//Western blot	"We found that low oxygen decreased protein expression of p53 by approximately fourfold, while p21 and p27 levels did not appear to be affected.we quantified the number of cells with detectable senescence-associated β-galactosidase (SA-βgal) activity and determined that 3% O2 dramatically decreased positive cells versus 21% O2."	--	--	--	--	Notch//PI3K-Akt//Wnt	Activation//Activation//Activation	qRT-PCR//Western blot	"Genes upregulated at 3% O2 are listed in Supplementary Table S2. The data revealed upregulation of key Notch mediators among others. RT-qPCR confirmed gene expression stimulation of key genes: Notch2, STAT6, and Jagged 1. Akt may therefore play a key role in promoting self-renewal, and thus we assessed whether oxygen tension affects Akt signaling. We incubated cells at 3% and 21% O2 for 30 and 60?min and observed strong Akt activation (phospho-Akt) by low oxygen after a 30-min transient exposure, which then returned to basal levels. Total Akt was unaffected .Since we observed 3% O2 stimulation of Lrp5 and frizzled 1 and 2 , we further examined canonical Wnt pathway activation. Western blot analysis of nuclear and cytoplasmic extracts of MIAMI cells demonstrated that 3% oxygen stimulated cytoplasmic β-catenin (1.5-fold) and, to a larger extent, nuclear β-catenin . Subsequently, we size separated, blotted, and probed the immunoprecipitated proteins with β-catenin antibody. Samples from cells at 3% O2 displayed more than twofold greater association between β-catenin and TCF4 versus 21% O2. we examined downstream targets of canonical Wnt activation. The cell cycle protein and direct Wnt target, Cyclin D1, was increased by 3% O2 about 2.2-fold in the cytoplasm and by more than 80-fold in the nucleus ."	HL	apoptosis	27059084
Sen_E_248	Hypoxic	Other	HADMPC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis//EdU assay	"The EdU incorporation rate was significantly higher in Hx-cultured hADMPCs than in Nx-cultured hADMPCs, suggesting that cell growth was increased in the Hx culture condition.Flow cytometry analysis revealed that ROS were generated at higher levels in hADMPCs when cultured in the Nx condition, suggesting that reduced production of ROS in the Hx condition may prevent the cells from entering replicative senescence.We also found that Nx-cultured hADMPCs were larger with a more irregular shape, which suggests that the Hx culture condition prevented hADMPCs from entering senescence [35]. To further investigate this phenomenon, cellular senescence was measured by staining for SA-β-Gal, which revealed that SA-β-Gal activity was increased in Nx-cultured hADMPCs at passage 17."	--	--	--	--	Notch	Activation	Western blot//qPCR	"As expected, levels of cleaved NOTCH1, an activated form of NOTCH1, were significantly increased (greater than twofold) in the Hx culture condition. Q-PCR analysis revealed that HES1, a downstream target of Notch signaling, was upregulated in Hx-cultured hADMPCs, which also indicated that Notch signaling was activated in the Hx culture condition."	L	delay aging	24878247
Sen_E_249	HFD	Other	--	Mice endothelium tissue	Cardiovascular disease	Accelerate	SA-β-gal activity assay//Western blot	"In accordance with expectations,the HFD group showed a significant elevation in SA β-gal-positive areas of the endothelium (stained as blue) in comparison with the vehicle control group.A faint staining pattern of SMP30 was found in the endothelium (marked by CD-31) of the aortic roots in mice fed with HFD."	--	--	--	--	NLRP3	Upregulation	Western blot	"The results of western blot analysis showed that D-gal significantly increased the expression of NLRP3 in HUVECs as compared with that of vehicle control. On the contrary, PSPC administration depressed the amplification of NLRP3 induced by D-gal. A similar pattern of NLRP3 was observed for the immunofluorescence activities in the brachiocephalic artery of mice which were fed with HFD or HFD+PSPC ."	L	delay aging	26164602
Sen_E_250	A2E	Chemical compounds	RPE	--	Age-related macular degeneration	Accelerate	SA-β-gal activity assay//qRT-PCR	"Our results showed that A2E treatment triggered cellular senescence, an effect that was intensified by blue light;We measured telomere length (T/S ratio) using RT-qPCR and found that photosensitization of A2E induced significant telomere erosion, which could be decreased by NAC."	--	--	--	--	NF-κB	Activation	Gene Ontology assay	"GO analysis of the upregulated genes also showed a significant enrichment (p <0.05) for 38 GO terms, including“positive regulation of NF-kappa B transcription factor activity”.These findings suggest that the NF-κB pathway is activated upon photosensitization of A2E in RPE cells."	HL	cellular senescence	29415988
Sen_E_251	KF866	Chemical compounds	Hs68	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"The cells were flattened and enlarged,and the cell density was much smaller than that of control because of cell senescence. In addition, the result reveals that FK866 significantly and dosedependently induced SA-βG activity, as detected by the double-substrates method."	--	--	--	--	NAD+-SIRT1	Downregulation	Acid extraction method//enzymatic cycling method	"FK866 significantly decreased intracellular NAD in a concentration- and timedependent manner.SIRT1 activity was estimated using the Ac-p53/p53 ratio  during the 5-day incubation with F50. As we expected, the Ac-p53/p53 ratio increased by about 20 % during day 1 and day 4, with the highest level achieved on day 5. The results showed that SIRT1 activity was decreased by the treatment of F50."	L	cellular senescence	26330291
Sen_E_252	U0126	Chemical compounds	HT-p21	--	Aging	Prevent	Cell morphological analysis	U0126  suppressed senescence.	--	--	--	--	mTOR-S6	Downregulation	Western blot	"As expected, U0126 inhibited ERK phosphorylation (day 1).Like rapamycin, U0126 inhibited S6 phosphorylation at day 1 ."	L	delay aging	19478560
Sen_E_253	LY294002	Chemical compounds	HT-p21	--	Aging	Prevent	SA-β-gal activity assay//Cell morphological analysis	"LY294002 decreased intensity of SA-β-Gal staining but did not abrogate it completely . Cells remained flat, with a typical nuclear appearance.LY294002 suppressed senescence."	--	--	--	--	mTOR-S6	Downregulation	Western blot	"Like rapamycin, LY294002 inhibited S6 phosphorylation at day 1 ."	L	delay aging	19478560
Sen_E_254	reconstituted HDL	Other	CAC	--	Aging	Prevent	SA-β-gal activity assay	"Treatment with 50, 100, or 150 μg/mL rHDL reduced the number of acidic β-gal+ CACs and improved the △Ψ of CACs (data not shown)."	--	--	--	--	mTORC2-Akt	Activation	IP//Western blot//SA-β-gal activity assay	"Akt-Ser473 phosphorylation increased after 10 minutes and peaked after  ≈4 hours , whereas the total Akt level remained unchanged. mTOR formed a complex with rictor in rHDL-treated CACs, whereas rapamycin inhibited the coprecipitation of both proteins.Control siRNA had no effect. The siRNA-treated CACs next were cocultured with rHDL for 4 hours. The siRNA-mediated suppression of rictor gene expression significantly decreased the rHDL-induced Akt phosphorylation compared with control siRNA transfection, whereas siRNA-mediated raptor suppression had no effect. Suppression of rictor gene expression also abolished the inhibitory effect of rHDL on CAC senescence."	L	delay aging	21415389
Sen_E_255	Autophagy	Other	WI-38	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	3-MA and LY also inhibited CDKN1A and CDKN2A upregulation as well as SA-GLB1/β-gal activity in serum-starved fibroblasts.	--	--	--	--	MTORC2	Activation	SA-β-gal activity assay//Western blot	"Serum-starved fibroblasts exposed to R showed lowered CDNK1A and CDKN2A protein levels and decreased SA-GLB1/β-gal activity .RPTOR silencing led, however, to inhibition of SA-GLB1/β-gal activity."	L	delay aging	31931659
Sen_E_256	Rapamycin	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Cell morphological analysis	"HUVECs that were prolonged treated with low dose rapamycin (18 days in culture) and then sub-cultured in the absence of rapamycin until passage 25–27 displayed normal cell morphology whereby the cellswere relatively smaller in size compared to the larger cell size and higher granularity of the vehicle-treated senescent cells. There was also a significant decrease in SA-β gal activity in these cells,whereby, the HUVECs culture treated with 1 nM rapamycin consisted of only 18.7% SA-β gal-positive cells compared to the higher percentage of SA-β gal-positive cells in the vehicle control cells."	--	--	--	--	MTORC1	Downregulation	Western blot	"The expression of phosphorylated MTOR (p-MTOR), which is the main component of MTORC1, was significantly suppressed at 0.5 nM rapamycin. Moreover, its downstream proteins, phosphorylated ribo-somal protein S6 (p-RPS6) and phosphorylated 4EBP1 (p-4EBP1) were significantly down-regulated with 0.5 nM rapamycin and at higher doses, which confirmed MTORC1 attenuation by low dose rapamycin treatment."	HL	cellular senescence	29857052
Sen_E_257	TMAO	Chemical compounds	--	Hippocampus	Aging	Accelerate	SA-β-gal activity assay	"R1-C mice showed a few SA-beta-GAL-positive cells,whereas the R1-T and P8-C groups had more cells showing prominent SA-beta-GAL staining. As expected, the P8-T group had the most cells showing robust SA-beta-GAL staining among all groups."	--	--	--	--	mTOR	Downregulation	Western blot//qRT-PCR	"The phosphorylation levels of mTOR, p70s6k and 4EBP2 were significantly decreased in P8-C compared with R1-C.These proteins were decreased significantly in the TMAO groups compared to the control groups, especially in P8-T."	L	cellular senescence	29749694
Sen_E_258	Rapamycin	Chemical compounds	"PA-SMC,P-EC"	--	Chronic obstructive pulmonary disease	Prevent	SA-β-gal activity assay	"The PDL was lower for PA-SMCs and P-ECs from patients with COPD compared with those from controls. Rapamycin treatment consistently increased the PDLs of  both PA-SMCs and P-ECs from patients with COPD and, to a lesser extent, from controls. Thus, PDLs for PA-SMCs and P-ECs from patients with COPD and controls no longer differed when both were treated with rapamycin. Rapamycin treatment also decreased the number of  β-Gal–positive cells to similar values in the COPD and control groups.Rapamycin (10 nM) reduced IL-6, IL-8, and CCL2 levels in cells derived from COPD patients and from controls,although the effects varied among patients."	--	--	--	--	mTOR	Downregulation	Western blot//ELISA	"Rapamycin treatment increased the PDL in PA-SMCs from SM22-TSC1–/– mice, decreased the β-Gal–positive cell count, and inhibited mTOR activity . The increased mTOR signaling and higher cytokine levels measured 3 months after tamoxifen exposure in these mice returned to normal after rapamycin treatment."	L	delay aging	29415880
Sen_E_259	Everolimus	Chemical compounds	"HuT 102,MT2,CEM,Jurkat"	--	Adult T-cell leukemia/lymphoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis//Western blot	"At both concentrations, everolimus caused a G1 cell cycle arrest in all tested cells and effects were more pronounced in the HTLV‐I‐negative cells CEM and Jurkat .On 20 nM everolimus treatment for 72 hr, the percentage of cycling cells (S + G2 + M) decreased by 55% in CEM and only by 34% in HuT‐102 cells. Everolimus did not cause any increases in the pre‐G1 region, presumably representing apoptotic cells, in all tested cells even at a 2000 nM treatment up to 72 hr. HuT‐102 cells treated with 20 nM everolimus for 4, 8 or 12 days were positively stained with SA‐β‐Gal, a hallmark of senescent cells, as early as 4 days post‐treatment. Indeed, HuT‐102 cells treated with 20 nM everolimus showed 56% and 82% SA‐β‐Gal positivity at 8 and 12 days, respectively. The senescent cells also assumed a characteristic enlarged, granular and flattened appearance in culture (data not shown). HTLV‐I transformed C91 cells were also tested for β‐galactosidase positivity and by day 8 post‐treatment with 20 nM everolimus, 72% of cells were SA‐β‐Gal positive, compared to 14% in control cells . However, MT2 cells were less sensitive to everolimus‐induced senescence as treatment for 12 days with 20 nM everolimus caused 27% SA‐β‐Gal positivity only, which was increased to 90% at day 16. Everolimus‐treated HuT‐102 and MT2 cells exhibited upregulation of p21 starting day 1 while p21 protein levels remained undetectable in HTLV‐I‐negative CEM and Jurkat cells."	--	--	--	--	mTOR	--	Western blot	"Treatment with everolimus abrogated mTORC1 and Akt signaling pathways, which is evidenced by the downregulation of p‐4EBP1 and p‐Akt proteins at 48 hr post‐treatment ."	L	apoptosis	21064094
Sen_E_260	Hypoxia	Other	HT-p21-9	--	Aging	Prevent	SA-β-gal activity assay//Cell morphological analysis	Hypoxia partially prevented a large flat cell morphology and β-gal staining.	--	--	--	--	mTOR	--	Western blot	Hypoxia decreased phosphorylation of S6K (substrate of mTOR) and S6.	L	delay aging	22847439
Sen_E_261	ROS	Chemical compounds	IMR-90	Liver	Aging	Accelerate	Flow cytometry//Western blot	"First, we nonspecifically elevated cellular ROS levels in proliferating IMR90 cells by hydrogen peroxide (H2O2). This procedure triggered cell cycle arrest, as judged by loss of ph-Rb and cyclin A and induction of p21, as well as CCFs and the SASP."	--	--	--	--	Mitochondria-ROS-JNK	--	Western blot//Knockdown//qRT-PCR	"JNK inhibitor treatment also diminished the SASP at the protein level in senescent cells, as shown by IL8 immunoblotting. Importantly, inhibition of JNK did not suppress mitochondrial ROS, in line with the idea that ROS act upstream of JNK activation. Knockdown of JNK1/2 strongly reduced CCF accumulation and the expression of SASP genes in senescent cells. Finally, inhibition of JNK in already senescent cells also resulted in reduction of CCFs and down-regulation of the SASP but did not rescue cell cycle arrest , corroborating our hypothesis that JNK mediates CCFs and the SASP."	HL	cellular senescence	32001510
Sen_E_262	Extracellular vesicles	Other	H9C2	--	Aging	Prevent	SA-β-gal activity assay	"DOX greatly increased βgal positive cells, which was significantly ameliorated by human serum EVs treatment."	--	--	--	--	miR-34a-PNUTS	--	qPCR	"In H9C2 cells, we found that EVs significantly decreased the expression level of miR-34a.Our study also found that miR-34a mimic downregulated PNUTS expression in H9C2 cells, while miR-34a inhibitor significantly elevated that."	L	cellular senescence	30499000
Sen_E_263	Salidroside	Chemical compounds	2BS	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry	"SAL significantly delayed replicative senescence of 2BS cells by at least 8 PDs (see Table 1). The two concentrations of SAL (5 μM and 10 μM) showed a similar gain in PDs. The growth rate of SAL-treated cells was dramatically increased compared to that of the control cells (Table 1). For the SA-β-gal activity,a biomarker of cellular senescence, only sporadic SA-β-galpositive cells were observed in young control cells. As anticipated, SA-β-gal activity was markedly elevated in 55PD control cells (91 7±7 1%), while cells at 55PD cultured in a 10 μM SAL-supplemented medium from 30PD showed a much lower positive rate (28 3±4 9%).Moreover, SAL treatment for 48 h significantly suppressed the elevated production of intracellular ROS in nearsenescent 2BS cells (50PD)."	--	--	--	--	miR-22-SIRT1	--	Knockdown//SA-β-gal activity assay//Western blot//qRT-PCR	"LentiPre22-infected cells showed a five fold increase of mature miR-22 compared with the young control cells and exhibited an enlarged senescence morphology and SA-β-gal-positive staining , accompanied with an increased protein level of senescenceassociated molecules p53, p21, and p16 . As anticipated, a decreased SIRT1 protein expression was observed in the Lenti-Pre22-infected cells . However, SAL could partly impede the senescence progression induced by lenti-Pre-miR-22. The increment of SA-βgal activity induced by overexpression of miR-22 was prevented in part by SAL. Besides, declined expression of SIRT1 and increased protein levels of p53, p21, and p16 in Lenti-Pre22-infected cells were partly reversed by SAL treatment. These results implied that SAL stimulates the SIRT1 partly through inhibition on miR-22."	HL	delay aging	31612074
Sen_E_264	Avenanthramide A	Chemical compounds	--	Colon	Colorectal cancer	Accelerate	SA-β-gal activity assay//Western blot	"The mice in AOM/DSS group showed a  high tumor burden in colon tissues, while AVN A treatment obviously suppressed AOM/DSS induced tumors. The proportion of cells with senescent cell morphology and SA-β-gal staining were increased in dose and time-dependent manner after exposed to indicated concentration of AVN A for 3, 5 or 7 days. The protein level of p21 increased in a dose-dependent manner when treated with AVN A for 3 days."	--	--	--	--	miR-129-3p-Pirh2-p53	Activation	Western blot//qRT-PCR	"AVN A treatment significantly elevated miR-129-3p expression in a dose-dependent manner. Overexpression of miR-129-3p dramatically suppressed mRNA level of Pirh2 in CRC cells, which was in agreement with our observations that AVN A treatment dramatically decreased the Pirh2 mRNA level .Moreover, western blot analysis also confirmed that the expression of Pirh2 was downregulated in miR-129-3p overexpressing cells."	L	delay aging	30888162
Sen_E_265	PAM	Chemical compounds	"NHOK,NHOF"	Oral cavity	Bisphosphonate-related osteonecrosis of the jaw	Accelerate	MTT assay//Flow cytometry//SA-β-gal activity assay//Cell morphological analysis	"We found a gradual decrease in cell viability in NHOK, starting as low as 1 μM PAM, whereas an abrupt decrease was evident in NHOF at approximately 25 μM PAM.Using 10 μM PAM, we found a significant loss of proliferation in NHOK with rounded and flattened phenotypes .The cell cycle analysis revealed an increased S-phase content in response to both 10 and 50 μM PAM doses in NHOK .In PAM-treated NHOK, SA-β-gal activity increased up to 3.5-fold compared with that in the control, whereas no changes were observed in NHOF."	--	--	--	--	Mevalonate	--	MTT assay//SA-β-gal activity assay	"We reconstituted geranylgeranylation and farnesylation using GGOH and FOH, respectively, and examined proliferation and senescence. Sublethal amounts of FOH, GGOH, and FOH/GGOH (1:0.5 ratio) were determined by MTT assay . Proliferation of PAM-treated NHOK was inhibited as expected. When NHOK were co-treated with PAM and FOH, similar results were observed; however, NHOK treated with PAM/GGOH or PAM/GGOH/FOH regained proliferative capacity by approximately half . When these cells were subjected to SA-β-gal staining, GGOH, but not FOH, reduced β-gal positivity by approximately half. Analysis of these data suggests that the senescence mechanism in PAM-treated NHOK is mediated, in part, through geranylgeranylation  of the mevalonate pathway."	L	apoptosis	21427353
Sen_E_266	Gomisin A	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay	"The aged HDF cells (PD61) showed markedly higher levels of SA-β-gal activity than the middle passage cells,while gomisin A significantly reduced aging induced SA-β-gal activity."	--	--	--	--	MAPK-NF-κB	Downregulation	Western blot	"The SIPS-HDF cells activated MAPK signaling including p-ERK, p-p38, and p-JNK, but gomisin A inhibited the SIPS-induced MAPKs. Furthermore, gomisin A blocked the NF-κB translocation from the cytosol to the nucleus."	L	delay aging	29319901
Sen_E_267	Gypenoside L	Chemical compounds	"ECA-109,HepG2"	--	Aging	Accelerate	SA-β-gal activity assay//qRT-PCR//EdU assay//Flow cytometry//Western blot	"Treatment with Gyp-L significantly increased the percentages of SA-β-gal-positive cells .The proportion of EdU-positive cells was higher in the control group, which was remarkably reduced in a concentration-dependent manner in the presence of Gyp-L, indicating that Gyp-L inhibited the proliferative activity of cancer cells.we detected the senescence-associated expression of SASP, such as IL-1α, IL-6, TIMP-1, CXCL-1 and CXCL-2, by qRT-PCR. As expected, the mRNA expression levels of all cytokines were increased by Gyp-L.Flow cytometry assay results demonstrated that a progressive increase of cells, retardant in S-phase, occurred in hepatic and esophagus cancer cells when treated with different concentrations of Gyp-L.Gyp-L significantly reduced the expression of all cell cycle regulators, such as CDK2, CDK4, CDK6, and cyclin D1, which was consistent with the arrested cell cycle."	--	--	--	--	MAPK//NF-κB//p38//ERK	Activation//Activation//Activation//Activation	Western blot	"We found that Gyp-L activated MAPK signals, mainly through p38 and ERK signaling pathways, in a dose-dependent manner in esophageal cancer.To explore its potential regulation in Gyp-L-induced senescence, a western blotting experiment was performed, which showed that the phosphorylation and activation of NF-κB was markedly up-regulated by Gyp-L in ECA-109 cells.Gyp-L also activated p38 and ERK in a dose-dependent manner in HepG2 cells."	L	delay aging	30889805
Sen_E_268	C2-ceramide	Chemical compounds	H1299	--	Lung cancer	Accelerate	Cell cycle analysis//SA-β-gal activity assay	"C2-ceramide accelerated PTX-induced G2-phase arrest of H1299 cells,as indicated by the portion of G2 population increased from 27.9% (PTX-treated) to 35.4% (20CT, PTX/C2-ceramide-treated);The percentage of senescent cells was significantly increased when PTX and C2-ceramide were co-administered to the cells,indicating C2-ceramide helped sensitize PTX-induced premature senescence both in a dose-dependent manner and time-dependent manner."	--	--	--	--	MAPK	Activation	Western blot	"To examine whether C2-ceramide sensitized cells to premature senescence through MAPK signaling pathways, protein levels of major stress-MAPKs (JNK and p38) and anti-apoptotic protein Bcl-2 were analyzed by western blotting. C2-ceramide treatment induced activation of p38 in a dose-responsive manner; Additionally, the activiation of JNKwas minor decreased with C2-ceramide treatment alone."	L	cellular senescence	20624405
Sen_E_269	Melatonin	Chemical compounds	IMR-90	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//Cell counting	"Indeed, treatment with melatonin significantly reduced the SA-β-gal activity in IMR90 cells cultured with media (OIS-CM) from H-RasV12transfected senescent IMR90 cells (65.5% in OIS-CM-treated group vs 20.2% in OIS-CM and melatonin-treated group, P<0.05). Consistent with the above observations, we also found that melatonin blocked the OIS-CM-induced growth arrest of IMR90 cells, as determined by focus formation assay (16.3% in OIS-CM-treated group vs and 64.1% in OIS-CM and melatonintreated group, P<0.05) and cell counting . We further observed that treatment with melatonin significantly reduced expression of OIS-CM-induced SASP genes (Illustrated by the case of IL8, 93.1-fold in OIS-CM-treated group vs 25.9-fold n OIS-CM and melatonin-treated group, P<0.05)."	--	--	--	--	MacroH2A1	Downregulation	Western blot	"Strikingly, melatonin treatment dramatically reduced macroH2A1 signaling during OIS."	HL	cellular senescence	28247536
Sen_E_270	Exosomes	Other	--	Heart	Cardiovascular disease	Prevent	--	"To determine whether exosomes could prevent aginginduced cardiac dysfunction, exosomes were injected into D-gal-treated mice. We found that exosomes attenuated the effects of D-gal in the left ventricular ejection fraction (EF) and fraction shorting (FS), and siMALAT1 blocked the function of exosomes. We also found that exosomes attenuated the effects of D-galactose (D-gal) on telomere length, and the beneficial effects of exosomes were blocked by siMALAT1."	--	--	--	--	lncRNA MALAT1-NF-κB-TNF-α	--	Knockdown//SA-β-gal activity assay//Western blot//qRT-PCR	"We further demonstrated that exosomes inhibited H2O2-induced NF-κB activity and the expression of NF-κB subunit p-p65 . Exosomes also inhibited H2O2-induced expression of TNF-α at both mRNA and protein levels .Transfection of cardiomyocytes with siMALAT1 led to a reduction in NF-κB activity and the expression level of NF-κB subunit p-p65. siMALAT1 also reduced the expression of TNF-α induced by H2O2 treatment. Moreover, transfection of siMALAT1 inhibited H2O2-induced p21 expression. siMALAT1 blocked the effect of exosomes on β-gal-activity and cell proliferation .These data suggest that exosomes prevent cell senescence through the lncRNA MALAT1/NF-κB/TNF-α pathway."	L	delay aging	31089420
Sen_E_271	PQQ	Chemical compounds	HK-2	--	Aging	Prevent	SA-β-gal activity assay//Westen blot	"Compared with HG group, the significantly increased of P16 and P21 could be reduced respectively in PQQ plus HG group. Compared with NG group, more SA-β-gal positive cells were observed in HG-induced HK-2 cells. However, PQQ treatment resulted in less SA-β-gal positive cells in comparison with the HG group."	--	--	--	--	Keap1-Nrf2	Activation	qRT-PCR//Western blot//Immunofluorescence	"The levels of protein Nrf2, GPx-3, GST, HO-1 and NQO-1 were reduced in HK-2 cells exposed to HG for 48 h (P < 0.05). However, the expression of Nrf2 and downstream pathway proteins were increased post PQQ stimulation. In addition, we found that HG significantly increased the protein level of Keap1. However, the protein expression of Keap1 was inhibited by PQQ. PQQ treatment also enhanced HG-induced mRNA expression levels of Nrf2 ."	L	apoptosis	31035086
Sen_E_272	Dehydroepiandrosterone	Chemical compounds	HAEC	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"When we pre-treated with 50 nmol/L of DHEA for 1h prior to LA treatment,the number of SA-β-Gal-positive cells significantly decreased compared to the cells treated with LA alone.However,pre-treatment with DHEA substantially increased the protein level of ppRB(an indicator of senescence)."	--	--	--	--	JNK	Activation	SA-β-gal activity assay//Western blot	"After HAECs were pre-treated with the JNK inhibitor, the inhibitory effect disappeared. Similarly, the increased expression of ppRB by DHEA treatment was also abolished after JNK inhibition."	L	delay aging	26051603
Sen_E_273	Probucol	Chemical compounds	HMC	--	Aging	Prevent	SA-β-gal activity assay//MTT assay	"SA-β-gal activity assay//MTT assay:SA- -gal staining was decreased in probucol + tBHP stimulated cells compared with the tBHPstimulated cells (45.32% ± 4.13% and 81.03% ± 5.86%, respectively; p < 0.01). Cell cycle analysis indicated that the cell percentage at the G0?G1, S, and G2?M phases was normalized. Optical microscopic observation showed that cell ageing changes were not apparent."	--	--	--	--	JAK2?STAT	Downregulation	Western blot	"Western blot： The protein expression of STAT1, STAT3, pSTAT1, and pSTAT3 were also increased in ageing cells compared with those in control cells. When probucol and AG490 were used, their expression decreased."	L	cellular senescence	23984931
Sen_E_274	pIFN- α	Chemical compounds	EA.hy926	Tumor tissue	Melanoma	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"We observed that upon exposure to pIFN-α,cells became enlarged, flattened, irregularly shaped and significantly more cells expressed SA β-gal+, suggesting a senescent phenotype as compared with untreated cell cultures."	--	--	--	--	IRF-1	--	Western blot	"Interestingly, treatment with 0.25 or 0.5 mg/ml pIFN-a induced the same level of IRF-1."	L	cellular senescence	21197417
Sen_E_275	27-hydroxycholesterol	Chemical compounds	"BV-2,PC-12"	--	Neurodegenerative disease	Accelerate	SA-β-gal activity assay	"In the present study, we demonstrated that 27HC induced apparent cellular senescence in nerve cells. Senescence-associated β-galactosidase(SA-β-Gal) assay revealed that 27HC induced senescence in both BV2 cellsand PC12 cells."	--	--	--	--	IL-6-STAT3	Activation	DCFH assay//Western blot//ELISA	"Furthermore, we demonstrated that 27HC promoted the accumulation of cellular reActivate oxygen species (ROS) innervecells and subsequently activation of IL-6/STAT3 signaling pathway. Notably, treatment with the ROS scavenger N-acetylcysteine (NAC) markedly blocked 27HC-induced ROS production and activation of IL-6/STAT3."	L	cellular senescence	28739487
Sen_E_276	Irradiation	Other	--	Submandibular Salivary Gland	Dry-mouth syndrome	Accelerate	Cell morphological analysis//SA-β-gal activity assay//RT-PCR	"Histological analysis performed over 12 weeks post-irradiation revealed a gradual increase in the appearance of large cells with notably enlarged, hyperchromatic nuclei, morphologically reminiscent of cells undergoing senescence (28).Salivary glands collected 8 weeks post-irradiation showed substantially increased SA-βgal activity located largely in ductal cells and also in some acini.Real-Time PCR analysis of salivary glands 2 and 8 weeks post-irradiation revealed strongly increased expression of the senescence-associated markers (31), p21, p19ARF, DcR2, and also the SASP genes, IL-6 and PAI-1, up to 21-fold."	--	--	--	--	IL-6	Upregulation	ELISA	Analysis of serum IL-6 protein levels by ELISA revealed strong elevation in IL-6 expression that appeared roughly 6 hours post-irradiation and lasted less than one day .	L	apoptosis	26759233
Sen_E_277	Thiostrepton	Chemical compounds	"MCF-7,MDA-MB-436"	--	Breast cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"MCF-7 cells treated with thiostrepton exhibited SA-β-gal activity and their morphology changed, with the cells becoming enlarged and flattened.The SA-β-gal activity was determined to be increased in a dose-dependent manner, with the highest activity observed at 4 μM.  MDA-MB-436 cells also exhibited senescence morphology, with positive SA-β-gal activity, after being exposed to thiostrepton."	--	--	--	--	FOXM1	Downregulation	RT-PCR	"After 24 h of thiostrepton exposure, MCF-7 cells exhibited downregulation of FOXM1."	L	apoptosis	31322278
Sen_E_278	Fucoidan	Chemical compounds	MSC	Adipose	Aging	Prevent	SA-β-gal activity assay//Cell cycle analysis	"A SA-β-gal assay showed that treatment with fucoidan significantly decreased MSC senescence caused by p-cresol exposure. Furthermore, cell cycle analysis revealed that fucoidan inhibited the decrease in proliferation caused by p-cresol."	--	--	--	--	FAK-Akt-TWST	Activation	Western blot//qPCR//SA-β-gal activity assay	"We evaluated activation of the FAK-Akt-TWIST signal pathway after treatment with fucoidan (10 μg/mL) for 0, 24, 48, or 72 h. As expected, phosphorylation of FAK and Akt was significantly increased after fucoidan treatment in a time-dependent manner, with the maximal effect seen at 48 h. The expression of TWIST was also significantly increased in a time-dependent manner . In addition, Akt inhibition blocked the mRNA and protein expression of TWIST, indicating that fucoidan mediated TWIST expression is dependent on FAK-Akt phosphorylation.Our results show that the inhibition of Akt signaling increased the number of SA-β-gal positive cells and changed the cellular morphology of MSCs, suggesting that fucoidan-mediated Akt signaling is involved in the protection of p-cresol-induced MSC senescence."	L	cellular senescence	29642406
Sen_E_279	Estrogen	Chemical compounds	B-MSC	--	Osteoporosis	Prevent	SA-β-gal activity assay//Western blot	The role of estrogen on anti-senescence was verified by the decreased SA-β-gal positive cells and alleviated expression of senescence markers.	--	--	--	--	ERβ-SATB2	Activation	Western blot//qRT-PCR//Knockdown//Colony formation assay	"Higher expression levels of SATB2, Nanog, Sox2 and Oct4, were observed in BMSCs treated with estrogen relative to the control group.A reduction in colony formation was observed with both siRNA-ERβ and ICI182, 170 treatment. Consistent with reduced stemness, lower expression of Nanog, Sox2 and Oct4 was evident. In the siRNA-ERβ or ICI182, 170 groups, SATB2 expression decreased up to 0.5-fold, conversely, estrogen treatment induced SATB2 expression by up to 1-fold in BMSCs. Similar effects were also observed at the protein level."	L	delay aging	29030963
Sen_E_280	Busulfan	Chemical compounds	WI-38	--	Aging	Accelerate	SA-β-gal activity assay//BrdU assay	"The growth of WI38 cells was permanently arrested after 24 h treatment with BU,while control untreated cells proliferated exponentially.This suggestion is supported by the observation that cells briefly treated with BU exhibited a significant reduction in BrdU incorporation (BU, 3.6 ± 1.5% vs Ctrl, 45.1 ± 4.7%, P< 0.0001) and a drastic increase in SA-β-gal staining (BU, 75.4 ± 6.6% vs Ctrl, 9.7 ± 4.9%, P< 0.0001) as compared with control untreated cells at 11 days after the initial treatment ."	--	--	--	--	ERK-p38 MAPK	Activation	Western blot//SA-β-gal activity assay//BrdU assay	"BU treatment incited a moderate p53 activation, but strong Erk,p38, and JNK phosphorylation, in a time-dependent manner.It was found that inhibition of Erk or p38 abrogated BU-induced increase in SA-β-gal staining and reduction in BrdU incorporation and cell proliferation in WI38 cells as compared with the cells treated with BU alone ."	L	cellular senescence	17512465
Sen_E_281	Oxytocin	Chemical compounds	NHDF	--	Aging	Prevent	SA-β-gal activity assay//Western blot//Knockdown	"OXTR knockdown or treatment with a MAPK kinase (MEK) inhibitor completely abolished the ability of OT to prevent the SASP-induced cellular senescence, as indicated by increased SA-β-Gal positive rate, upregulated levels of p21 and p16, and diminished cell proliferation."	--	--	--	--	ERK-Nrf2	Activation	SA-β-gal activity assay//Western blot//Knockdown	OT enhanced nuclear accumulation of Nrf2 in a dose-dependent manner . This was reversed by OXTR silencing or treatment with MEK inhibitor .Knockdown of Nrf2 completely abrogated the beneficial effects of OT on SASP-induced senescence .	HL	delay aging	30801661
Sen_E_282	Cisplatin	Chemical compounds	EC109	--	Esophageal cancer	Accelerate	SA-β-gal activity assay	Cisplatin significantly elevated cellular senescence in EC109 cells in a time-dependent manner.	--	--	--	--	ERK1/2	Activation	SA-β-gal activity assay//Western blot//PI staining//Annexin V binding assay	"Treatment of cisplatin obviously stimulated the phosphorylation of ERK1/2, p38, and JNK.inhibition of ERK1/2 significantly suppressed cisplatin-induced apoptosis and senescence in EC109 and EC109/CDDP cells ."	L	apoptosis	25236911
Sen_E_283	Crataegus extract	Other	Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay	"The Crataegus extract concentration-dependently reduced the increased SA-β-gal activity in cells at P2, P3, and P4."	--	--	--	--	eNOS	--	Flow cytometry//SA-β-gal activity assay	The protective effect of the Crataegus treatment in cells at P3 was not observed in the presence of L-NAME indicating the key role of eNOS-derived NO.	L	delay aging	26672612
Sen_E_284	Berberine	Chemical compounds	"U87 MG,U251MG"	Tumor tissue	Glioblastoma	Accelerate	SA-β-gal activity assay//EdU assay	"We therefore tracked the fates of U87 and U251 cells treated with berberine using SA-β-gal staining assay. Berberine treatment led to a significant increase in the percentage of senescent cells. After being treated with berberine (15 μM) for seven days, over 70% U87 and 40% U251 cells became senescent. Consistent with the emergence of a high percentage of SA-β-gal positive cells, EdU incorporation assay showed that the percentages of EdU-positive cells were greatly reduced seven days after treatment with berberine, suggesting that very few of the berberine-treated cells were in S phase."	--	--	--	--	EGFR-MEK-ERK	Downregulation	Western blot	"We therefore tested whether EGFR-initiated pathways are altered in glioblastoma cells treated with berberine. Interestingly, in both U87 and U251 cells treated with berberine, we observed a significant reduction in the level of EGFR. Furthermore, the levels of phosphorylated (Activate) form of RAF, MEK and ERK were all decreased .This result indicated that accompanying the declined level of EGFR, the RAF-MEK-ERK pathways was significantly downregulated in berberine-treated glioma cells."	L	cellular senescence	25504754
Sen_E_285	HCV infection	Other	CD4+T	Blood	HCV infection	Accelerate	SA-β-gal activity assay	SA-β-gal expression increased in senescent CD4+ T cells in HCV-infected patients compared with age-matched HS.	--	--	--	--	DNp63-miR18-1a-SIRT1	--	Flow cytometry//Western blot//RT-PCR	The protein levels of Sirt1 were significantly upregulated in CD4+T cells from 22 HCV-infected patients compared with 22 age-matched HS；We then silenced the expression of DNp63 in CD4+T cells from patients with HCV and found that lower expression of DNp63 in T cells by transfecting its specific siRNA led to an up-regulation of miR-181a and a down-regulation of Sirt1 expression.	L	cellular senescence	27354409
Sen_E_286	BrdU	Chemical compounds	"HeLa,A549"	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Senescence associated morphological changes were detected within 48 hours and treated cells show flatter, enlarged and granule rich morphology,similar to morphology of replicatively senescent cells reported previously. The senescent state of BrdU treated cells was also confirmed using SA-β-gal, the most widely used assay for cellular senescence."	--	--	--	--	DDR-ROS-ATM	--	Western blot//53BP1 foci formation assay	"Robust proliferation arrest and activation of ATM kinase was detected in cells exposed to BrdU after 48 hours, monitored by the presence of phosphorylation of H2Ax protein, a substrate of ATM kinase. Towards this, senescent cells generated by BrdU exposure were treated with ATM kinase inhibitor caffeine or Ku53393 or ROS quencher NAC after 48 hours as described in previous section. As an indicator of ATM kinase inhibition, the presence of 53BP foci was evaluated in these cells, which was found to be significantly lowered when ATM kinase was inhibited , but not in ROS quenched cells."	L	cellular senescence	25416819
Sen_E_287	Camptothecin	Chemical compounds	CRC	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	We found enlarged and flattened cell morphology and increased time-dependent SA-β-gal activity . This suggests that the CRC cells acquire properties of senescence upon CPT treatment.	--	--	--	--	DDR//AMPK-TSC2-mTOR//ATM-Chk2-p53-p21	Activation//--//Activation	Immunofluorescence//Western blot	"To investigate the activation of DNA damage signaling pathway by low-dose CPT, several key proteins of DDR were detected by immunofluorescence staining and Western blotting. In our study, the expression of γ-H2AX was increased over time as a result of CPT. Low-dose CPT up-regulated the phosphorylation of AMPK and TSC2 while down-regulated the phosphorylation of mTOR over time . Both p53 and p21 increased in a time-dependent manner with low-dose CPT treatment, and the protein levels decreased after the combination treatment of CPT with ATM inhibitor KU55933.Thus, it is possible that CPT induces premature senescence through ATM activation of the Chk2-p53-p21 pathway in HCT116 and RKO cells."	L	cellular senescence	24858802
Sen_E_288	Dihydroartemisinin	Chemical compounds	HepG2.2.15	Tumor tissue	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay//Western blot	"To further explore the underlying mechanisms of DHA on HepG2.2.15 cells, cellular senescence was detected by senescence-associated-β-Galactosidase assay. And the associated protein expression was measured by western blot.Exposure of HepG2.2.15 cells to DHA for 48 hours increased the senescent cells compared with the control."	--	--	--	--	DDR//Akt-mTOR	--//--	Western blot	"Compared with cells treated with vehicle, the p-ATM, p-ATR, γ-H2AX, P53 and P21 were elevated while the telomere shelterin TPP1 was significantly down-regulated in cells treated with DHA. These results demonstrated that DHA might induce HepG2.2.15 cellular senescence through DDR pathway.In the present study, some key molecules in AKT-mTOR signaling were also detected by western blot. The p-AKT, p-mTOR, p-p70S6K, p-4EBP1 were down-regulated and followed by autophagy associated protein LC3, p-AMPK, p62 increased obviously."	L	cellular senescence	31383247
Sen_E_289	Pevonedistat	Chemical compounds	Melanoma cell	--	Melanoma	Accelerate	SA-β-gal activity assay//Western blot//Flow cytometry	"Cells treated with pevonedistat for 12 or 24 h remained arrested, and exhibited 18% and 60% rereplication, respectively when analyzed 48 h later and were senescent. Furthermore,treatment of DM93 cells with vemurafenib induced robust G1 growth arrest and complete depletion of S-phase cells, and inhibited pevonedistat-induced rereplication ."	--	--	--	--	CRL4-CDT2-SET8-p21	--	Western blot//Clonogenic assay	"We treated DM93 cells with increasing doses of pevonedistat for 24 h. This resulted in a dose-dependent increase in several cullin ubiquitylation substrates, including CDT2, CDT1, p21 and p27,which reached significant levels at 1 μM drug concentration. Although CDT2 is increased by pevonedistat,it is likely to be inActivate because of the de-neddylation of cullin proteins.Time course analysis with 1 μM pevonedistat demonstrated early (at 3 and 6 h) increase in CDT1 as well as SET8 protein and activity (H4K20 monomethylation) followed by th appearance of p21 and p27 .Increases in CDT1, SET8 and p21 were all attributed to increased stability as well as increase in the stability of not only H4K20me1, but also H4K20me2 and H4K20me3. When added continuously in culture, pevonedistat still inhibited the proliferation of sg-p21 and sg-SET8 cells.Strikingly however,unlike control cells (sg-control), cells with reduced expression of p21 or SET8 resumed proliferation following the cessation of pevonedistat treatment . Thus, pevonedistat inhibits the proliferation of melanoma cells through the induction of SET8- and p21-dependent rereplication mechanism."	HL	delay aging	27333051
Sen_E_290	AZD6738	Chemical compounds	HeLa	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Knockdown	"Cells were treated with a highly selective ATR inhibitor, AZD6738.Compared to control cells, both RNASEH2B KO and RNASEH2A KO cells exhibited increased β-galactosidase staining , indicating that ATRi treatment accelerates cellular senescence in RNASEH2-depleted cells."	--	--	--	--	cGAS-STING	Upregulation	qRT-PCR	"Expression levels of cGAS-STING target genes (e.g. IFN-β, ISG54 and CCL5) were higher in RNASEH2 deficient cells and could be further enhanced by ATRi treatment, which suggest the activation of cGAS-STING pathway may be another reason for increased cellular senescence caused by ATR inhibition. As it is reported that RNASEH2 deficiency could invoke cGAS-STING activation and because of the essential role of cGAS-STING pathway in cellular senescence30,31,56,57, we assume that the activation of cGAS-STING pathway may also contribute to senescence phenotype in our study."	HL	apoptosis	30532030
Sen_E_291	SHR6390	Chemical compounds	"MCF-7,ZR-75-1"	Tumor tissue	Breast cancer	Accelerate	Flow cytometry//SA-β-gal activity assay	"Accordingly, SHR6390 induced a concentration- dependent G1- phase cell cycle arrest in RB- positive MCF7 and ZR- 75- 1 breast cell lines.The proportion of senescence SA- β- gal positive cells increased from control levels of 10.6%- 74.4% and 77.0% by 1 μmol/L SHR6390 and 1 μmol/L palbociclib in MCF7 cells, respectively. SA- β- gal positive cells increased from 18.0% to 85.8% and 88.6% after SHR6390 and palbociclib treatment in ZR- 75- 1 cells, respectively."	--	--	--	--	CDK4/6-Rb	Downregulation	Western blot	"SHR6390 prominently reduced RB expression .SHR6390 also inhibited RB phosphorylation in the MCF7/TR cell line, implying that RB protein- related changes are a universal phenomenon associated with CDK4/6 inhibitor treatment."	L	cellular senescence	30724426
Sen_E_292	Copper	Other	U87 MG	--	Glioblastoma	Accelerate	SA-β-gal activity assay//Cell viability assay//MTT assay	"SA-β-gal activity assay:U87-MG cells exposed to 250 or 500 μM CuSO4 presented an enlarged cellular volume and altered shape, resembling the typical senescent phenotype. Cell viability assay:With increasing concentrations of copper sulfate, the cell viability was accordingly decreased . MTT assay:the 250 or 500 μM copper sulfate group showed a dramatic decrease in cell proliferation when compared with the control group."	--	--	--	--	Bmi-1	Downregulation	Western blot//RT-PCR	"CuSO4-treated cells (250 μM) showed increased protein levels of p21 and p16, but a decreased level of Bmi-1, when compared with the control.Cells exposed to 250 μM CuSO4 showed statistically significant overexpression of ApoJ,TGF-β1,p21 and p16 (4.0-, 1.7-, 3.2- and 2.4-fold, respectively) but a marked decrease in Bmi-1."	L	cellular senescence	23468063
Sen_E_293	EGCG	Chemical compounds	3T3-L0	--	Aging	Prevent	SA-β-gal activity assay	"SA-β-gal activity significantly(p＜0.05) enhanced in H2O2treated cells with over 60% cells appearing senescent as compared to control group, which was significantly (p＜0.05) abrogated on treatment with EGCG."	--	--	--	--	Bcl-2	Downregulation	Western blot	Assessment of underlying molecular mechanism for apparent senolytic effects of EGCG revealed a strong upregulation of Bcl-2 protein expression in senescent cells which was dose dependently and significantly (p＜0.05) abrogated by EGCG treatment.	L	apoptosis	30456590
Sen_E_294	Cigarette smoke extract	Other	HFL-1	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"We found that fibroblasts synchronized by serum deprivation (accumulation of cells in the G1 phase) did not respond to serum restitution if they were exposed to CSE 5% solution. In contrast, CSE treatment of asynchronous fibroblasts resulted in accumulation of the cells in the S and G2 phases of the cell cycle.Multiple exposures to CSE ultimately increased SA β-gal activity and induced a flat and enlarged cell morphology."	--	--	--	--	ATM-p53-p21-pRb//p16-pRb//p53	Activation//Activation//Activation	Western blot	"Exposure to CSE induced activation of ATM, p53, and pRb, a marked increase in p53 and p21, and a mild increase in p16 accumulation.Multiple exposures to CSE markedly increased p53 and p16 accumulation and activated pRb.We evaluated the downstream effect of p53 with p21 accumulation up to 2 wk. Exposure to CSE increased p21 up to 2 wk."	L	cellular senescence	16840774
Sen_E_295	γ-irradiation	Other	TIG-3 p27	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	Chronic c-irradiation efficiently induced cellular senescence and 0.694 mGy/min was more potent than 0.347 mGy/min in this assay. This result was consistent with results obtained using the colony survival assay.	--	--	--	--	ATM-p53-p21	Activation	Western blot	TP53 or p21 levels were knocked down in BJ1/hT fibroblasts. This treatment abolished the cell-proliferation inhibition induced by chronic c-irradiation .The ATM inhibitor KU55933 inhibited the phosphorylation of TP53 and checkpoint kinase 2 (CHEK2) (ATM kinase substrates) and reduced p21 induction in response to c-irradiation.	L	cellular senescence	25093836
Sen_E_296	MLN8237	Chemical compounds	Hs294T	--	Melanoma	Accelerate	SA-β-gal activity assay//Cell morphological analysis//Cytokine array	"Indeed, after 5 days of treatment in vitro,we observed that the cellular size was greatly enlarged ,which is a characteristic associated with senescence.β-galactosidase activity was evaluated and found to be enhanced in drug-treated Hs294T cells and in other melanoma cell lines (SK-Mel-2, SK-Mel-5 and SK-Mel-28).The results demonstrated that IL-6, IL-7, IL-10, GM-CSF, IL-8, RANTES, GRO and GRO-a were upregulated in response to drug treatment."	--	--	--	--	ATM-Chk2//NF-kB	Activation//Activation	SA-β-gal activity assay//Knockdown//Luciferase reporter assay	"We knocked down either ATM or Chk2 and found that senescence was reduced >30% in knockdown cells,indicating that the ATM/Chk2 pathway mediates MLN8237-induced senescence.An NF-kB luciferase assay was also performed using Hs294T NF-kB reporter cells. NF-kB transcriptional activity was significantly increased after treatment with 1mM MLN8237 for 5 days ."	HL	cellular senescence	23180582
Sen_E_297	ST1968	Chemical compounds	"A2780,KB"	--	Cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"Moreover, only in KB cells ST1968 produced a dose-dependent appearance of β-galactosidase-positive cells at 72 h following treatment. The emergence of a senescence phenotype likely reflected a persistent cell cycle arrest. Indeed, as previously reported [10], treatment of A2780 cells with ST1968 resulted in a moderate and time-dependent arrest in G2, but in a complete accumulation of KB cells in G2/M (around 90% at 72 h)."	--	--	--	--	ATM-Chk2//ATR-Chk1	Activation//Activation	Western blot//TUNEL assay	Under these conditions the ATM inhibitor produced in A2780 cells an enhancement of the apoptosis induced by the camptothecin also supported by CPP32 cleavage. As expected the combination resulted in a substantial reduction of Chk2 phosphorylation at thr68.in KB cells the Chk1 inhibitor enhanced the ST1968-induced appearance of mitotic and apoptotic cells and almost completed eliminated the cells with senescence features.	L	cellular senescence	20042274
Sen_E_298	BIBR1532	Chemical compounds	"Calu-3,A549"	--	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"After a total dose of 8 Gy of conventional fractionation radiation (2 Gy over 4 fractions), SA-β-gal-positive cells were significantly increased when cells were treated with BIBR1532 . BIBR1532 significantly decreased IR-induced G2/M cell cycle arrest after irradiation in both non-small cell lung cancer (NSCLC) cell lines."	--	--	--	--	ATM-CHK1	Downregulation	Western blot//Flow cytometry	"In NSCLC cells, BIBR1532 significantly inhibited radiation-induced ATM/CHK1 phosphorylation.BIBR1532 treatment also inhibited IR-induced G2/M cell cycle arrest."	L	apoptosis	31419512
Sen_E_299	Pterostilbene	Chemical compounds	A549	--	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot	"Consistent with the mild inhibition of cell growth, treatment of A549 cells with relatively low concentrations of PT (5 and 10 μM) in the presence of 10% serum did not perturb cell cycle progression at 24 hr. However, treatment of A549 cells with the same concentration of PT in the absence of serum induced S-phase arrest .cell senescence was well induced by 72 hrs treated PT in HBECR cells than in HBECR/p53i cells, in a dose dependent manner in two different assays.A senescence inducer, p21 and p53 amount were increased in HBECR."	--	--	--	--	ATM-ATR-CHK1-p53	Activation	Western blot	"The ATM/ATR-CHK1/2 axis is activated upon treatment with low doses of PT, an effect that is indicative of replication stress."	HL	delay aging	27612029
Sen_E_300	20A	Other	HeLa	--	Cervical cancer	Accelerate	SA-β-gal activity assay//Western blot	"20A treatment resulted in a dose-dependent increase in the percentage of cells stained for β-galactosidase,suggesting that 20A causes senescence. 20A treatment elicited a significant time-dependent up-regulation of both p21 and p27 proteins in HeLa cells."	--	--	--	--	ATM	--	SA-β-gal activity assay//Western blot	"Loss of ATM significantly reduced senescence induced by 20A, irrespective of the presence or absence of p53 protein .The inhibition of ATM activation by KU55933 prevented 20A-induced accumulation of LC3-II."	HL	apoptosis	30759257
Sen_E_301	AGEs	Other	RTEC	--	Diabetes kidney disease	Accelerate	Immunostaining//SA-β-gal activity assay//SAHF//PI staining	Double immunofluorecent staining demonstrated that p16 positive cells were colocalized in the AGE-positive cells.P16-siRNA considerably reduced the ratio of SA-β-gal and SAHF-positive RTECs as well as the proportion of RTECs in the G0/G1 phase in AGE-BSA treated group .	--	--	--	--	ATF4-p16	Activation	Immunostainings//Western blot	Linear correlation analyses showed that nuclear ATF4 expression was positively correlated with AGE deposition.The expression of ATF4 and p16 was co-localized in the nucleus of the same SAHF positive cells . ATF4 siRNA resulted in a significant decrease in AGE-induced p16 expression and premature senescence of PTECs.	L	cellular senescence	25567807
Sen_E_302	Metformin	Chemical compounds	--	Tumor tissue	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay//Immunostaining	The SA-β-gal staining was significantly higher in the treated group than in the control group.immunohistochemical analysis of the harvested tumors revealed increased DEC1 expression compared with the control animals.	--	--	--	--	AMPK-SIRT1	Activation	Immunostaining//Western blot	"Immunohistochemistry analysis revealed increased positive staining of pAMPK at Thr-172, pSIRT1 at Ser-47, acetylated-p53 at Lys382 (Ac-p53) and p21 in harvested tumors from low-dose-metformin-treated animals compared with control animals , which is consistent with the western blot analysis results."	L	cellular senescence	28964787
Sen_E_303	Honokiol	Chemical compounds	NPC	Nucleus pulposus	Disc degenerative disease	Prevent	SA-β-gal activity assay//Western blot	"We found that the percentage of SA-β-gal-positive cells was increased in the oxidative stress group when these cells transfected with scramble lentivirus, while HKL treatment could reduce the proportion of senescent NPCs via SIRT3,While HKL treatment could reduce the proportion of senescent NPCs via SIRT3 activation, which was further confirmed by the Western blot analysis of p16INKa."	--	--	--	--	AMPK-PGC-1α-SIRT3	Activation	Western blot	"Our results showed that HKL could promote the ratio of p-AMPK to AMPK and the levels of PGC-1α and SIRT3 in a dose-dependent manner in NPCs. Compared with the control group, Compound C reduced the ratio of p-AMPK to AMPK with decreasing levels of PGC-1α and SIRT3, indicating that PGC-1α and SIRT3 were regulated by AMPK.With the administration of HKL, NPCs displayed decreased expression of SIRT3 in the PGC-1α-siRNA group, suggesting that SIRT3 is regulated by PGC-1α in HKL-treated NPCs."	L	apoptosis	30420619
Sen_E_304	78c	Chemical compounds	--	Skeletal muscle tissue	Aging	Prevent	Immunostaining	"Accompanying these physiological improvements observed in aged mice, 78c treatment reversed several morphological features of aging in skeletal muscle .Strikingly, the number of centrally located nuclei, presence of inflammatory cell infiltrates, and number of necrotic myofibers decreased by more than 70% in aged mice treated with 78c."	--	--	--	--	AMPK//mTOR-p70S6K//ERK	Activation//Downregulation//Downregulation	Western blot	"One-year-old 78c-treated mice exhibited significant activation of the pro-longevity AMPK pathway in spleen and skeletal muscle . Changes induced by 78c in the AMPK pathway were further confirmed in A549 cells and mouse bone marrow-derived macrophages, which express endogenous CD38 .On the other hand, 78c decreased the activation of the mTOR-p70S6K and ERK pathways in the spleen and skeletal muscle of 1-year-old mice."	L	delay aging	29719225
Sen_E_305	Metformin	Chemical compounds	MSC	--	Aging	Prevent	Western blot	"Moreover, a declined p16 and p53 expression was also detected in the metformin-treated group, indicating that the senescence characteristics of the endogenous Alpl+/- MSCs were rescued by the metformin treatment."	--	--	--	--	AMPK	Activation	Western blot	The expression levels of p-AMPKα and p-ACC were elevated in the Alpl+/- MSCs after the metformin injections .	HL	delay aging	30210899
Sen_E_306	Tea polyphenols	Other	HMSC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry//Southern blot	"We found that the percentage of SA-β-Gal-positive cells was significantly lower in the TP group than in the HG group . The rate of G1 phase was lower in the TP group than in the HG group. Further, the telomere length of HGMCs in the TP group was also significantly longer than that in the HG group ."	--	--	--	--	Akt-p53-p21//miR-126	Activation//--	Western blot//qRT-PCR	"With regard to the effect of TP, the expression of p-Akt was significantly higher and the expression of p53, p21 and Rb was significantly lower in the TP group than in the HG group.MiR-126 expression in the HG group was significantly lower than that in the NG group. In the TP group, the expression of miR-126 was significantly higher than that in the HG group (P < 0.05)."	L	cellular senescence	31089945
Sen_E_307	PBA	Chemical compounds	MCF-7	--	Aging	Accelerate	Cell morphological analysis//Immunoblotting//SA-β-gal activity assay	"Interestingly, we observed a drastic morphological change in the MCF-7 cells treated with PBA at concentrations higher .These treated cells appeared flattened and enlarged.Since PBA-induced growth inhibition was not accompanied with apoptosis,the possibility that PBA-induced growth inhibition may result in cellular senescence was assessed.Also,an increase in senescence-associated-β-galactosi-dase (SA-β-gal) activity was also observed in these cells, which is a marker of senescence."	--	--	--	--	Akt-p21	--	Immunoblotting	"Interestingly, a recent study showed that insulin receptor substrate (IRS), which is an upstream signaling molecule of both MAPKs and Akt/PKB, is activated in PBA treated mouse liver tissue. To confirm this, we investigated various signaling molecules in cells treated with 100–300 lM PBA.We only detected Akt activation, but neither JNK nor p38,in PBA treated MCF-7cells. Furthermore, we observed induction of p21WAF1and no effect on the level of p53 in a dose-dependent manner ."	L	cellular senescence	22548801
Sen_E_308	D-gal	Chemical compounds	B-MSC	Bone marrow	Aging	Accelerate	CCK-8 assay assay//Western blot//SA-β-gal activity assay	We found that cell survival rate was inhibited by D-gal in a time- and dose-dependent manner.The expression of p16 was gradually increased as the concentration raised.We found that SA-β-gal positive cells ratio was obviously increased by D-gal stimulation.	--	--	--	--	Akt-mTOR	Upregulation	Western blot	The expressions of p-AKT and p-mTOR were promoted by D-gal in a timeand dose-dependent manner.	L	Others	29777434
Sen_E_309	Ascorbic acid	Chemical compounds	B-MSC	Bone marrow	Aging	Prevent	Western blot//SA-β-gal activity assay	"The increased expression of p16 induced by D-gal could be reduced when treated with ascorbic acid (AA).After adding AA,the SA-β-gal positive cells ratio could be decreased compared to D-gal only group."	--	--	--	--	Akt-mTOR	Downregulation	Western blot	"Activation of AKT/mTOR signaling pathway was increased in the Dgal group, and weakened when AA was added ."	L	Others	29777434
Sen_E_310	Compound fuling granule	Chemical compounds	"HEY,SKOV3"	--	Ovarian cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot//RT-PCR//Immunofluorescence	"The cell cycle distribution of CFG-treated HEY and SKOV3 cells, determined by flow cytometry analysis, indicated that the percentage of S + G2/M was greatly decreased in HEY cells after CFG treatment, whereas in SKOV3 cells it was actually slightly upregulated.Quantitative PCR also showed that the cell cycle associated proteins were regulated by CFG, and this phenomenon was more obvious in HEY than in SKOV3 cells. Similarly, immunofluorescence staining of HEY cells with antibodies against Cdt1 (red, G1 phase) and Geminin (green, G2 phase) revealed that proportion of cells in the G2 phase was also reduced after CFG treatment. Furthermore, the analysis of the cell cycle related proteins by Western blotting showed that the expression of these proteins was indeed significantly changed in CFG treated cells.β-gal staining showed that CFG could induce cellular senescence in HEY cells only."	--	--	--	--	Akt-GSK3β	Downregulation	Western blot	"The results revealed a specific reduction in the level of pAKT protein in HEY and SKOV3 cells treated with CFG, compared with that of untreated cells, as well as with that of cells singly treated with TGFβ1, as controls. The total AKT level, however, remained unaffected by all treated conditions. The expression levels of AKT downstream substrates Bcl-Xl, BAD, GSK3β, SNAIL, and SLUG were also assessed. CFG treatment also decreased the Bcl-Xl/BAD complex, pGSK3β and SLUG without affecting the nonphosphorylated form of GSK3."	HL	apoptosis	28036353
Sen_E_311	SN-38	Chemical compounds	"LS174T,HCT116"	--	Colorectal cancer	Accelerate	Colony formation assay//Western blot//SA-β-gal activity assay	"Clonogenic assays performed on two different colorectal cell lines, LS174T and HCT116, confirmed that the number of colonies was reduced after treatment with sn38.Using western blot analysis, we observed an increase in p21waf1 expression after 48-72 hours of treatment.Using β-galactosidase staining, a known marker of senescence, results indicated that approximately 70% of HCT116 and LS174T cells had entered senescence after 3 days."	--	--	--	--	Akt//p21-p53	Activation//Activation	Flow cytometry//SA-β-gal activity assay//Colony formation assay//Western blot	"Using intracellular flow cytometry staining, we observed that around 25% of dividing PLD express the Ser473 phosphorylated form of Akt. By contrast the kinase was almost not activated in the non-dividing PLS subpopulation .Using β-galactosidase staining, we also confirmed using RNA interference that Akt inhibition reduced sn38-mediated senescence as compared to cells transfected with a control siRNA Interestingly, p21waf1 inactivation significantly reduced the number of persistent clones in response to sn38. As expected, p53 was upregulated and phosphorylated on its Ser15 residue following sn38 treatment. Results also confirmed that its inactivation by RNA interference prevented p21waf1 activation.Using western blot analysis, we observed an increase in p21waf1 expression after 48-72 hours of treatment."	L	apoptosis	26485768
Sen_E_312	Lactoferrin	Chemical compounds	hMSC	--	Aging	Prevent	SA-β-gal activity assay	SA-β-galactosidase staining revealed that lactoferrin suppressed the hydrogen peroxide-induced senescence of hMSCs.Lactoferrin suppressed the hydrogen peroxide-induced cell death of hMSCs in a dose-dependent manner.	--	--	--	--	Akt	Activation	Western blot//Fluorescence microscopy	"Our results showed that pretreatment with lactoferrin increased the hydrogen peroxide-induced phosphorylation of Akt compared with only hydrogen peroxide treatment. In addition, treatment of PI3K/Akt inhibitor, Wortmannin decreased the lactoferrin-induced inhibition of ROS generation or cell survival in  hydrogen peroxide-treated hMSCs."	L	apoptosis	28870012
Sen_E_313	Indoxyl sulfate	Chemical compounds	HUVEC	--	Chronic kidney disease	Accelerate	SA-β-gal activity assay	"IS significantly increased the percentage of SA β-gal-positive cells, as scored by counting the numbers of blue and total cells, compared to that observed in the control cells at 24 hours."	--	--	--	--	AhR	Activation	SA-β-gal activity assay//HDAC colorimetric assay//Immunoblotting	"Pretreatment with ANF (10 μmol/L) or CH223191 (10 μmol/L)39), AhR inhibitors, for one hour rescued the IS-induced cellular senescence in the HUVECs."	L	cellular senescence	24727683
Sen_E_314	Kynurenine	Chemical compounds	B-MSC	--	Osteoporosis	Accelerate	SA-β-gal activity assay//Western blot	"In the present study, we tested the idea that kynurenine induces the cell-function inhibitor and antiproliferation process of senescence in BMSCs.Treatment of BMSCs with KYN for 24hr significantly increased SA-β-galactosidase activity,a hallmark of senescence.Additionally, the expression levels of the Cyclin D kinase (CDK) inhibitor,p21 was significantly elevated under kynurenine treatment while the level of another CDK inhibitor, p16 remained unchanged.These data suggest that treatment with KYN promotes senescence in BMSCs."	--	--	--	--	AhR	Upregulation	SA-β-gal activity assay//Western blot	"Treatment of BMSCs with different doses of kynurenine resulted in elevated immunofluorescent AhR nuclear staining.inhibition of AhR by CH-223191 and 3’4’-DMF,also affected senescence. CH-223191 treatment prevented the increase of kynurenine-induced SA-beta-galactosidase activity.Treatment of BMSCs with 3’4’-DMF inhibited kynurenine-induced overexpression of senescence marker, p21. Additionally, AhR inhibition by DMF prevented the formation of senescence-associated chromatin foci. Together,these data support that KYN upregulates senescence and suppresses autophagy in BMSC through the AhR pathway."	L	delay aging	31812582
Sen_E_315	Palbociclib	Chemical compounds	"SW 13 ,NCI-H295R"	--	Adrenocortical carcinomas	Accelerate	SA-β-gal activity assay//Flow cytometry	"In SW-13 cells, 1 and 5 μM of both inhibitors induced cell cycle arrest, with a smaller proportion of cells in the S phase and an increased proportion of cells in the G1 and G2 phases, when compared with mock-treated cells.The cycle of NCI-H295R cells was also affected by drug treatments. 10 μM Palbociclib increased the proportion of cells in G2 phase, whereas 10 μM ribociclib increased the proportion of cells in S phase.In SW-13 cells treated with palbociclib or ribociclib, we observed a significant increase in the percentage of cells harboring β-galacto-sidase activity, an indicator of senescence."	Phospho-Rb	Downregulation	Western blot	"In SW-13 cells, the amount of both CDK4 and CDK6 proteins increased after treatment with palbociclib or ribociclib. Such treatments also significantly lowered the amounts of both Phospho-Rb and pRB."	--	--	--	--	HL	apoptosis	29283884
Sen_E_316	Ribociclib	Chemical compounds	"SW 13 ,NCI-H295R"	--	Adrenocortical carcinomas	Accelerate	SA-β-gal activity assay//Flow cytometry	"In SW-13 cells, 1 and 5 μM of both inhibitors induced cell cycle arrest, with a smaller proportion of cells in the S phase and an increased proportion of cells in the G1 and G2 phases, when compared with mock-treated cells. The cycle of NCI-H295R cells was also affected by drug treatments. 10 μM Palbociclib increased the proportion of cells in G2 phase, whereas 10 μM ribociclib increased the proportion of cells in S phase.In SW-13 cells treated with palbociclib or ribociclib, we observed a significant increase in the percentage of cells harboring β-galacto-sidase activity, an indicator of senescence."	Phospho-Rb	Downregulation	Western blot	"In SW-13 cells, the amount of both CDK4 and CDK6 proteins increased after treatment with palbociclib or ribociclib. Such treatments also significantly lowered the amounts of both Phospho-Rb and pRB."	--	--	--	--	HL	apoptosis	29283884
Sen_E_317	TPA	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay//Western blot//Immunostaining//Cell Cell proliferation assay	"Nuclear translocation of pErk1/2 by TPA treatment was accompanied with significant reductions of senescence markers in HDF old cells; over 10% decrease of SA-β-gal activity, and 50% decrease of p53 and p21WAF1expressions. Furthermore, treatment of old cells with TPA significantly reduced senescence markers such as PML body formation, and expressions of 53BP1 and H3K9me2,as opposed to no response in young cells;Treatment of HDF mid-old cells with TPA exhibited much more significant cell proliferation than that of the DMSO treated cells."	PERK1/2	--	Immunocytochemistry	TPA co-treatment further increased the effect of siPEA-15 transfection compared with other treatments.	--	--	--	--	L	cellular senescence	25725291
Sen_E_318	Adriamycin	Chemical compounds	MEF	--	Aging	Accelerate	SA-β-gal activity assay	Adr but not Etop induced cellular senescence .	PERK//p53//RKIP	Downregulation//Upregulation//Upregulation	Western blot	"As the A549 cell line is p16/p14 negative, these results suggested that Adr induced cellular senescence in a p16/Rb-independent manner. In contrast to reduction of p-ERK and increase of SA-β-Gal positive cells in response to Adrin p53-positive cell lines, p53-null cells (HCT116 p53 -/- ) did not show the reduction of p-ERK and senescence.However, reconstruction of p53 in HCT 116 p53-/-cells by transfection of wild-type p53 could restore the Adr-induced senescence. As we expected, Adr treatment induced the RKIP expression along with suppression of p-ERK . Previously, we showed that reduction of p-ERK showed the dependence with p53, and RKIP was induced by Adr."	--	--	--	--	L	cellular senescence	23814485
Sen_E_319	H2O2	Chemical compounds	"HDF,IMR-90"	--	Aging	Accelerate	SA-β-gal activity assay//BrdU assay//Cell morphological analysis//Flow cytometry	"Consistent with previous reports, normal cells (HDFs and IMR-90) G1 arrest with no change in BrdU-positive cell number after H2O2 treatment. At 5 days after H2O2 exposure, HDFs showed senescent-like morphology, including flattened, irregular shape and enlarged size, as well as senescence associated (SA)-β-galactosidase activity."	PCNA	Downregulation	BrdU assay//Western blot//Flow cytometry	"We further examined whether the PCNA protein levels were changed after treatment of HDFs and IMR-90 cells with sublethal concentrations of H2O2. PCNA levels were decreased at 30 min, reached lowest levels at 1 h, and returned to normal levels at 2 h after H2O2 exposure,consistent with both cell types. This result suggests that transient PCNA downregulation cause cell cycle arrest and inhibition of DNA synthesis in normal cells."	--	--	--	--	L	delay aging	22819841
Sen_E_320	H2O2	Chemical compounds	TIG-3	--	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay	"To confirm the features of senescence, cell cycle distribution was analyzed in H2 O2 treated TIG-3 cells. As compared to control cells, 150 M H2O2 increased the population of G1 phase cells from 52.9 0.52% to 69.0 1.23% and decreased the population of S phase cells from 32.7 0.29% to 15.4 3.04% at 24h after treatment. These results suggest that 150 M H2 O2 inhibited cell cycle progression at the G1 phase.48h after the addition of H2O2,79.4 12.2% of treated cells were SA-β-gal positive,whereas 1.7±1.2% of control cells were SA-β-gal positive ."	PARP//SIRT1//p53	--//--//--	Measurement of intracellular NAD+ level//SDS-PAGE//Western blot	"The depletion of intracellular NAD+ levels induced by 150 μM H2O2 treatment was significantly inhibited by the addition of ANI, a PARP inhibitor. The expression of acetylated p53 increased by 4h and continued to increase for up to 24h, while p53 expression increased up to 12h. The expression of p21, which is a transcriptional target of p53, was increased at 12h and continued to increase for up to 24h. On the other hand, p53 acetylation was increased by the addition of nicotinamide, a SIRT1 inhibitor."	--	--	--	--	L	cellular senescence	17595514
Sen_E_321	Cigarette smoke	Other	"SAEC,fibroblast"	Lung	Chronic obstructive pulmonary disease	Accelerate	SA-β-gal activity assay//Flow cytometry//Immunofluorescence	"A time-dependent increase in cellular senescence was observed in HFL1 and mouse primary lung fibroblasts, which was characterized by increased SA-β-gal activity. Using a fluorogenic senescence marker (C12FDG), we quantified the degree of cellular senescence by flow cytometry, which showed an increase in cellular senescence by CSE.Our results show increased p16 and p21 levels, as well as DNA damage, measured in terms of g-H2AX foci formation [catalog number Ab2893 (Abcam) and catalog number 05-636 (EMD Millipore, Billerica, MA, USA)] in CSE-treated HFL1 cells, which confirmed the establishment of cellular senescence in an in vitro model."	Parkin	--	Immunofluorescence	"However, Parkin (catalog number 2132S; Cell Signaling Technology) mitochondrial translocation was highly impaired in HFL1 cells by CSE ."	--	--	--	--	L	cellular senescence	25792665
Sen_E_322	UVB	Other	HDF	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry//PI staining//Annexin V binding assay	"This was termed senescence-associated betagalactosidase or SA-β-gal. Our study revealed strong activity of SA-β-gal in UVB-irradiated HDFs, which, as one of the biomarkers of senescence, indicated that cells were induced to a senescencelike state by UVB exposure. As shown by PI staining and the annexin V method, we found UVB irradiation caused cell cycle arrest, with most HDFs being arrested on G0/G1 phase, and it might play a key role in aging process by initiating cell aging."	p66Shc//FKHRL1	Upregulation//Upregulation	Western blot//qRT-PCR	p66Shc and FKHRL1 were significantly up-regulated by UVB irradiation.	--	--	--	--	L	apoptosis	20211546
Sen_E_323	OX-LDL	Chemical compounds	HUVEC	Umbilical cord	Cardiovascular disease	Accelerate	SA-β-gal activity assay//Western blot//CCK-8 assay	"Continuous exposure to 80 μg/ml ox-LDL for 24 h decreased the proliferation of HUVECs, up-regulated the expression of PAI-1 and P21, increased the ratio of cells in G0/G1 phase and positive cells of SA-β-gal staining compared with the control group."	p62//SIRT1	Upregulation//Downregulation	Western blot	"Ox-LDL also decreased the ratio of LC3 II/LC3 I, increased the protein level of p62 and decreased the expression of SIRT1 in a dose-dependent manner."	--	--	--	--	L	delay aging	31658172
Sen_E_324	Doxorubicin	Chemical compounds	NCI-H292	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"Flow cytometry：Flow cytometric examination of the cell cycle distribution of NCI-H292 cells showed a significant increase of cells with DNA content corresponding to G2/M at 80 nM of doxorubicin compared to the control and 20 nM (p<0.05), whereas the cells with DNA content corresponding to G0/G1 concurrently decreased (p<0.05). SA-β-gal activity assay：The number of β-gal-positive senescent cells was markedly increased in doxorubicin treated by comparison with untreated NCI-H292 cultures."	p53//γH2AX//p21	Upregulation//Activation//Upregulation	Western blot	"In order to determine the effect of doxorubicin on p53 protein levels western blotting analysis was performed.Doxorubicin at of 20, 40 and 80 nM induced a significant increase of p53 protein levels to 1.7 fold compared to the untreated condition (p<0.01).  By using a specific antibody directed against phosphorylated H2AX, we observed that 40 and 80 nM doxorubicin promoted a significant phosphorylation of H2AX at the Ser139 residue (γH2AX) compared to 20 nM and UT, favoring its activation. Data reported, panels C-E also demonstrated that the increase of p53 was accompanied by a significant up-elevation of p21 at 80 nM doxorubicin compared to all other conditions (p<0.001). Moreover, p21 protein levels were significantly higher at 40 nM doxorubicin compared to UT and 20 nM (p<0.001)."	--	--	--	--	L	cellular senescence	27836734
Sen_E_325	KR12	Chemical compounds	LS180	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"After 48?h of 50?nM KR12 treatment, a flat cell morphology was displayed in LS180 cells, and SA-β-gal activity was strongly increased compared with DMSO- or #6-treated cells, suggesting that KR12 induced cellular senescence.Cell cycle arrest is a critical process in cellular senescence that is induced by the CDK inhibitor p21WAF1/CIP1 (ref. 17), and 48-h KR12 exposure significantly increased the proportion of G2/M-phase cells.Increased compared with DMSO- or #6-treated cells, suggesting that KR12 induced cellular senescence."	p53//γH2AX	--//--	Western blot	"KR12 markedly induced phosphorylation of p53 at Ser-15, p21WAF1/CIP1 and phosphorylated histone variant H2AX (γH2AX), whereas KR12-mediated cleavage of PARP at the 48-h time point was not observed . Phospho-p53 (Ser-15) and γH2AX inductions in KR12-treated cells were also visually confirmed by indirect immunofluorescence staining."	--	--	--	--	L	apoptosis	25913614
Sen_E_326	Vildagliptin	Chemical compounds	Human primary Chondrocyte	--	Osteoarthritis	Prevent	SA-β-gal activity assay	"When vildagliptin was included in the experiment, it showed a strong suppression of SAβ-Gal activity, with an SA-β-Gal reading of about 17,000 Fu/mg."	p53//SIRT1//AMPK	--//--//--	Western blot//IP	"Compared to the nontreated chondrocytes, TNF-α induced an average of roughly 3.2-fold higher K382 acetylation of p53. The same TNF-α treatment only induced roughly 2.4- and 1.6-fold higher p53 K382 acetylation in the presence of 5 and 10 μM vildagliptin, respectively.Compared to nontreated chondrocytes, TNF-α caused a 75% reduction in SIRT1 protein expression. However, TNF-α only caused a 65% and 40% reduction in SIRT1 when 5 and 10 μM concentrations of vildagliptin were present in the media, respectively.  Compared to nontreated cells, the total AMPK level remained the same, but TNF-α caused a roughly 75% reduction in p-AMPK. However, the same TNF-α treatment only caused roughly 50% and 25% reductions in p-AMPK in the presence of two doses of vildagliptin, respectively."	--	--	--	--	L	cellular senescence	31026379
Sen_E_327	Cigarette smoke extract	Other	BEAS-2B	Lung	Aging	Accelerate	SA-β-gal activity assay	"Furthermore, we performed histochemical analysis of senescence associated-β-galactosidase (SA-β-gal) activity and found that Beas2b cells exposed to 10%-CSE exhibited significant (p<0.001) increase in SA-β-gal-positive (blue) cells in comparison to air-exposed or cysteamine-treated cells."	p53//SIRT1	Downregulation//Downregulation	Western blot	We observed a decrease in p53 in soluble protein fractions of 10%-CSE treated cells that is indicative of a reduction in DNA damage recognition and repair. Abrogation of Sirt1 was observed in the soluble protein fractions prepared from Beas2b cells upon exposure to 10% CSE in comparison to air-exposed cells; the loss of Sirt1 is indicative of cell cycle arrest and cellular senescence.	--	--	--	--	L	cellular senescence	27413169
Sen_E_328	Aldosterone	Chemical compounds	HPTC	Kidney	Aging	Accelerate	SA-β-gal activity assay	"An increase in SA-β Gal staining, which is typically observed in senescent cells, was detected in the kidney, particularly the proximal tubules, of aldosterone-infused rats,but not in vehicle-infused rats. Aldosterone (1 and 10 nmol/liter for 3 d)dose-dependently increased the percentage of SA-β Gal–expressing HPTCs compared with vehicle treatment in both TSIm-HPTCs and N-HPTCs ."	p53//p21//SIRT1	Upregulation//Upregulation//Downregulation	RT-PCR//Western blot	"Aldosterone infusion markedly increased the expression of p53 mRNA and protein.Aldosterone strongly increased the expression of p21 mRNA and protein.On the other hand, the gene expression of SIRT1, an enzyme that inactivates p53 by deacetylation, was reduced in aldoste-rone-infused rats compared with that in vehicle-infused rats."	--	--	--	--	L	cellular senescence	21190955
Sen_E_329	Cisplatin	Chemical compounds	NRK	--	Chronic kidney disease	Accelerate	Cell morphological analysis//SA-β-gal activity assay//Flow cytometry//BrdU assay	"NRK cells became enlarged and flattened morphologically. Positive staining for SA-β-Gal was observed at 24 h and increased to 15% at 48 h and 22% at 72 h.Another marker of senescence, C12FDG was also positive in cisplatin-treated cells and most obvious in 20 μM group. Cell cycle analysis showed that 20 μM cisplatin resulted in a marked increase in the percentage of cells in S phase. EdU was detected in cisplatin treated renal tubular cells. There were fewer EdU-positive cells in cisplatin-treated renal tubular cells compared with control group."	p53//p21//SIRT1	Upregulation//Upregulation//Downregulation	Western blot	"The p53 and p21 proteins, which are senescence modulators, were upregulated at 48 h after cisplatin treatment .Assessment of SIRT1 levels showed that cisplatin treatment downregulated SIRT1 at the protein level in NRK cells."	--	--	--	--	L	cellular senescence	30447351
Sen_E_330	Methoxyamine	Chemical compounds	RKO	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Examined senescence-activated β-gal activity following these treatments. Senescence-activated β-gal activity was examined on days 5 to 8 following ionizing radiation and was found to be positive in IUdR- and IUdR/methoxyamine–pretreated cells. Spot senescence-activated β-gal positive cells were also found in the control and methoxyamine-pretreated cells;During the course of the experiments, we noted that after ionizing radiation, IUdR- and IUdR/methoxyamine–pretreated cells exhibited senescence-like morphologic features ."	p53//p21//Rb	Upregulation//Upregulation//Activation	Western blot	"Indeed, both accumulation of p53 and induction of p21, the major mediator of p53-dependent senescence, increase more significantly in IUdR/methoxyamine–pretreated cells at both early and later times following ionizing radiation. Furthermore, IUdR/methoxyamine–pretreated cells show reduced hyperphosphorylated Rb(S780) (inActivate form) but greater hypophosphorylated Rb (Activate form) compared with IUdR-pretreated cells ."	--	--	--	--	L	apoptosis	16648559
Sen_E_331	TC-G 1008	Chemical compounds	"SW 13 53,Caco-2"	--	Osteoarthritis	Prevent	SA-β-gal activity assay//Flow cytometry	SA-β-gal activity assay:The specific GPR39 agonist TC-G 1008 ameliorates IL-1β-induced SA-βgal activity.Flow cytometry:The specific GPR39 agonist TC-G 1008 reduces IL-1b-induced cell cycle arrest in the G1 phase.	p53//p21//PAI-1	Downregulation//Downregulation//Downregulation	RT-PCR//Western blot	"RT-PCR//Western blot:The specific GPR39 agonist TC-G 1008 attenuates the expression of p53, p21, and PAI-1 induced by IL-1b in human primary chondrocytes."	--	--	--	--	L	cellular senescence	31237151
Sen_E_332	Resveratrol	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//BrdU assay//Cell morphological analysis	"30 M RV slowed down proliferation until cells finally came to a complete growth stop after 30 40 days of treatment. Cells that were growtharrested for at least 10 days were stained for SA-gal expression and showed up to 60% positive staining, indicating that 30 M RV induces a senescent phenotype in HCT 116 colon carcinoma cells. RV (30 M)-treated cells displayed a flattened and enlarged morphology and an abrogated bromodeoxyuridine-labeling index ( 5%)."	p53//p21//p38MAPK//ATM	--//--//--//Activation	SA-β-gal activity assay//Western blot//Knockdown	"However, staining for SA-β-gal expression revealed a significantly lower percentage of positive cells in the knock-out lines. For unknown reasons, the p53 clones of the HCT line displayed an overall weaker expression of SA-β-gal (up to 60% positive cells in p21WTversus up to 25% cells in p53 WT cells after the same RV treatment protocol).Furthermore, the growth arrest in p53 and p21 knock-out cells was reversible after withdrawal of RV, whereas halted WT cells were not able to resume proliferation upon RV removal. In accordance with the elevated ROS levels, the redox-sensitive protein kinase MAPK-p38 was found to be significantly.We could demonstrate that both inhibitors overcame RVtriggered p53 phosphorylation (Ser-15) and p21 induction. Moreover, long term incubation with RV and KU55993 was able to significantly lower the number of senescent (SA-gal-positive) cells when compared with RV alone. hyperphosphorylated 24 h after treatment with RV without changes in its total levels."	--	--	--	--	L	delay aging	17626009
Sen_E_333	Curcumin	Chemical compounds	"MCF-7,U2OS"	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	We tested the influence of this compound in human breast cancer MCF 7 cell line and human osteosrcoma U2OS cell line. Both cell lines underwent cellular senescence as revealed by increased activity of SA-β-gal as well as the induction of the p53 and p21 proteins detected in Western blot analysis.	p53//p21	Upregulation//Upregulation	Western blot	Induction of cellular senescence was further confirmed by examination of the protein level. We detected an increased level of the p53 (only in HCT116 p53+/+ cells) and p21 proteins.	--	--	--	--	L	cellular senescence	22613224
Sen_E_334	H2O2	Chemical compounds	ADSC	--	Aging	Accelerate	Immunostaining//SA-β-gal activity assay	"We found that the number of Ki-67 positive cells was dramatically decreased after H2O2 induction, indicating a significant decrease in the proliferation rate;The cells were treated with 100 μM H2O2 for 2 h and SA-β-gal staining was performed. It was noted that, following H2O2-induced senescence, the percentage of SA-β-gal positive cells increased significantly."	p53//p21	Upregulation//Upregulation	Semi-qPCR//qPCR	Cell cycle marker genes such as p21 and p53 were initially upregulated post H2O2 treatment.	--	--	--	--	L	cellular senescence	25654692
Sen_E_335	Pigment epithelium-derived factor	Other	MSC	--	Aging	Prevent	SA-β-gal activity assay	"Most of the normoxic cultured-cells were positive for SA-β-gal after ceasing to proliferate,whereas few were stained in the other culture at the same time, which was a highly significant difference."	p53//p16	Downregulation//Downregulation	Western blot	"Consistent with previous findings, the levels of p53 and p16 increased with the lifespan of normoxic cultured-MSCs. In contrast, PEDF lowered the overall transcript level and protein expression of p53 and p16 by Day 95."	--	--	--	--	L	cellular senescence	23359450
Sen_E_336	Scopoletin	Chemical compounds	IMR-90	--	Aging	Prevent	MTT assay//SA-β-gal activity assay	"The effect of scopoletin on the viability of IMR 90 cells were measured using MTT assay.Scopoletin at 16μM or below did not show cytotoxicity.Representative images of SA-β-Gal staining in control group (H2O2 treatment). The number of SA-β-gal positive cells in control groups was increased in a dose dependent manner.The quantification of SA-β-Gal staining level. While SA-β-Gal staining was increased with the concentration of hydrogen peroxide, scopoletin significantly inhibited the SA-β-Gal staining stimulated by hydrogen peroxide in IMR 90 cells."	p53//NF-κB//Nrf2//p-FOXO1	Activation//Downregulation//Upregulation//Upregulation	Western blot	"Scopoletin treatment significantly increased the expression level of p53. However, the levels of p-p53 and acetyl-p53, Activate forms of p53, expressions were decreased in the presence of scopoletin compared with blank group. Furthermore,the expression level of p21 having the DNA binding site of p53 in its promoter was decreased in similar to the expression pattern of Activate p53. These results indicate that scopoletin promotes activation of p53 in human lung fibroblast.It was found that the protein expression levels of p50 and p65, a dimer of NF-κB associated with inflammation, were reduced compared with blank group. In contrast, the expression levels of Nrf-2 and p-FoxO1 modulating the expression of superoxide dismutase in nucleus were enhanced in the presence of scopoletin compared with blank group in IMR 90 cells."	--	--	--	--	L	delay aging	25837273
Sen_E_337	Nutlin-3a	Chemical compounds	"Fibroblast,GM08402,NHF-hTERT,IMR-90,MRC-5"	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"A high percentage of cells that had been treated with nutlin-3a were stained positive for the low pH β-gal,indicating cells had undergone senescence.All three cell strains showed a morphologically senescent phenotype after nutlin-3a treatment. Again, almost 100% of the cells showed positive staining."	p53//miR-34a//miR-34b//miR-34//ING2	Activation//Upregulation//Upregulation//Upregulation//Downregulation	RT-PCR//qRT-PCR//Western blot	"In NHF-hTERT cells, the total amount of p53 expression was increased by nutlin-3a. In contrast, there was no increase of p53 expression with nutlin-3a treatment in the p53 null cells.mir34a, mir34b, and mir34c levels were shown to be up-regulated to varying amounts in various human tumor cell lines that were wild type for p53 after treatment with nutlin-3a after 24 hours. Interestingly, ING2 expression in the cells treated with nutlin-3a was remarkably decreased compared with nontreated cells while ING2 expression was not changed in nutlin-3b–treated cells.ING2 mRNA transcripts were consistently decreased by nutlin-3a treatment in all cell lines using a real-time PCR method."	--	--	--	--	HL	cellular senescence	18451145
Sen_E_338	Nutlin-3	Chemical compounds	"ACHN,Caki-2,RCC"	--	Renal carcinoma	Accelerate	SA-β-gal activity assay//Flow cytometry	"The observed inhibition of proliferation in p53 wild-type cells is due to a reduction in S-phase, indicated by measuring BrdU incorporation. This is indicative of G1 arrest, as expected for cells in which p53 activity has been rescued through inhibition of MDM2 binding with Nutlin-3 [26]. It is noteworthy that we have not observed evidence of apoptosis in RCC cells treated with Nutlin-3. This observation accords with recent studies demonstrating that Nutlin-3 can induce cell cycle arrest in RCC cells [27].We therefore examined senescence in RCC cells exposed to Nutlin-3 , a significant increase in senescence in cells expressing wild-type, but not mutant p53, as indicated by measurements of senescence-associated (SA) β-galactosidase, was detected."	p53//MDM2//p21	Upregulation//Upregulation//Upregulation	Western blot	"Treatment of RCC cells with Nutlin-3 leads to increased expression of p53 and some p53 target genes: MDM2, and p21 (CDKN1A)."	--	--	--	--	L	apoptosis	25067787
Sen_E_339	Nutlin-3	Chemical compounds	CADO-ES-1	--	Sarcoma	Accelerate	SA-β-gal activity assay	"After a 4-d exposure to nutlin-3 at a dose (2 lM) that had hardly exerted any apoptosis-inducing effect, CADO-ES-1 cells were stained for SA-β-Gal activity, the most widely used marker for cellular senescence. Nutlin-3-treated cells showed clear signs of senescence, whereas untreated cells did not."	p53	Activation	Western blot//qRT-PCR	"Immunoblot detection revealed a rise of p53 after nutlin-3 exposure in the ES cell lines with wt-p53.To confirm the p53-activating effect of nutlin-3, we determined the gene expression of three key transcriptional targets of p5326 MDM2, p21 and PUMA by real-time RT-PCR.Nutlin-3 induced concentration-dependent increases in mRNA levels in all three cases in the wt-p53 cell lines, but not in the mt-p53 one."	--	--	--	--	L	cellular senescence	21334198
Sen_E_340	low-Dox	Chemical compounds	WI-38	--	Aging	Accelerate	Cell morphological analysis	"At concentrations of 100 ng/ml, doxorubicin (low-Dox) caused senescent morphology, whereas 500 ng/ml of doxorubicin (high-DOX) caused slim cell morphology."	p53	Upregulation	Western blot	"At concentrations that caused senescence (100 ng/ml), DOX induced low levels of p53 and did not inhibit S6 phosphorylation, a marker of mTOR activity."	--	--	--	--	L	delay aging	21051933
Sen_E_341	PTP	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"SA β-galactosidase-stained HCT116 cells increased by 4.3- and 6.7-fold after treatment with 5 and 10 μM PTP, respectively, for 6 days. The cell cycle analysis revealed that HCT116 cells were arrested at the G1 phase of the cell cycle after 24 h of exposure to 10 μM PTP."	p53	Upregulation	Western blot	Treatment with 10 M PTP increased the p53 protein level in a time-dependent manner in HCT116 cells expressing wild-type p53.	--	--	--	--	L	apoptosis	25338966
Sen_E_342	Doxorubicin	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Knockdown	Doxorubicin induced senescence in a largely p53-dependent manner in HCT116 cells; significantly more senescent cells were observed in HCT116 p53+/+ cells treated with Doxorubicin compared with HCT116 p53?/? cells treated with Doxorubincin .	p53	--	SA-β-gal activity assay//Knockdown	Doxorubicin induced senescence in a largely p53-dependent manner in HCT116 cells; significantly more senescent cells were observed in HCT116 p53+/+ cells treated with Doxorubicin compared with HCT116 p53?/? cells treated with Doxorubincin .	--	--	--	--	HL	apoptosis	26840028
Sen_E_343	ABT-263	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//qRT-PCR	"In the present study, we found that the metformin/ABT-263 cotreatment induced an obvious cellular senescence in HCT-116 p53+/+ cells, whereas the cotreatment only slightly evoked the cellular senescence in HCT-116 p53?/? cells.In the present study, we found that the metformin/ABT-263 cotreatment induced an obvious cellular senescence in HCT-116 p53+/+ cells, whereas the cotreatment only slightly evoked the cellular senescence in HCT-116 p53?/? cells.ABT-263 significantly increased most of them, which was augmented by metformin in HCT-116 p53+/+ cells. However, these SASP components were unchanged or just mildly increased upon metformin/ABT-263 cotreatment in HCT-116 p53?/? cells."	p53	--	SA-β-gal activity assay	"We found that the metformin/ABT-263 cotreatment induced an obvious cellular senescence in HCT-116 p53+/+ cells, whereas the cotreatment only slightly evoked the cellular senescence in HCT-116 p53?/? cells."	--	--	--	--	L	apoptosis	28533436
Sen_E_344	Metformin	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//qRT-PCR	"In the present study, we found that the metformin/ABT-263 cotreatment induced an obvious cellular senescence in HCT-116 p53+/+ cells, whereas the cotreatment only slightly evoked the cellular senescence in HCT-116 p53?/? cells.In the present study, we found that the metformin/ABT-263 cotreatment induced an obvious cellular senescence in HCT-116 p53+/+ cells, whereas the cotreatment only slightly evoked the cellular senescence in HCT-116 p53?/? cells.ABT-263 significantly increased most of them, which was augmented by metformin in HCT-116 p53+/+ cells. However, these SASP components were unchanged or just mildly increased upon metformin/ABT-263 cotreatment in HCT-116 p53?/? cells."	p53	--	SA-β-gal activity assay	"We found that the metformin/ABT-263 cotreatment induced an obvious cellular senescence in HCT-116 p53+/+ cells, whereas the cotreatment only slightly evoked the cellular senescence in HCT-116 p53?/? cells."	--	--	--	--	L	apoptosis	28533436
Sen_E_345	Formaldehyde	Chemical compounds	IMR-90	--	Aging	Accelerate	SA-β-gal activity assay//EdU assay//Western blot	"We found that the ability of FA-treated IMR90 cells to enter into stable replication arrest, and senescence was completely dependent on p53."	p53	Upregulation	Western blot	"Stress-responsive phosphorylation of p53 at Ser15 was already detectable after a 30-min-long FA treatment and increased further at longer 1–3 h exposures . Ser15 phosphorylation and p53 protein levels continued to increase for several hours after FA removal. At 6 h post-exposure, a strong phosphorylation at Ser15 was observed with as low as 50 μM FA, which is within its physiological concentration range in human serum.22."	--	--	--	--	L	apoptosis	22722496
Sen_E_346	Irradiation	Other	"LNCaP,22Rv1"	--	Prostate cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"In contrast, an equivalent dose of IR (4 Gy) induced SA-β-gal expression in approximately 75% of the LNCaP cells and 50% of the 22Rv1 cells.increased the proportion of senescent cells 5 days after IR."	p53	Upregulation	Western blot	"IR (6 Gy) was sufficient to induce a rapid (<30 min) and sustained (>180 min) phosphorylation of p53 (at Ser15) by kinases such as ATM .In contrast, both the accumulation of p53 protein and transactivation of its downstream target, p21, were consistently delayed and more persistent in 22Rv1 cells."	--	--	--	--	L	apoptosis	17351335
Sen_E_347	Simvastatin	Chemical compounds	--	Embryo	Aging	Prevent	SA-β-gal activity assay//Histological staining//Multiplex cytokine assay	"Cotreatment of tissues with both simvastatin and rosuvastatin reduced the number of SA- β- Gal staining cells to that seen in controls, suggesting that a reduction in p38MAPK activation decreased senescence .Cotreatment of fetal membranes with CSE + S100 and CSE + S200 led to lower levels of GM- CSF and TNF- α."	p38MAPK	Downregulation	Western blot	"Cotreatment of CSE with  simvastatin  (CSE  155 ± 10.17,  CSE + S100 = 108.9 ± 32.54, CSE + S200 = 76.79 ± 14.13,  all  P < .05)  and  rosuvastatin (CSE = 155 ± 10.17,  CSE + R100 = 88.29 ± 9.177,  CSE + R200 = 85.49 ± 5.77, all P < .05) significantly decreased p38MAPK activation compared to CSE."	--	--	--	--	L	delay aging	29911323
Sen_E_348	Rosuvastatin	Chemical compounds	--	Embryo	Aging	Prevent	SA-β-gal activity assay//Histological staining //Multiplex cytokine assay	"Cotreatment of tissues with both simvastatin and rosuvastatin reduced the number of SA-β- Gal staining cells to that seen in controls, suggesting that a reduction in p38MAPK activation decreased senescence.Cotreatments of fetal membranes with rosuvastatin had more impact on fetal membrane SASP markers levels. There was a reduction in levels of GM- CSF and TNF- α."	p38MAPK	Downregulation	Western blot	"Cotreatment of CSE with  simvastatin  (CSE  155 ± 10.17,  CSE + S100 = 108.9 ± 32.54, CSE + S200 = 76.79 ± 14.13,  all  P < .05)  and  rosuvastatin (CSE = 155 ± 10.17,  CSE + R100 = 88.29 ± 9.177,  CSE + R200 = 85.49 ± 5.77, all P < .05) significantly decreased p38MAPK activation compared to CSE ."	--	--	--	--	L	delay aging	29911323
Sen_E_349	5‐FU	Chemical compounds	EA.hy926	--	Aging	Accelerate	SA-β-gal activity assay//BrdU assay//Cell morphological analysis//DAPI staining	"Short‐term exposure to 5FU caused profound alterations in EA.hy926 cells, overall indicating senescence. Positivity for SA β‐gal and p16INK4a significantly increased , whilst proliferation was inhibited . Morphologically, 5FU‐treated cells displayed an enlarged, flattened cytoplasm with a ‘fried egg’ appearance . These phenotypic changes were associated with the up‐regulation of the genes encoding VCAM‐1 and – although not to a significant extent – ICAM‐1, consistent with earlier evidence of a dysfunctional activation of endothelial cells undergoing senescence ."	p38//JNK//eNOS//SIRT1	--//--//Downregulation//Downregulation	SA-β-gal activity assay//Western blot//Densitometry analysis	"Induction of senescence by 5FU, as assessed by staining for SA β‐gal, was significantly reduced by inhibiting p38 and JNK, suggesting the involvement of these kinases. Compared with control, 5FU decreased the expression of both eNOS and SIRT1."	--	--	--	--	L	delay aging	28127745
Sen_E_350	LGX818	Chemical compounds	"A375,G-361,SK-MEL-24"	--	Melanoma	Accelerate	SA-β-gal activity assay//BrdU assay	"A time-dependent increase in β-gal staining was noted in cells treated with 10 nM LGX818 for periods of up to 72 h compared with vehicle-treated (non-treated) cells. Consistently, LGX818 treatment led to a significant decrease in the percentage of BrdU-positive cells. Elevated SA-β-gal activity and reduced BrdU incorporation were also observed in LGX818-treated SK-MEL-24 cells."	p27//pRb	Upregulation//Activation	Western blot	"Immunoblot analysis demonstrated that A375 and G361 cells exhibited increased levels of p27KIP1 (CDK-inhibitory protein 1) protein 24 h after LGX818 treatment.We observed a remarkable decrease in the phosphorylation of Rb in A375 cells following a 24 h treatment with LGX818 and, to a lesser extent, in LGX818-treated G361 cells."	--	--	--	--	L	cellular senescence	26586345
Sen_E_351	Rivaroxaban	Chemical compounds	HUVEC	--	Atherosclerosis	Prevent	SA-β-gal activity assay//Western blot//Flow cytometry	"Coincubation with XaI (rivaroxaban, 50 and 500 nM) significantly decreased SA-β-gal activity. Both 50 and 500 nM rivaroxaban significantly decreased p53 and p16 levels under HG conditions.Additionally,telomere length, an index of replicative senescence, was significantly shortened under HG for 30 days, and it was restored by coincubation with rivaroxaban."	p22phox//ICAM//VCAM1//PAR1	Downregulation//Downregulation//Downregulation//Downregulation	Western blot	"HG conditions also increased the expression of p22phox, and compared to HG-only conditions, exposure to rivaroxaban significantly restored p22phox expression.ICAM1 and VCAM1, adhesion molecules expressed on vascular endothelial cells, significantly increased under HG, and this increase was significantly reversed by rivaroxaban.PAR1 is involved in the inactivation of eNOS, which is increased under HG conditions and significantly suppressed by rivaroxaban."	--	--	--	--	L	delay aging	31266015
Sen_E_352	Oxidative stress	Other	MSC	--	Aging	Accelerate	SA-β-gal activity assay//Telomere length assay//Cell morphological analysis	Young MSCs incubated with sub-lethal doses of H2O2(100–150 μM) showed characteristic features of senescence concerning morphology and positive β-galactosidase staining . relative shortening referred to the original telomere length. Relative telomere loss was 2.91% per cpd (SD 0.43%) under chronic stress and 1.84% per cpd (SD 0.23%) in the control group.	p21//TRF1//TRF2//SIRT1//XRCC5	Upregulation//Downregulation//Upregulation//Upregulation//Upregulation	qRT-PCR	"In young MSCs, H2O2treatment caused a significant elevation in p21 expression after 1 h (2-fold of initial level) prior to a decrease to initial levels after 3 h. Significant p21 elevation up to a 4-fold rise could be detected in old MSCs 1 and 3 h after treatment.In young MSCs, TRF1 showed a significant decline in mRNA expression after 3, 6, 12 and 24 h. Senescent cells produced significantly less TRF1 after 6, 12 and 24 h. TRF2 expression in young and old cells was up-regulated significantly after 3 h and came down to initial ranks after 24 h。XRCC5 expression showed a slight increase in both groups witha maximum rise to the 1.5-fold in old cells. Oxidative stress caused a significant increase of SIRT1 gene expression after 1, 3, and 6 h in young MSCs. With a 2-fold increase maximum expression was found after 1 h and declined slowly to a level not significantly."	--	--	--	--	L	cellular senescence	21376036
Sen_E_353	MCF-7 mammospheres	Other	MCF-7	--	Breast cancer	Prevent	SA-β-gal activity assay	"Using the Telomeric Repeat Amplification Protocol to measure telomerase activity in monolayer and mammosphere cells, we observed that both cell types displayed telomerase activity, which increased after irradiation with 1 and 10 Gy. the telomerase activity in the mammospheres was statistically significantly more robust than in the monolayer population .and indeed analysis of senescence based on cellular β-galactosidase activity revealed that the percentage of senescent mammospheres is approximately half that of the monolayer population both prior to irradiation and three days after irradiation with 4 Gy."	p21//pRb	Downregulation//Downregulation	Western blot	"An examination of other key proteins involved in the regulation of senescence revealed that the mammosphere cells, in comparison to the monolayer cell population, expressed markedly lower levels of the senescence signaling protein, p21, especially in unirradiated cells. In the case of pRb there was a notable reduction in total protein following irradiation with 1 Gy and also a lower degree of phosphorylation after 10-Gy irradiation of the mammospheres."	--	--	--	--	L	apoptosis	20525204
Sen_E_354	Argentatin B	Chemical compounds	"HCT-15,PC-3"	--	Aging	Accelerate	SA-β-gal activity assay	"SA-β-gal activity assay:After incubation with argentatin B for 72 h, both cell lines exhibited phenotypic changes that resemble those observed in cells undergoing senescence, such as flattened morphology and enlarged cell size.When tested for senescence associated-β-galactosidase activity, a proportion of 43% HCT-15, and 66% PC-3 cells showed a positive staining, compared with 2% of untreated controls. These findings suggest that argentatin B inhibits cell proliferation by inducing senescence."	p21//p27	Upregulation//Upregulation	Western blot	"Treatment with argentatin B induced an increment of both, p21 and p27 in PC-3 cells after 48 h incubation, and it was persistent for at least 72 h after treatment."	--	--	--	--	L	cellular senescence	26633316
Sen_E_355	MLN4924	Chemical compounds	Lymphoma cell line	--	Lymphoma	Accelerate	PI staining//FACS analysis //Cell morphological analysis//SA-β-gal activity assay	"A prominent G2-M cell-cycle arrest was observed in all treated cell lines (Raji, U937,SU-DHL-4 and Toledo) in a dose-dependent manner；An increase in cell size with flattened shape, a characteristic of senescence, was observed in Raji and U937 cells;the expression of SA-β-gal was determined by SA-β-gal staining in MLN4924-treated cells，a substantial proportion of MLN4924-treated cells were positively stained."	p21//p27	--//--	Western blot	"MLN4924 significantly delayed p21/p27 turnover and extended the half-life of p21/p27 in both Raji and U937 cells.In contrast, MLN4924 had little effect on the transactivation of p21/p27 ."	--	--	--	--	HL	cellular senescence	25782162
Sen_E_356	Polyphenols of Artichoke(Cynara scolymus L.)Exerts	Other	"MDA-MB-231,ASC"	Adipose	Breast cancer	Accelerate	SA-β-gal activity assay//Western blot//Cell morphological analysis	"MDA-MB231 cells incubated without AEs showed no detectable SA-β-gal activity, whereas cells treated with 10 and 30?μM AEs revealed a marked X-gal staining in a dose-dependent manner after 10 days. Most of the SA-β-gal positive cells showed an enlarged and flattened morphology with increased volume and granularity that were consistent with cellular senescence status. Western blotting data demonstrated that the expression levels of p21Cip1/Waf1 and p16INK4a were significantly increased in a dose-depending manner in AEs-treated cells."	p21//p16	Upregulation//Upregulation	Western blot	Western blotting data demonstrated that the expression levels of p21Cip1/Waf1 and p16INK4a were significantly increased in a dose-depending manner in AEs-treated cells.	--	--	--	--	L	epigenetic alterations	26180585
Sen_E_357	PMA	Chemical compounds	SK-BR-3	--	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay	We found that PMA caused a large flat morphology with nucleoli enlargement and beta-Gal positivity .	p21//Cyclin D1	Activation//Activation	Western blot	PMA rapidly activated ERK1/2 followed by p21 and cyclin D1 induction.	--	--	--	--	L	delay aging	25587030
Sen_E_358	AMG 900+HDACI	Chemical compounds	PCA	--	Prostate cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Treated cells displayed a flattened morphology compared to untreated controls, and some treated DU-145 and PC3 cells showed cytoplasmic vacuoles and granularity.Consistent with our previously observed morphological transformations, DU-145 and PC3 cells treated with combinations of AMG 900 and HDACIs had increased SA β-galactosidase staining. LNCaP cells had a baseline level of blue SA β-galactosidase staining in untreated controls; combination treatment of LNCaP cells with AMG 900 and HDACIs resulted in increased SA β-galactosidase staining."	p21	Upregulation	Western blot	"Combination treatment further increased p21 levels, suggesting increased cellular senescence."	--	--	--	--	L	cellular senescence	24989836
Sen_E_359	Pioglitazone and Melatonin	Chemical compounds	MSC	--	Aging	Prevent	SA-β-gal activity assay	We investigated the inhibitory effects of pioglitazone and melatonin on MSC senescence induced by IS. The combination therapy of pioglitazone and melatonin significantly reduced IS-induced increase of SA-β-gal activity.	p21	Downregulation	Western blot	Pioglitazone?and?melatonin?ameliorated?the?IS‐induced?reduction?in?SMP30?expression?and?inhibited?the?increase in p21.	--	--	--	--	L	cellular senescence	29734669
Sen_E_360	RD	Chemical compounds	"PCa,DU 145"	--	Prostate cancer	Accelerate	Cell cycle analysis//qRT-PCR//ELISA//SA-β-gal activity assay	"After treatment with 0.5 μM RD, accumulation of cells with enlarged and flattened morphology was evident in PCa cells. The level of SASP mark IL-6 was found significantly increased in PCa cells after RD treatment by Elisa assay  and q-PCR assay . In agreement with a large morphology, increased SA-β-gal was also observed in response to RD . The SA-β-gal positive stained cells was significantly enhanced by LNCaP cells,DU145 cells, respectively, as compared to controls."	p21	--	SA-β-gal activity assay	"Deletion of p21CIP1 by targeting siRNA impaired RD-induced senescent (SA-β-Gal positive) cells in all three PCa cells.SA-summ staining was decreased 0.32±0.05-fold in LNCaP, 0.43±0.19-fold in PC3, and 0.31±0.03-fold in DU145 cells, respectively, indicating that RD-induced cellular senescence was, at least in part, in a p21CIP1-dependent manner."	--	--	--	--	L	cellular senescence	24322375
Sen_E_361	H2O2	Chemical compounds	HeLa	--	Cervical cancer	Accelerate	SA-β-gal activity assay	"C3 cells expressing hTERTC27 exhibited a significantly reduced growth rate after the H2O2 challenge compared to the control EGFP expressing A1 cells. Furthermore, at 7 days after H2O2 treatment, the C3 cells became enlarged and flattened, lost cell-to-cell contact, and stained positively forSA β-gal."	p21	Upregulation	Western blot	"Western blot analysis showed that in C3 cells, a sustained increase of p21Waf1 protein level was observed from day 1 to at least day 9."	--	--	--	--	L	cellular senescence	12565825
Sen_E_362	MLN4924	Chemical compounds	"HCT116,H1299,U87"	--	Cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Indeed, all three lines of cancer cells after MLN4924 treatment at 0.1 μM concentration demonstrated an enlarged and flattened shape, a reminiscence of senescence phenotype.SA-β-Gal staining showed that ～50% of HCT116 cells were stained positively compared with only ～1% cells with positive staining in the DMSO control group ."	P21	Upregulation	Western blot	"P21 was accumulated in a dose- and time-dependent manner in all three lines of cancer cells treated with MLN4924.P21, on accumulation by MLN4924, remained elevated in HCT116 cells or even continued to accumulate in H1299 cells after drug removal."	--	--	--	--	L	apoptosis	21677879
Sen_E_363	BI-D1870	Chemical compounds	"HCT116,MCF-7"	--	Cancer	Accelerate	SA-β-gal activity assay//Knockdown	"BI-D1870 almost completely prevented γIR-induced apoptosis of p53-deficient HCT116 cells and, similar to U0126, produced the senescent phenotype in both wild-type and p53-deficient cells regardless of whether or not they were irradiated. BI-D1870 also induced senescence in MCF-7/casp3 breast carcinoma cells, indicating a more general response to this compound ."	p21	Upregulation	Western blot	"Therefore, we analyzed p21 expression in BI-D1870-treated cells and found that this compound induced a substantial p21 accumulation in HCT116 wild-type cells albeit to a lesser extent compared with γIR .Interestingly, BI-D1870-mediated p21 accumulation appears to occur independently of p53 that was only stabilized following γIR, but not in response to BI-D1870.Consistent with our observation that BI-D1870 was able to induce senescence in MCF-7/casp3 cells as well, this event was also accompanied by p21 upregulation."	--	--	--	--	L	apoptosis	24136223
Sen_E_364	H2O2	Chemical compounds	HMESC	Blood	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay//Flow cytometry	"H2O2 treatment was found to lead to development of senescent-like morphology: cells become enlarged, flattened,and heterogeneous. senescent cells demonstrated SA-β-Gal staining which increased gradually,and the most remarkable effect was reached at 7 days after treatment: more 95% H2O2-treated cells were SA-β-Gal positive .The analysis of the cell cycle phase distribution in hMESCs showed that a pulse H2O2 treatment led to the arrest in all of the cycle phases ."	p21	Upregulation	Flow cytometry//Western blot	"200uM H2O2 promoted a significant elevation in protein expression of p21 in 7 h after treatment. it has been reported that, in bone marrow-derived mesenchymal stem cells exposed to sublethal doses of H2O2,a rapid decrease of proliferation rate was detected within 3 days and correlated with G1 phase arrest of the cell cycle when p21 was accumulated at the same time."	--	--	--	--	L	apoptosis	24062878
Sen_E_365	Heat shock	Other	MSC	Blood	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis//Western blot//DAPI staining	"Inhibition of proliferation was confirmed by cell staining with antibodies to Ki-67, a marker of proliferative activity. Seventy-two hours after heat shock, only a few cells were Ki-67-positive. Cell cycle analysis by flow cytometry revealed that heated cells were arrested mostly in G2/M phase.The modified morphology of MSCs subjected to HS: they are enlarged,more flattened, and express X-gal. Three days after HS, the number of SA-β-gal-positive cells increased to about 70 %. HS induced expression of p21 protein, a cell cycle inhibitor and major regulator of the senescence program."	p21	Upregulation	Western blot//PCR	"HS induced expression of p21 protein, a cell cycle inhibitor and major regulator of the senescence program. Four hours after recovery, p21 upregulation was obvious both at mRNA and protein levels. During 72 h after HS, the p21 expression gradually increases up to three times."	--	--	--	--	L	apoptosis	24078383
Sen_E_366	Nicotinamide	Chemical compounds	UC-MSC	--	Aging	Accelerate	SA-β-gal activity assay	"When treating with nicotinamide alone, the percentage of SA-β-gal-positive cells increased to 12.3 ± 2.5%; after treating with H2O2, nicotinamide significantly counteracted DECM-mediated anti-senescent effects by raising the percentage of SA-β-gal-positive cells to 57.2 ± 5.5% ."	p16//SIRT1//p38	Upregulation//Downregulation//--	Western blot//RT-PCR	The treatment with nicotinamide significantly increased p16INK4αin the H2O2-treated cells by 52.4% at the mRNA level and by 4.2-fold at the protein level compared with the untreated cells.The nicotinamide supplement also decreased SIRT1 in the H2O2-treated cells by 22.8% at the mRNA level and by 68.9% at the protein level .The western blot assay showed that exposure to nicotinamide and H2O2 increased phosphorylation of p38 by 4.2-fold compared with the control cells.	--	--	--	--	L	delay aging	28107614
Sen_E_367	TBK1-II	Chemical compounds	"HCC1954,SK-BR-3,Neu monolayer cell"	Mammary Gland	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"Remarkably, large, β-galactosidase-positive cells were observed in ~20% of lenti-shRNATbk1 transduced, and TBK1-II treated cultures .Strikingly, TBK1-II treatment (2 μM) virtually eliminated accumulation of cells in all phases and dramatically increased the percentage of cells with >4N chromosomes (M3 gate). This effect was also observed by forward- and side-scattering flow cytometry analysis."	p16//p65-NFκB	Activation//--	Western blot	"The NF-κB family proteins, RelA (p65), c-Rel, RelB, p50, and p52, bind to DNA as dimers, the most common being a p65-p50 heterodimer (43). P65-NFκB activity is induced by phosphorylation of serine536 (44). In untreated HER2+ BC cells, p65-NFκB was highly phosphorylated on serine536. Importantly, TBK1-II treatment of mouse and human HER2+ BC cells dramatically suppressed serine536-phosphorylation, hence activity of p65-NFκB. In addition, expression of the pro-senescence cyclin-dependent kinase inhibitor p16INK4A (45) was dramatically induced in both mouse and human HER2+ BC cells."	--	--	--	--	HL	cellular senescence	24487029
Sen_E_368	5-Aza-20-Deoxycytidine	Chemical compounds	"HepG2,Hep3B"	--	Cancer	Accelerate	SA-β-gal activity assay//SAHF//Immunostaining//Cytokine array	"Incubation with 5-aza-dC led to a significant increase (P < 0.001) in the number of SA-β-gal–positive HepG2 cells；We therefore investigated SAHF formation by immunofluorescence microscopy of H3K9me3 in HepG2 cells.Treatment with 20mmol/L 5-aza-dC for 72 hours triggered not only the typical increase of cell size, but also resulted in the characteristic accumulation of H3K9me3 in subnuclear dots.The incubation with 5-azadC caused increased levels of sICAM-1, interleukin (IL)1ra, and IL-8 in the culture supernatants."	p16//p53	Upregulation//Upregulation	Immunohistochemistry//Western blot	"In this experimental setting, only 5-aza-dC but not 5-aza-CR induced an upre-gulation of p16(INK4a)；In contrast, 5-aza-dC rather led to an increase in p53 protein levels, which might be related to the senescence-inducing capacity of this drug."	--	--	--	--	HL	cellular senescence	23924947
Sen_E_369	Arid1B	Chemical compounds	MEF	--	Hepatocellular carcinoma	Accelerate	Knockdown//SA-β-gal activity assay//BrdU assay	"Knockdown of Arid1b blunted replicative senescence,as evidenced by increased colony formation, a higher percentage of cells incorpo- rating BrdU, and a decrease in the percentage of senescence-associated β-galactosidase (SA-β-Gal)-positive cells when compared with control MEFs."	p16//p21a//p53	Upregulation//Upregulation//Upregulation	DAPI staining//IF	"Indeed, the expression of ARID1B not only induced p16INK4a and p21CIP1a but also up-regulated p53 levels and caused DNA damage and oxidative stress ."	--	--	--	--	HL	delay aging	27737960
Sen_E_370	Teng-Long-Bu-Zhong-Tang	Chemical compounds	CT26	--	Colorectal cancer	Accelerate	SA-β-gal activity assay	TLBZT treatment resulted in significant cell senescence in CT26 colon carcinoma compared with controls (P<0.01).	P16//p21//Rb	Upregulation//Upregulation//Downregulation	Western blot//Immunohistochemistry	"We examined p16, p21 and RB phosphorylation in CT26 colon carcinoma after three weeks of TLBZT treatment by immunohistochemistry and western blot.TLBZT significantly upregulated p16 and p21 expression, and downregulated RB phosphorylation in CT26 colon carcinoma and compared with controls (P<0.01)."	--	--	--	--	L	cellular senescence	23758730
Sen_E_371	NE	Chemical compounds	NHBE	--	Cystic Fibrosis	Accelerate	Western blot	These results suggest that NE may activate airway epithelial senescence in CF via p16-mediated inhibition of CDK4 and failure of phospho-Rb-triggered DNA synthesis.NE treatment injured the epithelial monolayer in a dose-dependent manner.	p16//CDK4	Upregulation//Downregulation	Western blot//Kinase assay	"Western analyses demonstrated a significant increase in p16 protein expression in response to NE treatment；NE treatment significantly decreased phosphorylation of Rb, the substrate for CDK4 activity ."	--	--	--	--	L	cellular senescence	23316069
Sen_E_372	BBR	Chemical compounds	--	Mammary Gland	Breast cancer	Accelerate	SA-β-gal activity assay	"NAX014 and, to a lesser extent, BBR administration increased the number of cells with a senescent-like phenotype in mammary tumor samples, as evidenced by the increased SA-β-gal staining."	p16	Upregulation	qRT-PCR	NAX014 induced a significant dose-dependent upregulation of p16INK4a mRNA level.	--	--	--	--	L	cellular senescence	26168818
Sen_E_373	NAX014	Chemical compounds	--	Mammary Gland	Breast cancer	Accelerate	SA-β-gal activity assay	"NAX014 and, to a lesser extent, BBR administration increased the number of cells with a senescent-like phenotype in mammary tumor samples, as evidenced by the increased SA-β-gal staining."	p16	Upregulation	qRT-PCR	NAX014 induced a significant dose-dependent upregulation of p16INK4a mRNA level.	--	--	--	--	L	cellular senescence	26168818
Sen_E_374	H2O2	Chemical compounds	WI-38	--	Aging	Accelerate	SA-β-gal activity assay//Immunofluorescence	"We found that p16 overexpression or H2O2 treatment alone induced senescence in WI-38 cells and the combination of both resulted in an additive effect. Meanwhile, the senescence-associated  heterochromatin foci (SAHF) assay confirmed the observations in senescence cell staining. Both 3MeK9H3 and HMGA1, two classic markers of SAHF, localized to the specific heterochromatic foci in cells transfected with p16 and treated with H2O2."	p16	--	Co-IP	"Consistent with the observations in 293T cells, our CoIP experiments showed that the level of p16 phosphorylation and the association of CDK4 with p16 increased upon the H2O2 treatment in WI-38 cells."	--	--	--	--	L	apoptosis	28120917
Sen_E_375	Cigarette smoke	Other	"SAEC,NHBE"	--	Aging	Accelerate	Flow cytometry	"Cigarette smoke (CS) is known to cause mitochondrial dysfunction leading to cellular senescence in lung cells.Using an in vitro lung epithelial cellular senescence model, CSE treatment every alternate day for 15 days in SAEC cells showed significantly reduced mitochondrial membrane potential (TMRE), and increased MitoTracker green (mitochondrial mass), and MitoSOX red staining (mtROS) confirmed by FACS-enabled flow cytometry."	OXPHOS	Downregulation	Western blot	"However, BEAS2B cells treated with CSE for 15 days showed significant reduction in complexes I and II, but all the other complexes remain unaltered."	--	--	--	--	L	cellular senescence	31593750
Sen_E_376	High glucose	Other	RTEC	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//SAHF	"The expressions of senescence-associated markers, including P16, P21, cell membrane DcR2, cytoplasmic SA-β-Gal activity, nuclear formation of SAHF, were increased significantly at 48?h in HG-treated RTECs."	OPTN	Downregulation	Western blot//SA-β-gal activity assay	OPTN siRNA assay showed that silencing of OPTN gene significantly inhibited HG-induced mitophagosome formation and enhanced RTEC senescence .	--	--	--	--	L	cellular senescence	29367621
Sen_E_377	Etoposide	Chemical compounds	PA-1	--	Embryonal carcinoma	Accelerate	Flow cytometry//Immunofluorescence//Cell morphological analysis	"G2M arrest and nuclear swelling were evident on day 3 after ETO treatment, with restoration of normal cell cycle and nuclear size 4 d later. Concurrent nuclear area assessments and DNA content measurements demonstrate that the nuclei of ETO treated cells increased in size irrespective of the stage of the cell cycle, but was most evident in G2M and polyploid cells. Increased nuclear area and DNA content were also accompanied by an increase in cellular granularity, as determined by an increase in side scatter detected by flow cytometry analysis, and autophagy (see below). The majority of cells displayed flattened morphology, but only a proportion displayed p16Ink4a nuclear positivity. Furthermore, p16Ink4a expression was largely confined to the cytoplasm ."	OCT4A//p21//p53//p16	Activation//Upregulation//Upregulation//--	Flow cytometry//Western blot	"Both the expression and variation of expression of OCT4A and p21Cip1 increased on day 3 after ETO treatment; and increased further on day 5 and a high number of double-positive cells confirmed.Immunoblotting confirmed that p53 increased in response to ETO from day 1, resulting in the induction of p21Cip1, which reached its maximum on day 5. In ETO-treated cells (day 4), the cytoplasm was highly enriched with LAMP2, while p16ink4a-positive aggresomes (larger and more numerous than in control) were sequestered in autophago-lysosomes."	--	--	--	--	L	cellular senescence	26102294
Sen_E_378	RSV	Chemical compounds	U2OS	--	Aging	Accelerate	MTT assay// FACS analysis//Immunofluorescence//Western blot//SA-β-gal activity assay	"RSV inhibited the proliferation of U2OS cells in a dose-dependent manner. Analysis of cell cycle distribution by flow cytometry indicated that RSV dose-dependently induced S-phase arrest. There was a remarkable increase in the amount of γ-H2AX, a marker for DNA double-strand breaks, in RSV-treated cells, as revealed by immunofluorescence. Meanwhile, ATM, a master regulator of DNA damage response, was activated by RSV.In addition, typically of cells experiencing replication stress, the level of phosphorylated CHK1 level was increased. Consistent with previous report in HCT116 colon cancer cells12, there was a significant induction of cellular senescence. It appeared that the cells arrested at S-phase could progress to senescence, as the majority of cells remained in S-phase when they became senescent."	Nucleosides//p53//CXCR2	--//--//--	RT-PCR//Flow cytometry//SA-β-gal activity assay	"Importantly, RSV-induced senescence was greatly reduced by nucleosides. We tested the inhibitory effect of nucleosides on RSV-induced senescence in two additional cell lines HT1080 (fibrosarcoma) and A549 (lung cancer) and obtained similar results. Indeed, CXCR2 transcription was significantly increased by RSV in a dose- and time-dependent manner . The increased expression of CXCR2 was confirmed by flow cytometry analysis of CXCR2 (CD182). However, after CXCR2 expression reached its peak level at day 5, it began to subside in the following days.We confirmed that the upregulation of CXCR2 following RSV treatment was dependent on p53, since the expression of CXCR2, like that of p21, in response to RSV was greatly reduced when p53 was depleted. Importantly, depletion of CXCR2 greatly attenuated RSV-induced senescence."	--	--	--	--	L	cellular senescence	28303009
Sen_E_379	Salicin	Chemical compounds	HUVEC	--	Vascular disease	Prevent	SA-β-gal activity assay//Flow cytometry	"When endothelial cells were exposed to 10 ng/mL TNF-a, those not treated by salicin displayed significantly greater cellular senescence after 48 h, as compared to cells that were not exposed to TNF-a. In contrast, salicin prevented senescence in a dose-dependent manner; endothelial cells treated with 50 and 100 mM of salicin showed proportionately less cellular senescence, with the 100 mM assay relative SA-β-Gal level of the 100 mM assay approaching that of the assay not treated with TNF-a.Cell cycle analysis indicated that whereas TNF-a-affected cells showed a higher level of cell cycle dysfunction compared to cells that were not exposed to TNF-a, salicin demonstrated a protective effect against cell cycle disruption at G0/G1."	Nrf2	--	Western blot	"While nuclear levels of NRF2 were reduced in the group exposed to TNF-a, replicating previous research that TNF-a hinders nuclear translocation of NRF2. Importantly, we found that salicin promoted nuclear translocation of NRF2."	--	--	--	--	L	delay aging	31220953
Sen_E_380	Low dose Emodin	Other	MCF-7	--	Breast cancer	Accelerate	SA-β-gal activity assay//Western blot	"In order to confirm the synergistic effect of Emodin and 5-FU in cellular senescence, SA-β-gal staining was detected and the results showed that cellular senescence (shown as SA-β-galt blue cells) was obviously detectable in sequential Emodin and 5-FU treatment at low dose. Hence, we investigated changes in the expression of senescence marker,p21, p16, p27 and E2F1 protein. The western blot analysis confirmed the up-regulation of p21, p16, p27 protein and the downregulation of E2F1 protein after the sequential treatment at low dose ."	NRARP	Downregulation	Western blot	The western blot analysis has confirmed the down-regulation of NRARP protein after the sequential treatment at low dose.	--	--	--	--	L	cellular senescence	30274778
Sen_E_381	Nucleus accumbens-1	Other	"SKOV3/N130,HeLa/N130"	--	Aging	Prevent	SA-β-gal activity assay//BrdU assay/Knockdown//Western blot//Flow cytometry	"We observed that during activation of this NAC1 deletion mutant, the cells showed a decreased proliferation rate upon continuous passaging as compared with the cells without activation of this NAC1-dominant negative mutant. We further found that the decreased proliferation was accompanied by increases in the numbers of SA-β-gal–positive cells and in the numbers of cells with altered cellular morphology such as flattening and enlargement.p21, a cyclin-dependent kinase inhibitor and an inducer of cellular senescence,was also increased. Inactivation of NAC1 also significantly enhanced the proliferation-inhibitory and the colony formation–inhibitory effects, and caused a G2–M cellcycle arrest, suggesting that senescence occurs in G2–M phase."	Np63	--	Knockdown//Western blot//SA-β-gal activity assay	"We found that the expression of DNp63 protein was markedly downregulated in cells with deficiency of NAC1 after treatment with g-irradiation ,The role of DNp63 in NAC1-mediated evasion of senescence was further verified by overexpressing DNp63 in NAC1-deficient cells.Ectopic expression of DNp63 in SKOV3/N130 or HeLa/N130 cells with inactivation of NAC1 or in A2780 cells with silencing of NAC1 significantly blunted the activation of senescence caused by g-irradiation."	--	--	--	--	L	delay aging	22665267
Sen_E_382	H2O2	Chemical compounds	Endothelial cell	--	Cardiovascular disease	Accelerate	SA-β-gal activity assay//Western blot	"We treated primary human endothelial cells in passages 2–3 with 50 μM H2O2 every second day for two weeks. As expected and previously published , this treatment induces senescence as evaluated by senescence associated (SA)-β-Galactosidase staining. we also quantified a known senescence marker, the cell cycle inhibitor p21 and its nuclear localization by immunostaining. H2O2increases the percentage of cells positive for nuclear p21 as well as the total protein levels of p21."	NOX4//Trx-1//Cathepsin D	Upregulation//Downregulation//Activation	qRT-PCR//Western blot//ELISA	"Relative NOX4 expression and NOX4 protein levels are increased under H2O2treatment. After two weeks treatment with H2O2,Trx-1 protein levels are decreased.Two weeks treatment with H2O2 induces over-activation of Cathepsin D."	--	--	--	--	L	apoptosis	24632182
Sen_E_383	AngII	Chemical compounds	MNC	Blood	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"After coincubation with Ang II (200 nmol/L) for 24 h, the number of SA-β-Gal-positive or G0/G1 resting cells increased significantly."	NOX2//NOX4//NOX5	Upregulation//Upregulation//Upregulation	RT-PCR//Western blot	"Results in late EPCs treated with Ang II, revealed that differential expression of NOX mRNA existed. Within 5 kinds of NOX mRNA, NOX2, NOX4 and NOX5 mRNA levels were significantly increased.Similarly, in Western blot,Ang II (200nmol/L) resulted in maximum increase in NOX5 protein level at 3h versus NOX2 and NOX4 at 12h. However, siRNA targeting NOX2 or NOX4 yielded a significant decrease in SA-β-Gal positive or G0/G1 resting cells."	--	--	--	--	L	cellular senescence	21841319
Sen_E_384	GATA4	Chemical compounds	"Fibroblast,IMR-90"	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//BrdU assay	"Ectopic expression of GATA4 induced senescence in human foreskin fibroblasts and IMR-90 fibroblasts ,as shown by increased senescence-associated β-galactosidase (SA-β-Gal) activity and decreased 5-bromo-2′-deoxyuridine (BrdU) incorporation. More important, depletion of GATA4 with stably expressed short hairpin RNAs (shRNAs) partially decreased IR-induced SA-β-Gal activity and delayed replicative senescence."	NF-κB	Activation	Immunocytochemistry//Western blot	"GATA4 expression triggered NF-κB activation, and GATA4 depletion inhibited NF-κB activation during senescence."	--	--	--	--	HL	cellular senescence	26404840
Sen_E_385	Cyanidin	Chemical compounds	WI-38	--	Aging	Prevent	MTT assay//Western blot//RT-PCR	"The cyanidin-treated cells showed a significant dose-dependent increase in cell viability.The young age group of H2O2-treated prematurely senescent cells showed a decrease in lifespan with a PDL of 28, while the treatment of cyanidin increased the PDL to 34. To investigate the protective mechanisms of cyanidin against cellular aging, we observed the mRNA and protein expressions of NF-kB, iNOS, and COX-2. Although the mRNA and protein expressions of NF-kB increased under SIPS, cyanidin at 10 mg/ml reduced mRNA expression significantly without alternation of protein expression."	NF-kB//iNOS//COX-2	Downregulation//Downregulation//Downregulation	Western blot//RT-PCR	"Although the mRNA and protein expressions of NF-kB increased under SIPS, cyanidin at 10 mg/ml reduced mRNA expression significantly without alternation of protein expression.COX-2 and iNOS expressions were up-regulated in the PSC group compared to the young group. However, the treatment of cyanidin decreased the mRNA and protein expressions of COX-2 and iNOS significantly."	--	--	--	--	L	delay aging	20190403
Sen_E_386	Galangin	Chemical compounds	Hs68	--	Aging	Prevent	SA-β-gal activity//MTT assay//Western blot	HS68 cells were pretreated with galangin (30 lM) for 1 hour followed by incubation with H2O2 (200 lM) for 24 hours prior to SA-β-gal staining. We found that H2O2 significantly increased the number of senescent cells (green) as compared with the control. These data demonstrate that galangin can significantly inhibit H2O2-induced cell senescence .The MTT assay results showed that galangin dosedependently increased the viability of H2O2-induced HS68 cells.	NF-kB	Downregulation	Western blot	"The data demonstrated that galangin reduced the levels of H2O2-induced inflammation-related proteins, IL6, TNF-a, IL-1b, and p-NF-jB p65 ."	--	--	--	--	L	cellular senescence	28834114
Sen_E_387	Atorvastatin	Chemical compounds	VSMC	--	Atherosclerosis	Prevent	SA-β-gal activity assay//Telomere length assay	"We incubated VSMCs with low-concentration t-BHP, which we have previously shown accelerates telomere shortening in culture.Senescence-associated β-galactosidase activity and telomere shortening were accelerated by t-BHP, but attenuated by atorvastatin treatment."	NBS-1//Hdm2	--//Upregulation	Comet assay//Western blot	"In contrast, HDFnbs1-/-  cells showed defective DNA repair, with incomplete repair even at 7 hours, which was not affected by atorvastatin.The induction of NBS-1 by atorvastatin at 15 minutes suggests that NBS-1 regulation is determined by posttranslational mechanisms. In VSMCs, atorvastatin pretreatment for 48 hours induced robust Ser166Hdm2 phosphorylation, which normalized 30 minutes after DNA damage, with minimal changes in total Hdm2 expression."	--	--	--	--	L	cellular senescence	18723444
Sen_E_388	FK866	Chemical compounds	ARPE?19	--	Retinal disease	Accelerate	SA-β-gal activity assay//qPCR//Western?blot	"β-galactosidase staining and related quantification revealed a time-dependent increase in the number of β-gal-positive cells in FK866-treated cultures .Similarly, the expression of p21Waf/Cip1, p16INK4a, ApoJ and CTGF was increased and SIRT1 expression and activity decreased time-dependently."	NAD+//SIRT1	Downregulation//Downregulation	SA-β-gal activity assay//qPCR//Western?blot	"Congruent with β-galactosidase staining, the expression of each of these markers was increased in association with increasing concentrations of FK866 and the associated decline in NAD+ .  Additionally, the expression and activity of SIRT1 was dose-dependently decreased ."	--	--	--	--	L	delay aging	29905535
Sen_E_389	Nicotinamide  mononucleotide	Chemical compounds	ARPE?19	--	Aging	Prevent	SA-β-gal activity assay//qPCR//Western?blot	"The number of β-galacto-sidase positive cells was also decreased in cultures exposed to NMN .Additionally, the compound prevented FK866-induced RPE senescence as indicated by the suppression of p16INK4a and p21Waf/Cip1 expression and the reduction of SIRT1 expression ."	NAD+//SIRT1	Upregulation//Upregulation	qPCR//Western?blot	"NMN dose-dependently enhanced NAD+ levels in cells exposed to FK866 .Importantly, NMN also prevented the FK866-induced decrease in SIRT1 expression."	--	--	--	--	L	delay aging	29905535
Sen_E_390	Rapamycin	Chemical compounds	REF	--	Aging	Prevent	Cell morphological analysis//SA-β-gal activity assay//Flow cytometry	"Rapamycin was added to REF cells at passage 7 , and the cells were grown for 3 additional passages in rapamycin-containing media. Afterwards, rapamycin was removed, and during the subsequent passages the cells were becoming smaller in size,thereby reflecting a gradual restoration of the non-senescent phenotype as evidenced by Giemsa staining.The population lost such senescence markers as SA-β-Gal staining and restored the lost ability to proliferate as evidenced by an increase of S-phase cells."	mtert	Upregulation	RT-PCR	"Interestingly, transcription of telomerase gene (mtert) is additionally augmented in rapamycin-derived cells."	--	--	--	--	L	delay aging	24296616
Sen_E_391	Embonic acid	Other	H1299	--	Aging	Accelerate	SA-β-gal activity assay	"EA treatment caused a profound increase in the expression of senescence-associated β-galactosidase by H1299 cells. In the absence of EA, the senescent signal,SA-β-gal+ H1299 cells, was not present ."	m-NAD(P)-ME	Downregulation	In vitro analysis	"By in vitro testing of a chemical compound library, we found a natural chemical, EA, which can inhibit m-NAD(P)-ME much more potently than c-NADP-ME."	--	--	--	--	L	cellular senescence	26008970
Sen_E_392	Lithium	Other	BAEC	--	Cardiovascular disease	Accelerate	SA-β-gal activity assay	Lithium treatment for 5 days increased 4.5- fold the number of SA-β-galactosidase positive cells as compared with sodium-treated control cells.	MMP1//PAI-1	Upregulation//Upregulation	qRT-PCR	Lithium treatment for 24 h resulted in a significant 13-fold increase of MMP-1 and a 2.7-fold increase of PAI-1 mRNA levels.	--	--	--	--	L	cellular senescence	19407340
Sen_E_393	H2O2	Chemical compounds	HEMn	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"The cells treated with  H2O2 at 62.5?μM cells were stained with darker blue color than young cells. In addition, the size of cells got larger with the dose of  H2O2 similar to the phenotype of old cells."	MITF//Nrf2	Downregulation//Upregulation	Western blot	"The expression level of MITF in senescent cells and H2O2-treated cells decreased by 16% and 39% compared to that of young cells, respectively;The expression levels of Nrf2 were increased 15% and 5% in senescent cells and H2O2-treated cells compared with young cells, respectively."	--	--	--	--	L	cellular senescence	30805890
Sen_E_394	DOX	Chemical compounds	K562	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis//SAHF	"A significantly enlarged cell size, increased SA-β-gal activity, and increased SAHF in cells treated with 50 nM DOX for 4 days were noted."	miR-375	Upregulation	qRT-PCR	"By comparing miRNA expression profiles between treated and untreated K562 cells, 10 upregulated miRNAs were found in DOX-treated K562 cells .The expression of miR-375 remained to be the highest among the 4 miRNAs ."	--	--	--	--	HL	cellular senescence	22606351
Sen_E_395	MIF	Chemical compounds	HCM	--	Aging	Prevent	CCK-8 assay//SA-β-gal activity assay//RT?qPCR	"MIF treatment in cells exposed to radiation increased cellular proliferation, decreased the expression levels of the senescence?associated genes Cdkn1a and Cdkn2c , recovered the impaired relative telomere length and activity ,and reduced the percentage of SA?β?gal?positive cells."	miR-34a	Downregulation	qRT-PCR	Exogenous MIF significantly decreased the expression of miR?34a induced by radiation.	--	--	--	--	L	delay aging	30226567
Sen_E_396	Radiation	Other	HCM	--	Aging	Accelerate	CCK-8 assay//SA-β-gal activity assay//qRT-PCR//Cell proliferation assay	"Radiation markedly inhibited cellular proliferation and increased the expression levels of the cellular senescence?associated genes Cdkn1a and Cdkn2c.Radiation exposure also significantly shortened the relative telomere length, impaired the relative telomerase activity and increased the percentage of SA?β?gal?positive cells."	miR-34a	Upregulation	qRT-PCR	miR?34a expression levels in HCMs were significantly increased following exposure to radiation.	--	--	--	--	L	delay aging	30226567
Sen_E_397	Lipid lowering therapy	Other	PBMC	Blood	Coronary artery disease	Prevent	FISH	The aggressive LLT group showed reduced LDL cholesterol levels in CAD patients after 12 months of therapy.	miR-23a//TRF2	Downregulation//Upregulation	qRT-RCR//Flow cytometry	"Aggressive LLT markedly decreased levels of miR-23a (2.78±1.29 vs. 2.09 ±1.17, P < 0.01) and increased levels of TRF2 (2.98 ± 1.44 vs.3.52 ± 1.34, P < 0.01)."	--	--	--	--	HL	telomere attrition	28646123
Sen_E_398	PTC-209	Chemical compounds	"MRC-5,MCF-7,MDA-MB-231"	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//EdU assay	"The stained cells were counted and plotted. We also examined the expression of senescence-associated proteins such as p21, p53, pRB and p16. The results showed that the PTC-209 strongly induced expression of p53, p21 and p16, and increased expression of hypo-phosphorylated pRB in MRC5 cells. Furthermore, PTC-209 strongly induced premature senescence in these cells as indicated by increase in SA-β-gal positive cells and corresponding decrease in EdU positive cells. PTC-209 also strongly induced premature senescence in MDA-MB-231 and MCF7 breast cancer cells."	miR-200c//miR-141	Upregulation//Upregulation	qRT-PCR//Luciferase reporter assay//EdU assay//Western blot//SA-β-gal activity assay	"PTC-209 treatment resulted in upregulation of both miR-200c and miR-141 . The results of qRT-PCR were further confirmed by promoter-reporter assays, which showed that the PTC-209 upregulated miR-200c/141 promoter activity in a dose-dependent manner .The results showed that the PTC-209 strongly induced p21 in control IH cells and that inhibition of either miR-200c or miR-141 could suppress p21 induction by PTC-209. The results indicated that the PTC-209 treatment led to the induction of premature senescence in control IH cells but not in cells expressing inhibitors of either miR-200c or miR-141."	--	--	--	--	L	cellular senescence	27105531
Sen_E_399	Busulfan	Chemical compounds	"U2OS,MG-63"	--	Osteosarcoma	Accelerate	SA-β-gal activity assay	"Our data showed that busulfan treatment significantly increased the number of β-galactosidase-positive cells, suggesting that busulfan may induce the senescence of osteosarcoma cells."	miR-200a//miR-200b//miR-200c//miR-141//miR-429//ZEB1//ZEB2	Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Downregulation//Downregulation	qRT-PCR	"We found that the five members in the miRNA-200 family were all upregulated after busulfan treatment in both cell lines.We found that expression of both ZEB1 and ZEB2 was significantly decreased by busulfan treatment in both cell lines .All five members of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) can inhibit epithelial–mesenchymal transition through activating E-cadherin transcription repressors ZEB1 and ZEB2."	--	--	--	--	L	apoptosis	24815002
Sen_E_400	21% O2	Other	HDF	--	Aging	Accelerate	Growth curve assay//SA-β-gal activity assay	The recorded cell counts demonstrated increased cell proliferation under 21% O2 compared to 5% O2with a major significant gap after 72 h.The percentage of blue cells is significantly higher in old fibroblasts grown under 21% O2 compared to those grown under 5% O2.	miR-181a//MMP1//COL1A1	Downregulation//Upregulation//Downregulation	qPCR	"Our results show that in comparing cells cultured under 21% O2 with those cultured under 5% O2, we observe downregulation of miR-181a in young cells while an opposite highly significant upregulation was observed in old cells.The results show that there is a significant activation of MMP1 mRNA expression in both young and old cells, indicating that HDF cultured under 21% O2are more aged with respect to those cultured under 5% O2. The same statement is valid also for mRNA expression of COL1A1 which is significantly downregulated under 21% O2 in old cells compared to 5% O2, an indication that cells are more aged."	--	--	--	--	L	delay aging	30405877
Sen_E_401	Simvastatin	Chemical compounds	HUVEC	--	Atherosclerosis	Prevent	SA-β-gal activity assay//qPCR//Western blot	"When HUVECs were treated with TNF-α together with valsartan or simvastatin, miR-155 expression was significantly reduced, accompanied by a parallel upregulation in SIRT1 expression and a decrease in TNF-α-induced HUVEC senescence ."	miR-156	Downregulation	qPCR//Western blot	"When HUVECs were treated with TNF-α together with valsartan or simvastatin, miR-155 expression was significantly reduced, accompanied by a parallel upregulation in SIRT1 expression ."	--	--	--	--	L	apoptosis	31752013
Sen_E_402	Valsartan	Chemical compounds	HUVEC	--	Atherosclerosis	Prevent	SA-β-gal activity assay//qPCR//Western blot	"When HUVECs were treated with TNF-α together with valsartan or simvastatin, miR-155 expression was significantly reduced, accompanied by a parallel upregulation in SIRT1 expression and a decrease in TNF-α-induced HUVEC senescence ."	miR-155 	Downregulation	qPCR//Western blot	"When HUVECs were treated with TNF-α together with valsartan or simvastatin, miR-155 expression was significantly reduced, accompanied by a parallel upregulation in SIRT1 expression ."	--	--	--	--	L	apoptosis	31752013
Sen_E_403	UNC2025	Chemical compounds	"A172,SF188,U251"	--	Glioblastoma	Accelerate	Cell Cycle analysis//Flow cytometry//SA-β-gal activity assay//BrdU assay//PI staining	"The amount of BrdU incorporation significantly decreased following UNC2025 treatment, indicating decreased proliferation in SF188 and U251 cells, while only a trend of decreased proliferation was observed in A172;treatment of A172, SF188, and U251 cells with UNC2025 induced beta-galactosidase activity (blue staining), a prominent marker of senescence.[25] .At a molecular level, p16 and p21 are markers of senescence [24]."	MERTK	--	Densitometry analysis//Western blot	"Afterone hour of UNC2025 treatment, MERTK phosphorylationwas reducedin all three celllines and in a dosedependentmanner."	--	--	--	--	L	cellular senescence	27783662
Sen_E_404	Rapamycin	Chemical compounds	Fibroblast	--	Werner syndrome	Prevent	Western blot//Immunochemical staining	"At the end of 42 days, growth rates reached 1.3 population doubling (PD) per week for WRN knockdown cells with rapamycin compared with 0.4 PD per week without rapamycin. Moreover, long-term rapamycin treatment restored normal nuclear morphology of WRN knockdown fibroblasts."	LC3-II//p62	Upregulation//Downregulation	Western blot	"Rapamycin induced increases in LC3-II and decreases in p62, consistent with enhanced degradation of autophagosomes."	--	--	--	--	L	genomic instability	24308646
Sen_E_405	Adhesion molecule on glia	Other	U87 MG	--	Glioma	Accelerate	SA-β-gal activity assay//Knockdown	β-galactosidase activity was reduced in the group treated with AMOG siRNA as compared with the Control group as seen with single cells and cell aggregates.	L1	--	Western blot	AMOG siRNA reduced AMOG expression (p = 0.0041) and increased L1 expression (p = 0.0029) in comparison to the Control siRNA group in U-87 MG cells .	--	--	--	--	HL	cellular senescence	31510944
Sen_E_406	Radiation	Other	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"HUVECs treated with low doses of ionizing radiation showed a significant increase in SA-β-gal+ cells in a dose-dependent manner (p?<?0.05), suggesting that the low doses of ionizing radiation could cause cell senescence ."	Ku86//p16	Downregulation//Upregulation	Western blot	We also found that the increased ionization caused a significant reduction in Ku86 expression and a significant increase in p16Ink4a expression in a dose-dependent manner.	--	--	--	--	L	cellular senescence	30616437
Sen_E_407	Ang II	Chemical compounds	EPC	--	Aging	Accelerate	SA-β-gal activity assay//Telomerase activity assay	AngII was able to accelerate EPCs senescence as shown by the increased percentage of positive SA-β-gal staining cells and the decreased telomerase activity concomitantly with the increase in the mRNA expression of NADPH oxidase gp91phoxsubunit and intracellular ROS production shown by fluorescent dichlorofluorescein.	Klotho	Downregulation	Western blot//PCR	AngII was able to accelerate EPCs senescence as shown by the decrease in the expression of both Klotho mRNA and secreted Klotho protein.	--	--	--	--	HL	delay aging	20832068
Sen_E_408	CGRP	Chemical compounds	EPC	--	Aging	Prevent	SA-β-gal activity assay//Telomerase activity assay	AngII was able to accelerate EPCs senescence as shown by the increased percentage of positive SA-β-gal staining cells and the decreased telomerase activity concomitantly with the increase in the mRNA expression of NADPH oxidase gp91phoxsubunit and intracellular ROS production shown by fluorescent dichlorofluorescein.These effects were reversed by exogenous administration of CGRP in a dose-dependent manner.	Klotho	Upregulation	Western blot//PCR	"AngII was able to accelerate EPCs senescence as shown by the decrease in the expression of both Klotho mRNA and secreted Klotho protein,The effect was reversed by exogenous administration of CGRP in a dose-dependent manner."	--	--	--	--	HL	delay aging	20832068
Sen_E_409	RUT	Chemical compounds	EPC	--	Aging	Prevent	SA-β-gal activity assay//Telomerase activity assay	"The percentage of positive SA-β-gal staining cells was increased, the telomerase activity was decreased and the expressions (both mRNA and protein) of both CGRP I and Klotho were down-regulated in Ang II-treated EPCs. Pretreatment with rutaecarpine reversed these effects in a dose-dependent manner."	Klotho	Upregulation	Western blot//PCR	"AngII was able to accelerate EPCs senescence as shown by the decrease in the expression of both Klotho mRNA and secreted Klotho protein,The effect was reversed by exogenous administration of RUT in a dose-dependent manner."	--	--	--	--	HL	delay aging	20832068
Sen_E_410	"1,25(OH)2D3"	Chemical compounds	"U87,U251"	--	Glioma	Accelerate	SA-β-gal activity assay//Western blot	"The results showed that 1,25 dihydroxyvitamin D3 significantly increased the senescent rate of glioma cells (U87 and U251).Our data showed that 1,25 dihydroxyvitamin D3 not only increased the expression of CDKN1A in U87 and U251 cells, but also unregulated the level of INK4A, another marker of senescence."	KDM6B	Upregulation	Western blot	"The data indicated that 1,25 dihydroxyvitamin D3 obviously increased the expression of KDM6B in U87 and U251 cells."	--	--	--	--	L	delay aging	30825201
Sen_E_411	HDAC inhibitor(sodium butyrate(NaBu) and valproic acid(VPA))	Chemical compounds	"AD-MSC,UCB-MSC"	"Blood,Adipose"	Aging	Accelerate	SA-β-gal activity assay	"We extended the treatment period up to 7 days, where we observed tha MSCs acquired a senescent phenotype based on SA-β-gal staining."	JMJD3//p16//SUZ12//BMI1//EZH2//c-Myc	Upregulation//Upregulation//Downregulation//Downregulation//Downregulation//Downregulation	RT-PCR//Western blot	"hUCB- and hADMSCs showed decreased expression of c-MYC, BMI1 and SUZ12. JMJD3 was upregulated by 1-day treatment of HDAC inhibitors, and its expression level peaked at 3 days of treatment. p16INK4Awas slightly increased from 3 days of treatment of HDAC inhibitors."	--	--	--	--	L	delay aging	20049504
Sen_E_412	Hydrogen sulfide	Chemical compounds	Aortic Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay	Early passage cells seeded at PD = 44 treated with H2S donors demonstrated a reduction in the number of SA-β-Gal positive cells two passages later.	IL-8//SRSF2//HNRNPD	Upregulation//Upregulation//Upregulation	ELISA//TaqMan low density array	"Upon treatment with H2S donors, the only consistent change for all donors was an upregulation of IL8 expression, although this was not to levels comparable with younger passage cells.A significant increase of HNRNPD and SRSF2 were the only consistent changes in splicing factor expression produced by treatment with any H2S donor tested."	--	--	--	--	L	cellular senescence	30026406
Sen_E_413	Doxycycline	Chemical compounds	MCF-7	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"Doxycycline treatment resulted not only in a strong induction of RasG12V, but concomitantly induced senescence alterations including increased p21 expression, SA-β-gal activity and the characteristic pHP1c staining ."	IkBζ	Upregulation	qRT-PCR	The expression of the senescence markers was again associated with a strongly increased IkBζ expression.	--	--	--	--	L	cellular senescence	23781024
Sen_E_414	Bleomycin	Chemical compounds	MCF-7	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Bleomycin treatment induced the typical senescence alterations, including an enlarged morphology, increased SA-β-gal activity as well as a strong nuclear recruitment of pHP1c ."	IkBζ	Upregulation	qRT-PCR	"Importantly, the expression of IkBζ was increased 3.6-fold, indicating that upregulation of IkBζ is independent of the senescence-inducing stimulus."	--	--	--	--	L	cellular senescence	23781024
Sen_E_415	Ionizing radiation	Other	MCF-7	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"In order to establish MCF7 cells as a model for irradiationinduced senescence, we investigated further senescence markers,in addition to the enlarged morphology and SA-β-galactosidase activity."	IkBζ	Upregulation	qRT-PCR	"In addition to the established SASP factors, also expression of IkBζ, which was almost undetectable in control cells, was increased about 5-fold in senescent MCF7 cells."	--	--	--	--	L	cellular senescence	23781024
Sen_E_416	Fluidic substrate	Other	NCI-H23	--	Lung cancer	Accelerate	Cell viability assay//Cell cycle analysis	"The viability of the cancer cells on non-crosslinked P(CL-co-DLLA) substrates was significantly decreased to 57% and 32% for 48 h and 72 h respectively.Cells on crosslinked P(CL-co-DLLA) substrate showed a reduced G0/G1 phase (13.87%) and increased S phase (75.55%). However, cells on non-crosslinked P(CL-co-DLLA) substrate showed an accumulation of G0/G1 phase (66.3%) and reduction of S phase (13.92%)."	IGFBP5//p53	Upregulation//Upregulation	Immunofluorescence//Confocal microscopy//RT-PCR	"At 72 h, cells on the non-crosslinked P(CL-co-DLLA) substrate showed a significant induction of IGFBP5 mRNA .At day 3, p53 bands were significant only for cells grown on the non-crosslinked P(CL-co-DLLA) substrate."	--	--	--	--	L	cellular senescence	29187894
Sen_E_417	PGE2	Chemical compounds	HDF	--	Aging	Accelerate	SA-β-gal activity assay//MTT assay//BrdU assay	"Treatment with PGE2 increases SA-β-gal activity and decreases cell proliferation in a dose and time-dependent manner. Since PGE2 stimulates cell proliferation in vascular smooth muscle cells (Yau and Zahradka 2  3) and esophageal cancer cells ,we treated cells with submicromolar concentrations of PGE2and measured cell proliferation by cell counting. No significant reduction or increase in cell proliferation was observed in cells treated with up to 1 lM PGE2. A decrease in cell proliferation by PGE2 treatment was further confirmed by the reduction of intracellular BrdU incorporation in PGE2-treated cells."	IGFBP5	Upregulation	RT-PCR//Western blot//Luciferase reporter assay//SA-β-gal activity assay	"The expression levels of IGFBP5 mRNA were measured in cells treated with PGE2 or forskolin. Both PGE2 and forskolin increase IGFBP5 mRNA levels. As expected, IGFBP5 protein levels are also enhanced by forskolin. The PGE2-induced increase of IGFBP5 protein expression could be decreased by pretreatment with EP1 and EP4 receptor antagonists. To test whether the increased levels of IGFBP5 mRNA and protein by PGE2 and forskolin treatment is mediated by promoter activation, plasmids containing luciferase controlled by the IGFBP5 promoter were transfected into AD293 cells and luciferase activity was measured after PGE2 treatment. After 48 h of PGE2 treatment, luciferase activity increases by fourfold. PGE2-induced increases in SA-β-gal activity and p53 protein level are repressed by IGFBP5 knockdown."	--	--	--	--	HL	cellular senescence	21191810
Sen_E_418	Ionizing radiation	Other	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"We confirmed that incidence of the senescence-like phenotype increased after exposure to 4-Gy IR. Like in senescent cells, cells began to exhibit an enlarged and fl attened cell shape and increased their SA- β -gal activity up to 22% and 39%, respectively, at 2 and 4 Gy of IR."	IGFBP5	--	MTT assay//SA-β-gal activity assay//Tube formation assay	"IGFBP5-downregulated cells were increased in cell proliferation compared with the control cells during irradiation. Based on SA- β -gal staining, IR increased SA- β -gal activity in control virus-transduced cells but not in IGFBP5 miRNA transduced cells. By tube formation assay, we observed that decrease in endothelial cell tube formation by irradiation was recovered by IGFBP5 down-regulation.These results demonstrate that IR-induced IGFBP5 is associated with radiation-enhanced cellular senescence and IGFBP5 downregulation can regulate radiation damage."	--	--	--	--	HL	cellular senescence	24164458
Sen_E_419	Homocysteine	Chemical compounds	HUVEC	Aorta	Aging	Accelerate	SA-β-gal activity assay//Western blot//qRT-PCR//Flow cytometry	"As expected, homocysteine could accelerate EC senescence when compared with standard conditions. Interestingly, homocysteine-increased p16, p21, and p53 expressions as well as SA-β-Gal positive cells, apoptosis cells, and cell cycle ."	hTERT	Downregulation	Western blot	"Indeed, homocysteine also accelerated the reduction in hTERT mRNA and protein expression from P6 to P10. In addition, homocysteine decreased the expression of hTERT in a dose-dependent manner in P4-5 HUVECs."	--	--	--	--	L	cellular senescence	25359865
Sen_E_420	CO	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//qRT-PCR//ELISA	"The pretreatment with CORM-A1 significantly alleviated the 5FU-elicited senescence of HUVECs. The CO treatment alone did not alter the basal senescence level of HUVECs, but reversed 5FU-induced endothelial senescence in a dose-dependent manner.5FU significantly increased PAI-1 and TNF-α expression, and the upregulation of these SASPs was attenuated by CO treatment."	HO-1//eNOS//SIRT1	Upregulation//Upregulation//Upregulation	qRT-PCR//Western blot	"5FU significantly decreased the HO-1 mRNA expression, whereas downregulation of HO-1 mRNA expression was enhanced by the CO treatment. 5FU significantly decreased eNOS and SIRT1 protein expression, whereas the downregulation of eNOS and SIRT1 protein expression was increased by the CORM-A1 treatment.The SIRT1 deficiency prevented CORM-A1 inhibition of 5FU-induced p21, PAI-1, TNF-α expression."	--	--	--	--	L	delay aging	31704100
Sen_E_421	β-Hydroxybutyrate	Chemical compounds	"HUVEC,HASMC"	--	Aging	Prevent	SA-β-gal activity assay//qRT-PCR//Flow cytometry	"To test the anti-senescence efficacy of β-HB, primary human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (hASMCs) were exposed to H2O2 with or without β-HB. As expected, H2O2 (150 mM, 3 days) exposure increased numbers of senescence-associated β-galactosidase- (SA β-gal) positive cells with senescence-related morphological transformations: enlarged, flat, and multinucleated appearance of cells. The addition of β-HB (4 mM, 3 days) markedly reduced senescence, while acetoacetate (AcAc, 4 mM, 3 days) had no effects on H2O2-induced senescence.As expected, β-HB also prevented senescence-related morphological transformations.Quantitative real-time PCR (qRT-PCR) of HUVECs samples indicated that β-HB effectively suppressed the expression of IL-6 and IL-1a triggered by H2O2. Quantitation of cell-cycle distribution showed that β-HB dramatically induced G0 with simultaneous reductions of G1 and S/G2 phases ."	HnRNPA1//OCT4A	Binding//Upregulation	SA-β-gal activity assay//Western blot//Pull-down assay//MALDI-TOF mass analysis//qRT-PCR	"We identified hnRNP A1 as a β-HB-binding protein using MALDI-TOF mass analysis. To confirm binding affinity, a pull-down assay was performed using SP-β-HB beads, and hnRNP A1 was validated with a specific antibody. The binding between hnRNP A1 and β-HB-conjugated beads was disturbed when the interaction was challenged with excess β-HB, S-β-HB, β-HB ester, or butyrate acting as binding competitors. Furthermore, silencing hnRNP A1 triggered senescence of HUVECs and accelerated the response to H2O2 .Both β-HB and S-β-HB were able to upregulate Oct4A, Lamin B1, p27, and phospho-eIF2a in thoracic aorta, indicating cell quiescence. Interestingly, β-HB-induced Oct4 protein elevation was only observed in the aorta, brain, and heart. Oct4A mRNA was also increased byβ-HB and S-β-HB injection, especially in the aorta, brain cortex, and heart."	--	--	--	--	L	delay aging	30197300
Sen_E_422	Hypoxia	Other	IMR-90	--	Aging	Prevent	SA-β-gal activity assay//Immunofluorescence//BrdU assay//SAHF//Western blot	"Indeed, compared to normoxia (20% O2) in hypoxia we observed reversal of H-RasV12- driven senescence induction as shown by negative staining of the cells for SA-β-gal activity.We found that HDFs ectopically expressing H-RasV12 were positive for Ki67 antigen and incorporated BrdU to a higher extent under low oxygen conditions when compared to normoxia.We also tested whether H-RasV12 overexpression results in generation of SAHFs, and here we showed that SAHF formation takes place only under normoxic conditions but not when the cells were cultured under hypoxic conditions.We found that the cells grown under hypoxic conditions have reduced protein levels of all of the senescence hallmarks tested including p53, p16INK4a, p21CIP1 and HP1γ."	HIF-1a//MIF	Activation//Upregulation	Western blot//RT-PCR	"As shown by protein analyses as well as mRNA expression levels, indeed, stabilization of HIF-1a was detected in both cell lines in hypoxia but not in normoxia .Thus we also assessed MIF expression in the same setting and detected a modest increase in MIF protein as well as mRNA levels under the hypoxic conditions."	--	--	--	--	L	delay aging	24984035
Sen_E_423	tris-C60	Chemical compounds	HEK	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"Interestingly, unlike hexa-C60, all doses of tris-C60 induced a significant increase (～12%) in cells arrested in G0/G1phase with fewer cells entering the S phase.No senescent cells were observed in the control samples.However, all doses of tris-C60(from 25 to 100 μg/ml) induced significant senescence at 24 and 48 h. Moreover, when tris-C60was removed by washing and cells incubated with fresh medium, the number of cells undergoing senescence was significantly reduced 24 and 48 h post-tris-C60treatment, suggesting that tris-C60 induced senescence was reversible."	HERC5//p16//p21//p53	Downregulation//Upregulation//Upregulation//Upregulation	RT-PCR//Western blot	"A significant number of cell cycle related genes were altered by less than 2-fold in response to 100 μg/ml tris-C60 treatment at the 24 h time point. Surprisingly, a notable 5-fold decrease was observed in the expression level of HERC5, a cyclin E binding protein. These results were confirmed with Taqman RT-PCR using different concentrations of tris-C60.A significant and simultaneous decrease in the level of HERC5 protein was noted in the tris-C60treated cells, with no detectable levels at the 100 μg/ml dose.An increase in p16,p21 and total p53 protein expression levels was observed in the tris-C60 treated cells indicating the involvement of these key cell cycle regulatory proteins."	--	--	--	--	HL	cellular senescence	20045429
Sen_E_424	Costunolide	Chemical compounds	"A172,U87 MG"	--	Glioblastoma	Accelerate	SA-β-gal activity assay	"Costunolide-induced increase in β-gal-positive cells, indicative of senescence, was diminished in the presence of ROS inhibitor."	GS(P)//TKT	Downregulation//Downregulation	Western blot	"Costunolide-mediated decrease in tumor volume was accompanied by decreased expression of TERT, Nrf2, G6PD, TKT, and GS(P) levels . Costunolide-induced senescence was accompanied by decreased expression of GS(P) and increased glycogen accumulation  in an ROS-dependent manner. The extent of glycogen accumulation was cell line dependent."	--	--	--	--	HL	apoptosis	27148686
Sen_E_425	Malignant ascitic fluids	Other	"HPMC,A2780,SKOV3"	Retina	Ovarian cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"By doing so, we found that the percentage of cells in the S-phase of the cell cycle in cultures exposed to malignant ascitic fluids was decreased by 40 ± 2 % (p < 0.01) compared to their counterparts subjected to the control ascitic fluids. This effect coincided with an increased activity of SA-β-Gal, an indicator of cellular senescence, by 25 ± 5 % (p < 0.03) compared to the control group .At the same time, we found that cultures exposed to benign ascitic fluids contained ~10 ± 4 % prematurely senescent cells (no significant difference), whereas in cultures exposed to malignant ascitic fluids the subset of senescent cells increased to34 ± 4 % (p < 0.01)."	GRO-1//HGF	Upregulation//Upregulation	SA-β-gal activity assay	"We found that the concentrations of 3 of these factors, i.e. GRO-1, HGF and TGF-β1, differed in malignant versus benign ascitic fluids. The levels of these factors were uniformly higher in the malignant ascitic fluids.We found that the activity of SA-β-Gal in the HPMCs was increased when they were exposed for 72h to exogenous GRO-1."	--	--	--	--	L	cellular senescence	27444787
Sen_E_426	X-ray	Other	Saos-2	Bone	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"X-ray irradiation at these doses substantially induced heterochromatic focus formation and β-galactosidase expression,both of which are considered markers of cell senescence [13], in periosteal cells after 3 days.Quantitative analyses were performed for all of the oxidative stresses,a finding common to all stressors was that the percentage of cells in the G1/G0 phase decreased in a dose-dependent manner."	g-H2AX//p53//p21/CP1	Upregulation//Upregulation//Upregulation	Western blot	"After 2 h of x-ray irradiation or H2O2treatment, all of the oxidative stresses upregulated g-H2AX and p53 without appreciable changes in PCNA (when normalized by actin) in periosteal cells. In contrast, a cyclin-dependent kinase inhibitor, p21WAF1/cip1, was upregulated by x-ray."	--	--	--	--	L	cellular senescence	25293814
Sen_E_427	CS extract	Other	HTBE	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//Cell Cell proliferation assay	"Furthermore,CSE treatment in control cells significantly increased GDF15 protein (up to 43-fold) and SA β-gal activity (up to 43% SA β-gal positive cells), inhibited cell proliferation (up to 54% decrease), and relocated HMGB1 protein from the intracellular milieu into the extracellular milieu."	GDF15	--	SA-β-gal activity assay//Western blot//Cell proliferation assay	"Disruption of GDF15 markedly reduced CSEinduced cellular senescence, represented by less induced SA β-gal activity, less inhibition of cell proliferation, and less HMGB1 release."	--	--	--	--	HL	cellular senescence	27093475
Sen_E_428	Propolis extrac	Other	HDF	--	Aging	Prevent	SA-β-gal activity assay//Trypan blue staining	"Pretreatment the cells with 50 and 100 mg/ml concentrations of EEP decreased the number of positive β-galactosidase cells significantly (P < 0.01);The results of trypan blue  exclusion  test  indicated  that  propolis at the concentration of 100 mg/ml not only did not reduce the number of viable cells in EEP-treated cells, but also it preserved the viabilityof irradiated HDF cells."	FOXO3a//NGF	Upregulation//Upregulation	qPCR	Data analysis revealed that EEP itself at concentration of 100mg/ml markedly increased the expressions of FOXO3A and NGF genes in HDF cells.	--	--	--	--	L	cellular senescence	28826096
Sen_E_429	UVB irradiation	Other	HDF	--	Aging	Accelerate	MTT assay//SA-β-gal activity assay	"Incremental doses of UVB cause cellular viability decline dose-dependently and at 296 to 696 mJ/cm2doses, the inhibitory effects were significant (P< 0.001);The proportion of positive β-galactosidase cells among UVB-irradiated cells was significantly (P < 0.01) greater than among non-irradiated ones."	FOXO3a	Upregulation	qPCR	UVB irradiation significantly upregulated the FOXO3A expression compared to the control cells .	--	--	--	--	L	cellular senescence	28826096
Sen_E_430	AMG 232+radiation	Other	"H460,A549,HCT116,A375,SJSA-1,MCF-7,H226"	"Lung,Colon,Melanoma,Mammary Gland"	Cancer	Accelerate	SA-β-gal activity assay	We first examined the activity of senescence-associated β-galactosidase (SA-β-Gal) and found that combined treatment of AMG 232 and radiation resulted in a significant increase in SA-β-gal positive cells compared with treatment with either radiation or AMG 232 alone in all cell lines tested.	FoxM1	Downregulation	qRT-PCR//Western blot//Immunofluorescence	"FoxM1 is a critical proproliferative transcription factor, and its inhibition leads to cellular senescence. Immunofluorescent imaging in A375 cells revealed that treatment with either AMG 232 or radiation alone at 48 hours resulted in a minor reduction in nuclear FoxM1 staining, whereas combination treatment resulted in a significant reduction in the number of FoxM1-positive cells. Furthermore, immunoblotting and RT-PCR analysis confirmed a reduction in protein and mRNA levels of FoxM1 following the combined treatment of AMG 232 and radiation in A375 ."	--	--	--	--	L	apoptosis	26162687
Sen_E_431	DFO	Chemical compounds	Chang	--	Aging	Accelerate	Cell morphological analysis//Flow cytometry	"As expected, progressive enlargement ofcellsizethatisoneofthetypicalsenescentphenotypes was clearly displayed .As expected, the intracellular ROS level increased continuously and the increased ROS was accompanied by the reduced ratio of GSH/GSSG, suggesting that oxidative stress was involved in the DFO-induced senescence."	Fis1	Downregulation	Western blot	"Under exposure to DFO, expression level of Mfn2 protein increased transiently, but Fis1 protein was progressively decreased ."	--	--	--	--	L	cellular senescence	16883569
Sen_E_432	Hecogenin	Chemical compounds	A549	--	Lung cancer	Accelerate	Flow cytometry//SA-β-gal activity assay	"At 50 μM, there was a small decrease in cells at S phase and a small increase in cells at G0/G1 and G2/M . This effect was enhanced with increased concentrations of hecogenin acetate. At 75 μM, 74% of cells were induced to cell cycle arrest in G0/G1 while 84.3 % of cells were induced to G0/G1 cell cycle arrest by hecogenin acetate 100 μM;Control cells showed only few SA-β-Gal staining spots, in contrast to cells treated with hecogenin acetate 50 μM where clusters of senescent cells were evident."	ERK1/2//MMP2	--//--	Western blot	Hecogenin acetate completely abolished ERK 1/2 phosphorylation induced by H2O2.Hecogenin acetate was able to inhibit the increase in MMP-2 content caused by H2O2 treatment.	--	--	--	--	L	cellular senescence	25115457
Sen_E_433	Metformin	Chemical compounds	"WI-38,IMR-90"	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"Metformin inhibited replicative senescence in WI‐38 and IMR‐90 cells. Treatment of cells with metformin delayed IR‐induced senescence, as assessed initially by SA‐β‐gal‐positive cells and subsequently confirmed by examination of two well‐established protein markers of senescence, p16 and p21. All of these markers of senescence were decreased by metformin treatment."	DICER1	Upregulation	qRT-PCR//Western blot//SA-β-gal activity assay	"Livers of metformin‐treated mice had higher DICER1 protein levels than control mice .DICER1 mRNA levels further increased by metformin treatment, which may reflect an effect on DICER1 at the transcriptional level.  SiRNA‐mediated downregulation of DICER1 levels increased cellular senescence and blocked the ability of metformin to lower the number of SA‐β‐gal‐positive cells in both WI‐38 and IMR‐90 cells. Conversely, overexpression of DICER1 decreased cellular senescence ."	--	--	--	--	HL	cellular senescence	26990999
Sen_E_434	Etoposide	Chemical compounds	HepG2	--	Aging	Accelerate	SA-β-gal activity assay	"After treatment of HepG2 cells with a relatively lower dose of etoposide (10μM), we observed the cells showing the senescence-like growth arrest. When the cells were treated with the low dose of etoposide (10 μM), the activity of senescence-associated β-galactosidase (SA-β-Gal), a well-known late senescence marker, gradually increased in a time-dependent manner."	DDR//p53//PRODH//DAO	--//--//--//--	Western blot//SA-β-gal activity assay//BrdU assay//CHIP	"Consistently, inhibition or depletion of DDR components (ATM, ATR, or Chk1) effectively prevented etoposide-induced senescence. The phosphorylation levels of p53 at Ser20 dramatically increased until 24 h after treatment with the low dose of etoposide accompanying the increase of p53 protein, and sustained for up to 48h, which is consistent with the prolonged activation of Chk1. Knockdown of p53 remarkably decreased etoposide-induced senescence as determined by SA-β-Gal staining and 5-Bromo-2 -deoxyuridine (BrdU) incorporation assay, suggesting that senescence induced by the low dose of etoposide is highly dependent on p53.Chromatin immunoprecipitation (ChIP) assay using the anti-p53 antibody in HepG2 cells revealed that p53 bound to the genomic regions of PRODH and DAO when treated with etoposide."	--	--	--	--	HL	cellular senescence	27545311
Sen_E_435	3×mAbs	Chemical compounds	"PC-9,H1975"	--	Lung cancer	Accelerate	SA-β-gal activity assay	"Indeed, treatment of cultured PC9 and H1975 cells with 3×mAbs induced prominent activity of SA‐β‐Gal."	DCR2//p16//p21//p27/KIP	Upregulation//Upregulation//Upregulation//Upregulation	Western blot	"Elevation of additional senescence markers was noted in vitro, such as DCR2 (TNFRSF10D) and several inhibitors of cyclin‐dependent kinases, namely p16, p21, and p27/KIP."	--	--	--	--	L	apoptosis	29212784
Sen_E_436	U0126	Chemical compounds	"HT-p16,HT-p21,MEL10"	--	Glaucoma	Accelerate	Western blot//Colony formation assay//SA-β-gal activity assay	"Unlike rapamycin, U0126 completely eliminated cyclin D1. Both rapamycin and U0126 suppressed geroconverssion in p21- and p16-induced senescence, rendering cells that were able to resume proliferation and form colonies after arrest was released. Furthermore, treatment with U0126 alone resulted in senescent morphology."	Cyclin D1	Upregulation	Western blot	"Although rapamycin moderately decreased PD0332991-induced cyclin D1, U0126 completely eliminated it."	--	--	--	--	L	delay aging	23852369
Sen_E_437	PD0332991	Chemical compounds	"MEL10,RPE"	--	Glaucoma	Accelerate	SA-β-gal activity assay	"In addition, PD0332991-treated cells acquired senescent morphology, which became even more prominent when the drug was removed.In RPE cells,PD0332991 (a CDK 4/6 inhibitor) inhibited cell proliferation and resulted in the senescent morphology, typical for these cells.Senescent cells wereunable to proliferate following removal of PD0332991."	Cyclin D1	Upregulation	Western blot	"Most importantly, PD0332991 strongly induced cyclin D1."	--	--	--	--	L	delay aging	23852369
Sen_E_438	Rapamycin	Chemical compounds	"MEL10,RPE"	--	Glaucoma	Prevent	Western blot//SA-β-gal activity assay	"In this particular cell line, U0126 treatment by itself did not block phosphorylation of S6 and therefore caused senescent morphology,which was prevented by rapamycin."	Cyclin D1	Downregulation	Western blot	"Although rapamycin moderately decreased PD0332991-induced cyclin D1, U0126 completely eliminated it."	--	--	--	--	L	delay aging	23852369
Sen_E_439	MLN4924	Chemical compounds	"QBC939,RBE"	--	Intrahepatic cholangiocarcinoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis//Western blot//PI staining	"Our flow cytometry analysis of DNA content evidenced a prominent increase in G2-M population 24h after treatment in cholangiocarcinoma cells. The arrest was confirmed to persist after longer treatment periods (48 and 72 h). In line with the role as a G2-M regulator, sharp increases of cell cycle inhibitors p21, p27, WEE1 (a well defined CRL substrate and an inhibitor of G2-M phase transition), and obvious decrease of a hallmark of M phase, p-Histone H3 (p-H3, ser10), were observed in QBC939 and RBE cells.in RBE cells, MLN4924 triggered senescence as demonstrated by an enlarged and flattened cellular shape as well as the expression of senescence-associated β-galactosidase."	CRL	Upregulation	Western blot	MLN4924 induced the accumulation of CRL substrates. Four tumor tissues were randomly selected from each group and lysed for immunoblotting analysis as indicated.	--	--	--	--	HL	apoptosis	25229838
Sen_E_440	NS-398	Chemical compounds	Fibroblast	--	Aging	Prevent	Flow cytometry	We demonstrated that the proportions of cells that progressed through the G0/G1into the S phase were increased by NS-398 compared with the controls.	COX-2//p53//PCNA//MMP1	Downregulation//Downregulation//--//Downregulation	Western blot	Treatment with NS-398 during replicative senescence inhibited the senescence-associated increase in COX-2 protein expression completely in the replicative senescent fibroblasts.NS-398 inhibited the senescence-associated increase in p53 expression during replicative senescence almost completely.NS-398 inhibited the senescence-associated decrease in PCNA protein expression during the replicative senescence of dermal fibroblasts.Treatment with NS-398 during replicative senescence decreased the senescence-associated increase in MMP-1 expression.	--	--	--	--	L	cellular senescence	15130753
Sen_E_441	GSE24.2	Other	"F9-A353V,DC-C,DC-3,XDC1787-C,F26IIB"	--	Dyskeratosis congenita	Prevent	SA-β-gal activity assay	A fibroblastoid cell line established from a healthy relative of a DC patient (XDC-1787-C) was used as internal control. Expression of GSE4 and GSE24.2 significantly decreased cell senescence.	c-Myc//TERT	Activation//Activation	Western blot	Both GSE24.2 and GSE24.2-NLS1.3 activated c-myc and TERT promoters in the three cell lines analyzed to similar levels although some of the activity increases were not statistically significant in F9 cells.	--	--	--	--	L	cellular senescence	26571381
Sen_E_442	GSE4	Other	"F9-A353V,DC-C,DC-3,XDC1787-C,F26IIB"	--	Dyskeratosis congenita	Prevent	SA-β-gal activity assay	A fibroblastoid cell line established from a healthy relative of a DC patient (XDC-1787-C) was used as internal control. Expression of GSE4 and GSE24.2 significantly decreased cell senescence.	c-Myc//TERT	Activation//Activation	Western blot	"GSE4 and GSE4-NLS1 peptides showed similar capacity than GSE24.2 to activate c-myc and TERT promoters in the cell lines analyzed, including the F9-A353V mutant cells."	--	--	--	--	L	cellular senescence	26571381
Sen_E_443	Palbociclib	Chemical compounds	"AGS,MKN45"	--	Gastric cancer	Accelerate	SA-β-gal activity assay	"Palbociclib-mediated antiproliferative effects were virtually identical in AGS and MKN-45 cells. SA-β-gal activity assay:the reduced proliferation in these cells was accompanied by an increase in the proportion of senescent cells, as assessed by senescence associated (SA)-β-galactosidase (SA-β- gal) staining."	CDK4/6//p53	Downregulation//Upregulation	Western blot//SA-β-gal activity assay	"Western blot： Inhibition of CDK4/6 activity with suboptimal doses of Palbociclib (0.05 μM) together with the inhibition of autophagy using doses of 0.5 μM o f Spautin-1 (SP-1), resulted in a reduction in AGS cell proliferation that was greater than the inhibition induced by Palbociclib-only treatment .SA-β-gal activity assay：the proportion of giant, multinucleated senescent cells that were positive for SA-β-Gal activity was higher in cells treated with both drugs .Western blot:Through immunofluorescence and western blotting, an increase in total p53 levels in AGS cells treated with Palbociclib was evident,p53-deficient cells display a reduced ability to induce senescence following Palbociclib treatment."	--	--	--	--	L	cellular senescence	28947133
Sen_E_444	Valproic acid	Chemical compounds	"D283-MED,Daoy "	--	Medulloblastoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"We confirmed that cellular senescence was indeed induced in those flattened D283-MED and DAOY cells by valproic acid (0.6 and 1 mmol/L) in a time- and dose-dependent manner. More interestingly, in D283-MED cells treated with valproic acid (0.6 mmol/L), we observed blue staining in the gradually dissociating cell spheroids as well. The induced senescence started from day 3 and peaked on day 7 when the whole spheroids were densely stained. A higher valproic acid concentration (1 mmol/L) led to more dramatic increase of cellular senescence as evidenced by further depletion of spheroids and increased β-galactosidase staining of attached D283-MED cells. In D283-MED and DAOY cells, shift of cell population to G1-G0 phases started after 3 days of valproic acid (1 or 2.7 mmol/L) treatment. More significant cell cycle arrest, however, was detected on day 7, when cells in G1-G0 phases increased and cells in G2-M phases decreased concurrently."	CDK4 	Downregulation	Western blot//qPCR	"The expression of CDK4, however, was significantly altered by valproic acid. Suppression of CDK4 mRNA expression was most prominent in D283-MED cells, and a corresponding decline in protein levels, although less dramatic, was also observed. In DAOY cells, although the inhibition of mRNA transcript levels was not major, a dramatic depletion of CDK4 protein was observed."	--	--	--	--	L	apoptosis	16373706
Sen_E_445	CGN	Chemical compounds	"HT29,SW480 ,NCM460"	--	Colorectal cancer	Accelerate	MTT assay//BrdU assay//Flow cytometry//SA-β-gal activity assay	"CGN treatment markedly decreased cell viability in a dose- dependent manner in both HT- 29 and W480 cell lines, but had less cytotoxic effect in NCM460 cells.Consistently, BrdU assays showed that there were a significantly lower percentage of BrdU- positive cells in CGN- treated cells compared with controls.Colorectal cancer cells accumulated in the G2/M phase and de-creased in the G0/G1 phase upon CGN treatment, indicating that  CGN induces G2/M arrest. SA- β- gal assays showed that CGN significantly enhanced senescence as indicated by a significant increase in the percentage of SA- β- gal- positive cells ."	CDK4	Downregulation	Western blot	"CDK4 expression was significantly decreased, but CDK6 expression was not clearly affected upon CGN treatment (data not shown), suggesting that CGN selectively inhibits CDK4 by downregulation of CDK4 expression."	--	--	--	--	L	apoptosis	29484762
Sen_E_446	Ionizing radiation	Other	"CNE-2,U2OS"	--	Nasopharyngeal carcinoma	Accelerate	MTS assay//Cell cycle analysis//SA-β-gal activity assay	"IR induced around 54% CNE2 cell senescence at 48 h,up to 79% at 72 h. Similar results were observed in U2OS cells. 6 Gy of IR induced 32% senescent cells at 48 h,up to 56% at 72 h ;The proliferation of CNE2-R cells was retarded compared to CNE2 cells, and more CNE2-R cells were arrested in G0/G1 phase than CNE2 cells.More β-Gal-positive cells were observed in CNE2-R cells than CNE2 cells."	CDC6	Upregulation	Western blot	"We observed that IR steadily elevated CDC6 protein levels 24, 48, and 72 h after IR exposure, though the cell proliferation was retarded."	--	--	--	--	L	cellular senescence	30158672
Sen_E_447	H2O2	Chemical compounds	NIH-3T3	--	Aging	Accelerate	SA-β-gal activity assay	H2O2 alone (not in combination with quercetin) promoted the expression of senescence-associated β-galactosidase activity in NIH 3T3 cells.	Caveolin-1//p53	Activation//Activation	Luciferase reporter assay	"72 h after induction of oxidative stress with 150 μM H2O2, caveolin-1 promoter activity was increased by ~two fold.3 d after stimulation with H2O2(150 μM for 2 h), the p53 responsive element was activated by ~five- to sixfold."	--	--	--	--	L	delay aging	12134086
Sen_E_448	Resveratrol/quercetin	Chemical compounds	C6	--	Glioma	Accelerate	SA-β-gal activity assay	"Senescence induction by Rsv plus Quer, measured by the activity of acidic β‐galactosidase, a biochemical marker for lysosome acidification,(40) was cooperative, since each treatment alone produced around 20% of SA‐β‐gal positive cells, whereas combination of Rsv and Quer induced staining in almost all cells."	Caspase-3/7	Activation	Annexin V binding assay//PI staining	"Rsv (50 μM) increased caspase 3/7 activity after 48 h of treatment at an intensity similar to 50 μM etoposide, used as a positive control. Quer (100 μM) was unable to induce caspase 3/7 even at 72 h of treatment. Neither 10 μM Res nor 25 μM Quer alone were able to induce caspase 3/7 activation; however, a strong activation was observed with the cotreatment, suggesting a synergistic effect of these compounds in caspase 3/7 activation."	--	--	--	--	L	apoptosis	19496785
Sen_E_449	Resveratrol	Chemical compounds	"U2OS,A549"	--	Cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"Thus, in both cell lines, resveratrol induced the growth arrest, showing prominent feature of stress-induced senescence—an increased SA-β-galactosidase activity. Moreover, many cells in both lines increased in size showing enlarged nuclei—the morphology typical for the senescent cells (not shown)."	BRCA1	Upregulation	Western blot	"In A549 cells, the total amount of BRCA1 protein detected by D-9 antibody slightly increased between 6 and 30 h of treatment."	--	--	--	--	L	genomic instability	19559722
Sen_E_450	ZF1	Other	ASC	"Adipose,Bone marrow,Dental pulp,Perinatal tissue"	Aging	Prevent	SA-β-gal activity assay//qRT-PCR	"Cells(culture passages 5th–7th) were treated for 72 h with ZF1 at the final concentrations of 0.01,10,and 20 μg/mL. Although 0.01 μg/mL ZF1 was ineffective,both 10 and 20 μg/mL ZF1 significantly reduced the number of senescent hASCs positively blue stained for SA β-gal (p < 0.05).In contrast, hASCs exposed to both 10 μg/mL and 20 μg/mL ZF1 resulted in a similar statistically significant increase in TERT transcription as compared with the control hASCs (SOLV)."	BMI1//p53//p21	Upregulation//Downregulation//Downregulation	qRT-PCR	"We show that,in hASCs,ZF1 was also able to enhance the gene expression of BMI1, a pleiotropic transcriptional regulatoracting as a major repressor of senescence .On the contrary,in hBM-MSCs,hDP-MSCs,and hWJ-MSCs, he ZF-induced increase in TERT transcription was associated with a down-regulation in both TP53 (p53) and CDKN1A(p21) transcription."	--	--	--	--	L	delay aging	31146388
Sen_E_451	Timosaponin A-III	Chemical compounds	"MCF-7,MDA-MB-231"	--	Aging	Accelerate	MTT assay//SA-β-gal activity assay//EdU assay	"The results showed that TA-III strongly decreased cell proliferation of both cell lines in a dose-dependent manner.MDA-MB-231 and MCF7 cells were treated with TA-III for 48 hours, and co-stained with SA-β-gal and EdU, and nuclei were stained with DAPI (4',6-diamidino-2-phenylindole).The number of the stained cells were then counted and plotted . The results indicate that TA-III strongly induces senescence in both MDA-MB-231 and MCF7 cells."	BMI1	Downregulation	qRT-PCR//SA-β-gal activity assay//EdU assay	"We examined expression of BMI1 gene at the transcription level by qRT-PCR analysis of mock and TA-III-treated breast cancer cells. The results indicated that TA-III downregulated mRNA levels of BMI1.Exogenous BMI1 inhibits premature senescence induction by Timosaponin A-III in breast cancer cells,TA-III treatment resulted in increase in number of SA-β-gal positive and corresponding decrease in EdU positive cells in MDA-MB-231-B0 (control) cells."	--	--	--	--	L	cellular senescence	29528145
Sen_E_452	Bromodomain inhibitor	Chemical compounds	MM.1S	--	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay	"JQ1-treated MM.1S cells revealed a pronounced decrease in the proportion of cells in S-phase, with a concomitant increase in cells arrested in G0/G1 ;Treatment with JQ1 resulted in pronounced cellular senescence by beta-galactosidase staining."	BET bromodomain	Binding	Gene set enrichment analysis//Western blot//RT-PCR	"Gene sets defined by adjacency to Myc-binding motifs were in almost all cases significantly enriched in JQ1-suppressed genes we studied the consequence of JQ1 treatment on the expression of 230 cancer-related genes in a human MM cell line (MM.1S),Downregulation of MYC was further confirmed by RT-PCR and immunoblot."	--	--	--	--	HL	cellular senescence	21889194
Sen_E_453	C-1311	Chemical compounds	"A549,H460"	--	Lung cancer	Accelerate	Cell morphological analysis//SA-β-gal activity assay//Flow cytometry	"Cells were treated with C-1311 and stained for SA-β-gal, a marker of senescence. In A549 cells, increased SAβ-gal staining was visible within 48 hours of treatment. After 8 days of continuous drug exposure, more than 80% of the cells displayed SA-β-gal activity and flattened and enlarged morphology that was consistent with senescence phenotype. Although H460 cells also stained positively for SA-β-gal, the percentage of cells undergoing senescence was 2-fold lower than in A549 cells.In contrast, C-1311 exposure led to the substantial accumulation in the G1 phase in H460 cells,although G2-M arrest was also evident."	Beclin1//ATG5	--//--	--	"SAβ-gal staining indicated that knockdown of Beclin 1 significantly attenuated C-1311–induced senescence in A549 cells.After 144 hours of C-1311 exposure, downregulation of ATG5 in A549 cells resulted in an approximately 25% inhibition of senescence compared with ATG5-positive cells."	--	--	--	--	L	apoptosis	23823138
Sen_E_454	TBHP	Chemical compounds	HMC	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	SA-β-gal activity assay:SA-gal staining was significantly increased in the tBHPstimulated cells compared with the control cells. Flow cytometry:Flow cytometry was used to characterize the nature of cell cycle arrest. The cell cycle was arrested at the G0?G1 phase in the tBHP-stimulated cells (90.76% ± 6.34%) compared with the control cells.	Bcl-2//Bax//STAT1//STAT3	Downregulation//Upregulation//Activation//Activation	Western blot	Bcl-2 protein expression decreased (p < 0.05) while Bax protein expression significantly increased (p < 0.01) in tBHP-induced cells compared with the control cells.Exposure of cells to 30 mol/L tBHP resulted in activation of STAT1 and STAT3 as manifested by an increase in STAT phosphorylation.	--	--	--	--	L	cellular senescence	23984931
Sen_E_455	Idebenone	Chemical compounds	ARPE?19	--	Aging	Prevent	SA-β-gal activity assay	"When pretreated with 5 μ M idebenone, the increase in SA-β-Gal expression mediated by H2O2 was significantly ameliorated."	Bax//Bcl-2	Downregulation//Upregulation	qPCR	"After normalization to the control group, expression of BAX was 100% in control cells, 136 ± 28% in H2O2 treated cells, 115 ± 9% in cells treated with H2O2 and 5 μ M idebenone, and 103 ± 35% in cells treated with H2O2 and 7.5 μ M idebenone. Expression of Bcl-2 was 100% in control cells, 70 ± 20% in H2O2- treated cells, 83 ± 49% in cells treated with H2O2 and 5 μ M idebenone, and 115 ± 57% in cells treated with H2O2 and 7.5 μ M idebenone."	--	--	--	--	L	apoptosis	26044821
Sen_E_456	photosensitizer 8-methoxy-psoralen and ultraviolet A radiation	Other	Fibroblast	--	Aging	Accelerate	SA-β-gal activity assay	Senescence of human primary fibroblasts was induced in 8-MOP-preincubated cells after irradiation with broad-spectrum UVA or monochromatic irradiation with 350 ±10 nm representing conditions that benefit ICL formation .Numbers of cells staining positive for γ-H2AX in primary human fibroblasts increased from 11% in untreated to 82% in PUVA-treated cells at 24 h after irradiation.	ATR	Activation	SA-β-gal activity assay//Western blot//Knockdown	"The amount of SA-β-gal–positive cells was markedly reduced in the ATR siRNA-treated group compared with the ATM- or control siRNA-treated cells. From this, we conclude that depletion of ATR releases PUVA-treated fibroblasts from senescence. Notably, similar results were obtained in SV40-transformed WI26 VA4 fibroblasts, which also senesce after psoralen photoactivation .To test whether H2AX phosphorylation after PUVA depends on ATR, we ablated ATR expression in primary human fibroblasts by siRNA. ATR expression was almost abolished 24 h after transfection."	--	--	--	--	L	delay aging	16436511
Sen_E_457	Telomeric plasmid	Other	MGC803	--	Gastric cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//MTT assay	"Cells were transfected with telomeric plasmid pRST5. Twenty-four hours later, the cell growth was obviously inhibited . 0.5 mg mL 1 pRST5 plasmid transfection decreased cell viability by 27% and increased cell senescence by 62% ( p < 0.05). However, empty vector pBlueScript caused no obvious cell growth inhibition."	ATM//p53//TRF1//TRF2	--//Upregulation//Upregulation//Upregulation	Western blot//RT-PCR	"Compared to control groups, cells transfected with telomeric plasmids showed an obvious increase of p53 protein level in a dose dependent manner.In addition, cells transfected with plasmid pRST5 displayed increase of TRF1 and TRF2 mRNA and protein level.20 mM wortmannin effectively inhibited the phosphorylation of ATM and the increase of p53, TRF1, and TRF2, suggesting that the upregulation of these proteins might be correlated with ATM activity."	--	--	--	--	L	cellular senescence	20535839
Sen_E_458	Nitric oxide	Chemical compounds	"HeLa,MRC-5"	--	Aging	Accelerate	SA-β-gal activity assay//qRT-PCR //ELISA	"NO treated HeLa cells stained positive for SA-βgal activity, a hallmark of cellular senescence and the percentage of stained cells increased proportionally to the dose of SNP . The senescent state was further confirmed by recording the induction in the expression of p21, NF-κb and IL8 and reduction in the expression of proliferation cell nuclear antigen (PCNA)at RNA level. Additionally, the levels of IL8 and IL6 cytokines, a part of the senescence associated inflammatory phenotype were also significantly elevated after SNP or DETA."	ATM	Activation	Cell viability assay	"Towards this, cells were treated with NO in the presence of a specific ATM kinase inhibitor, KU-55933 [46]. It is known that ATM kinase inhibition leads to an increase in ROS levels [44,45,47], which was observed when HeLa cells were treated with KU-55933, which increased further on NO treatment and was accompanied with significant loss of cell viability, as determined by a reduction in their proliferation as well as their metabolic activity ."	--	--	--	--	L	cellular senescence	27845209
Sen_E_459	Selenium Compounds	Chemical compounds	"MRC-5,CRL-1790,PC-3,HCT116"	--	Cancer	Accelerate	SA-β-gal activity assay//BrdU Assay	"The selenium treatment resulted in the expression of SA-β-galactosidase in the non-cancerous MRC-5 and CRL-1790 cells in a dose-dependent manner from a concentration as low as 0.1 uM(Na2SeO3or MSeA) and 5 uM (MSeC). Strikingly, there was no detectable SA-β-galactosidase in the cancerous PC-3 and HCT 116 cells treated with selenium at doses that result in the majority of the MRC-5 cells senescing or even higher doses.Compared with the MRC-5 cells without selenium treatment, cellular exposure to Na2SeO3, MSeA, and MSeC resulted in a 4-,6.6-, and 2.3-fold reduction in BrdUrd incorporation, respectively."	ATM	--	SA-β-gal activity assay//Immunofluorescence	"Results from the SA-β-galactosidase analysis demonstrated that inhibition of ATM kinase activity prevented senescence induction in MRC-5 cells exposed to Na2SeO3(1uM), MSeA (1uM), or MSeC (50uM). Treatment of MRC-5 cells with anti-oxidants, NAC (a H2O2scavenger) and Tempo (a superoxide dismutase mimic), significantly suppressed senescence in MRC-5 cells treated with the selenium compounds.Tempo is more potent than NAC in the attenuation of senescence induced by Na2SeO3and MSeA. ROS contribute to the selenium-induced DNA damage response because the pATM Ser-1981 focus formation."	--	--	--	--	L	apoptosis	20157118
Sen_E_460	MNNG	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"Interestingly, at 100 μM of MNNG treatment,the HCT-116 cells showed a major change in their cell cycle arrest profile in which the G0/G1 phase arrest was significantly increased, and the G2/M phase arrest was decreased as compared to control cells.Our result showed that senescence-associated β-galactosidase staining increased in cells treated with 100 μM MNNG as compared to untreated cells."	APC	Downregulation	Western blot//Northern blot	"After 50 h of treatment with MNNG, the APC mRNA levels decreased, which paralleled with the decreased levels of APC protein."	--	--	--	--	L	apoptosis	14728717
Sen_E_461	Ceramide	Chemical compounds	"WI-38,HDF"	--	Aging	Accelerate	Cell morphological analysis	"Young HDF were able to label 67.5 ± 9.5% of their nuclei by [3H]thymidine in response to serum stimulation. In contrast, senescent cells had a labeling index of <2% , cells grown in 10 μM C6-ceramide had a labeling index of 12 ± 5% ,and cells grown in 15 μM C6-ceramide had a labeling index of 2.5 ± 0.5% and morphologically resembled senescent cells."	AP1//Rb	--//--	Western blot	"Upon serum stimulation young HDF are able to respond by activation of AP-1 (lanes 1 and 2), whereas ceramide-treated cells (lanes 5 and 6) like senescent cells (lanes 7 and 8) were unable to respond by activation of AP-1. Remarkably, C6-ceramide in concentrations ranging from 3 to 20 μM was able to progressively inhibit Rb phosphorylation in young HDF in response to serum stimulation as indicated by Western blot analysis . In addition, C6-ceramide (15 μM) was able to induce complete Rb dephosphorylation by 20-24 h, thus mimicking senescent HDF."	--	--	--	--	L	cellular senescence	8530509
Sen_E_462	Metformin	Chemical compounds	HAEC	--	Aging	Prevent	SA-β-gal activity assay//Van Geison staining//Histochemical staining//Flow cytometry//Immunofluorescence	"SA-β-gal activity assay:SA-β-gal staining in HAEC, early versus late passage controls, as well as in cells continuously grown in the presence of metformin from p5 to p16，chronic administration of metformin delays endothelial cell senescence. SA-β-gal activity assay:In addition, a significant reduction in the SA-β-gal staining of aorta was observed in metformin-administered mice in comparison to untreated ApoE?/?mice. Van Geison staining//Masson:These changes were further confirmed with Van Geison staining indicating increased presence of collagen tissue and Masson's trichrome staining indicating accumulation of fibrous connective tissue with ruptured medial layer in ApoE?/?mice."	AMPKα//hTERT//SIRT1//DOT-1L	Activation//Upregulation//Upregulation//Upregulation	Western blot	"Western blot：Metformin treatment resulted in a significant activation of AMPKα in early and late passage endothelial cells,albeit, the responsiveness was marginally more in early passage in comparison to late passage cells.Metformin and AICAR significantly increased hTERT levels by 8h. To explore if AMPKα-mediated hTERT expression involves SIRT1 activation, HAEC were treated either with metformin or AICAR and found that these AMPK activators increased SIRT1 levels.To test this, cells were treated either with AICAR or metformin. AMPK activators dose- and time-dependently enhanced DOT-1 L and H3K79 trimethylation (me3) in HAEC ."	--	--	--	--	L	cellular senescence	29366775
Sen_E_463	Ethanol	Chemical compounds	Endothelial cell	--	Atherosclerosis	Prevent	SA-β-gal activity assay	"Ethanol could decrease SA-β-gal positive cells in the plaque surface. Furthermore, to explore the effects of ethanol on endothelial cells, the ratio of Ac-p53/p16-to CD31-stained areas was assessed. The area ratios of Ac-p53/CD31 and p16/CD31 were significantly attenuated by ethanol, suggesting the inhibitory effects of ethanol on endothelial senescence."	ALDH2	Activation	Western blot	"In addition, the 0.3 g/kg dose of ethanol increased the protein expression and activity of ALDH2, while the lower and higher doses had little effect .The 0.3 g/kg dose of ethanol also increased the ALDH2-positive staining area. These results indicate that the appropriate dose of ethanol promotes ALDH2 activation in the artery vessel wall."	--	--	--	--	L	delay aging	30885430
Sen_E_464	Doxorubicin	Chemical compounds	MCF-7	--	Cancer	Accelerate	SA-β-gal activity assay//BrdU assay//Cell morphological analysis	"Doxorubicin induced a flat, senescence-like cell morphology, increased senescence-associated β-galactosidase (SA-β-gal)-positive cells to approximately 80%, and blunted BrdU incorporation into the DNA of proliferating cells by > 95% ;IFN-γ + TNF also induced the flat senescence-associated morphology,increased SA-β-gal activity."	Ago2	--	Western blot//Immunostaining//qPCR	Ago2 translocation could also be demonstrated by western blot analysis of nuclear extracts of doxorubicin-treated MCF-7 cells；Cytokine-induced translocation of Ago2 into the nucleus of MCF-7 cells was verified by western blot analysis of nuclear extracts. A204 rhabdomyosarcoma (blue dots) or MCF-7 breast cancer cells (red dots) confirmed the downregulation of all five cell cycle genes which are known to be regulated by Ago2. after 24 h and 48 h.	--	--	--	--	L	cellular senescence	30476917
Sen_E_465	IFN-γ	Chemical compounds	MCF-7	--	Cancer	Accelerate	SA-β-gal activity assay//BrdU assay//Cell morphological analysis	"Doxorubicin induced a flat, senescence-like cell morphology, increased senescence-associated β-galactosidase (SA-β-gal)-positive cells to approximately 80% , and blunted BrdU incorporation into the DNA of proliferating cells by > 95% ;IFN-γ + TNF also induced the flat senescence-associated morphology , increased SA-β-gal activity."	Ago2	--	Western blot//Immunostaining//qPCR	Ago2 translocation could also be demonstrated by western blot analysis of nuclear extracts of doxorubicin-treated MCF-7 cells；Cytokine-induced translocation of Ago2 into the nucleus of MCF-7 cells was verified by western blot analysis of nuclear extracts. A204 rhabdomyosarcoma (blue dots) or MCF-7 breast cancer cells (red dots) confirmed the downregulation of all five cell cycle genes which are known to be regulated by Ago2. after 24 h and 48 h.	--	--	--	--	L	cellular senescence	30476917
Sen_E_466	TNF	Chemical compounds	MCF-7	--	Cancer	Accelerate	SA-β-gal activity assay//BrdU assay//Cell morphological analysis	"Doxorubicin induced a flat, senescence-like cell morphology, increased senescence-associated β-galactosidase (SA-β-gal)-positive cells to approximately 80% , and blunted BrdU incorporation into the DNA of proliferating cells by > 95% ;IFN-γ + TNF also induced the flat senescence-associated morphology , increased SA-β-gal activity."	Ago2	--	Western blot//Immunostaining//qPCR	Ago2 translocation could also be demonstrated by western blot analysis of nuclear extracts of doxorubicin-treated MCF-7 cells；Cytokine-induced translocation of Ago2 into the nucleus of MCF-7 cells was verified by western blot analysis of nuclear extracts. A204 rhabdomyosarcoma (blue dots) or MCF-7 breast cancer cells (red dots) confirmed the downregulation of all five cell cycle genes which are known to be regulated by Ago2. after 24 h and 48 h.	--	--	--	--	L	cellular senescence	30476917
Sen_E_467	TMZ	Chemical compounds	"LN-229,U87 MG"	--	Aging	Accelerate	SA-β-gal activity assay//Immunofluorescence staining//SAHF	"TMZ is able to induce senescence in LN-229 and, to a lesser extent, in U87 MG cells. Senescence starts to become detectable 48 and 72 h after TMZ addition in LN-229 and U87 MG cells, respectively, and persisted over the whole post-incubation time period (up to 144 h). We also performed a cytochemical senescence detection assay using the chromogenic substrate 5-bromo-4-chloro-3-indoyl β-D-galactopyranoside (X-gal), which yields an insoluble blue compound when cleaved by β-gal. Further, we used another marker for senescence, the senescence-associated heterochromatic foci (SAHF), which are usually enriched for histone H3 methylated on lysine 9 (H3K9), which were not observed in non-treated but induced in TMZ-treated cells."	3-MA	--	Flow cytometry	 The data shows that 3-MA completely abolished senescence after TMZ treatment.	--	--	--	--	L	cellular senescence	23383259
Sen_E_468	Genistein	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry	"The effect of genistein on SA-β-gal activity was also observed and genistein was found to effectively suppress the expression of SA-β-gal in a dose-dependent manner.It was observed that treatment of HDFs with 40 and 80 mg/ml of genistein for 24 h decreased the number of early apoptotic cells (LR) significantly when compared to 18.1% in vehicle control (0 mg/ml) group.HDFs in G0/G1 phase was diminished in quantity upon different doses of genistein (20 mg/ml, 40 mg/ml, and 80 mg/ml), indicating a dose-dependent inhibition in cell cycle arrest by genistein."	 p66Shc//FKHRL1	Downregulation//Downregulation	Western blot//qRT-PCR	"p66Shc and FKHRL1 were significantly up-regulated by UVB irradiation, and genisteintreatment of HDFs result edinadose-dependent decrease in their expression. The phosphory-lation of p66Shc and FKHRL1 were also down-regulated by different concentrations of genistein, which indicated genistein, as one of antioxidants, counteracts the UVB-induced oxidative stress at least in part by regulating the expression and activation of p66Shc and FKHRL1 protein."	--	--	--	--	L	apoptosis	20211546
Sen_E_469	Purple sweet potato color	Other	--	Mice endothelium tissue	Cardiovascular disease	Prevent	SA-β-gal activity assay//Western blot	"In the HFD+PSPC group, the area of SA β-gal-positive region in vascular vessels was markedly decreased,PSPC treatment significantly increased the expression of SMP30 in the endothelium, similar to that in the control group,in which strong immunoreactivity for SMP30 was detected. Meanwhile, 50 or 100 μg/L PSPC obviously attenuated the proportion of senescent cells.Moreover, D-gal administration for 24 and 48 hours decreased the level of SMP30 in HUVECs in contrast with the control group, and PSPC reversed this phenomenon and recovered the expression of SMP30."	 NLRP3	Downregulation	Western blot//Immunofluorescence	"The results of western blot analysis showed that D-gal significantly increased the expression of NLRP3 in HUVECs as compared with that of vehicle control. On the contrary, PSPC administration depressed the amplification of NLRP3 induced by D-gal. A similar pattern of NLRP3 was observed for the immunofluorescence activities in the brachiocephalic artery of mice which were fed with HFD or HFD+PSPC."	--	--	--	--	L	delay aging	26164602
Sen_E_470	5-FU	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Western blot//Flow cytometry//Cell activity assay//ELISA//PI staining	"Treatment with DOXO and IRINO resulted in the marked increase of the size of cells and their nuclei, whereas no such effects were produced by OXA. Cells treated with 5-FU exhibited the intermediate morphological changes. All drugs induced growth arrest and the increase in cell granularity, as shown by SSC/FSC parameters measured by flow cytometry. It should be noted that treatment with DOXO and IRINO produced the largest HCT116cells . Moreover, the SA-β-galactosidase activity was the most pronounced in these cells. The fraction of SA-β-gal positive cells increased with every cycle of 5-FU treatment. Next, we analyzed the cell cycle distribution using PI staining.Following DOXO or IRINO treatment, the percentages of diploid cells in G0/G1 phase of the cell cycle were significantly reduced . The DOXO treatment decreased also fractions of diploid cells in the G2/M phase and/ or tetraploid cells arrested in the G0/G1 phase.Finally, DOXO or IRINO treatments produced the strongest increase in the fraction of polyploid cells. We found that 5-FU, DOXO, or IRINO treatment led to strong and prolonged accumulation of the cell cycle inhibitor - p21 and the geroconversion marker - CYCLIN D1 ,we showed that repeated cycles of IRINO and especially DOXO led to the marked augmentation of VEGF  and IL-8 secretion."	--	--	--	--	--	--	--	--	HL	repair AND renewal	29053388
Sen_E_471	OXA	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Western blot//Flow cytometry//Cell activity assay//ELISA//PI staining	"Treatment with DOXO and IRINO resulted in the marked increase of the size of cells and their nuclei, whereas no such effects were produced by OXA. Cells treated with 5-FU exhibited the intermediate morphological changes . All drugs induced growth arrest and the increase in cell granularity, as shown by SSC/FSC parameters measured by flow cytometry. It should be noted that treatment with DOXO and IRINO produced the largest HCT116cells. Moreover, the SA-β-galactosidase activity was the most pronounced in these cells .The fraction of SA-β-gal positive cells increased with every cycle of 5-FU treatment. Next, we analyzed the cell cycle distribution using PI staining.Following DOXO or IRINO treatment, the percentages of diploid cells in G0/G1 phase of the cell cycle were significantly reduced. The DOXO treatment decreased also fractions of diploid cells in the G2/M phase and/ or tetraploid cells arrested in the G0/G1 phase .Finally, DOXO or IRINO treatments produced the strongest increase in the fraction of polyploid cells. We found that 5-FU, DOXO, or IRINO treatment led to strong and prolonged accumulation of the cell cycle inhibitor - p21 and the geroconversion marker - CYCLIN D1 ,we showed that repeated cycles of IRINO and especially DOXO led to the marked augmentation of VEGF and IL-8 secretion."	--	--	--	--	--	--	--	--	HL	repair AND renewal	29053388
Sen_E_472	IRINO	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Western blot//Flow cytometry//Cell activity assay//ELISA//PI staining	"Treatment with DOXO and IRINO resulted in the marked increase of the size of cells and their nuclei, whereas no such effects were produced by OXA. Cells treated with 5-FU exhibited the intermediate morphological changes . All drugs induced growth arrest and the increase in cell granularity, as shown by SSC/FSC parameters measured by flow cytometry. It should be noted that treatment with DOXO and IRINO produced the largest HCT116cells. Moreover, the SA-β-galactosidase activity was the most pronounced in these cells .The fraction of SA-β-gal positive cells increased with every cycle of 5-FU treatment. Next, we analyzed the cell cycle distribution using PI staining.Following DOXO or IRINO treatment, the percentages of diploid cells in G0/G1 phase of the cell cycle were significantly reduced. The DOXO treatment decreased also fractions of diploid cells in the G2/M phase and/ or tetraploid cells arrested in the G0/G1 phase .Finally, DOXO or IRINO treatments produced the strongest increase in the fraction of polyploid cells. We found that 5-FU, DOXO, or IRINO treatment led to strong and prolonged accumulation of the cell cycle inhibitor - p21 and the geroconversion marker - CYCLIN D1 ,we showed that repeated cycles of IRINO and especially DOXO led to the marked augmentation of VEGF and IL-8 secretion."	--	--	--	--	--	--	--	--	HL	repair AND renewal	29053388
Sen_E_473	Doxorubicin	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Western blot//Flow cytometry//PI staining//ELISA	"On the 13th day the CHEMO-treated cells exhibited several features of senescence: flatten morphology , increased size and granularity , augmented SA-β-gal activity and polyploidization. Moreover, the elevated expression of DDR proteins: γ-H2A.X, p-p53, and p21, and geroconversion markers [7]: cyclin D1 and p-S6 was detectable. In addition, the cells up-regulated secretion of SASP factors: VEGF and IL-8 ."	--	--	--	--	--	--	--	--	L	repair AND renewal	28030837
Sen_E_474	Methylene blue	Chemical compounds	IMR-90	Liver	Aging	Prevent	Cell counting	"The life span of IMR90 cells in tissue culture at 20% O2 maintained with MB was extended by>20 PDL relative to controls, indicating a delay of cellular senescence."	--	--	--	--	--	--	--	--	L	cellular senescence	17928358
Sen_E_475	Doxorubicin	Chemical compounds	MCF-7	--	Breast cancer	Accelerate	SA-β-gal activity assay	"The MCF7 cells adhered to the etched coverslips and essentially grew as colonies. After 6 days, the cells on the coverslips were processed for β-galactosidase staining as described . Both doxorubicin (10-100 nM) and 4HT (50-1000 nM) induced senescence in MCF-7 cells in a dose-dependent fashion."	--	--	--	--	--	--	--	--	L	cellular senescence	21881167
Sen_E_476	4 hydroxytamoxifen	Chemical compounds	MCF-7	--	Breast cancer	Accelerate	SA-β-gal activity assay	"The MCF7 cells adhered to the etched coverslips and essentially grew as colonies. After 6 days, the cells on the coverslips were processed for β-galactosidase staining as described [109]. Both doxorubicin (10-100 nM) and 4HT (50-1000 nM) induced senescence in MCF-7 cells in a dose-dependent fashion."	--	--	--	--	--	--	--	--	L	cellular senescence	21881167
Sen_E_477	Cilostazol	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay	"Treatment with cilostazol inhibited the senescent phenotype induced by sirolimus or everolimus at 10 days. Under treatment with sirolimus or everolimus (2.5 nmol/l), 49.2% or 53.0% of cells were SA-βgal positive, versus only 13.6% or 14.6% of cilostazol (100 μmol/l)-treated cells under the same conditions."	--	--	--	--	--	--	--	--	L	cellular senescence	19520256
Sen_E_478	Cysteamine	Chemical compounds	ARPE?19	--	Aging	Prevent	SA-β-gal activity assay	CSE was observed to increase the number of blue cells while treatment with cysteamine or fisetin decreased the number of observed blue cells.	--	--	--	--	--	--	--	--	L	cellular senescence	28767736
Sen_E_479	Fisetin	Chemical compounds	ARPE?19	--	Aging	Prevent	SA-β-gal activity assay	CSE was observed to increase the number of blue cells while treatment with cysteamine or fisetin decreased the number of observed blue cells.	--	--	--	--	--	--	--	--	L	cellular senescence	28767736
Sen_E_480	Tc52	Chemical compounds	VH7	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Using the same pulse-treatment setup as before, we observed a time- and dose-dependent cellenlargement, accompanied by increasing SAβGal-activity. Tc53-treated cells were undistinguishable from controls. There was a clear gain in positive staining with time and concentration of Tc52."	--	--	--	--	--	--	--	--	L	cellular senescence	27412346
Sen_E_481	Gemcitabine	Chemical compounds	"Miapaca-2,PANC-1"	Tumor tissue	Patients with pancreatic ductal adenocarcinoma	Accelerate	SA-β-gal activity assay//qRT-PCR	"Gemcitabine efficiently induced senescence in Miapaca-2 and Panc-1 cells in a dose-dependent manner but not in L3.6 pl cells (data not shown), as evidenced by increased SA β-gal staining. Moreover, gemcitabine significantly increased the levels of senescence-associated molecules including P53, P21, P19, PML, and DCR2 in Miapaca-2 and Panc-1 cells, except P53 in Panc1 cells ."	--	--	--	--	--	--	--	--	L	cellular senescence	27311854
Sen_E_482	Doxorubicin	Chemical compounds	"HCT116,H1299"	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	Activation of the DNA damage response (DDR) pathway was accompanied by the appearance of such markers of senescence as increased SA-β-Gal activity and cell cycle arrest.	--	--	--	--	--	--	--	--	L	cellular senescence	29352261
Sen_E_483	Rg3	Chemical compounds	Chondrocyte	Bone	Osteoarthritis	Prevent	SA-β-gal activity assay//Telomerase activity assay	"To examine the effect of Rg3 on chondrocyte senescence, we measured SA-β-Gal activity 5 days after exposure of the cells to IL-1b, with or without Rg3, for 24 h.IL-1b stimulation resulted in a significant increase in the numbers of SA-β-Gal-positive cells in comparison with control cells treated with the vehicle alone. However, co-incubation with IL-1b and Rg3 significantly suppressed expression of the senescence marker.Rg3 at 1 and 2.5 lM significantly increased the telomerase activity of chondrocytes in comparison with IL-1b-treated cells."	--	--	--	--	--	--	--	--	L	cellular senescence	22454193
Sen_E_484	EGCG+SFN25	Chemical compounds	HT29	--	Colorectal cancer	Prevent	SA-β-gal activity assay	"HT-29 AP-1 cells, when cultured on cover slips and exposed to individual treatment of EGCG (20 or 100 mM) for 24 h, showed induction of senescence which was not observed in the case of SFN25 mM.Interestingly,on combining EGCG with SFN,the EGCG-associated senescence was attenuated."	--	--	--	--	--	--	--	--	L	cellular senescence	17657594
Sen_E_485	Urolithin A	Chemical compounds	HSF	--	Aging	Prevent	qRT-PCR//Western blot	"Collagen mRNA expression was significantly increased in cells treated with 20 μM and 50 μM urolithin A, and mRNA expression of MMP-1 significantly decreased in a urolithin A dose-dependent manner.We found that type I collagen expression in urolithin A-treated cells was upregulated, while MMP-1 expression was significantly downregulated. After a 5-day treatment with urolithin A, the intracellular ROS level was significantly reduced., suggesting that urolithin A attenuated ROS in senescent cells."	--	--	--	--	--	--	--	--	L	cellular senescence	30215291
Sen_E_486	PD-0332991	Chemical compounds	"MCF-7,LCC9"	--	Aging	Accelerate	SA-β-gal activity assay	"Interestingly, while PD-0332991 treatment resulted in a significant fraction of cells staining positively for senescence-associated β-galactosidase (in agreement with other studies), endocrine therapy did not mediate this response."	--	--	--	--	--	--	--	--	HL	cellular senescence	21367843
Sen_E_487	Pyocyanin	Chemical compounds	HepG2	--	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay	"Exposure of HepG2 cells to pyocyanin resulted in the expression of SA-β-gal activity.Control cells expressed low SA-β-gal activity, while cells treated  with  pyocyanin  (2–40 ug ml-1)  exhibited increased SA-β-gal activity in a concentration-dependent manner (data not shown)."	--	--	--	--	--	--	--	--	L	cellular senescence	24461061
Sen_E_488	Sulforaphane	Chemical compounds	"MCF-7,SK-BR-3,MDA-MB-231"	--	Breast cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"An increase of 12.1 and 10.7% in the levels of MCF-7 and MDA-MB-231 cells in the G2/M phase of the cell cycle and an increase of 5.8% in the levels of SK-BR-3 cells in the G0/G1 phase of the cell cycle were observed after 10 μM SFN treatment.After 7 days of SFN removal(5  and  10  μM),an  increase  in senescence-associated  beta-galactosidase (SA-β-gal)-positive cells was observed in three breast cancer cells considered ."	--	--	--	--	--	--	--	--	HL	cellular senescence	28912888
Sen_E_489	Palbociclib	Chemical compounds	"HuH-7,SK-HEP-1"	Patient-derived HCC tissue	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Only two of the cell lines, Huh7 and skHep1, were consistently positive for staining. Furthermore, after palbociclib treatment, these two cell lines displayed flat and enlarged morphology, suggesting that they could have undergone senescence.Analysis of tumours collected after treatment with vehicle or palbociclib (for 16?days) showed that palbociclib-treated tumours were positive for the senescence marker SAβGAL ."	--	--	--	--	--	--	--	--	L	cellular senescence	27849562
Sen_E_490	6-diazo-5-oxo-L-norleucine	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"Exposure of both, early-passage (20 PDL) and late-passage (52 PDL) HUVEC cultures to DON strongly inhibited cell proliferation. Furthermore, exposure of early-passage HUVEC to the glutaminase inhibitor induced phenotypic alterations typically of premature senescence within two passages,The percentage of SA-β gal positive cells increased from 7.4 ± 1% to 25 ± 3% in young HUVEC exposed to 10 lM DON, and reached 66.0 ± 4% when 40 lM DON was used."	--	--	--	--	--	--	--	--	L	cellular senescence	18317946
Sen_E_491	Doxorubicin	Chemical compounds	"A549,MCF-7"	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"SA-β-gal activity assay:Both GFP and FLAG-Wip1 expressing cells acquired a fully senescent phenotype, with morphological alterations and SA-β-gal staining typical of premature senescent cells."	--	--	--	--	--	--	--	--	L	cellular senescence	23612976
Sen_E_492	CANE	Chemical compounds	"A549DR,A549"	--	Lung cancer	Accelerate	SA-β-gal activity assay	A significantly (p < 0.05) 7.5- fold higher SA-β-gal expression was observed in the cells treated with 50 lg/ml CANE compared to control.	--	--	--	--	--	--	--	--	L	cellular senescence	29405784
Sen_E_493	Doxorubicin	Chemical compounds	MKN28	--	Gastric cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//SAHF//Cell morphological analysis	"After treatment, most cells became flattened and had comparatively enlarged morphology. Positive level of senescence-associated SA-β-gal staining was increased in AGS cells; SAHF formation increased in treated MKN28 cells. Flow cytometry analysis demonstrated that proportions of cells in G0/G1 phase ncreased in treated cells. In MKN28 cells, we also noticed a significant increase in proportions of cells in G2/M ."	--	--	--	--	--	--	--	--	L	cellular senescence	24738879
Sen_E_494	Doxorubicin	Chemical compounds	"HEC-1B,Ishikawa"	--	Endometrioid adenocarcinoma	Accelerate	SA-β-gal activity assay	"After the treatment with 0.1 μg/ml DOX for 120 h, among the cells that remained in the HEC-1B and Ishikawa cultures, 100% cells were β-galactosidase-positive. These data thus confirmed that treatment of cells of HEC-1B and Ishikawa lines with DOX for 120 h induces cell senescence in at least a portion of the population."	--	--	--	--	--	--	--	--	L	cellular senescence	20372780
Sen_E_495	Curcumin	Chemical compounds	"MCF-7,HCT116"	--	Cancer	Accelerate	SA-β-gal activity assay//Cell cycle analysis	The increased activity of SA-β-gal was confirmed by the flow cytometry measurement of C 12 FDG fluorescence.Cell cycle analysis revealed that in both cancer cell lines one-day treatment with curcumin led to arrest of the cells in the G2/M phase of the cell cycle.	--	--	--	--	--	--	--	--	L	cellular senescence	26916504
Sen_E_496	Disulfiram and doxorubicin	Chemical compounds	MDA-MB-231	--	Breast cancer	Accelerate	SA-β-gal activity assay	"We found that doxorubicin or DSF treatment cultures showed X-gal-positive cells (29.9% and 23.0%, respectively), and that doxorubicin plus DSF treatment resulted in an additive effect (42.4%)."	--	--	--	--	--	--	--	--	L	cellular senescence	23974104
Sen_E_497	Condurango-glycoside-A	Chemical compounds	HeLa	--	Cervical cancer	Accelerate	SA-β-gal activity assay// Cell Cell proliferation assay//PI staining//Flow cytometry	"β-galactosidase activity was tested in the treated cells;The growth in the CGA-treated (0.12, 0.24 and 0.36 lg/ll) HeLa cells decreased gradually dose dependently, but not in the control cells;CGA induced cell cycle arrest in the HeLa cells."	--	--	--	--	--	--	--	--	L	cellular senescence	23807740
Sen_E_498	IS	Chemical compounds	MSC	--	Aging	Accelerate	SA-β-gal activity assay	The results showed that IS treatment increased the number of MSCs that stained positive for SA-β-gal activity and that IS increased senescence of MSCs in a concentration-dependent manner.	--	--	--	--	--	--	--	--	L	cellular senescence	29734669
Sen_E_499	Ligusticum chuanxiong	Chemical compounds	HMSC	--	Aging	Prevent	SA-β-gal activity assay	The results showed that L. chuanxiong was able to decrease the level of senescence of the hMSCs after five passages in culture.	--	--	--	--	--	--	--	--	L	cellular senescence	28040510
Sen_E_500	DHJST	Chemical compounds	HMSC	--	Aging	Prevent	SA-β-gal activity assay	The results showed that DHJST was able to decrease the level of senescence of the hMSCs after five passages in culture.	--	--	--	--	--	--	--	--	L	cellular senescence	28040510
Sen_E_501	Co-EPM	Chemical compounds	HL60	--	Malignant mesothelioma	Accelerate	SA-β-gal activity assay	"Co-EPM gave a significant amount of senescent cells (con-centrations above 10 mM, p o 0.001, paired t-test)."	--	--	--	--	--	--	--	--	L	cellular senescence	24057048
Sen_E_502	STR1720	Chemical compounds	MDA-MB-231	--	Breast cancer	Prevent	SA-β-gal activity assay	Activation of SIRT1 via SRT1720 decreased senescence induction.	--	--	--	--	--	--	--	--	L	cellular senescence	29653746
Sen_E_503	EX527	Chemical compounds	MDA-MB-231	--	Breast cancer	Accelerate	SA-β-gal activity assay	24 h after EX527 treatment we recognized an increase in senescence where the cellular death rate dropped beneath the control cultures insignificantly.	--	--	--	--	--	--	--	--	L	cellular senescence	29653746
Sen_E_504	Homocysteine	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"Coculture of HUVECs with homocysteine resulted in an increase in percentage of SA-β-gal-positive cells with a maximum effects achieved at 4 μM . In the prolonged culture, the number of SA-β-gal-positive cells at 4μM progressively rose from ~5% at day 1 to 24% at day 7. Over the 7-day period in culture, homocysteine produced as much as about five-fold increase in the percentage of senescent endothelial cells."	--	--	--	--	--	--	--	--	L	cellular senescence	23336586
Sen_E_505	ROS	Chemical compounds	UCB-MSC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"After treatment with hydrogen peroxide, the level of intracellular ROS was measured using H2DCFDA, which is converted to a fluorescent product, DCF, upon oxidation [37]. The ROS accumulation after hydrogen peroxide treatment in hUCB-MSCs was greater than that in human fibroblast and cancer cells.While the morphologies of the human fibroblast cells did not change significantly, hUCB-MSCs became larger and flatter after treatment with hydrogen peroxide. Staining cells with SA-β-Gal, a marker for detecting cellular senescence, revealed that hUCB-MSCs underwent senescence."	--	--	--	--	--	--	--	--	L	cellular senescence	22066510
Sen_E_506	Docosahexaenoic acid	Chemical compounds	RPE	--	Aging	Accelerate	SA-β-gal activity assay	"Under the same light intensity, the ageing rate of RPE cells was significantly (p < 0.01) higher in the presence than in the absence of DHA .Light exposure at 3500 lux for 24 h in the presence of 25 lM DHA increased the percentage of senescent cells from 49.7% ± 4.6% to 68.3% ± 1.5%."	--	--	--	--	--	--	--	--	L	cellular senescence	25108204
Sen_E_507	H2O2	Chemical compounds	NIH-3T3	--	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay//qRT-PCR//Western blot//DAPI staining//Flow cytometry	"SA-β-gal activity assay: H2O2-treated NIH3T3 cells gradually  became enlarged, flattened and were largely positive for SA-GLB1 staining from day 3. DAPI:The SAHFs in these cells were evident as large and irregularly shaped  nuclear puncta. The arrest of cell growth was apparent,Western blot:and the levels of TRP53 protein. qRT-PCR:and Cdkn1a, and Il6 mRNA were elevated. Flow cytometry:H2O2  treatment also elevated intracellular ROS ."	--	--	--	--	--	--	--	--	L	cellular senescence	27791464
Sen_E_508	H2O2	Chemical compounds	Chondrocyte	--	Aging	Accelerate	SA-β-gal activity assay//Telomere length assay//Cell morphological analysis//Cell Cell proliferation assay	"SA-β-gal activity assay:Early passage chondrocytes incubated with sub-lethal doses of H2O2 (75–100 mM) showed characteristic features of senescence concerning morphology and positive β-galactosidase staining. Following treatment with sub-lethal doses of H2O2, a significant decrease of proliferation rate was detected in early. Determination of Telomere Length:correlated with cpd in both groups (p < 0.01). With prolonged H2O2 treatment, significant increase in telomere shortening occurred."	--	--	--	--	--	--	--	--	L	cellular senescence	21284033
Sen_E_509	PFG	Chemical compounds	"TIG-1,HeLa"	--	Aging	Accelerate	SA-β-gal activity assay//MTT assay//Flow cytometry	"MTT assay:PFG inhibited the proliferation of both cells in a dosedependent manner. SA-β-gal activity assay:PFG treatment resulted in the expression of SA-β-gal in the non-cancerous TIG-1 cells in a dose-dependent manner. Flow cytometry:PFG produced highly significant increment of cells in sub G1, S and G2/M, along with the reduction of cells in G0/G1."	--	--	--	--	--	--	--	--	L	cellular senescence	30836860
Sen_E_510	H2O2	Chemical compounds	MEF	--	Aging	Accelerate	SA-β-gal activity assay	"SA-β-gal activity assay:The proportion of SA-β-galactosidase-positive cells was 60.5% among H2O2-treated cells, but less than 10% among untreated cells, at day 9."	--	--	--	--	--	--	--	--	L	cellular senescence	23623979
Sen_E_511	ROS	Chemical compounds	NPC	NP tissue	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"The H2O2-induced oxidative stress did significantly increase the population of G1 phase cells, and the percentage SA-β-Gal-positive cells (blue), and staining intensity ."	--	--	--	--	--	--	--	--	L	cellular senescence	29890141
Sen_E_512	Trichostatin A	Chemical compounds	U87	--	Glioblastoma	Accelerate	Flow cytometry//SA-β-gal activity assay//NMA analysis	"Although the TSA-induced reduction in the number of colonies formed 10 days after treatment did not reach statistical significance, TSA produced a mean decrease of 30, 73, and 53 %, respectively, in colony sizes. The results suggest that TSA inhibits the proliferation and survival of U87 GBM cells. In addition, TSA at 500 nM induced G2/M cell-cycle arrest.The presence of senescent cells was confirmed by a SA-β-galactosidase activity assay, in which senescent cells displayed morphological alterations similar to those observed in the NMA analysis."	--	--	--	--	--	--	--	--	L	cellular senescence	24464841
Sen_E_513	JQ-101	Chemical compounds	"LNCaP,PC-3,H1299,A549"	--	Cancer	Accelerate	SA-β-gal activity assay//Transwell assay//MTS assay	"JQ-101 suppressed LNCaP and H460 tumor cell growth in a dose-dependent manner.Transwell chamber assay system with matrigel coated on the top of an ECM-like membrane to prevent the transmigration of non-invasive cells. Exposure to JQ-101 significantly decreased invasion compared to vehicle control, producing a 3.5-fold reduction in PC3 cell invasion and a 4.2-fold reduction in A549 cells.In contrast,apoptosis was not observed in H1299 cells (data not shown);instead, JQ-101 treatment induced cell senescence in H1299cells."	--	--	--	--	--	--	--	--	L	cellular senescence	25189993
Sen_E_514	H2O2	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"To investigate whether our findings regarding TF inducibility were present in other forms of senescence, we exposed young HUVECs to 200 mM H2O2 for 2 h. This invoked stress-induced premature senescence (SIPS), which was manifested by growth arrest and positive staining for SA-β-gal in about 50% of cells ."	--	--	--	--	--	--	--	--	L	cellular senescence	25038529
Sen_E_515	NO?	Chemical compounds	Fibroblast	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Immunofluorescence	"Treatment with 3 μM and 10 μM, but not 0.9 μM, Sper/NO? induced enlarged SA-βgal positive cells .Sper/NO? treated cells showed increased levels of γH2A.X foci, compared to untreated control cells ."	--	--	--	--	--	--	--	--	HL	cellular senescence	22970173
Sen_E_516	SAHA	Chemical compounds	MSC	--	Aging	Prevent	SA-β-gal activity assay	"Conversely, in cells treated with SAHA, we detected a reduction of senescent cells as compared to the control."	--	--	--	--	--	--	--	--	L	cellular senescence	18694296
Sen_E_517	MS-275	Chemical compounds	MSC	--	Aging	Accelerate	SA-β-gal activity assay	The MS-275 treatment induced an increase in senescent cells as detected by a senescence-associated β-galactosidase assay.	--	--	--	--	--	--	--	--	L	cellular senescence	18694296
Sen_E_518	H2O2	Chemical compounds	Chang	--	Aging	Accelerate	Cell morphological analysis//SA-β-gal activity assay	"Under exposure to subcytotoxic doses (100–200 mM), however, the cells gained senescent phenotypes, demonstrated by an acquisition of SA-β-gal activity with enlarged cellular morphology and increase of cellular granularity ."	--	--	--	--	--	--	--	--	L	cellular senescence	16883569
Sen_E_519	N-Acetylcysteine	Chemical compounds	Endothelial cell	--	Aging	Prevent	Flow cytometry//PCR//SA-β-gal activity assay//Telomerase activity assay	"Incubation with N-acetylcysteine starting from populationdoubling 26 prevented the increase in ROS formation and the reduction of intact mitochondrial DNA. Furthermore, the reduction of nuclear TERT activity was blocked by N-acetylcysteine. Moreover, N-acetylcysteine prevented the reduction in overall TERT activity during further passaging and delayed the onset of replicative senescence."	--	--	--	--	--	--	--	--	L	delay aging	14963003
Sen_E_520	Atorvastatin	Chemical compounds	Endothelial cell	--	Aging	Prevent	Flow cytometry//PCR//SA-β-gal activity assay//Telomerase activity assay	"Increase in ROS formation was significantly reduced by atorvastatin. Incubation with atorvastatin also inhibited the loss of intact mitochondrial DNA and abrogated the reduction of nuclear and overall TERT activity and protein. Furthermore, incubation with atorvastatin delayed the onset of senescence of endothelial cells ."	--	--	--	--	--	--	--	--	L	delay aging	14963003
Sen_E_521	L2-Cmu	Chemical compounds	--	Heart	Aging	Prevent	PI stainingng//ELISA	"L2-Cmu treatment in females did not adversely affect cardiac function, but instead restored diastolic function to more youthful levels.Importantly, late-life L2-Cmu treatment improved mean lifespan (P=0.023) and increased median lifespan by 9% (P=0.03) in females. Aging in females was characterized by a significant rise in IL-1β, IL-4, IL-5, IL-6, IL-10,IL-12(p40), IL-12(p70), IL-17, CXCL-10, CXCL-1, MIP-1α, MIP-2, and TNFα, but several of these cytokines and chemokines were restored to a more youthful level with mAb treatment. In contrast, only G-CSF, IL-6,and RANTES were elevated in old male plasma, but mAb treatment led to a marked increase in the majority of these markers."	--	--	--	--	--	--	--	--	L	delay aging	29921922
Sen_E_522	C-phycocyanin	Chemical compounds	--	"Kidney,Spleen,Ovary"	Aging	Prevent	Cell morphological analysis	"Surprisingly, the organ coefficients of ovary, spleen, and kidney from control and D-gal+PC groups were higher than those of the D-gal group .These data indicate that D-gal may impair the ovary, spleen, and kidney, and that this damage can be reversed partially by PC.Conversely, after PC administration most D-gal-induced oocytes showed normal morphology, similar to the control group . For both the in vivo and in vitro maturation models, we found that the aneuploidy rate of sister chromatids was higher in the D-gal group compared to control (P < 0.001). After PC administration, decreased percentages of aneuploidy oocytes were observed both in vivo and in vitro (P < 0.001)."	--	--	--	--	--	--	--	--	L	delay aging	27008700
Sen_E_523	Quercetin	Chemical compounds	RPE	--	Aging	Prevent	SA-β-gal activity assay	This increase in cellular senescence was significantly attenuated by preincubation with quercetin in a dose-dependent manner.	--	--	--	--	--	--	--	--	L	delay aging	18385095
Sen_E_524	JQ1	Chemical compounds	MKN28	--	Gastric cancer	Accelerate	SA-β-gal activity assay//Western blot	"When MKN28 cells treated with two different doses of JQ1 for 3 days and the activity of SA-β-Gal was measured, we observed a dose-dependent increased number of SA-β-Gal-positive cells with enlarged and flattened shape. Consistently, the expression of p21, a senescence marker, was dramatically induced by different doses of JQ1 while the levels of Cyclin B1 were down-regulated in JQ1-treated MKN28 or SGC-7901 cells.Consistently, the expression of p21, a senescence marker, was dramatically induced by different doses of JQ1 while the levels of Cyclin B1 were down-regulated in JQ1-treated MKN28 or SGC-7901 cells."	--	--	--	--	--	--	--	--	L	delay aging	29434197
Sen_E_525	Protease inhibitors	Chemical compounds	Fibroblast	--	Lipodystrophic syndromes	Accelerate	SA-β-gal activity assay//BrdU assay	"Strong cellular staining for 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal) at pH 4, indicating physiological lysosomal β-galactosidase activity, was detected in control fibroblasts and in those bearing LMNA mutations or treated with PIs.LMNA mutations and PI treatment also induced a striking decrease in fibroblasts’ replicative capacity, measured in terms of bromodeoxyuridine (BrdU) incorporation in halfconfluent cells ."	--	--	--	--	--	--	--	--	L	delay aging	17612587
Sen_E_526	Tenovin-6	Chemical compounds	HF043	--	Aging	Accelerate	SA-β-gal activity assay//Immunostaining	"We found that treated cells had dramatic increases in both SAβGAL and Lysotracker staining ,compared to the controls (DMSO). These changes are indicative of lysosomal stress and induction of senescence.Notably, we also observed a statistically significant increase in mean nuclear area from 200 lm2 in control cells to 245 lm2 which occurred after only 72 h TnV6 treatment.We observed a dramatically increased and highly reticular mitochondrial load following TnV6 treatment, compared to control proliferating fibroblasts (DMSO alone) which exhibited a low mitochondrial load, with the majority of cells showing a perinuclear distribution of mitochondria.A marked increase in senescent-like actin stress fibres was observed in cells treated with TnV6 compared with vehicle-only control cells, which showed more diffuse actin patterns characteristic of proliferating cells ."	--	--	--	--	--	--	--	--	L	delay aging	30666570
Sen_E_527	ATRA	Chemical compounds	NB4	--	Acute leukemia	Accelerate	SA-β-gal activity assay//Immunofluorescence//Western blot	"Consistent with this notion, prolonged ATRA treatment (7 d) of human NB4 cells markedly induced the expression of senescence-associated beta-galactosidase (SA-β-Gal), as indicated by LacZ staining. Furthermore, expression of the cell-cycle regulators p21 and p19 was increased with ATRA treatment, as shown by immunohistochemistry and Western blot analyses."	--	--	--	--	--	--	--	--	L	delay aging	25092303
Sen_E_528	Antioxidant	Chemical compounds	NIH-3T3	--	Aging	Prevent	SA-β-gal activity assay	"H2O2 alone (not in combination with quercetin) promoted the expression of senescence-associated β-galactosidase activity in NIH 3T3 cells. However, quercetin successfully prevented this H2O2-induced premature senescence.Treatment with vitamin E successfully prevented the H2O2-induced expression of acid β-galactosidase activity."	--	--	--	--	--	--	--	--	L	delay aging	12134086
Sen_E_529	Doxorubicin	Chemical compounds	MSC	--	Aging	Accelerate	Cell proliferation assay//MTT assay//qRT-PCR	"When MSCs were treated with DOXO at a concentration of 5 mol/l, the proliferation rate decreased significantly, starting immediately after treatment and lasting for 7 days . Furthermore, DOXO treatment significantly decreased MSC viability compared with the control group, as measured by the MTT assay.Furthermore, the expression of the senescence-associated genes cellular tumor antigen p53 and p16 was significantly increased in the DOXO treatment group compared with the control group ."	--	--	--	--	--	--	--	--	L	delay aging	29207187
Sen_E_530	SB203580	Chemical compounds	HCEC	--	Aging	Prevent	SA-β-gal activity assay	"The percentage of SA-β-gal positive cells was significantly lower in HCECs treated with SB203580 than in control cells (25.2% and 64.9% [passage 3],25.5% and 71.3% [passage 4], and 35.2% and 63.1% [passage 5], respectively). Western blotting analysis demonstrated that the expression of p16 and p21 was reduced in the cells cultured with SB203580, whereas HCECs expressed high levels of p16 and p21 in the absence of SB203580."	--	--	--	--	--	--	--	--	HL	delay aging	28672399
Sen_E_531	Bleomycin	Chemical compounds	HAEC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Interestingly, HAECs displayed enlarged size, flattened morphology as premature senescence-like phenotype.The rate of senescent cells was significantly increased in bleomycin-treated group compared with the control group."	--	--	--	--	--	--	--	--	L	delay aging	27878894
Sen_E_532	Bleomycin	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"SA-β-galactosidase activity, as senescence marker in the cells .It has been shown that bleomycin could significantly induce HUVECs undergoing senescence in a dose- and time-dependent manner."	--	--	--	--	--	--	--	--	L	delay aging	28064010
Sen_E_533	Etoposide	Chemical compounds	"HepG2,U2OS"	--	Liver cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis//Flow cytometry	"In any case, U2OS cells treated with etoposide finally represented the features of senescent cells, including cell cycle arrest, enlarged morphology, and the SA-β-Gal activity within 7 days."	--	--	--	--	--	--	--	--	L	delay aging	24223226
Sen_E_534	Bleomycin	Chemical compounds	U2OS	--	Liver cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Furthermore, another DNA damage-inducing drug bleomycin, which has a different mode of action from etoposide to induce DNA double-strand breaks, also induced premature senescence in U2OS cells."	--	--	--	--	--	--	--	--	L	delay aging	24223226
Sen_E_535	NAC	Chemical compounds	"A375,NIH-3T3"	--	Aging	Prevent	SA-β-gal activity assay//SAHF//Western blot	"The results show that AAPH dramatically increased the SA β-Gal activity in A375 and NIH3T3 cells, which was significantly suppressed by NAC.AAPH caused robust SAHF formation in A375 cells,which was significantly reduced by NAC .Co-treatment with NAC reversed the AAPH-induced activation of the p53-p21 pathway."	--	--	--	--	--	--	--	--	L	delay aging	30555576
Sen_E_536	Caffeine	Chemical compounds	"A375,NIH-3T3"	--	Aging	Prevent	SA-β-gal activity assay//SAHF//Western blot	"We found that caffeine indeed inhibited AAPH-induced increase in the SA β-Gal activity in A375 and NIH3T3 cells. Further, caffeine suppressed AAPH-induced SAHF formation in A375 cells, increases in p53 phosphorylation and p21 protein levels both in A375 and in NIH3T3 cells."	--	--	--	--	--	--	--	--	L	delay aging	30555576
Sen_E_537	Rapamycin	Chemical compounds	HCAEC	--	Aging	Prevent	SA-β-gal activity assay//Cell cycle assay//qRT-PCR	"We found that SA-β-Gal activity in rapamycin-treated HCAECs was clearly reduced with every schedule of rapamycin treatment,It was observed that the H2O2-treated HCAECs had a higher G2/M fraction than the control HCAECs (24.0 ± 1.8% vs. 12.2 ± 4.8%), wherein the rapamycin-treated HCAECs revealed a comparatively higher G2/M fraction than that of H2O2-treated HCAECs (I, 29.4 ± 1.8%; II, 28.1 ± 5.3%; III, 27.5 ± 3.7%; IV, 29.2 ± 4.7% vs. H2O2-treated, 24.0 ± 1.8%).The levels of these including IL-1α, IL-1β, IL-8, GROα, TNFα, MCP1, and GMCSF were significantly upregulated with SIPS. However, in rapamycin-treated HCAECs, all examined SASP factors were drastically reduced with every schedule of rapamycin treatment."	--	--	--	--	--	--	--	--	L	delay aging	32164764
Sen_E_538	Bleomycin	Chemical compounds	HCA2	--	Aging	Accelerate	SA-β-gal activity assay//RT-PCR//Western blot	"We exposed presenescent human fibroblasts (strain HCA2) to a senescenceinducing dose of bleomycin, which generates extensive DNA damage. RT-PCR showed that, relative to untreated presenescent controls, transcripts encoding both proteins increased steadily over 7 days. Quantitative real time PCR (qPCR) confirmed a 6- to 7-fold senescence-associated increase in these transcript levels. The gradual increase over several days matched the kinetics with which the SASP develops (10). In these and subsequent experiments, we confirmed senescence by growth arrest (not shown), morphology, and staining for senescence-associated -galactosidase (SA-β-gal),Both proteins were barely detectable in presenescent cells, but the levels increased significantly when cells became senescent."	--	--	--	--	--	--	--	--	L	delay aging	19805069
Sen_E_539	4-hydroxytamoxifen	Chemical compounds	ALT	--	Acute leukemia	Accelerate	SA-β-gal activity assay//BrdU assay//Western blot	"After 4 d of 4OHT treatment, many of the cells had undergone the characteristic morphological changes of senescence and stained positive for senescence-associated (SA) β-galactosidase (SA-β-gal) activity . Most of the cells that were morphologically senescent contained APBs, Triple staining for BrdU, p21, and TRF1 revealed that most of the APB-positive cells were p21 positive and BrdU negative ."	--	--	--	--	--	--	--	--	L	delay aging	19468068
Sen_E_540	Resveratrol	Chemical compounds	HCPC	--	Heart failure	Prevent	SA-β-gal activity assay//Western blot	"However, with respect to DOXO, DOXO + RES co-treatment resulted in a significant reduction in p16INK4a expression (27% vs DOXO). These data were confirmed by a substantial reduction (76% vs DOXO) of β-galactosidase enzymatic activity assay. Thus, the treatment with RES prevented the onset of senescence in hCPCs."	--	--	--	--	--	--	--	--	L	delay aging	25889431
Sen_E_541	Rapamycin	Chemical compounds	Fibroblast	--	Dyskeratosis congenita	Prevent	SA-β-gal activity assay	"We performed ?-galactosidase assays to test if the prolonged survival in the rapamycin treated fibroblast cultures of the patient (II-2) correlated with decreased senescence. We detected decreased senescence in the control fibroblasts, fibroblasts of the mother I-2 and the affected patient II2 at day 30 when treated with rapamycin."	--	--	--	--	--	--	--	--	HL	delay aging	26546739
Sen_E_542	H2O2	Chemical compounds	BM-MSC	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"In the control cells, only 9.3 ± 1.9% cells were positive for SA-β-gal staining but, after treatment with H2O2, the percentage of SA-β-gal-positive cells increased to 63.5 ± 5.8% at 100 μM, 86.4 ± 5.4% at 200 μM, and 93.4 ± 7.3% at 400 μM. Furthermore, the cell cycle phase distribution was examined. Cells treated with 100 μM and 200 μM H2O2 exhibited a significantly increased proportion in the G0/G1 phase (by 11.1% and 11.9% in comparison to the control, respectively). Meanwhile, H2O2-treated cells showed a lower percentage in the S phase (10.2 ± 0.9% in control cells, 3.5 ± 1.3% at 100 μM, and 3.7 ± 0.2% at 200 μM)."	--	--	--	--	--	--	--	--	L	delay aging	25975679
Sen_E_543	N-acetylcysteine	Chemical compounds	Keratinocyte	--	Aging	Prevent	SA-β-gal activity assay	"NAC pretreatment of HaCaT and HEK001 cells and NHEKs reduced senescence, as evidenced by a decrease in the β-galactosidase activity induced by PM2.5 treatment."	--	--	--	--	--	--	--	--	HL	delay aging	31551408
Sen_E_544	Capecitabine	Chemical compounds	Endothelial cell	--	Aging	Accelerate	SA-β-gal activity assay	"Compared with sera obtained prior to starting capecitabine, those samples taken at the end of treatment significantly increased the frequency of SA β‐gal positive cells.Measurement of sVCAM‐1 and sICAM‐1 concentrations in the same sera revealed that levels of sVCAM‐1 were significantly higher after than before chemotherapy. By contrast, there was no statistically significant elevation in sICAM‐1 values, although a tendency for that direction was noted. Furthermore, concentrations of CD146 significantly increased after treatment."	--	--	--	--	--	--	--	--	L	delay aging	28127745
Sen_E_545	Glucocorticoid	Chemical compounds	MSC	--	Aging	Accelerate	ELISA//qRT-PCR//Knockdown	"The proliferation rates of MSCs 4 weeks after being treated to block endogenous GCs were significantly higher than controls .Treatment with RU486 or GR siRNA significantly up-regulated the expression of telomerase mRNA . The telomere lengths of MSCs treated with RU486 were significantly longer than those in controls . The MSCs treated with GR siRNA also had relatively longer telomeres than those in controls, but the differences are marginally significant (p=0.0625). In addition, total SOD activity, which is a key antioxidant, was 30–40% higher in MSCs that had been treated with RU486 or GR siRNA than in controls and these differences were statistically significant."	--	--	--	--	--	--	--	--	L	delay aging	23963647
Sen_E_546	C75	Chemical compounds	HSC	--	Aging	Prevent	SA-β-gal activity assay//Western blot//BrdU assay//RT-PCR	"C75 treatment of HSCs showed a marked ability to prevent the activation of the senescent phenotype indicated by higher levels of BrdU staining and low SA-β-gal activity . Senescent cells treated with C75 significantly reduced IL1A, IL1B and IL6 mRNA levels in HSCs.Significant inhibition of cell cycle inhibitors and SASP genes in RAS-induced senescent cells were observed after treatment with C75."	--	--	--	--	--	--	--	--	L	delay aging	30962418
Sen_E_547	Palmitic acid	Chemical compounds	HepG2	--	Aging	Accelerate	qPCR//SA-β-gal activity assay//Western blot	"PA treatment led to a reduction of SMARCD1 expression in HepG2 cell, and induced cellular senescence in HepG2 cells, demonstrated by an increased number of cells with high levels of SA-β-Gal activity, p16/p21 expression, p-p38 expression, and γH2AX expression in the PA-treated HepG2 cells."	--	--	--	--	--	--	--	--	L	delay aging	28868154
Sen_E_548	Everolimus	Chemical compounds	B220	--	Eμ-Myc lymphoma	Accelerate	SA-β-gal activity assay//Western blot	"Everolimus treatment was associated with robust acquisition of senescence-associated β-galactosidase (SA-β-gal) activity in tumors after 4 and 7 days of treatment that was lost upon disease relapse at day 11, indicating that they no longer retain the capacity to undergo senescence . Consistent with a senescence response, activation of the senescence regulatory kinase p38 mitogen-activated protein kinase (p38MAPK) occurred after 4 days of everolimus treatment ( 24 ). We also observed an increase in H3K9 trimethylation (H3K9me3), a chromatin marker of transcriptional silencing mechanistically linked to cellular senescence, likely through its role in directing the silencing of E2F target genes . We also observed a gene expression profile, including increased expression of transcripts encoding the extracellular signaling molecules ICAM1, IGFBP7, and interleukin (IL)-6 that is refl ective of a senescence response in B220 but not B220 cell populations in bone marrow isolated from mice treated for 4 days with everolimus ."	--	--	--	--	--	--	--	--	L	delay aging	23242809
Sen_E_549	Dehydroleucodine	Chemical compounds	"HeLa,MCF-7"	--	Melanoma	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"We observed that cells treated with 20 μM DhL for 48 h were larger and flatter than control cells, and a striking increase in the number of cells that stained positive for SA-β-Gal activity in situ (nearly 60%) was observed. For the simultaneous and therapeutic protocols, SA-β-Gal was of 40 picoM/g × 105 and 60 picoM/g × 105, respectively, in tumor supernatants of control mice, and for DhL mice SA-β-Gal activity was 80 picoM/g × 105 and 100 picoM/g × 105, respectively, indicating that DhL increased by 65% SA-β-Gal activity following both protocols. Also, the number of cells from dissected tumors that were positive for SA-β-Gal activity in situ increased. Following the simultaneous and therapeutic protocols, 5% and 8% of cells, respectively, were senescent in tumors of control mice, while in tumors of DhL mice, these values increased to 25 and 30%, respectively ."	--	--	--	--	--	--	--	--	L	delay aging	26718258
Sen_E_550	Paclitaxel	Chemical compounds	MKN45	--	Gastric cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"SA-β-galactosidase activity staining showed a clear increase in cellular senescence in these cells after PTX treatment compared with control MKN45 cells. PTX causes a prometaphase arrest cell cycle that, if sustained, generates DNA damage and senescence."	--	--	--	--	--	--	--	--	L	delay aging	25483095
Sen_E_551	Glutathione	Chemical compounds	HeLa	--	Werner syndrome	Prevent	SA-β-gal activity assay	Treatment of Hela cells grown under the atmosphere of 1% O2 with GSH prior to WRN depletion improved proliferation and was accompanied by a remarkable reduction in senescence.	--	--	--	--	--	--	--	--	L	delay aging	24757718
Sen_E_552	Furanoflavones pongapin	Chemical compounds	MCF-7-1A1	--	Breast cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot	"ANF's EC50 value for inhibition of MCF7-1A1 cell proliferation was determined to be > 20 μM. Nevertheless, the methanolic extract (EC50 for inhibition of proliferation of MCF7-1A1, 3.8 ± 0.4 μg/mL) from the seeds of P. pinnata, and the plant's secondary metabolites pongapin (EC50 for inhibition of MCF7-1A1 proliferation, 0.6 ± 0.15 μM), lanceolatin B (EC50 for inhibition of MCF7-1A1 proliferation, 0.7 ± 0.12 μM) do block MCF71A1 cells at G0-G1 and repress cyclin D1 levels , when cells were treated with 2× EC50 concentration of extract or metabolites.Interestingly, it was found that the P. pinnata seed-extract, pongapin and lanceolatin B do induce β-galactosidase in MCF7-1A1 cells. Approximately 60–70% cells were positive for β-galactosidase activity out of which more than 20% cells were strongly positive (cells staining dark blue). The control MCF7-1A1 cultures showed less than 10% cells positive for β-galactosidase and were weakly stained (cells stained light blue)."	--	--	--	--	--	--	--	--	L	delay aging	30448188
Sen_E_553	Lanceolatin B	Chemical compounds	MCF-7-1A1	--	Breast cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot	"ANF's EC50 value for inhibition of MCF7-1A1 cell proliferation was determined to be > 20 μM. Nevertheless, the methanolic extract (EC50 for inhibition of proliferation of MCF7-1A1, 3.8 ± 0.4 μg/mL) from the seeds of P. pinnata, and the plant's secondary metabolites pongapin (EC50 for inhibition of MCF7-1A1 proliferation, 0.6 ± 0.15 μM), lanceolatin B (EC50 for inhibition of MCF7-1A1 proliferation, 0.7 ± 0.12 μM) do block MCF71A1 cells at G0-G1 and repress cyclin D1 levels, when cells were treated with 2× EC50 concentration of extract or metabolites.Interestingly, it was found that the P. pinnata seed-extract, pongapin and lanceolatin B do induce β-galactosidase in MCF7-1A1 cells. Approximately 60–70% cells were positive for β-galactosidase activity out of which more than 20% cells were strongly positive (cells staining dark blue). The control MCF7-1A1 cultures showed less than 10% cells positive for β-galactosidase and were weakly stained (cells stained light blue)."	--	--	--	--	--	--	--	--	L	delay aging	30448188
Sen_E_554	Doxorubicin	Chemical compounds	A431	--	Squamous cell carcinoma	Accelerate	SA-β-gal activity assay	"DOX induces PS in A431 cells. A431 cells treated with 0.5 μm DOX show time-dependent increases in SA-β-gal activity. Inset, SA-β-gal staining of A431 cells following DOX treatment."	--	--	--	--	--	--	--	--	HL	delay aging	21471201
Sen_E_555	Resveratrol	Chemical compounds	A431	--	Squamous cell carcinoma	Accelerate	SA-β-gal activity assay//Cell morphological analysis//DAPI staining//Immunofluorescence//Western blot	"We show that A431 cells treated with RES at concentrations between 10 and 50 μm for 48 h became enlarged and flattened and showed increased activity of SA-β-gal, a marker of senescence induction. On the other hand, most of the untreated control cells were SA-β-gal-negative. The SA-β-gal activity increased in a dose-dependent manner. The punctate nuclear accumulations of HP1γ and PML and the pancytoplasmic distribution of mtHsp70, which are known to be associated with senescence, were evident in RES-treated A431 cells . Senescence-associated features were also observed in other human SCC cells, such as SCC-13. However, confluence-induced quiescent cells were not SA-β-gal-positive (data not shown).The SA-β-gal activity also increased gradually over time in response to RES (30 μm) treatment.The dose- and time-dependent induction of p21WAF1, a cell cycle inhibitor associated with senescence, was detected in RES-treated A431 cells."	--	--	--	--	--	--	--	--	HL	delay aging	21471201
Sen_E_556	Doxorubicin	Chemical compounds	HepG2	--	Aging	Accelerate	SA-β-gal activity assay	"The presence of DOXO induced about 60% of SA β-gal-positive HepG2 cells and 35% of H9c2 cells. The addition of SCIC2 and SCIC2.1 led to a reduction of ~20% and ~15% in the number of SA β-gal-positive HepG2 and H9c2 cells, respectively."	--	--	--	--	--	--	--	--	L	delay aging	31942817
Sen_E_557	SCIC2	Chemical compounds	HepG2	--	Aging	Prevent	SA-β-gal activity assay	"The presence of DOXO induced about 60% of SA β-gal-positive HepG2 cells and 35% of H9c2 cells . The addition of SCIC2 and SCIC2.1 led to a reduction of ~20% and ~15% in the number of SA β-gal-positive HepG2 and H9c2 cells, respectively."	--	--	--	--	--	--	--	--	L	delay aging	31942817
Sen_E_558	SCIC2.1	Chemical compounds	HepG2	--	Aging	Prevent	SA-β-gal activity assay	"The presence of DOXO induced about 60% of SA β-gal-positive HepG2 cells and 35% of H9c2 cells. The addition of SCIC2 and SCIC2.1 led to a reduction of ~20% and ~15% in the number of SA β-gal-positive HepG2 and H9c2 cells, respectively."	--	--	--	--	--	--	--	--	L	delay aging	31942817
Sen_E_559	Ang II	Chemical compounds	Glomerular mesangial cell	--	Aging	Accelerate	Western blot//SA-β-gal activity assay	"Compared with the normal control group, the western blotting analysis showed that the expression levels of the senescence-related proteins p53 and p21 rose gradually as the duration of the 10-6 mmol/L Ang II treatment increased. The rate of positive β-galactosidase staining reached 65.43±1.31% after treatment of Ang II for 72 h, which was significantly higher than the rate obtained in the normal control group."	--	--	--	--	--	--	--	--	L	delay aging	30389500
Sen_E_560	Probucol	Chemical compounds	Glomerular mesangial cell	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"Probucol pretreatment significantly decreased the rate of positive β-galactosidase staining in human glomerular mesangial cells exposed to Ang II;Additionally,probucol significantly inhibited the Ang II-induced expression of the senescence-related proteins p53 and p21."	--	--	--	--	--	--	--	--	L	delay aging	30389500
Sen_E_561	RG108	Chemical compounds	pBM-MSC	Bone marrow	Aging	Prevent	qRT-PCR	We analyzed the influence of RG108 on the expressions of anti-senescence genes TERT and bFGF by qRT-PCR. The results showed that transcripts of TERT and bFGF genes were significantly increased in RG108-treated pBM-MSCs.	--	--	--	--	--	--	--	--	HL	delay aging	32125888
Sen_E_562	Estrogen	Chemical compounds	"MSC,Chondrocyte"	"Bone marrow,Bone"	Aging	Prevent	Telomere length assay//Southern blot	"Telomere length declined over the entire observation period for all experimental groups to values ranging from 6.4 to 9.8 kbp,with increasing concentrations of E2 treatment, mean telomere shortening decreased(MSCs).Telomere length declined for all experimental groups to values ranging from 8.2 to 10.2 kbp. Telomere shortening correlated with cpd (P < 0.001). With increasing concentrations of E2 treatment, mean telomere shortening decreased(Human chondrocytes)."	--	--	--	--	--	--	--	--	L	delay aging	21469181
Sen_E_563	GlyH-101	Chemical compounds	Erythrocyte	Blood	Beta Thalassemia	Prevent	Osmotic tolerance test	"However,percent hemolysis of GlyH-101-treated erythrocytes was 5.9±1.3% (p,0.05) after exposure to hypotonic solution.According to Freikman et al. [27], a reduction in hemolysis of erythrocytes after hypotonic solution challenge is considered as an indicator of oxidative stress-induced erythrocyte aging."	--	--	--	--	--	--	--	--	L	delay aging	23383265
Sen_E_564	Rapamycin	Chemical compounds	HDF	--	Aging	Prevent	MTT assay//SA-β-gal activity assay//Western blot	"After treatment with rapamycin, proliferation of all senescent cells was dose-dependent, with the highest cell viability observed at 25 nm rapamycin. When cells were treated with rapamycin,a reduction in SA-β-gal-positive cells was observed(19.39?±?2.42%).Western blot analysis showed a significant decrease in the levels of p53 and p21 after treatment with rapamycin."	--	--	--	--	--	--	--	--	L	delay aging	28067204
Sen_E_565	Adriamycin	Chemical compounds	MCF-7	--	Aging	Accelerate	SA-β-gal activity assay	A senescent state is also induced in MCF-7 by a 4-h pulse of 0.25 μM adriamycin and chase over 3 days.	--	--	--	--	--	--	--	--	L	delay aging	17161377
Sen_E_566	Pan-mTOR  inhibitors	Chemical compounds	"MEL10,SK-BR-3"	--	Aging	Prevent	SA-β-gal activity assay//Cell morphological analysis	Treatment with PD0332991 caused senescent morphology in SKBR3 cells. Co-treatment with pan-mTOR inhibitors prevented senescent morphology and hypertrophy.Pan-mTOR inhibitors also prevented senescent morphology of MEL10 cells induced to senesce by treatment with low concentration of nutlin-3a.	--	--	--	--	--	--	--	--	L	delay aging	28077803
Sen_E_567	MLN4924	Chemical compounds	PC-3	--	Prostate cancer	Accelerate	SA-β-gal activity assay	"Remarkably, treatment of MLN4924 in PC3 cells triggered cellular senescence."	--	--	--	--	--	--	--	--	L	delay aging	20237562
Sen_E_568	WS-CoQ10	Chemical compounds	PSAF	--	Alzheimer's disease	Prevent	SA-β-gal activity assay//Western blot	"After culturing PSAF for over 27 passages, cells with no supplementation of PTS or WS-CoQ10 started to exhibit a wide cellular morphology, a sudden decrease in growth, and a high percentage of cells that were positive for blue SA-β-galactosidase (SA-β-gal) stain, a marker of cellular senescence. Slightly fewer SA-β-gal positive cells were found in the PTS supplemented PSAF and PSAF cultured with WS-CoQ10 had the lowest percentage of SA-β-gal stained cells.ad the lowest percentage of SA-β-gal stained cells.In conjunction to these findings, decreased levels of MnSOD, p21, Rb, and p16Ink4A were found in WS-CoQ10 cultured PSAF compared to cells without supplementation ."	--	--	--	--	--	--	--	--	L	delay aging	25034304
Sen_E_569	Apocynin	Chemical compounds	Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"The fact that NAC, NADPH oxidase inhibitors (apocynin and VAS-2870), and indomethacin significantly reduced SA-β-gal activity, and also the increased expression of the senescence markers (p53, p21, and p16)."	--	--	--	--	--	--	--	--	L	delay aging	26672612
Sen_E_570	Indomethacin	Chemical compounds	Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay	"Treatment of endothelial cells at P1 with increasing concentrations of the eNOS inhibitor L-NAME (0.1 10mM) significantly increased SA-β-gal activity.The fact that NAC, NADPH oxidase inhibitors (apocynin and VAS-2870), and indomethacin significantly reduced SA-β-gal activity, and also the increased expression of the senescence markers (p53, p21, and p16)."	--	--	--	--	--	--	--	--	L	delay aging	26672612
Sen_E_571	VAS-2870	Chemical compounds	Endothelial cell	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"The fact that NAC, NADPH oxidase inhibitors (apocynin and VAS-2870), and indomethacin significantly reduced SA-β-gal activity, and also the increased expression of the senescence markers (p53, p21, and p16)."	--	--	--	--	--	--	--	--	L	delay aging	26672612
Sen_E_572	Salvia haenkei	Chemical compounds	Fibroblast	--	Aging	Prevent	SA-β-gal activity assay//Cell viability assay	"While untreated cells stopped growing at passage 30,cells treated with SH continued to proliferate. Moreover,senescence in treated cells was significantly decreased when compared to control as assessed by the SA-β-Gal staining.The reduction in the percentage of SA-β-Gal staining in these cells was comparable to the one observed in Pten null MEFs showing a correspondence between these two models. Importantly, treatment of cells with SH for a period of three months was not associated to increased cell death, as demonstrated by the cell viability assay."	--	--	--	--	--	--	--	--	L	delay aging	27922821
Sen_E_573	Linoleic acid	Chemical compounds	HAEC	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	Treatment with LA increased the frequency of SA-β-Gal positive cells.The expression of ppRB(an indicator of senescence) decreased after LA treatment.	--	--	--	--	--	--	--	--	L	delay aging	26051603
Sen_E_574	H2O2	Chemical compounds	MRC-5	--	Aging	Accelerate	MTT assay//Flow cytometry//Cell morphological analysis//SA-β-gal activity assay//SAHF	"The cell viability was reduced significantly after 24 h of incubation with H2O2, being about 60% of the cells without H2O2 treatment.there was no evident sub-G0/G1peak, excluding cell death in the H2O2-treated cell line.The PSC cells displayed an increase in cell size and became flattened, and at least 80% of them showed blue staining indicating SA-β-gal activity .PSC cells displayed pronounced punctate heterochromatin foci in nuclei,demonstrating SAHF positive cells.Mussel oligopeptides (100 mg/ml) significantly attenuated the intracellular SAHF level (P < 0.01)."	--	--	--	--	--	--	--	--	L	delay aging	24238886
Sen_E_575	TBHP	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay//Comet assay//Western blot	"Exposure of HUVECs to 55 μmol/l tBHP increased the percentage of senescent cells 3.8-fold tBHP-induced DNA damage, as shown by the increased olive tail moment of the comet assay, and up-regulated p21 protein expression."	--	--	--	--	--	--	--	--	L	delay aging	22563892
Sen_E_576	H2O2	Chemical compounds	Erythrocyte	Blood	Beta Thalassemia	Accelerate	Osmotic tolerance test	"Percent hemolysis of H2O2-treated erythrocytes was only 2.0±0.3% after exposure to hypotonic solution.According to Freikman et al.[27], a reduction in hemolysis of erythrocytes after hypotonic solution challenge is considered as an indicator of oxidative stress-induced erythrocyte aging."	--	--	--	--	--	--	--	--	L	delay aging	23383265
Sen_E_577	5-Fu	Chemical compounds	SMMC?7721	--	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"We acquired only SMMC?772  cells treated with rapamycin and 5?Fu in combination exhibited the distinctive morphology of senescent cells and were positive for senescence?associated β?galactosidase(SA?β?Gal), a hallmark of senescent cells24 .5?Fu treatment on SMMC?772  cells caused a significant loss of the cell cycle S/G2/M phase, addition of rapamycin induced a G  arrest in SMMC?772  cells. "	--	--	--	--	--	--	--	--	L	apoptosis	18075305
Sen_E_578	R1530	Chemical compounds	"H460,HCT116"	--	Cancer	Accelerate	SA-β-gal activity assay//BrdU Assay	"Not all polyploid  cells underwent apoptosis in the presence of R1530. A substantial fraction remained viable but stopped replication and acquired a senescence phenotype.The representative cell in the time-lapse sequence ceased to proliferate after one cycle of abortive mitosis/endo-reduplication but continued to grow and nearly tripled its initial size. These morphological changes correlated very well with the decrease in the BrdU labeling index and the kinetics of staining for senescence-associated β-galactosidase activity (SA-β-Gal), the most widely recognized senescence marker11."	--	--	--	--	--	--	--	--	L	apoptosis	20814247
Sen_E_579	Ginsenoside Rh2	Chemical compounds	"MDA-MB-231,MCF 10A"	--	Breast cancer	Prevent	WST-1 assay//ELISA	"CM from senescent MDA-MB-231 cells significantly inhibited the cell proliferation of MCF-10A cells, which was clearly ameliorated by treatment of senescent MDA-MB-231 cells with Rh2. Additionally , the enzyme-linked immunosorbent assay (ELISA)further confirmed the highly secreted SASP components IL-6 and IL-8, which were significantly diminished by Rh2 treatment."	--	--	--	--	--	--	--	--	HL	apoptosis	30871042
Sen_E_580	Doxorubicin	Chemical compounds	"MDA-MB-231,MCF 10A"	--	Breast cancer	Accelerate	DAPI staining//Western blot//SA-β-gal activity assay	"Non-treated and treated (100 nM doxorubicin) cells were labeled with Lysotracker Red. Notably, treated cells displayed a marked redistribution of lysosome with diffused perinuclear pattern. Apart from enhanced lysosomal content, an increased percentage of canonical marker SA-β-gal in treated cells was correspondingly observed. We therefore labeled the non-treated and treated (100 nM doxorubicin) cells with Mitotracker Red.Treated cells significantly altered the number of 53BP1 foci compared with Nontreated con. Senescence was further confirmed by elevated levels of proteins p16 and p21 in treated cells using Western blot analysis ."	--	--	--	--	--	--	--	--	HL	apoptosis	30871042
Sen_E_581	Doxorubicin	Chemical compounds	"SW982,NHDF,FU-SY-1"	--	Synovial sarcoma	Accelerate	SA-β-gal activity assay	"When control and doxorubicin-treated cultures were assayed for β-gal activity, only the FU-SY-1 SS cell line showed a significant (p<0.05) increase over controls in the percentage of cells considered β-gal positive."	--	--	--	--	--	--	--	--	HL	apoptosis	16705698
Sen_E_582	Rapamycin	Chemical compounds	HCEC	Cornea	Aging	Prevent	SA-β-gal activity assay//EdU Assay//Flow cytometry//Western blot//TUNEL assay	"Cells treated with rapamycin demonstrated lower EdU incorporation, hence lower proliferation rate, compared to control cells.There were higher cells in G0 cell cycle in rapamycin treated cells compared to the control. Cells treated with rapamycin demonstrated significantly lower number of senescent cells compared to the control group at three weeks .Likewise, the expression of senescence marker p16 was lower in the rapamycin treated cells by Western blot.The results indicted a lower percentage of apoptotic cells in rapamycin treated HCEC compared to control."	--	--	--	--	--	--	--	--	L	apoptosis	28054657
Sen_E_583	Berberine	Chemical compounds	A549	--	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry 	"Berberine treatment at 3.125 μM and 6.25 μM concentration induced a significant (P < 0.05) increase in SA-β-gal activity in A549 cells as compared to control.These microscopic observations were also corroborated by flow cytometry data wherein a significant (P < 0.05) decrease in mean pixel bright field intensity was observed in cells exposed to 3.125–12.5 μM berberine, while the effect seemed to decrease albeit non-significantly at higher concentrations."	--	--	--	--	--	--	--	--	L	apoptosis	31978448
Sen_E_584	PTX	Chemical compounds	"HeLa,SiHa,HaCaT"	--	Cervical cancer	Prevent	SA-β-gal activity assay//Flow cytometry	"In HeLa and SiHa cells treated with PTX + CIS the percentage of SA-β? Gal(+) was significantly lower (22.9 ± 7.5% and 27.2 ± 5.4 %, respectively) which represents a 3.6 and 3-times lower diminution in relationship to senescence induced by CIS alone ( P < 0.001). In untreated control groups, the apoptotic index was ≤ 13. In contrast, in all treated groups, important levels of apoptosis were detected, because when HeLa and SiHa tumor cells were treated with PTX alone, the apoptotic indexes were 43.8 ± 4.4 and 46.2 ± 2.4 respectively ( P < 0.001  vs  untreated group)."	--	--	--	--	--	--	--	--	L	apoptosis	22074157
Sen_E_585	PTX	Chemical compounds	"HeLa,SiHa,HaCaT"	--	Cervical cancer	Prevent	SA-β-gal activity assay	"We also observed that PTX greatly reduces the senescence induced by ADR, since the percentage of senescence found in PTX + ADR treated cultures of HeLa cells (senescence = 26.6 ± 4.4%) and SiHa cells (senescence = 24.4 ± 6.7%) represents a diminution of 2.5 and 2.7 folds in relation to the ADR treated group (p < 0.001 for both groups). PTX, ADR or their combination did not induce senescence in HaCaT cells."	--	--	--	--	--	--	--	--	L	apoptosis	20482878
Sen_E_586	Vemurafenib	Chemical compounds	"M14,Malme 3M,SK-MEL-28,UACC-62"	--	Melanoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"In M14 and Malme 3M cells, an increased proportion of the surviving cells was found in G0/G1 after 7 days of Vemurafenib treatment.All cells displaying an enlarged phenotype showed increased senescence-associated β-galactosidase (SA-β-Gal) activity, supporting the notion that Vemurafenibcan induce senescence features in BRAF-dependent melanoma cell lines."	--	--	--	--	--	--	--	--	L	apoptosis	23321925
Sen_E_587	Cisplatin	Chemical compounds	"SUNEl,HT29"	--	Cancer	Accelerate	Cell morphological analysis//SA-β-gal activity assay	"48h after exposure to cisplatin, all of the treated cells became larger and flatter, resembling the morphology of human fibroblasts undergoing senescence. After exposure to low doses of cisplatin, the percentage of SA-β-gal positive cells began to increase at 48 h post-exposure time and reached a peak at 72 h in SUNEl cells and 96 h in HT29 cells. Then the percentage of SA-β-gal positive cells stabilized, correlating to the time when cell growth arrest occurred."	--	--	--	--	--	--	--	--	L	apoptosis	10568814
Sen_E_588	UDCA	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	Cell morphological analysis//SA-β-gal activity assay	"The experiment to assess morphological changes associated with UDCA treatment led to the observation that UDCA induces flat and spread out morphology similar to that described for the senescent cells.The staining for senescence marker βOur results show a significant suppression of telomerase activity by UDCA-galac-tosidase revealed intense β-galactosidase staining pattern in UDCA treated HCT116 (UDCA_P3) cells, when compared with untreated HCT116 cells, suggesting that UDCA induces senescence in HCT116 cells."	--	--	--	--	--	--	--	--	HL	apoptosis	17019713
Sen_E_589	ATO	Chemical compounds	MSC	Blood	Aging	Accelerate	SA-β-gal activity assay	The SA-β-gal staining results showed that 1 mM ATO induced senescence of MSCs.There were almost no senescent cells in control whereas the percentages of senescent cells were about 50%-70% in MSCs treated with 1 mM ATO .	--	--	--	--	--	--	--	--	L	apoptosis	21257625
Sen_E_590	Rapamycin	Chemical compounds	PBMC	--	Lymphatic filariasis	Prevent	SA-β-gal activity assay	"Similarly, increase in SA-β-Gal positive cells (78%; p = 0.0026) were detected in response to rWmhsp60, whereas rapamycin pretreatment decreased the SA-β-Gal positive cells to 10%."	--	--	--	--	--	--	--	--	L	apoptosis	25849993
Sen_E_591	3-methyladenine	Chemical compounds	B-MSC	--	Aging	Prevent	SA-β-gal activity assay//BrdU assay//ELISA	3-MA reduced SA-βgal positive cells increased cell proliferation and suppressed IL-6 production .	--	--	--	--	--	--	--	--	L	apoptosis	25961745
Sen_E_592	N-acetylcysteine	Chemical compounds	B-MSC	--	Aging	Prevent	BrdU assay//SA-β-gal activity assay//ELISA	"Furthermore, NAC increased BrdU incorporation , blunted HG-induced SA-βgal positive cells and suppressed IL-6."	--	--	--	--	--	--	--	--	L	apoptosis	25961745
Sen_E_593	DPI	Chemical compounds	B-MSC	--	Aging	Prevent	Western blot//SA-β-gal activity assay//ELISA	"Furthermore，DPI blocked HG-induced p21, increased BrdU incorporation, inhibited SA-βgal and suppressed IL-6 in a manner comparable to NAC."	--	--	--	--	--	--	--	--	L	apoptosis	25961745
Sen_E_594	Antimitotic drugs	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay	"SA-β-gal staining showed discernible differences in the extent of senescence,as PTX and ZM significantly increased the percentage of SA-β-gal positive-cells while Mon-treated cells hardly displayed signs of senescence. Increased SA-β-gal staining was also observed for Noc- and PTX-treated HCT116 cells."	--	--	--	--	--	--	--	--	HL	apoptosis	30037855
Sen_E_595	Malvidin	Chemical compounds	Chondrocyte	Bone	Osteoarthritis	Prevent	SA-β-gal activity assay	"Notably, after 7 days of Malvidin administration, the percentage of apoptotic chondrocytes stained with SA-β-gal significantly decreased in OA rats compared with the control group."	--	--	--	--	--	--	--	--	L	apoptosis	28852776
Sen_E_596	Tetra-Pt	Chemical compounds	Saos-2	--	Cancer	Accelerate	SA-β-gal activity assay	"In contrast, 87.2% SAOS2 cells were senescent after 30 days of treatment."	--	--	--	--	--	--	--	--	HL	apoptosis	28521363
Sen_E_597	4SC-202	Chemical compounds	"HEK293T,UM-UC-3,VM-CUB1,HBLAK"	--	Urothelial Carcinoma	Accelerate	Flow cytometry//SA-β-gal activity assay//Colony formation assay//Western blot	"Compared to SAHA, the effect of 4SC-202 on clonogenic growth was more durable, resulting in persistent inhibition even 48 h after treatment. In HEK-293 cells, clonogenicity was also more strongly inhibited by 4SC-202 treatment.Neither 4SC-202 nor SAHA significantly increased the fraction of senescent cells in UM-UC-3 and VM-CUB1 cells. An increased fraction of SA-β-Gal positive cells was instead observed in non-urothelial HEK-293 cells and especially in the urothelial HBLAK controls.Notably, induction of p21CIP1, a classical marker of cell cycle arrest induction by HDAC inhibitors, was less prominent with 4SC-202 compared to SAHA in VM-CUB1 and UM-UC-3 cells after 24 h treatment. Significant p21CIP1 induction was only detected in both UCCs after 48 h of 4SC-202 treatment."	--	--	--	--	--	--	--	--	L	apoptosis	27250763
Sen_E_598	19i	Chemical compounds	"HEK293,UM-UC-3,VM-CUB1,HBLAK"	--	Urothelial carcinoma	Accelerate	Flow cytometry//MTT assay//SA-β-gal activity assay//Cell morphological analysis	"Based on the results from the MTT assays, in the following experiments, cells were usually treated with 2 μM 19i or with 2.5 μM SAHA. Treatment with 2 μM 19i impaired the clonogenic potential of UC cells comparably to treatment with the pan-HDACi SAHA. This was also the case for HEK-293 cells, but HBLAK again were less sensitive .Efficacious concentrations of 19i elicited an increased fraction of cells in the G2/M phase in UC cells and in the non-urothelial HEK-293 cells.Over time, cells became larger and flatter, indicative of cellular senescence .Indeed, some 19i-treated cells, especially from the VM-CUB1 cell line, stained positive for senescence-associated β-galactosidase."	--	--	--	--	--	--	--	--	L	apoptosis	30064501
Sen_E_599	RSC96 Schwann cell-derived exosomes	Chemical compounds	"DRG,RSC96"	--	Aging	Prevent	SA-β-gal activity assay	"Following treatment of RSC96 Schwann cell-derived exosomes (20 ug/ml) for 24 h, the rate of positive staining for SA-β-gal was reduced to approximately 10%, which was closer to that of the control group."	--	--	--	--	--	--	--	--	L	apoptosis	30387453
Sen_E_600	Antroquinonol	Chemical compounds	AsPC-1	--	Pancreatic cancer	Accelerate	Flow cytometry//SA-β-gal activity assay	"As a result, a 72-h treatment of antroquinonol induced a small population (3%) of cellular senescence.The flow cytometric analysis of DNA content by PI staining showed that antroquinonol induced a timedependent G1 arrest of the cell cycle and a subsequent apoptosis(sub-G1 phase) in AsPC-1 cells ."	--	--	--	--	--	--	--	--	L	apoptosis	21840189
Sen_E_601	Resveratrol	Chemical compounds	HPMC	--	Aging	Prevent	SA-β-gal activity assay	"These studies showed that 0.5 mM RVT reduced the activity of SA-β-Gal by 15715% (Po0.05) and by 31710% (Po0.05) in young and late-passage HPMCs, respectively."	--	--	--	--	--	--	--	--	L	apoptosis	22579575
Sen_E_602	MLN4924	Chemical compounds	"SJSA-1,MG-63"	--	Osteosarcoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"We performed a β-galactosidase staining assay and found that most MLN4924-treated OS cells were stained , confirming MLN4924-induced senescence, In flow cytometry cell cycle analysis using propidium iodide DNA staining, a low concentration of MLN4924 (0.04 uM) modestly affected the cell cycle distribution, and a high concentration (1 μM) increased the population of cells in the G2 phase while reducing the S phase population.Furthermore, we observed that a fraction of cells became flat and greatly enlarged after MLN4924 treatment, suggesting an increase in cell senescence."	--	--	--	--	--	--	--	--	HL	apoptosis	27223074
Sen_E_603	EGCG	Chemical compounds	"NB4,K562"	--	Myeloid leukemia	Accelerate	SA-β-gal activity assay//Flow cytometry	"SA-β-gal assay demonstrated that after treatment with EGCG, an increase in the SA-β-gal+ cell number was observed in a time dependent manner.It supports gene expression analysis results – both chemical agents caused cell cycle arrest in G0/G1 phase with a lesser effect of EGCG on K562 cells."	--	--	--	--	--	--	--	--	L	apoptosis	30194939
Sen_E_604	Hinokitiol	Chemical compounds	"A549,H1975,H1299,H3255,PC-9,PC-9-IR"	Tumor tissue	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"The effect of hinokitiol on cellular senescence was assessed through SA-β-Gal staining, and we found that hinokitiol treatment (5 μM, 72 h) induced cellular senescence in H1975 cells and, more significantly, in human lung stromal fibroblasts.This result indicated that hinokitiol induced the accumulation of cancer cells in the S phase of the cell cycle. Interestingly, this effect on cell cycle distribution was not significantly observed in human lung stromal fibroblasts treated with hinokitiol."	--	--	--	--	--	--	--	--	HL	apoptosis	25105411
Sen_E_605	C-1311	Chemical compounds	HepG2	--	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"In HepG2 cells, increased β-galactosidase staining relative to control cells occurred 72 h after treatment with C-1311. SA-β-gal-positive cells continued to increase, and after 144 h of C-1311 exposure, the entire population of HepG2 cells displayed SA-β-gal staining. In addition to increased SA-β-gal staining, these cells had an enlarged and flattened morphology typical of senescent cells."	--	--	--	--	--	--	--	--	L	apoptosis	23319370
Sen_E_606	Disorazole C1	Chemical compounds	"HCT116,H1299,UPCI:SCC103"	--	Cancer	Accelerate	SA-β-gal activity assay	"Disorazole C1 treatment resulted in positive β-galactosidase staining even at concentrations below the growth IC50 (1 nM). The percentage of β-galactosidase-positive cells with disorazole C1 treatment was comparable with that seen with doxorubicin. Disorazole C1 also produced positive β-galactosidase human colon cancer (HCT116), lung cancer (H1299), and oral squamous carcinoma (UPCI:SCC103) cells."	--	--	--	--	--	--	--	--	HL	apoptosis	19066338
Sen_E_607	A83-01	Chemical compounds	eMSC	--	Aging	Prevent	SA-β-gal activity assay//Flow cytometry	A83-01 treated P6 eMSC showed little SA-β-Gal staining whereas the untreated control eMSC displayed blue staining indicative of senescent cells.A83-01 treatment increased the proportion of cells in G2/M phase (p?<?0.05) indicative of an increased rate of cell division.	--	--	--	--	--	--	--	--	L	apoptosis	26461813
Sen_E_608	Chloramphenicol	Chemical compounds	H1299	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"The photographic images show morphological changes in chloramphenicol-treated H1299 cells. Both cells show blue-violet X-gal crystal accumulation in senescence-associated β-galactosidase staining, suggesting that chloramphenicol-associated mitochondrial stress might trigger senescence biogenesis.The morphology of these chloramphenicol-treated cells was changed to the more flattened, enlarged, and irregular shape characteristic of cell senescence."	--	--	--	--	--	--	--	--	L	apoptosis	15905168
Sen_E_609	MTX	Chemical compounds	Melanoma cell	--	Melanoma	Accelerate	SA-β-gal activity assay	"MTX treatment also induced senescence in melanoma cells as evident by the induction of β-galactosidase activity with post 48 h MTX treatment at 5 μM, with an additional 72 h rescuing of cells in regular medium ."	--	--	--	--	--	--	--	--	HL	apoptosis	24862567
Sen_E_610	Etoposide	Chemical compounds	A549	--	Lung cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"After 48 h drug exposure, cells exhibited an enlarged and flattened morphology with a typical blue coloration, at doses above 107 M and 106 M for F14512 and etoposide, respectively."	--	--	--	--	--	--	--	--	L	apoptosis	21924246
Sen_E_611	F14512	Chemical compounds	A549	--	Lung cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"After 48 h drug exposure, cells exhibited an enlarged and flattened morphology with a typical blue coloration, at doses above 107 M and 106 M for F14512 and etoposide, respectively."	--	--	--	--	--	--	--	--	L	apoptosis	21924246
Sen_E_612	Erlotinib	Chemical compounds	Epithelial cell	Cervical	Cervical cancer	Accelerate	SA-β-gal activity assay	"The ability to form colonies decreased strongly after cells were treated with erlotinib for 6 8 days. During this time, a large percentage of surviving cells became positive for β-galactosidase , a marker for cell senescence."	--	--	--	--	--	--	--	--	L	apoptosis	21982220
Sen_E_613	Gemcitabine	Chemical compounds	PANC-1	--	Pancreatic cancer	Accelerate	SA-β-gal activity assay	"Cellular senescence was determined using SA-β-gal staining on Day 6 and Day 9.EX527 and GEM alone induced cellular senenscence compared to Control, however their combination treatment did not result in any synergistic effect."	--	--	--	--	--	--	--	--	L	apoptosis	25843411
Sen_E_614	EX527	Chemical compounds	PANC-1	--	Pancreatic cancer	Accelerate	SA-β-gal activity assay	"Cellular senescence was determined using SA-β-gal staining on Day 6 and Day 9. EX527 and GEM alone induced cellular senenscence compared to Control, however their combination treatment did not result in any synergistic effect."	--	--	--	--	--	--	--	--	L	apoptosis	25843411
Sen_E_615	H2O2	Chemical compounds	ARPE?19	--	Aging	Accelerate	SA-β-gal activity assay	"In the present study, H2O2 treatment led to a significant increase in the expression of SA-β-Gal (p = 0.01)."	--	--	--	--	--	--	--	--	L	apoptosis	26044821
Sen_E_616	Lidamycin	Chemical compounds	BEL-7402	--	Liver cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"We observed SA-β-gal expression, a senescence marker, at 72 h after lidamycin treatment. The treated cells showed phenotypic changes that resembled features of normal senescence, including enlarged and flattened morphology, increased granularity, vacuolization, and enhanced SA-β-gal- positive cells.Moreover, the induction of senescence-like phenotype in BEL-7402 cells was increased dose-dependently."	--	--	--	--	--	--	--	--	L	apoptosis	15309709
Sen_E_617	BET inhibitor JQ1	Chemical compounds	"MyLa,SeAx,HuT 78,HH"	--	T-cell lymphoma	Accelerate	Flow cytometry//Cell morphological analysis	"JQ1 inhibited CTCL proliferation and induced cell cycle arrest.Following 24 h of treatment with JQ1, marked increase in G1 phase and reduced S phase were observed in all cell lines compared to untreated cells. Senescence induces morphological and flow cytometric changes like enlarged cells with a vacuole-rich cytoplasm resulting in increased forward/side scatter values [2]. R1 was defined as SSC (Side Scatter)low FSC (Forward Scatter)low region and R2 was defined as SSChigh FSChigh region in viable cells as previously described [10]. Treatment of MyLa cells with JQ1 increased the cell number in the R2 region and decreased that in the R1 region."	--	--	--	--	--	--	--	--	L	apoptosis	28593508
Sen_E_618	Bleomycin	Chemical compounds	Fibroblast	Lung	Idiopathic pulmonary fibrosis	Accelerate	Western blot//qRT-PCR	"In ex vivo experiments, we found that lung epithelial cells of bleomycin-treated WT aged mice demonstrated increased senescent phenotype, as evidenced by greater expression of p21 and PAI-1 in these cells."	--	--	--	--	--	--	--	--	L	apoptosis	27979858
Sen_E_619	OX-LDL	Chemical compounds	HBMEC	--	Aging	Accelerate	SA-β-gal activity assay	We observed that ox-LDL induced senescence in both HBMECSC and HBMECmiR-125a-5p.	--	--	--	--	--	--	--	--	L	apoptosis	27903586
Sen_E_620	Resveratrol	Chemical compounds	U87 MG	--	Glioma	Accelerate	SA-β-gal activity assay	We found that overexpression of Pokemon reduced RSV-induced cell senescence in U87MG cells.	--	--	--	--	--	--	--	--	L	apoptosis	25875864
Sen_E_621	Metformin	Chemical compounds	MDA-MB-468	--	Breast cancer	Accelerate	Cell morphological analysis	"We determined that 1 mM metformin proved to be a threshold concentration at which impaired cell proliferation was evident at 72 hours, Heterochromatic nuclei were observed in metformin treated cells, indicative of senescence in cells previously exposed to 1 mM metformin. Morphologically, cells exposed to metformin are enlarged and flattened, consistent with induction of stress-induced senescence."	--	--	--	--	--	--	--	--	HL	apoptosis	23395946
Sen_E_622	Metformin	Chemical compounds	--	Tumor tissue	Squamous cell carcinoma	Accelerate	SA-β-gal activity assay	"Average staining intensity of stromal GALB, which is a marker of senescence, increased from 32.4% to 50.2% after treatment with metformin."	--	--	--	--	--	--	--	--	L	apoptosis	28185288
Sen_E_623	4-hydroxynonenal	Chemical compounds	ARPE?19	--	Retinal damage	Accelerate	SA-β-gal activity assay	"The positive staining of β-galactosidase was significantly greater after 30 μM HNE treatment, and the proportion of positively stained cells reached 52.0% ± 4.8%."	--	--	--	--	--	--	--	--	L	apoptosis	31070214
Sen_E_624	Cyanidin-3-glucoside	Chemical compounds	ARPE?19	--	Retinal damage	Prevent	SA-β-gal activity assay	"At concentrations of 1 and 5 μM, C3G exhibited significant (P < 0.05) inhibitory effect on the expression of senescence-associated β-galactosidase. The proportion of positively stained cells decreased to 33.2% ± 1.5% in the 5 μM C3G group."	--	--	--	--	--	--	--	--	L	apoptosis	31070214
Sen_E_625	Paclitaxel	Chemical compounds	"MSC1,MSC2,Hs68,Dermal Fibroblast,MRC-5"	Bone marrow	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	Exposure to 15?nM paclitaxel led to a prolonged accumulation of MSCs in the G2 phase of the cell cycle for up to 96?hours. Both tested MSCs exhibited a swift and significant increase in senescent β-GAL-positive cells ranging between 12 and 20% of cells at 24?hours after treatment and between 20 and 30% after 72?hours.	--	--	--	--	--	--	--	--	L	apoptosis	29321693
Sen_E_626	Imatinib(IM)	Chemical compounds	Primary tumor cell	Tumor tissue	Fibrosarcoma	Accelerate	SA-β-gal activity assay//qRT-PCR//Immunohistochemistry	"IM-treated tumors showed a significant up-regulation of the cell-cycle inhibitor p21Cip1 (cyclin-dependent kinase inhibitor (CDKI)1A/CDKN1A) and a marked decrease in cell proliferation, as evidenced by Ki-67 staining.in a subset of IM-treated cases for which material was available, senescence-associated β-galactosidase activity was clearly detectable in the post-IM specimens.Taqman quantitative real-time PCR (Applied Biosystems Division, Foster City, CA) of RNA obtained from macrodissected areas of the post-therapy samples (Pt7 and Pt11) showed a proinflammatory signature characterized by the expression of IL6, TGFB1, PAI1, CXCL1, IL1B, and IL8, which is a cytokine and chemokine profile consistent with the senescence-associated secretory pathway described previously."	--	--	--	--	--	--	--	--	HL	apoptosis	27608549
Sen_E_627	Cisplatin	Chemical compounds	MSC 	--	Breast cancer	Accelerate	SA-β-gal activity assay	We have observed that a part of MSC population underwent senescence after 48 h treatment with 1 μg/ml cisplatin .	--	--	--	--	--	--	--	--	HL	apoptosis	26759169
Sen_E_628	Pochoxime-derived inhibitor NW457	Chemical compounds	HT-1080	--	Soft tissue sarcomas	Accelerate	SA-β-gal activity assay	"HT1080 cells displayed a dose-dependent accumulation of senescent cells, which was strongly enforced by pretreatment with 10 nM NW457."	--	--	--	--	--	--	--	--	HL	apoptosis	26044951
Sen_E_629	Y-27632	Chemical compounds	HDPDC	Odontoma	Odontomas	Prevent	SA-β-gal activity assay	"Compared with the Y-27632 treated hODCs, the hODCs of Y-27632-negative at passage 15 were positive for the activity (cells stained in blue) at significantly (po0.05) higher rates."	--	--	--	--	--	--	--	--	L	apoptosis	27514999
Sen_E_630	Cisplatin	Chemical compounds	A549	--	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"Visual examination revealed that the cells surrounding the recovering clones displayed morphologic changes that are associated with senescence, namely increased cell size and flattened shape.Detectable by flow cytometry, increased forward (cell size) and side (cellular granularity) scatter intensity is an additional characteristic associated with senescence . At day 17 of the recovery phase, quantification of senescence-associated β-galactosidase (SA-β-Gal) activity revealed that the fraction of SA-β-Gal-positive cells was 3.5-fold higher after treatment #3 compared to treatment #1 . recovery of F/S-low fraction featuring a normal cell cycle distribution was maximally delayed after treatment #3 and the remaining F/S-high cells (day14 rec) were primarily arrested in the G2/M-phase."	--	--	--	--	--	--	--	--	L	apoptosis	26895954
Sen_E_631	MTA	Chemical compounds	A549	--	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"Visual examination revealed that the cells surrounding the recovering clones displayed morphologic changes that are associated with senescence, namely increased cell size and flattened shape.Detectable by flow cytometry, increased forward (cell size) and side (cellular granularity) scatter intensity is an additional characteristic associated with senescence . At day 17 of the recovery phase, quantification of senescence-associated β-galactosidase (SA-β-Gal) activity revealed that the fraction of SA-β-Gal-positive cells was 3.5-fold higher after treatment #3 compared to treatment #1 . recovery of F/S-low fraction featuring a normal cell cycle distribution was maximally delayed after treatment #3 and the remaining F/S-high cells (day14 rec) were primarily arrested in the G2/M-phase."	--	--	--	--	--	--	--	--	L	apoptosis	26895954
Sen_E_632	JQ1	Chemical compounds	"G-292,MG-63,MNNG/HOS,SJSA"	--	Osteosarcoma	Accelerate	SA-β-gal activity assay//Flow cytometry//PI staining	"JQ1 (7.5 μM, 24 hr) increased the percentage of G1 phase cells in G292, MNNG/HOS and SJSA cells, but not MG‐63 cells.a prominent increase in premature senescence of these cells was observed when tested in the same condition by senescence‐associated β‐galactosidase (SA‐β‐gal) staining. MG‐63 cells showed no increase in the number of cells undergoing senescence."	--	--	--	--	--	--	--	--	HL	apoptosis	25307878
Sen_E_633	Tamoxifen	Chemical compounds	"GBM3,GBM6,GBM11"	--	Glioma	Accelerate	SA-β-gal activity assay	"We found that treatment of cells with TAM alone induced senescence, whereas combination of TAM + OV augmented OV-mediated cytotoxicity (oncolytic cell killing), as revealed by inhibition of cell proliferation (~36% decrease vs. mock, p = < 0.001) and decreased the number of β-gal-positive senescent cells relative to treatment with OV alone."	--	--	--	--	--	--	--	--	HL	apoptosis	29991800
Sen_E_634	LY2801653	Chemical compounds	"TFK-1,SZ-1"	--	Cholangiocarcinoma	Accelerate	SA-β-gal activity assay//Western blot	We have analyzed senescence by measuring the senescence associated β-galactosidase (SA-β-Gal) activity assay in TFK-1 and SZ-1 cells after treatment with DMSO and LY2801653. In both cell lines we observed a significant increase in the percentage of SA-β-Gal activity after 48 and 96h compared to their controls.Moreover P21 is one of the major players linking cell cycle arrest and induction of senescence . We observed a strong expression of P21 compared to the untreated controls under 10mM LY2801653 at 96h.	--	--	--	--	--	--	--	--	HL	apoptosis	26757360
Sen_E_635	DMSO	Chemical compounds	"TFK-1,SZ-1"	--	Cholangiocarcinoma	Accelerate	SA-β-gal activity assay	We have analyzed senescence by measuring the senescence associated β-galactosidase (SA-β-Gal) activity assay in TFK-1 and SZ-1 cells after treatment with DMSO and LY2801653. In both cell lines we observed a significant increase in the percentage of SA-β-Gal activity after 48 and 96h compared to their controls.	--	--	--	--	--	--	--	--	HL	apoptosis	26757360
Sen_E_636	AZD2014	Chemical compounds	"DIPG 4,SF7761"	Tumor tissue	Diffuse intrinsic pontine glioma	Accelerate	SA-β-gal activity assay	"Effects of everolimus and AZD2014 on senescence, as measured by the percentage of cells staining positive for β-galactosidase.here, both compounds appeared to increase the percentage of senescent cells in a dose-dependent manner, but there was no clear difference between the two."	--	--	--	--	--	--	--	--	HL	apoptosis	29207163
Sen_E_637	Everolimus	Chemical compounds	"DIPG 4,SF7761"	Tumor tissue	Diffuse intrinsic pontine glioma	Accelerate	SA-β-gal activity assay	"Effects of everolimus and AZD2014 on senescence, as measured by the percentage of cells staining positive for β-galactosidase.here, both compounds appeared to increase the percentage of senescent cells in a dose-dependent manner, but there was no clear difference between the two."	--	--	--	--	--	--	--	--	HL	apoptosis	29207163
Sen_E_638	Cyclosporine A	Chemical compounds	"T98G,U373 MG,U87 MG"	--	Glioma	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot//Cell morphological analysis	"CsA increases the number of cells in the G1 phase of cell cycle and significantly reduces the number of proliferating cells in the S phase. p21WAF1/Cip1 protein is an universal inhibitor of cyclin kinases and plays an important role in inhibiting cell proliferation. Western blot analysis of p21WAF1/Cip1 level was performed on human glioma cells: U87-MG (wild-type p53), T98G and U373-MG (p53 mutated) following CsA treatment.The levels of p21WAF1/Cip1 protein increased in all examined glioma cell lines. The highest up-regulation was observed in T98G and the moderate p21WAF1/Cip1 protein accumulation was observed in U373-MG and U87MG cells. In T98G cells the increase of p21WAF1/Cip1 protein was observed at 5 h, reaching the high level at 15 h, which remained elevated 25 h after CsA treatment.Untreated U87-MG and T98G cells demonstrated very rare cells positive for the SA-β-Gal staining. After 24 h of CsA treatment the percentage of cells positive for SA-β-Gal was doubled in U87-MG cells compared to control, while only few T98G cells were positively stained. SA-β-Gal positive U87-MG cells increased in size and flattened out, thereby attaining a morphology of senescent-like cells."	--	--	--	--	--	--	--	--	L	apoptosis	16087277
Sen_E_639	MLN8237	Chemical compounds	"GIST882,GIST48,GIST430"	--	Gastrointestinal stromal tumor	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot	"Flow cytometry analysis of DNA content in cells treated with MLN8237 for six days demonstrated that this compound caused marked accumulation of cells at G2/M as well as >4N DNA content in all three GIST cell lines. MLN8237 treatment significantly increased SA-β-gal activity in GIST cells. Furthermore, administration of MLN8237 also increased the expression of DEC1 and DcR2, two well-known senescence biomarkers [25, 26], in a dose-dependent manner, while the levels of phospho-p70 S6 kinase remained steady. As measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the expression of interleukin 6 (IL-6), a cytokine associated with the senescence-associated secretory phenotype (SASP) [25, 26], was also up-regulated in GIST48 cells treated with MLN8237 ."	--	--	--	--	--	--	--	--	L	apoptosis	24901229
Sen_E_640	MLN4924	Chemical compounds	"GBM,U251,A172"	--	Glioblastoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot//Cell morphological analysis	"Fluorescence-activated cell sorting analysis revealed that MLN4924 notably triggered G2/M cell-cycle arrest in GBM cells.MLN4924 induced significant accumulation of WEE1, whereas it decreased the expression of p-H3 sharply, indicating that G2 cell-cycle arrest was induced by MLN4924.During the investigation of mechanistic basis for the inhibitory effect of MLN4924, we observed that MLN4924 induced an enlarged and flattened cellular shape in U251 cells , which suggested that the cells underwent senescence. senescence-associated β-galactosidase (SA-β-gal; a classical biochemical marker of senescence) was determined by SA-β-gal staining in these cells. As expected, a substantial fraction of MLN4924-treated U251 cells were positively stained, which demonstrated that MLN4924 triggered senescence in U251 cells."	--	--	--	--	--	--	--	--	L	apoptosis	25904638
Sen_E_641	Idebenone	Chemical compounds	Human lamina cribrosa Astrocyte	Eye	Glaucoma	Prevent	SA-β-gal activity assay	A significantly reduced SA -β-Gal activity was noted when cells were pretreated with 10mM idebenone and then exposed to 600mM H2O2.	--	--	--	--	--	--	--	--	L	apoptosis	23661043
Sen_E_642	Temozolomide	Chemical compounds	"LN-229,A172,U87 MG"	--	Glioblastoma	Accelerate	SA-β-gal activity assay	TMZ (50 μM) induced a high level of senescence in LN229 cells and a moderate level in A172 and U87MG cells .	--	--	--	--	--	--	--	--	L	apoptosis	27626497
Sen_E_643	Artesunate	Chemical compounds	"LN-229,A172,U87 MG"	--	Glioblastoma	Prevent	SA-β-gal activity assay	TMZ-induced senescence was significantly reduced in LN229 and A172 cells when they where post-treated with ART. The generally more resistant U87MG cells were not responding . TMZ-induced senescence was also reduced by ART treatment in glioblastoma stem-like cells.	--	--	--	--	--	--	--	--	L	apoptosis	27626497
Sen_E_644	Adriamycin	Chemical compounds	HT-1080	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"About 50% of the attached cells became senescent after 3 days of Adriamycin treatment. cells were arrested with hydroxyurea, released, and further treated with 30 nmol/L Adriamycin for 5 to 25 hours. Whereas control cells remained growth arrested, 15% of Src-expressing cells had already progressed into mitosis by 10 hours."	--	--	--	--	--	--	--	--	L	apoptosis	16204065
Sen_E_645	U0126	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis//Knockdown	"Moreover, although all three MAPK inhibitors did not greatly influence cell cycle distribution of unstressed and irradiated cells, p53- and p21-deficient cells rescued by U0126 from γIR-induced apoptosis showed an enlarged and flattened morphology, exhibiting increased senescence-associated β-galactosidase (SA-β-Gal) activities.Remarkably, these senescence markers were even evident when checkpoint-deficient and wild-type HCT116 cells were treated solely with U0126."	--	--	--	--	--	--	--	--	L	apoptosis	24136223
Sen_E_646	Tamoxifen	Chemical compounds	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay//Annexin V binding assay	"When HUVECs were exposed to NC, tamoxifen-induced cell senescence increased about fourfold, whereas 3-MA affected senescence only marginally. In contrast, exposure of HUVECs to GC alone resulted in a greater than fivefold increase in the proportion of senescent cells, and the presence of 3-MA led to a significant attenuation of development of premature senescence."	--	--	--	--	--	--	--	--	L	apoptosis	18203850
Sen_E_647	3-methyladenine	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Annexin V binding assay	"When HUVECs were exposed to NC, tamoxifen-induced cell senescence increased about fourfold, whereas 3-MA affected senescence only marginally. In contrast, exposure of HUVECs to GC alone resulted in a greater than fivefold increase in the proportion of senescent cells, and the presence of 3-MA led to a significant attenuation of development of premature senescence. "	--	--	--	--	--	--	--	--	L	apoptosis	18203850
Sen_E_648	STI571	Chemical compounds	K562	--	Chronic myeloid leukemia	Prevent	SA-β-gal activity assay	"In combination with radiation, STI571 overcame the effect of radiation and abolished radiation-induced formation of β-galactosidase-positive cells to near completion ."	--	--	--	--	--	--	--	--	L	apoptosis	18281522
Sen_E_649	BETi+ATRi	Chemical compounds	λ820	--	Lymphoma	Accelerate	Flow cytometry//Western blot	"Consistent with data from λ820 cells, low concentration of BETi results in slowed progression through S-phase, whereas high concentrations of BETi prevent cell cycle entry, as shown by cell cycle distribution determined by flow cytometry and by 3H-thymidine incorporation . On the other hand, the combination-treated cells had elevated transcript levels of genes involved in senescence-associated secretory pathway, including the NFκB family member Rela .The expression of DDIT3/CHOP and ATF4, mediators of ER stress, and thesenescence-associated cytokines Cxcl1 and Cxcl2 were induced by VE-821 or the combination treatment ."	--	--	--	--	--	--	--	--	HL	apoptosis	26804177
Sen_E_650	Bleomycin	Chemical compounds	--	Lung	Idiopathic pulmonary fibrosis	Accelerate	ELISA//Knockdown	"There was a significant decrease in the expression of msh2, msh6, and ogg1 transcripts in CLU?/? bleomycin-challenged mice compared to CLU?/? saline-control mice . Moreover, there was a significant decrease in msh6 in CLU?/? compared to wildtype mice following bleomycin challenge at Day 28. There was an increase in whole lung p21 and IL1? proteins and KC transcript expression in the bleomycin-challenged CLU?/? compared with their wildtype counterparts at this time point."	--	--	--	--	--	--	--	--	HL	apoptosis	29133960
Sen_E_651	Lidamycin	Chemical compounds	MCF-7	--	Breast cancer	Accelerate	SA-β-gal activity assay	"The percentage of cells with senescence-associated β-galactosidase (SA-β-gal) expression was similar in MCF-7/DOX and MCF-7 cells 72 h after exposure to lidamycin, depending on lidamycin concentrations."	--	--	--	--	--	--	--	--	L	apoptosis	19725468
Sen_E_652	CHCl3:Me-OH	Chemical compounds	HDF	--	Aging	Accelerate	SA-β-gal activity assay	"Organic solvent (CHCl3:Me-OH) caused a 3-fold increase in the number of SA-β-gal positive cells (photo b) but 42% decrease in overall cell number than the control (photo a), indicating that the organic solvent had strong cytotoxic and pro-senescent effects."	--	--	--	--	--	--	--	--	L	apoptosis	26161621
Sen_E_653	PCO-rHDL	Chemical compounds	HDF	--	Aging	Prevent	SA-β-gal activity assay	"However, PCO in solvent dose-dependently inhibited cellular senescence up to 65% and 70% at 9 and 46 ?M (final), respectively, along with an increase in cell number, suggesting that PCO had anti-senescent and cell proliferation effects (photos c and d). Moreover, PCO-rHDL  showed a stronger anti-aging effect and greater cellular proliferation in a dose-dependent manner. Compared to the PBS control, PCO-rHDL-treated cells (photos f and g) showed 68% and 80% reduction of SA-β-gal positive cells, whereas rHDL-treated cells (photo e) showed 52% reduction. PCO-rHDL also showed a cell proliferation effect of up to 1.9-fold and 1.6-fold for (1:5)-rHDL and (1:1)-rHDL, respectively, compared to rHDL alone (photo e)."	--	--	--	--	--	--	--	--	L	apoptosis	26161621
Sen_E_654	Valproic acid	Chemical compounds	"DU 145,PC-3"	--	Prostate cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"Contrary to DU-145 cells, in PC-3 cells, a 24 h-exposure to 2 mM VPA caused a G2 cell cycle arrest.The light scatter plot shows enlargement and flattening of cells with increased granularity in the VPA-treated group.Induction of senescence (blue β-gal staining) and inhibition of proliferation (brown Ki-67 staining)simultaneously is depicted .By examining SA-β-gal activity we confirmed that VPA did induce cellular senescence in PCa. The greatest induction of senescence was in DU-145 cells exposed to 0.4% w/v VPA."	--	--	--	--	--	--	--	--	L	apoptosis	17477369
Sen_E_655	Midostaurin	Chemical compounds	KRAS-mutant cell	--	Lung cancer	Accelerate	SA-β-gal activity assay	Midostaurin also increased the number of residual IR-induced DNA double-strand breaks and caused apoptosis and senescence in irradiated KRAS-mutant cells.	--	--	--	--	--	--	--	--	HL	apoptosis	25667133
Sen_E_656	Convallatoxin	Chemical compounds	"NSCLC,A549"	--	Lung cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis//Western blot	"Exposure of A549 cells to CON at 10 and 100 nM showed a significant increase in cells in the G2/M phase at all times tested, followed by an increase in cells in subG1 over the time.We also evaluated the expression of a key molecular driver of G2/M phase, cyclin B1, after 24 h of treatment by WB analysis.CON down-regulates cyclin-B1. CON induced at 50 nM an increase of ~80% of β-gal-positive cells. At 10 nM, an increase of larger regular nuclei was observed as well as the cells become flat, increase their volume and display a vacuole-rich cytoplasm, characteristic of senescence."	--	--	--	--	--	--	--	--	L	apoptosis	28176244
Sen_E_657	Curcumin	Chemical compounds	"HROC257 T0 M1,HROC50 T1 M5,HROC60,HROC183 T0 M2"	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"By contrast, all substances and combinations caused senescence in HROC tumor cells with a tendency towards higher β-galactosidase activity after single treatment. Numbers of cells in G0/G1 phase decreased (HROC257 T0 M1 > HROC50 T1 M5 > HROC60 > HROC183 T0 M2; a representative example shows Curcumin/Gemcitabine treated HROC257 T0 M1 (IDOhigh) cells; sub-G1 defines dead cells). The best antiproliferative effect was inducible in HROC183 T0 M2(IDOlow) cells after Indoximod/Curcumin treatment . Percentages of cells in S-phase were 17 % ± 9 % versus 33 % ± 11 % ."	--	--	--	--	--	--	--	--	L	apoptosis	30891459
Sen_E_658	MLN4924	Chemical compounds	"786-O,ACNH"	--	Renal carcinoma	Accelerate	SA-β-gal activity assay//Flow cytometry	The results suggested that the low concentration of MLN4924 (0.1 μM) affected the cell-cycle distribution moderately and the high concentrations (0.5 μM) increased the G2 phase population . Results confirmed MLN4924induced senescence as most renal cancer cells were stained after MLN4924 treatment by β-galactosidase staining assay.	--	--	--	--	--	--	--	--	L	apoptosis	29667067
Sen_E_659	Etoposide	Chemical compounds	IMR-90	--	Aging	Accelerate	SA-β-gal activity assay//Western blot//Flow cytometry	"We confirmed the induction of the senescence phenotype in these cells by evaluation of cell cycle arrest, expression of senescence markers p16, p21, and p53 and senescence‐associated β‐galactosidase (SA‐β‐gal) staining. Treatment with etoposide induced cell cycle arrest in these cells."	--	--	--	--	--	--	--	--	HL	apoptosis	28607003
Sen_E_660	Rapamycin	Chemical compounds	PBMC	Blood	Lymphatic filariasis	Prevent	SA-β-gal activity assay	"Similarly, increase in SA-β-Gal–positive cells (78%; p = 0.0026) were detected in response to rWmhsp60, whereas rapamycin pretreatment decreased the SA-β-Gal–positive cells to 10%."	--	--	--	--	--	--	--	--	L	apoptosis	25849993
Sen_E_661	MLN4924	Chemical compounds	"A549,H460,H1299"	--	Lung?cancer	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot	"MLN4924 also induced G2 phase cell cycle arrest, as demonstrated by the accumulation of G2-M phase transition inhibitor WEE1, the downregulation of M phase marker p-histone H3 and the increased frequency of cells in G2 phase.whereas in A549 and H1299 cells MLN4924 triggered senescence, as demonstrated by an enlarged and flattened cellular shape and the expression of senescence-associated β-galactosidase."	--	--	--	--	--	--	--	--	HL	apoptosis	24853380
Sen_E_662	Metformin	Chemical compounds	"HN 30,HN 31"	--	Squamous cell carcinoma	Accelerate	SA-β-gal activity assay	"Metformin decreased clonogenic survival following radiation and increased radiation-induced SA-β-gal activity in HN 31 cells (C176F, disruptive TP53), but had little effect in HN 30 cells (wild type TP53). Furthermore, after inhibition of wild type p53 expression, metformin was found to potentiate SA-β-gal activity and decrease clonogenic survival."	--	--	--	--	--	--	--	--	L	apoptosis	22090360
Sen_E_663	TBHP	Chemical compounds	"Primary mice Chondrocyte,Primary human Chondrocyte"	--	Osteoarthritis	Accelerate	SA-β-gal activity assay//Western blot	"The TBHP-treated chondrocytes exerted higher SA-β-gal activity and p16INK4a protein level relative to the control group, whereas TFEB overexpression significantly prevents this increment."	--	--	--	--	--	--	--	--	L	apoptosis	30154423
Sen_E_664	SN-38	Chemical compounds	HCT116	--	Colorectal cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"They remained metabolically Activate and showed a senescence-like phenotype—flattened morphology, increased granularity, and expression of senescence-associated β-galactosidase activity .Cells treated with 20 nm SN-38 for 24 hours underwent a G2 arrest (SN24h)."	--	--	--	--	--	--	--	--	L	apoptosis	15374978
Sen_E_665	LPD	Chemical compounds	"SMMC-7721,HepG2"	--	Hepatocellular carcinoma	Accelerate	SA-β-gal activity assay	"The cell senescence induced by LPD in SMMC-7721 and HepG2 cells.In HepG2 cells with wild-type p53 which is essential for inducing senescence,increased SA-β-gal staining relative to NC-LPD was observed after treatment with RRM2-LPD. More SA-β-gal-positive cells were observed in the ADR-NC-LPD treated group, whereas the ADRRRM2-LPD treated group possessed the most SA-β-gal-positive cells."	--	--	--	--	--	--	--	--	L	apoptosis	24060417
Sen_E_666	Trabectedin	Chemical compounds	"U2OS,SW872"	--	Sarcoma	Accelerate	SA-β-gal activity assay//Flow cytometry	"DNA content histograms of SW872 (left) and U2OS (right) 24 and 48 hrs after treatment (10 nmol/l trabectedin). In both cell lines, trabectedin caused a marked G2/M arrest after 24 hrs, which was strongly enhanced by additional hyperthermia (upper row).treatment with additional hyperthermia prolonged trabectedin‐induced cell cycle arrest in both investigated cell lines (lower row). Hyperthermia alone caused no significant alterations in cell cycle distributions (data not shown).Particularly U2OS—instead of undergoing apoptosis—showed a strong senescence response and a heat‐dependent continuously increasing number of senescent cells over 72 hrs (data not shown) to 144 hrs. In comparison, SW872, which preferentially underwent apoptosis, showed no detectable induction of senescence."	--	--	--	--	--	--	--	--	L	apoptosis	26933761
Sen_E_667	Hyaluronan	Chemical compounds	MSC	Bone marrow	Aging	Prevent	Flow cytometry//SA-β-gal activity assay	"MSCs cultivated in L-HA either at 0.16% or 0.5% concentration showed a significant reduction in cycling cells compared with the controls, and this was accompanied by a concomitant increase in quiescent cells.Flow cytometry analysis of MSC cultures evidenced that all the experimental conditions, but 0.16% HCC, modified the pattern of cell cycle profiles with respect to control conditions.The apoptosis process was not affected by incubation with the different HA mixtures.while enescence was noticeably reduced , as detected by annexin V flow cytometry analysis and in situ β-galactosidase assay.The number of MSC clones was reduced after incubation with all the analyzed HA mixtures."	--	--	--	--	--	--	--	--	L	apoptosis	30001217
Sen_E_668	H2O2	Chemical compounds	SRA01/04	--	Age-related cataract	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Morphological changes in SAR01/04 cells began to appear 3 days after exposure to 50 μM H2O2. Two weeks later, the morphology of the treated cells resembled that of senescent cell: with gross enlargement, flattening, and the accumulation of granular cytoplasmic inclusions .In SRA01/04 cells exposed to 50 μM H2O2 for 2 weeks, the proportion of SA-β-gal staining cells was 90.3%±6.2%, but in normal SRA01/04 cells, the SA-β-gal staining was absent ."	--	--	--	--	--	--	--	--	L	apoptosis	22043305
Sen_E_669	H2O2	Chemical compounds	WI-38	--	Aging	Accelerate	SA-β-gal activity assay//Immunofluorescence	"We found that p16 overexpression or H2O2 treatment alone induced senescence in WI-38 cells and the combination of both resulted in an additive effect. Meanwhile, the senescence-associated  heterochromatin foci (SAHF) assay confirmed the observations in senescence cell staining. Both 3MeK9H3 and HMGA1, two classic markers of SAHF, localized to the specific heterochromatic foci in cells transfected with p16 and treated with H2O2 ."	--	--	--	--	--	--	--	--	L	apoptosis	28120917
Sen_E_670	Antioxidant	Chemical compounds	"CdLS 417,CdLS 565"	--	Cornelia de Lange syndrome	Prevent	SA-β-gal activity assay	"We found that both antioxidant drugs independently increased the number of passages the cells made in vitro by about 50%, using untreated CdLS cell as control for lifespan . These data are further supported by the decrease in both the number of β-galactosidase positive cells(data not shown) and their staining intensity."	--	--	--	--	--	--	--	--	HL	genomic instability	29860495
Sen_E_671	Cyclin-dependent kinase inhibitors	Chemical compounds	TIG-3	--	Aging	Accelerate	Cell proliferation assay//Cell morphological analysis//SA-β-gal activity assay//PCR	"As judged by cell proliferation assays, cells expressing the Cdk inhibitors had a significantly lower rate of division than cells transduced with the empty vector.?As well as being growth arrested, the majority of the infected cells were enlarged and flattened in appearance (data not shown).The cells also had increased expression of the mRNA for PAI-1,which is involved in regulating the turnover of extracellular matrix proteins.Ectopic expression of any of the Cdk inhibitors was sufficient to induce positive staining for SA-β-gal activity."	--	--	--	--	--	--	--	--	L	Others	9512419
Sen_E_672	Caloric restriction	Other	White blood cell	Bone	Aging	Prevent	Bone Density and Fat Content//The tightrope success test//Quantitative image analysis	"In line with this, both WT and TgTERT miceshowed BMD loss through life, as measured by DEXA, however,bone loss was significantly higher in mice under the control diet compared to calorie restricted mice.CR mice from both genotypes performed significantly better than mice under the control diet.The rate of telomere shortening was significantly slower in CR mice of both genotypes compared to the corresponding cohorts under the control diet.Similarly, WT and TgTERT mice under CR showed a lower rate of accumulation of short telomeres compared to the corresponding cohorts under the control diet."	--	--	--	--	--	--	--	--	L	telomere attrition	23349740
Sen_E_673	Stress recovery	Other	"MCAS,HEC-1"	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"Importantly, persistence of high p21 levels in HGPS cells was associated with cellular senescence, as demonstrated by the significant increase in the percentage of beta‐galactosidase‐positive cells observed in HGPS, but not in control cultures, upon stress recovery and by the increase in senescence‐associated heterochromatin foci (SAHF) , which were detectable in almost all beta‐galactosidase‐positive HGPS cells."	--	--	--	--	--	--	--	--	HL	deregulated nutrient sensing	30109767
Sen_E_674	Irradiation	Other	MEF	--	Aging	Accelerate	SA-β-gal activity assay	Senescence was induced by either sub-lethal gamma irradiation (10 Gy) or replicative exhaustion as described previously and was confirmed through staining for senescence-associated beta-galactosidase (SA-βgal) activity .	--	--	--	--	--	--	--	--	L	repair AND renewal	29579719
Sen_E_675	Ionizing radiation	Other	MCF-7	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"IR-exposed MCF7 cells exhibited specific characteristics of cellular senescence, such as enlarged, flattened morphological changes and positive senescence-associated β-galactosidase staining. These cells also showed pRb hypophosphorylation, p53 accumulation and p21 induction in western blot analyses."	--	--	--	--	--	--	--	--	HL	repair AND renewal	26717900
Sen_E_676	Ionizing radiation	Other	MRC-5	--	Aging	Accelerate	SA-β-gal activity assay//BrdU assay//Immunostaining	"This abolished cell growth and labelling indices for BrdU, Ki67 and caused expression of senescence-associated β-galactosidase (Sen-β-Gal) to an extent equal to the deep replicative senescence seen when cells had reached their normal proliferative limit."	--	--	--	--	--	--	--	--	L	repair AND renewal	20160708
Sen_E_677	Cigarette smoke	Other	A549	Lung	Aging	Accelerate	SA-β-gal activity assay//BrdU assay//Western blot//Cell morphological analysis	"When the A549 cells were exposed to CSE at 0.01 vol/vol% for 36 h, they exhibited a phenotype that is typical of cellular senescence (i.e., an increase in SA β-gal activity) , a distinct, flat, and enlarged morphology, and an increase in lysosomal mass. When A549 cells were exposed to 0.01 vol/vol% of CSE solution before growth stimulation with 10% FCS, cellular uptake of BrdU was reduced to half the uptake by the control cells, suggesting that irreversible growth arrest had occurred. When cells were exposed to CSE at 0.01 vol/vol% for 36 h, washed with PBS, and then stimulated with 10% FCS for a long period of time, a reduction of BrdU uptake was still observed ,confirming the irreversibility of CSE-induced growth arrest. Quantitative analyses for cellular senescence showed that exposure of A549 cells to CSE caused a dose-dependent and timedependent increase in SA-β-gal activity, with 60% of the A549 cells expressing SA-β-gal activity after exposure to 0.05 vol/vol% of CSE solution for 36 h. Exposure of A549 cells to CSE also increased the total number of cells expressing SA-β-gal, indicating that the increase in the percentage of cells expressing SA-β-gal was not merely due to a decrease in overall cell number that may have occurred after cell death."	--	--	--	--	--	--	--	--	L	cellular senescence	15333326
Sen_E_678	Human respiratory syncytial virus	Other	"HEp-2,A549"	Lung	Aging	Accelerate	SA-β-gal activity assay	We observed that the infection of A549 and HEp-2 cells by HRSV induces the accumulation of senescent cells positive forSA-β-gal activity. This activity could also be detected in spontaneous syncytia of both immortalized cell lines ( 20-40%) but was greatly magnified in both mononuclear cells and syncytia upon HRSV infection.	--	--	--	--	--	--	--	--	L	cellular senescence	26809688
Sen_E_679	Garcinol	Other	A549	--	Lung cancer	Accelerate	SA-β-gal activity assay	"Notably, the fraction of SA-β-Galepositive cells was further increased by the combination of IR and garcinol treatment, indicating that garcinol enhances senescence."	--	--	--	--	--	--	--	--	L	cellular senescence	22417805
Sen_E_680	Irradiation	Other	"A549,H1299"	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"For cellular senescence analysis, an SA-βGal assay in NSCLC cells was performed 3 days after irradiation. SA-βGal–positive cells increased significantly in carbon-irradiated A549 cells and in H1299 cells treated with NU7441 and carbon irradiation.p21 expression in A549 cells was consistent with the result of the SA-βGal assay; in contrast, no activation was observed in H1299 cells."	--	--	--	--	--	--	--	--	L	cellular senescence	27341700
Sen_E_681	Cigarette smoke extract	Other	ARPE?19	--	Aging	Accelerate	SA-β-gal activity assay	CSE was observed to increase the number of blue cells while treatment with cysteamine or fisetin decreased the number of observed blue cells.	--	--	--	--	--	--	--	--	L	cellular senescence	28767736
Sen_E_682	Smoking	Other	HDF	"Blood,Embryo"	Aging	Accelerate	SA-β-gal activity assay	"Cellular senescence was accelerated by treatment with smoker HDL2 and HDL3, as evidenced by SA-β-gal staining.However, the current result suggests that even moderate smoking could impair the anti-senescence activity of HDL."	--	--	--	--	--	--	--	--	L	cellular senescence	24798380
Sen_E_683	CrVI	Other	" Fibroblast,WI-38"	Blood	Aging	Accelerate	SA-β-gal activity assay	CrVI and CdII treated cultures exhibited elevated numbers of β-galactosidase positive cells even after two weeks of treatment. Similar high values of β-galactosidase positive CrVI and CdII treated cells were recorded after 10 weeks of treatment.	--	--	--	--	--	--	--	--	L	cellular senescence	15236767
Sen_E_684	Platinum(II)phenanthroimidazole G-quadruplex ligand	Other	"A549,HuH-7,MRC-5"	--	Cancer	Accelerate	Cell cycle analysis	"However treatment with 2.0*PIP induced a mild but significant G1 arrest (p<0.001) and reduced the number of cells in S phase (p<0.01) in telomerase positive A549 cells.As early as 7 days after ligand treat-ment, a concentration-dependent increase in senescent cells staining positive for β-galactosidase in telomerase positive A549 and Huh7 cancer cells was observed, as compared to the DMSO treated control cells. Treatment of normal primary MRC5 cells also led to an increase in cells staining positive for β-galactosidase and to an increase in the number of cells with a broad,flattened morphology."	--	--	--	--	--	--	--	--	L	cellular senescence	26724375
Sen_E_685	Chronic hypoxic conditioning	Other	PwR-1E	--	Aging	Accelerate	SA-β-gal activity assay//ELISA	"SA-β-gal activity assay:An increase in blue staining in the hypoxic population indicates a notable presence of senescent-associated b-galactosidase activity.ELISA: the protein levels of key cytokines interleukin-1b (IL-1b), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor (TNFa) were determined in the media of the sublines using a multiplex ELISA system."	--	--	--	--	--	--	--	--	L	cellular senescence	19584087
Sen_E_686	Lonizing irradiation	Other	"U2OS,MCF-7"	--	Aging	Accelerate	SA-β-gal activity assay	"SA-β-gal activity assay:At later time intervals (from the 7th day after irradiation),flat nuclei,which are characteristic of senescence cells were observed."	--	--	--	--	--	--	--	--	L	cellular senescence	27760841
Sen_E_687	COPD	Other	Promo Cell	--	Chronic?obstructive?pulmonary?disease	Accelerate	SA-β-gal activity assay	SA-β-gal activity assay:The experiments showed that serum harvested from the COPD patients causes bronchial epithelial cells to present features characteristic of a senescent phenotype.	--	--	--	--	--	--	--	--	L	cellular senescence	30154415
Sen_E_688	NES-hTERT	Other	GM847	--	Aging	Accelerate	Growth curve assay//SA-β-gal activity assay//Flow cytometry//Cell cycle analysis	"NHF-expressing NES-hTERT arrested growth prematurely,Growth arrest was accompanied by flattened and enlarged morphology reminiscent of senescent cells,DNA profiles using propidium iodide (PI) and flow cytometry indicated that the cells were arrested in the G1?S transition, which is typical of the growth arrest associated with senescence."	--	--	--	--	--	--	--	--	L	cellular senescence	20089117
Sen_E_689	Chromosome 5	Other	A2058	--	Melanoma	Accelerate	Telomerase activity assay//SA-β-gal activity assay	"Assay of telomerase activity:A2058#5 clone showed a 90% decrease in telomerase activity，this indicates that normal human chromosome 5, at its physiological level, suppressed hTERT expression and telomerase activity in A2058 cells. SA-β-gal activity assay:A2058#5S clones presented with significant morphological changes compared to parental A2058 cells, characterized by an elongated and somewhat enlarged and flat shape,s, introduction of chromosome 5 greatly reduced the growth rate of A2058 cells. Additionally, the majority of A2058#5S clones entered cellular senescence at around 20 PDs, as determined by SA-b-Gal staining."	--	--	--	--	--	--	--	--	L	cellular senescence	20621064
Sen_E_690	UVB	Other	Fibroblast	Skin	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry	"SA-β-gal activity assay:we initially assayed senescence-associated (SA) β-galactosidase (β-gal) activity, after irradiating fibroblasts with 350 J/m2 of UVB. 40% of the cells displayed SA β-gal positivity 48 hours after exposure to UVB at 350 J/ m2. Flow cytometry//hematocytometer : Flow cytometric analysis also showed that the percentage of cells in the G0/G1 phase was significantly increased 48 hours after exposure to UVB. An investigation of cell growth after exposure to UVB revealed a time-dependent decrease."	--	--	--	--	--	--	--	--	L	cellular senescence	25165029
Sen_E_691	Lipogenesis	Other	Chang	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"This enhanced lipogenesis by mSREBP-1 overexpression alone clearly induced senescence, as shown by an increase in SA-β-galactosidase activity, arrest of cellular growth, increased cell granularity represented by SSC, and increased cell size represented by FSC."	--	--	--	--	--	--	--	--	L	cellular senescence	20615871
Sen_E_692	Pressure	Other	Fibroblast	--	Aging	Accelerate	SA-β-gal activity assay	"As represented by the amount of SA-β-gal staining, NNF cultured at higher pressures showed increased senescence at ATM 60 and ATM 120 compared to ATM 30 and controls (ATM). Significance was reached for ATM 120 versus all other pressures."	--	--	--	--	--	--	--	--	L	cellular senescence	15734488
Sen_E_693	UVB	Other	NIH-3T3	--	Aging	Accelerate	SA-β-gal activity assay	We found that UVB induced cell senescence was in a dose-dependent manner.	--	--	--	--	--	--	--	--	L	cellular senescence	23804320
Sen_E_694	Radiation	Other	"HNSCC,FaDu-DN,FaDu-EBV,FaDu-HE"	--	Squamous cell carcinoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot	"In the first 12 hours after radiation treatment all the cell lines showed a similar pattern of cell cycle changes – reduction of G1 phase and an increase of S and G2 phases. After irradiation, at 48h and 72h FaDu-HPV (p<0.01), FaDu-EBV (p<0.05) and FaDu-HE (p<0.001) cell lines had significantly higher percentages of senescent cells in comparison with respective FaDu-DN cell line at indicated time points. Our samples displayed reduced AKT and ERK activities accompanied by elevated p21 after radiation in agreement with upregulated senescence level in FaDu HPV/EBV cell lines."	--	--	--	--	--	--	--	--	L	cellular senescence	26635065
Sen_E_695	Gamma irradiation	Other	"MRC-5,HFF"	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"Then, the percentage of SA-β Gal stained cells was determined at different time points over 5 days after irradiation treatment. The highest percentage of SA-β Gal stained MRC-5 fibroblast cells (63 ± 4 %) was noted after the highest irradiation dose (20 Gy) and the longest time lapse (120 h) [72]. Therefore, HFF strains were only irradiated by 20 Gy. After 120 h the percentage of SA-β Gal stained HFF cells was similar to the corresponding value for the MRC-5 fibroblasts. protein expression levels of p21 and p16 were found to be significantly up-regulated in irradiation induced senescent fibroblasts compared to controls. Unexpectedly, a number of cytokines and cytokine receptors (IL11, EGFR, CXCL-1,2,3,5,6,14) were significantly down-regulated on irradiation induced senescence in MRC-5 and HFF strains, resulting in a significant down-regulation of the KEGG pathway “cytokine–cytokine receptor interaction” (hsa04060) representing SASP."	--	--	--	--	--	--	--	--	HL	cellular senescence	27464526
Sen_E_696	UVB	Other	Keratinocyte	--	Aging	Accelerate	SA-β-gal activity assay	"Keratinocytes exposed to increasing doses of UVB radiation exhibited significant increases (of 6- to 8-fold) in SA β-gal activity, a biomarker for cellular senescence, relative to the unexposed control cells. Similar results were obtained in immunofluorescent histochemical analyses using p53, p21, p16 or PML, which are also known biomarkers of cellular senescence."	--	--	--	--	--	--	--	--	L	cellular senescence	22335598
Sen_E_697	X-irradiation	Other	A549	--	Chronic obstructive pulmonary disease	Accelerate	Immunostaining	"This dose increased the numbers of H2AX foci per cell three fold and the numbers of phosphorylated 53BP1 foci per cells six fold, thereby validating the induction of DSBs by X-irradiation ."	--	--	--	--	--	--	--	--	L	cellular senescence	22267761
Sen_E_698	High glucose	Other	HMSC	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry//Southern blot	The HG group had a significantly higher percentage of SA-β-Gal-positive cells than the NG group (P < 0.05);Cell cycle arrest was observed in G1 phase in the HG group;The telomere length of HGMCs in the HG group was significantly shorter than that in the NG group (P < 0.05).	--	--	--	--	--	--	--	--	L	cellular senescence	31089945
Sen_E_699	γ-irradiation	Other	"A172,HCT116,MCF-7,U2OS,U87"	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis//BrdU assay	"Microscopic analysis revealed that after induction of DNA damage, all five cell lines adopted a senescent phenotype with a large, flattened shape and multiple or enlarged nuclei, and enhanced the expression of SA-β-galactosidase.Quantification of BrdU-positive cells showed that DNA damaged cells strongly reduced the incorporation of BrdU,confirming the absence of S-phase activity."	--	--	--	--	--	--	--	--	L	cellular senescence	19648966
Sen_E_700	X-irradiation	Other	Endothelial cell	--	Chronic obstructive pulmonary disease	Accelerate	Immunostaining	X-irradiation increased the percentages of lung microvascular endothelial cells that stained positive  p16.	--	--	--	--	--	--	--	--	L	cellular senescence	22267761
Sen_E_701	Autophagy	Other	BEC	--	Primary biliary cirrhosis	Accelerate	SA-β-gal activity assay	"Percentage of cells positive for SA-β-gal was significantl higher in cultured BECs treated with H2O2(SA-β-gal-labeling index, 37.0±13.1), Etoposide (34.0±5.7), and serum deprivation (34.2±11.7), when compared with control without treatment. Percentage of cells positive for SA-β-gal was significantly decreased by a treatment with the autophagy inhibitor 3MA(5 mM) ."	--	--	--	--	--	--	--	--	L	cellular senescence	20212459
Sen_E_702	UV	Other	NIH-3T3	--	Aging	Accelerate	SA-β-gal activity assay	"In addition, NIH 3T3 cells stimulated with UV-C light (10 J/m2) showed an increased acid β-galactosidase activity after 11 d (our unpublished results)."	--	--	--	--	--	--	--	--	L	delay aging	12134086
Sen_E_703	High glucose	Other	Endothelial cell	--	Type 2 diabetes mellitus	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Accordingly, the percentage of senescent EC reached a significant level after 48 h of treatment with hGluc (44.271.31% vs. 18.171.52% in Ctr, Po0.01). SA β-gal positive cells in samples co-treated with EgtthGluc were 28.371.22% vs. 44.271.31% in hGluc (Po0.01). Moreover, microscopy examination revealed that the hGluc senescent EC become large and with more spindle-shaped morphology."	--	--	--	--	--	--	--	--	L	delay aging	27101740
Sen_E_704	Serum starvation	Other	WI-38	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"Alternatively, CDKN2A (cyclin dependent kinase inhibitor 2A), another cell-cycle arrest protein, and a reliable cell senescence marker [25 28] was stably induced in serum-starved fibroblasts. SA-GLB1/β-gal activity, another cell senescence marker [29] was also induced in fibroblasts serum-starved for 7 d."	--	--	--	--	--	--	--	--	L	delay aging	31931659
Sen_E_705	X-ray	Other	HPAEC	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis//Western blot	"Our data indicated that HPAEC underwent cellular senescence upon exposure to 10 Gy X-rays as determined by increased SA-β-gal activity, detected cytochemically as blue perinuclear staining at 4 days post-irradiation.X-ray-exposed HPAEC also exhibited changes in cell morphology, displaying unusually large cells and flattened cytoplasmic appearance compared to sham-irradiated controls. We also observed the upregulation of p21/waf1 within 3h post-irradiation, consistent with inhibition of the cell cycle in advance of senescence."	--	--	--	--	--	--	--	--	HL	delay aging	24205274
Sen_E_706	Homologous recombination	Other	OE33	--	Esophageal cancer	Prevent	SA-β-gal activity assay//Knockdown//Western blot	"To study the impact of HR suppression on the efficacy of telomerase inhibitor, HR in OE33 cells was first inhibited by lentivirus-based shRNAs targeting RAD51. RAD51-knockdown was confirmed by western blotting and HR suppression by plasmidbased assay. Cell growth: relative to control (CS) cells, the viability of RAD51-suppressed (R), GRN163L-treated CS and GRN163L-treated R cells was reduced by 34±5%, 24±6% and 65±5%, respectively. Thus,inhibition of HR or telomerase significantly reduced proliferation rate in OE33 cells, and combined treatment was associated with a significant 41% increase in cell death, relative to GRN163L used alone.Thus, simultaneous suppression of telomerase and HR led to a significant 36% (12-fold) increase in apoptosis, relative to telomerase inhibition alone.Evidence of senescence: cells were also evaluated for bgalactosidase staining, a marker for senescence. A subset of cells subjected to both telomerase and HR suppression stained positive for β-galactosidase, indicating senescence."	--	--	--	--	--	--	--	--	HL	delay aging	23604115
Sen_E_707	Ionizing radiation	Other	MCF-7	--	Aging	Accelerate	SA-β-gal activity assay	"Based on the phase contrast pictures, we observed that the irradiated cells alone become flattened and enlarged. Incidences of cells with senescent morphological features seem suppressed in cells irradiated in the presence of the studied inhibitors. Using microscopy and a chromogenic substrate, we determined cellular senescence through visualization of SA-β-galactosidase activity. Obviously, MCF-7 cells irradiated with a dose of 6 Gy do not die but enter premature senescence. SA-β-galactosidasepositive cells amounted to 79 % compared to mock-treated cells 3 days postirradiation."	--	--	--	--	--	--	--	--	L	delay aging	25801233
Sen_E_708	Elovanoids	Other	RPE	--	Aging	Prevent	SA-β-gal activity assay	"After 7 d incubation, OAβ altered RPE cell morphology and activated SASP, as revealed by the SA-β-Gal staining, as well as enhanced the expression of a set of senescence genes, AMD, matrix metalloproteinases, and autophagy-related genes. A point of interest is that some matrix metalloproteinases were affected, but not all were expressed in RPE cells. In other cells, SASP is primarily proinflammatory and has been shown to comprise chemokines, metalloproteinases, proteases, cytokines, and insulin-like growth factor binding proteins. The senescence genes studied are p16INK4a (Cdkn2a), p21CIP1(Cdkn1A), p27KIP (Cdkn1B), p53 (Tp53 or TRP53), IL6, and MMP1. ELV-N32 and ELV-N34 reverted these effects."	--	--	--	--	--	--	--	--	HL	delay aging	31712409
Sen_E_709	Nano-hydroxyapatite/chitosan/poly lactide-co-glycolide	Other	HUCMSC	--	Aging	Prevent	qRT-PCR//Western blot	"We detected markers of senescence in P3 or P27 hUCMSCs that cultured on conventional culture dish (hUCMSCs/CD) or nHA/CS/PLGA nano-scaffold (hUCMSCs/NS). As expected, the mRNA and protein levels of P53 were lower in P27 hUCMSCs/NS, as compared to hUCMSCs/CD. nHA/CS/PLGA scaffold prevented the increase of P53 proteins in hUCMSCs during in vitro passage.Culture on the nano-scaffold resulted in significant increases in the expression of BMP2, bFGF, EGF and CXCL5 in hUCMSCs when comparing with conventional culture dish . The expression of these above genes in P27 hUCMSCs/NS was ~10 times higher than that in P27 hUCMSCs/CD. nHA/CS/PLGA scaffold largely prevented the decline of these genes controlling stem cell function after culture of 27 passages."	--	--	--	--	--	--	--	--	L	delay aging	32323459
Sen_E_710	Radiation	Other	T47D	--	Breast cancer	Accelerate	SA-β-gal activity assay//Flow cytometry	"Cell cycle analysis revealed induction of a G2 arrest in the total population of T47D cells after 5 × 3 Gy, from 14.7% to 21.5%. After fractionated radiation with 5 × 3 Gy, the total population of T47D cells showed a 3.6-fold increase of cells in the G0 phase of the cell cycle, from 3.31% to 11.9% .At 0 Gy, 2% of the total population was X-gal-positive/senescent cells . Fractionated radiation induced a dose dependent increase of X-Gal+/senescent cells in the total population, with a maximal effect at 5 × 3 Gy (25-fold increase, P = 0.09)."	--	--	--	--	--	--	--	--	L	delay aging	20158881
Sen_E_711	Garlic	Other	HaCaT	--	Aging	Prevent	SA-β-gal activity assay	"Percentage?of?senescence?cells?in?the?non‐UV?irradiated?HaCaT?cells?was?low,?and?garlic?treatment?(100?μg/mL)?slightly?but?significantly?decreased?SA‐β‐gal?activity? in?non‐UV?exposed?HaCaT?cells."	--	--	--	--	--	--	--	--	L	delay aging	27483310
Sen_E_712	Fibroblast-Derived Extracellular Matrix	Other	ad-MSC	Adipose	Aging	Prevent	qRT-PCR//Western blot	"The average population doubling time for ad-MSCs on the fd-ECM increased significantly.Gene expression of several anti-senescence markers was significantly upregulated in ad-MSCs cultured on fd-ECM .The expression of several genes such as P16, P21, and P53 was downregulated in the presence of fd-ECM ."	--	--	--	--	--	--	--	--	L	delay aging	27527147
Sen_E_713	Brown alga Undaria pinnatifida	Other	BM-MSC	--	Aging	Prevent	MTT assay//Western blot	"The viability was significantly increased in UP-Ex-MSCs compared to untreated hBM-MSCs. The senescence proteins p53, p21, and p16 were increased in P-17 cells and this increase was reversed in P-17 UP-Ex-MSCs."	--	--	--	--	--	--	--	--	L	delay aging	30460058
Sen_E_714	Gamma-tocotrienol	Other	HDF	Foreskin	Aging	Prevent	Flow cytometry//qRT-PCR//SA-β-gal activity assay	"γ-Tocotrienol  c-Tocotrienol significantly decreased (p,0.05) the percentage of senescent HDFs in the G0/G1phase. In contrast,c-tocotrienol significantly increased (p,0.05) the percentage of senescent HDFs in the G2/M phase.However,c-tocotrienol produced  significant downregulations of MMP1 mRNA expression in pre-senescent and senescent HDFs compared to untreated cells (p,0.05).c-Tocotrienol produced significant(p,0.05) upregulations of COL1A1 in young, pre-senescent,and senescent HDFs. c-Tocotrienol also significantly upregulated ELN mRNA in young and senescent HDFs. c-Tocotrienol significantly downregulated IL6, CCND1 and RB1 mRNA expression in senescent HDFs (p,0.05)..The incubation of senescent cells with 70 mM c-tocotrienol did not alter the percentage of SA-β-gal-positive cells."	--	--	--	--	--	--	--	--	L	delay aging	22358238
Sen_E_715	UV irradiation	Other	--	Skin	Aging	Accelerate	qRT-PCR	"mRNA expression of type I collagen, the major structural protein in the human skin, was significantly reduced by acute UV irradiation in the dermis.In contrast, mRNA expression of collagen-degrading MMP-1, the primary collagen-degrading enzyme in human skin, was significantly elevated by acute UV irradiation in the dermis.(Aging characteristics：reduced type I collagen production and increased fragmentation of the dermal collagenous extracellular matrix)."	--	--	--	--	--	--	--	--	L	delay aging	23881607
Sen_E_716	HIV infection	Other	CD4 peripheral T-cell	Blood	AIDS	Accelerate	Immunostaining//Flow cytometry	"However, although the memory T-cell subset did not show more activation, significantly higher levels of senescence and proliferation were observed in vertically HIV-infected patients than in the healthy subjects. Furthermore, the effector memory CD4 T cells of vertically HIV-infected subjects displayed higher senescence, activation and proliferation levels than healthy subjects. Regarding the TemRA CD4 T-cell subset, vertically HIV-infected subjects showed higher senescence and activation levels than healthy subjects,but similar levels of proliferation were observed."	--	--	--	--	--	--	--	--	L	delay aging	22735071
Sen_E_717	CD9-Lac/CaCO3/Rapa	Other	HDF	--	Aging	Prevent	SA-β-gal activity assay	"HDFs were treated with free Rapa or CD9-Lac/CaCO3/Rapa for 72 h, followed by 3 passages before analysis because the proliferative effect of Rapa was found to be high after 3 passages.The number of HDFs (P23) positive for β-galacto sidase staining clearly decreased following treatment with Rap-a or CD9-Lac/CaCO3/Rapa, which can be attributed to mTOR inhibitory activities of Rapa.The population doubling time was signficantly reduced in free Rapa- or CD9-Lac/CaCO3/Rapa-treated HDFs (P23) when compared to untreated old HDFs."	--	--	--	--	--	--	--	--	L	delay aging	28393891
Sen_E_718	Hp	Other	HDF	Foreskin	Aging	Accelerate	SA-β-gal activity assay	The expression of senescence-associated-β-galactosidase was only significantly elevated in cells chronically exposed to 5 mM HP.	--	--	--	--	--	--	--	--	L	apoptosis	17924880
Sen_E_719	Sulfur mustard	Other	MSC	Bone marrow	Chronic wound healing	Accelerate	SA-β-gal activity assay	"Using a SM concentration of 40 μM (IC25), most of the MSC demonstrate a senescence typical expression of ?-galactosidase.In absence of SM, 37.0 ± 1.2% of all cells were positive for Ki-67 within the nucleus. With increasing concentration of SM the number of Ki-67 positive nucleus deceased to 0.8 ± 0.1% at IC25(40 μM). Under exposure of IC1(1 μM) the number of proliferating cells were decreased by 26%."	--	--	--	--	--	--	--	--	L	apoptosis	28818580
Sen_E_720	Gamma irradiation	Other	Prostate epithelial cell	Prostate	Prostate cancer	Accelerate	Colony formation assay//SA-β-gal activity assay	"For the gamma irradiated cells, 10 Gy and higher completely destroyed colony- forming ability. After treatment with single and multiple doses of gamma irradiation, senescence in primary prostate epithelial cells was apparent."	--	--	--	--	--	--	--	--	HL	apoptosis	26590118
Sen_E_721	High glucose	Other	B-MSC	--	Aging	Accelerate	BrdU assay//Western blot//SA-β-gal activity assay//Cell morphological analysis	"BMSCs cultured in HG exhibited a time-dependent reduction in cumulative PD and BrdU incorporation.Cells cultured in HG for 2 weeks already show increased p16 and p21. HG also induced a time-dependent increase in SA-βgal positive cells .By contrast, glucose at 25 mM induced morphological changes consistent with senescence."	--	--	--	--	--	--	--	--	L	apoptosis	25961745
Sen_E_722	Fc-OH-TAM	Other	Breast cancer cell	--	Breast cancer	Accelerate	Flow cytometry//SA-β-gal activity assay//BrdU assay	"As previously described, after 48 h, OH-TAM significantly increased the percentage of cells in the G0/G1 phase for both ERa(+) cell lines (MCF-7, ZR-75-1) while no modification of cell cycle distribution was observed in either of the ERa negative cell lines (MDA-MB231, SKBR-3). Interestingly, Fc-OH-TAM affected cell cycle distribution differently from OH-TAM. In ERa(+) cells, 1μM of Fc-OH-TAM first increased the percentage of cells in the S phase at 24 h, and this increase was then followed by an arrest in G0/G1 at 48 h (Table 2). Fc-OH-TAM significantly increased the percentage of BrdU-positive cells (48.09%) (in the S phase) compared to what is observed for non-treated cells or for cells treated with OH-TAM (35.63%), thus indicating a cell cycle progression from G0/G1 to S phase. Next, pulse/chase experiments were performed as follows: after the 2 h incubation period in the presence of BrdU, cells were washed, left to recover for 24 h, and then analyzed .OH-TAM increased the percentage of SA-βgalactosidase cells in ERa(+) cells but not in ERa() cells, indicating that G0/G1 cell cycle arrest was associated with senescence induction in MCF-7 cells treated with OH-TAM. Interestingly, FcOH-TAM treatment increased SA-β-galactosidase staining in both cell lines (MCF-7 and MDA-MB-231)."	--	--	--	--	--	--	--	--	L	apoptosis	20116857
Sen_E_723	OH-TAM	Other	Breast cancer cell	--	Breast cancer	Accelerate	Flow cytometry//SA-β-gal activity assay//BrdU assay	"As previously described [29,30], after 48 h, OH-TAM significantly increased the percentage of cells in the G0/G1 phase for both ERa(+) cell lines (MCF-7, ZR-75-1) while no modification of cell cycle distribution was observed in either of the ERa negative cell lines (MDA-MB231, SKBR-3). Interestingly, Fc-OH-TAM affected cell cycle distribution differently from OH-TAM. In ERa(+) cells, 1μM of Fc-OH-TAM first increased the percentage of cells in the S phase at 24 h, and this increase was then followed by an arrest in G0/G1 at 48 h. Fc-OH-TAM significantly increased the percentage of BrdU-positive cells (48.09%) (in the S phase) compared to what is observed for non-treated cells or for cells treated with OH-TAM (35.63%), thus indicating a cell cycle progression from G0/G1 to S phase. Next, pulse/chase experiments were performed as follows: after the 2 h incubation period in the presence of BrdU, cells were washed, left to recover for 24 h, and then analyzed.OH-TAM increased the percentage of SA-βgalactosidase cells in ERa(+) cells but not in ERa() cells, indicating that G0/G1 cell cycle arrest was associated with senescence induction in MCF-7 cells treated with OH-TAM. Interestingly, FcOH-TAM treatment increased SA-β-galactosidase staining in both cell lines (MCF-7 and MDA-MB-231)."	--	--	--	--	--	--	--	--	L	apoptosis	20116857
Sen_E_724	Zn	Other	HCAEC	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry//qRT-PCR//Western blot	"Almost all Zn-treated cells (approximately 90%) had undergone cell death by passage 11, whereas only approximately 40% of control cells had undergone cell death by this point. Measurement of SA-β-gal staining and p16 expression as biomarkers of senescence revealed increases induced by the Zn treatment at late passages."	--	--	--	--	--	--	--	--	HL	apoptosis	28918363
Sen_E_725	Alpha particles	Other	MSC	Bone marrow	Aging	Accelerate	SA-β-gal activity assay	"Also, the percentage of senescent cells augmented in the cultures treated with Xrays either with a 40 or 2000 mGy dose."	--	--	--	--	--	--	--	--	L	apoptosis	28252222
Sen_E_726	Hypoxia	Other	Human Cardiac Progenitor Cell	Heart left ventricle	Mitochondrial Dysfunction	Prevent	SA-β-gal activity assay	"Senescence-associated β-Gal positivity was used as a marker of cellular senescence. hCPC-1% exhibited ~70% fewer SA-β-Gal+ cells than hCPC-21%, suggesting hypoxia delays hCPC senescence and supports self-renewal."	--	--	--	--	--	--	--	--	HL	apoptosis	30629785
Sen_E_727	Mitochondrial ROS	Other	Human Cardiac Progenitor Cell	Heart left ventricle	Mitochondrial Dysfunction	Accelerate	SA-β-gal activity assay//Flow cytometry	"Mitochondrial ROS was subsequently artificially increased while maintaining hypoxic conditions by inhibition of complex III with 100 μM antimycin A (AMA) for 9 days in hCPC-1%.  However, a 220% increase in SA-β-gal+ positive cells was observed in hCPC-1% treated with AMA, suggesting mitochondrial ROS can directly drive hCPC senescence."	--	--	--	--	--	--	--	--	HL	apoptosis	30629785
Sen_E_728	Radiation	Other	UMSCC1	--	Squamous cell carcinoma	Accelerate	SA-β-gal activity assay//Flow cytometry//Cell morphological analysis	"Radiation treatment resulted in significant levels of SA-β-gal activity in cell lines expressing either wild-type (HN 30) or nondisruptive mutant TP53 (Detroit, R175H). Furthermore, in these cells with SA-beta-gal staining, the morphologic characteristics of cellular senescence were observed, specifically a large, flattened cell with the classic “fried egg” appearance on microscopy."	--	--	--	--	--	--	--	--	L	apoptosis	22090360
Sen_E_729	Radiation	Other	MSC	Bone marrow	Aging	Accelerate	SA-β-gal activity assay	"Indeed, a huge percentage of cells entered senescence six hours following IR, both for the low and high dose radiation."	--	--	--	--	--	--	--	--	L	apoptosis	25544750
Sen_E_730	Hyperbaric air	Other	HDF	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Both HA- and NMH-treated cells exhibited the typical senescent cell morphology, such as cell enlargement, a reduced cytoplasm-to-nuclear ratio, saturation density, and increased sa-β-gal activity, after 7 days of culture . After this time point, the cells gradually displayed the characteristics of replicatively senescent cells in a time-dependent manner. About 50% blue-stained cells have been shown after 14 days of culture under both conditions."	--	--	--	--	--	--	--	--	HL	apoptosis	18465208
Sen_E_731	Normobaric mild hyperoxia	Other	HDF	--	Aging	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"Both HA- and NMH-treated cells exhibited the typical senescent cell morphology, such as cell enlargement, a reduced cytoplasm-to-nuclear ratio, saturation density, and increased sa-β-gal activity, after 7 days of culture. After this time point, the cells gradually displayed the characteristics of replicatively senescent cells in a time-dependent manner. About 50% blue-stained cells have been shown after 14 days of culture under both conditions."	--	--	--	--	--	--	--	--	HL	apoptosis	18465208
Sen_E_732	Heat	Other	HUVEC	--	Aging	Accelerate	SA-β-gal activity assay	"SA-β-Gal expression was observed in 1.9% of cells at 37C, and 3.8% at 39C, and 4.0 % at 42C.Senescent cells significantly increased at 39 and at 42 C."	--	--	--	--	--	--	--	--	L	apoptosis	25142166
Sen_E_733	SP600125+IR	Other	"ARO,KTC-2"	--	Anaplastic thyroid cancer	Accelerate	SA-β-gal activity assay//Cell morphological analysis	"We also observed that most of SP600125 plus IR-treated cells were still attached to dishes and had enlarged granular phenotype resembling senescent state.The number of SA-β-gal–positive cells was markedly increased when SP600125 was combined with irradiation, whereas singular treatment showed weak or moderate induction of SA-β-gal activity. Our previous study has demonstrated that the fraction of cell with high PKH-2 fluorescence and increased SSC represents senescent state (10).The combination treatment with both SP600125 and IR significantly increased the subpopulation of PKH-2hi/SSChi compared to singular treatment."	--	--	--	--	--	--	--	--	L	apoptosis	16571083
Sen_E_734	Hypoxia	Other	HPDC	Bone	Aging	Prevent	SA-β-gal activity assay	"Greater senescence‐associated β‐galactosidase expression was observed in hPDCs cultured in normoxia relative to those cultured in hypoxia.Likewise, the relative absorbance value of β‐galactosidase was significantly higher for hPDCs cultured under normoxic conditions compared with those cultured under hypoxic conditions."	--	--	--	--	--	--	--	--	L	apoptosis	29082591
Sen_E_735	Ionizing radiation	Other	"A549,H460,H1299"	--	Lung cancer	Accelerate	SA-β-gal activity assay	Senescence-associated β-Galactosidase staining of indicated stable clones at 73 h following IR treatment.	--	--	--	--	--	--	--	--	L	apoptosis	26943034
Sen_E_736	6 Gy irradiation	Other	22RV1	--	Prostate cancer	Accelerate	SA-β-gal activity assay	"We demonstrated by SA-β-Gal staining that 6 Gy irradiation increased cellular senescence in 22RV1 significantly more than in 22RV1-F and 22RV1-DF, 1 week after irradiation ."	--	--	--	--	--	--	--	--	L	apoptosis	17914094
Sen_E_737	Hyperthermia	Other	"U2OS,SW872"	--	Sarcoma	Accelerate	SA-β-gal activity assay//Flow cytometry	"DNA content histograms of SW872 (left) and U2OS (right) 24 and 48 hrs after treatment (10 nmol/l trabectedin). In both cell lines, trabectedin caused a marked G2/M arrest after 24 hrs, which was strongly enhanced by additional hyperthermia (upper row).treatment with additional hyperthermia prolonged trabectedin‐induced cell cycle arrest in both investigated cell lines (lower row). Hyperthermia alone caused no significant alterations in cell cycle distributions (data not shown).Particularly U2OS—instead of undergoing apoptosis—showed a strong senescence response and a heat‐dependent continuously increasing number of senescent cells over 72 hrs (data not shown) to 144 hrs. In comparison, SW872, which preferentially underwent apoptosis, showed no detectable induction of senescence."	--	--	--	--	--	--	--	--	L	apoptosis	26933761
Sen_E_738	Gli1 PEI–SNAs	Other	U87 MG	--	Glioblastoma	Accelerate	SA-β-gal activity assay	"SAβGal staining demonstrated that U87-MG cells treated with Gli1 PEI–SNAs broadly undergo senescence, as indicated by teal SAβGal staining, while cells treated with Scr PEI–SNAs do not."	--	--	--	--	--	--	--	--	L	apoptosis	30260647
Sen_E_739	Radiation	Other	K562	--	Chronic myeloid leukemia	Accelerate	SA-β-gal activity assay//Flow cytometry	"After 5-day incubation, a substantial part of irradiated cells underwent phenotypic changes characteristic of senescence, associated with β-galactosidase staining. At the concentration used, STI571 alone did not induce such changes.Radiation alone induced a depletion of the G1- and S-phase compartments together with prolonged accumulation in the G2 phase."	--	--	--	--	--	--	--	--	L	apoptosis	18281522
Sen_E_740	Radiation	Other	NT2/D1	--	Aging	Accelerate	SA-β-gal activity assay//Flow cytometry//Western blot	"On the other hand, 2 Gy of radiation induced senescence in both undifferentiated NT2/D1 and NT2/D1 1W cells in early phase of differentiation.Results also indicate that, after 2 Gy of radiation, both undifferentiated NT2/D1 cells and differentiated NT2/D1 1W cells have increased number of cells in sub-G1 phase, while number of cells in G1 and S phase is reduced .Also, we observed overall increased cell number in G0/G1 phase of NT2/D1 1W, accompanied with smaller number of cells in S phase compared to undifferentiated NT2/D1 cells .Western blot analysis showed that 2 Gy dose of radiation increased the level of p21Waf1/Cip expression only in NT2/D11W cells."	--	--	--	--	--	--	--	--	L	apoptosis	31509479
Sen_E_741	Ionizing radiation	Other	"DLD1 (KRAS wt/mut),DWT7 (wt/-)"	--	Lung cancer	Accelerate	SA-β-gal activity assay//DAPI staining	"However, upon additional irradiation with 2 Gy, the senescence response was reactivated (while IR alone did not cause senescence)."	--	--	--	--	--	--	--	--	L	apoptosis	24648348
Sen_E_742	UVA	Other	PrEC	--	Aging	Accelerate	SA-β-gal activity assay	"However, they did contain many enlarged cells, which stained positive for senescence-associated β-galactosidase, indicating that bystander PrEC cultures respond in part by becoming senescent."	--	--	--	--	--	--	--	--	L	genomic instability	19651821
Sen_E_743	UVB	Other	Keratinocyte	--	Aging	Accelerate	Western blot	"We found that UVB exposure increased the levels of γH2AX, p16INK4A, and cleaved caspase-3 in the epidermis of wild-type mice, indicating increased senescence and apoptosis. Furthermore,the  induction  of  γH2AX,  p16INK4A,  and  cleaved caspase-3  levels  was  attenuated  in  TRPC7+/? and TRPC7?/? mice."	--	--	--	--	--	--	--	--	HL	genomic instability	31755176
Sen_E_744	Resveratrol	Chemical compounds	MSC	Bone marrow	Aging	Prevent	SA-β-gal activity assay//Colony formation assay	SA-β-gal activity significantly increased in LP-MSCs compared with that in EP-MSCs(SIRT1 expression) treated with either EtOH or with resveratrol.The CFU-F assay was performed. The results showed that resveratrol enhanced the colony-forming ability of EP-MSCs.	β-catenin	Downregulation	Western blot	"Western blot results showed that in EP-MSCs, ERK phosphorylation was reduced by resveratrol, resulting in a decrease of Activate β-catenin (non-phosphorylated)."	ERK	Downregulation	Western blot	"Western blot results showed that in EP-MSCs, ERK phosphorylation was reduced by resveratro."	L	delay aging	26456654
Sen_E_745	Acrolein	Chemical compounds	HFL-1	--	Aging	Accelerate	SA-β-gal activity assay//Cell counting//Cell viability assay	"Repetitive acrolein exposure reduced cell viability in a dose-dependent manner.During that time period, cell growth was significantly reduced in cells previously exposed to acrolein Cells previously exposed to acrolein exhibited a significant increase in SA β-gal activity compared with control cells."	WRN	Downregulation	Western blot	"In HFL-1 cells exposed to 25 μM acrolein, steadystate levels of WRN were reduced at 48 hr (p = 0.07) and significantly reduced at 72 hr ."	p53-p21	Activation	Western blot//SA-β-gal activity assay//Cell counting	"Although both p53 and p21 levels were higher in acrolein-exposed cells than in controls during the period, they appeared to be slightly lower on day 3. In addition, both p53 and p21 levels did increase in control cells over the 3-day period . Suppression of p53 prevented acrolein-induced growth inhibition. Consistent with the cell growth data, p53 knockdown significantly attenuated SA β-gal activity in acrolein-exposed cells."	L	cellular senescence	24747221
Sen_E_746	CO	Chemical compounds	 WI-38	--	Aging	Prevent	SA-β-gal activity assay//Western blot//RT-PCR	"Exposure of WI-38 cells to H2O2 for 4 days significantly increased the number of SA-b-Gal-positive cells compared to the control group. However, treatment with CORM-A1 markedly reversed the number of H2O2-induced SA-b-Gal-positive cells.  CORM-A1 significantly reduced the expression of TNF-a IL-6, p21, and PAI-1 in H2O2- induced senescent cells."	miR-34a	Downregulation	RT-qPCR	CORM-A1 strongly decreased the expression of miR-34a.	miR-34a-Sirt1	Downregulation	SA-β-gal activity assay//RT-PCR	"CORM-A1 treatment significantly increased both mRNA and protein of Sirt1 levels.CORM-A1 strongly decreased the expression of miR-34a. CORM-A1 significantly decreased the number of miR-34a-overexpressing SA-b-Gal-positive cells. Notably, p21 and PAI-1 were upregulated by miR-34a overexpression, whereas CORM-A1 significantly reduced miR-34a-induced p21 and PAI-1 levels. Furthermore, the miR-34a-induced Sirt1 downregulation was reversed by CORM-A1."	L	cellular senescence	32228197
Sen_E_747	17β-E2	Chemical compounds	HUVECs	--	Aging	Prevent	Western blot/SA-β-gal activity assay	"In control siRNA-transfected HUVEC cells, H2O2 induces a remarkable increase in the phospho- ryaltion of Rb and 17b-E 2 significantly inhibits H2O2 s effect.17bE2 significantly inhibits H2O2-induced increase in the  number of SA-b-gal-positive cells.(孟丽加的)17b-E 2 loses the capacity to thwart H2O2 -induced increase in the number of SA-b-gal- positive cells."	SIRT3	Upregulation	RT-PCR//Western blot//Luciferase reporter assay	"As shown in the results from the real-time PCR, 17b-E 2 increases the expres- sion levels of SIRT3 mRNA in a dose-dependent manner in HUVEC cells.Immunot blot analysis shows that the protein expression levels of SIRT3 are elevated, when HUVEC cells are exposed to different concentrations of 17b-E 2. We con-  structed a Luciferase-based reporter system to mea- sure the transcriptional activity of SIRT3. As expected, 17b-E 2 increases SIRT3 promoter activity and exhibits the maximum effect at the concentration of 0.1 μM."	--	--	--	--	L	cellular senescence	32172411
Sen_E_748	Aesculus	Chemical compounds	hADMSCs	--	Aging	Prevent	SA-β-gal activity assay//MTT assay	The Cells that were only given 10 μM MIA stress showed considerable amount of aged cells as compared to control and A. indica preconditioned (10μg and 20μg) groups.A. indica preconditioning with (10μg and 20μg) resulted in increased viability and proliferation of cells as compared to stress group.	--	--	--	--	NF-κB	Downregulation	qPCR//ELISA	"The levels of TNF-α, IL-6, IL-1β, and MMP-13 mRNA expression increased 1.88, 2.89, 1.55, 1.21 and 8.30 folds in the stress group respectively as compared to the control group and A. indica treated groups. Similarly, the quantitative expression of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was measured by the mRNA level of NF-κB p65 and p50 (NF-κB 1) subunits in all the groups. The mRNA level of p65 and p50 markers increased 1.61 and 6.86 folds in the MIA induced stress group as compared to the control and A. indica treated groups.HADMSCs in control group and A. indica preconditioned groups (10μg and 20μg) showed substantially less IL-1β and TNF-α protein expression."	L	apoptosis	34679084
Sen_E_749	MATN3	Chemical compounds	NPCs	--	Intervertebral disc degeneration	Prevent	SA-β-gal activity assay//CCK-8 assay	"SA-β-Gal staining assay showed that the antisenescence effect of USC-exos was mitigated, and it  showed that SA-β-Gal staining-positive NPCs in USC shMATN3 -exos group increased compared to those in the USC conMATN3 -exos group but was still lower than the control group.The results revealed that the proliferation of NPCs was markedly promoted in response to USC-exos stimulation."	TGF-β	Upregulation	Western blot	"WB analysis of TGF-β canonical SMAD pathway and noncanonical pathway (AKT) activation. In the USCconMATN3-exos group, the level of TGF-β and the extent of p-SMAD, COL2, and ACAN expression were significantly increased."	--	--	--	--	L	loss of proteostasis	34136064
Sen_E_750	Maltol	Chemical compounds	HEK293	--	Aging	Prevent	Immunochemical staining//RTCA	"D-Gal treatment greatly increased the percentage of AGEs-positive expression in the liver and kidney tissues, respectively, comparing with the normal control group. These results con- firmed the aging changes of the liver and kidney. In contrast, supple- ment of maltol at 50 and 100 mg/kg for 4 weeks effectively inhibited the expression of AGEs in the liver and kidney, suggesting clearly that maltol effectively prevent D-Gal-induced senescence in the liver and kidney.Long-time D-Gal treatment significantly enhanced theoverproduction of MDA and reduced the activity of SOD and CATwhen compared with normal control group,whereas this situation was reversed in the maltol-treatment groups.Real-time monitoring results showed that different con-centrations of maltol significantly improved HEK293 cells viabilitywithin 24 hr after D-Gal incubation."	--	--	--	--	p53-p21-p16//PI3K-Akt	Activation//Activation	Western blot//Western blot	"Increased expressions of p53, p21, and p16 in the D-Gal-treated liver and kidney were observed compared to that in normal control group, confirming that the treatment of with D-Gal triggers both the key activation factors of aging, eventually leads to premature senescence of liver and kidney.More importantly, (删除？) western blot analy- sis also revealed that p53, p21, and p16 protein levels were all down- regulated in maltol treatment groups, further veri- fying again the antiaging effect of maltol.//The protein expression levels of p-PI3K and p-Akt were significantly decreased in liver and kidney tissues of D-Gal-induced mice. Treatment of maltol enhanced protein expression levels of PI3K and Akt phosphorylation."	L	cellular senescence	34028092
Sen_E_751	High glucose	Chemical compounds	Chondrocyte	--	Osteoarthritis	Accelerate	Western blot//SA-β-gal activity assay	"The expression of senescence-related markers (p53, p21, and p16) increased markedly with increase in glucose concentration. SA-β-gal staining results revealed that HG significantly increased the number of SA-β-gal- positive cells in a concentration-dependent manner."	--	--	--	--	AMPK	Downregulation	Western blot	"Western blot results revealed that the ratio of p-AMPK/AMPK decreased in a concentration-dependent manner. Western blot analyses results revealed that HG decreased the phosphorylation level of AMPK, whereas AICAR increased the phosphor- ylation level of AMPK, suggesting that AICAR has the capacity to activate AMPK in HG induced chondrocytes."	L	apoptosis	34006821
Sen_E_752	BBR	Chemical compounds	"T24 cells,5637cells,253J cells"	--	Bladder cancer	Accelerate	SA-β-gal activity assay//MTT assay//Colony formation assay	"The results showed that BBR treatment significantly increased the number of SA-β-gal-positive cells, indicating that BBR induces cell senescence in 253J cells.MTT assays showed that BBR significantly decreased cell viability in a  dose-dependent manner. The results of the colony formation  assay showed that BBR induced a concentration-dependent decrease in  the number of colonies.BBR treatment increased the proportion of  cells in the G0/G1 phase, accompanied by a decrease in the proportion  of cells in the S and G2/M phases in T24 cells. BBR increased the proportion of cells in the S phase in 5637 cells, along with a decline in the  proportion of that in G0/G1 and G2/M phases. In 253J cells, BBR caused  an increase in the proportion of cells in the G2/M phase.A western blot  analysis of the cell cycle-associated proteins revealed that the protein  levels of CDK2, CDK1, cyclin A, and cyclin D1 were significantly  decreased in BBR-treated BCa cells."	miR-17-5p	Upregulation	qRT-PCR	"qRT-PCR assays showed that among these five miRNAs, only miR-17-5p level was upregulated by BBR. Further analysis revealed that BBR promoted the expression of miR-17-5p in a concentration-dependent manner. "	JAK1-STAT3	Downregulation	qPCR//Western blot//SA-β-gal activity assay//Dual-Luciferase reporter assay	"BBR treatment did not decrease the mRNA levels of JAK1 and STAT3. Moreover, the decreased protein levels of JAK1 and STAT3 caused by BBR treatment could not be restored by MG132 treatment. The results of western blot and IHC ana- lyses of xenograft tumors confirmed that BBR decreased JAK1, STAT3, and p-STAT3 protein levels in vivo.BBR  significantly decreased the protein levels of JAK1 and JAK2. Both nuclear STAT3 and p-STAT3 protein levels were  downregulated by BBR treatment.Luciferase analysis  confirmed an obvious decrease in the transcriptional activity of STAT3  in BBR-treated cells."	L	apoptosis	33887260
Sen_E_753	PTX	Chemical compounds	PC3 cells	--	Prostate cancer	Prevent	SA-β-gal activity assay//WST-1 assay//Flow cytometry//ELISA	"The levels of the β-galactosidase enzyme were deter- mined to measure senescence. Built on the premise that chemotherapy induces senescence, there is major logi- cal senescence in the DTX group, as reported, which shows a significant increase compared with the control group. For its part, the senescence values of the PTX group demonstrated lower values than UCG (Δ% = 35%), but are statistically and significantly lower compared with the DTX group, since it represents a Δ% = 77% (p < 0.05). The PTX + DTX group exhibited a smaller percentage of senescence than DTX, but slightly higher than the PTX-treated group.It presents an evident decrease in viability by combining DTX and PTX.It can be observed that PTX, mainly at 4 and 8 mM, by itself reaches levels of cytotoxicity comparable to those obtained with the combination of both drugs in particular to 48 and 72 h.The percentage of apoptosis was considerably higher in the groups treated with PTX?+?DTX or with PTX even in comparison with the DTX group.The DTX (Δ%?=?115%) and PTX (Δ%?=?225%) groups also demonstrated increased apoptotic activity."	--	--	--	--	--	--	--	--	L	apoptosis	33711972
Sen_E_754	GMPS	Chemical compounds	" HeLa cells,SiHa cells"	--	Cervical cancer	Accelerate	SA-β-gal activity assay	"The senescence of the cells in each group was observed, and it was found that GMPS knockdown could induce the senescence of HeLa and SiHa cells.The results of the clone formation experiments indicated that GMPS knockdown could significantly decrease the colony-forming ability of the two CC cell lines.(不知道这句话的实验名称)(孟丽加的)"	--	--	--	--	--	--	--	--	L	cellular senescence	33649833
Sen_E_755	5-AZA-Dc	Chemical compounds	"Breast cancer cells,ovarian cancer cells"	--	Aging	Accelerate	Western blot//Flow cytometry	"5-AZA-dC treat- ment induced a significant increase in p21 expression in all cell lines compared to untreated controls. For Rb, there was a significant decrease in expression in PEO1 and PEO4 cells compared to untreated controls.The G1 phase was decreased for all 6 cell lines, reaching statistical significance for PEO1 and MDA-MB-231 treated cells. The S phase was significantly increased in PEO1 and MDA-MB-231 treated cells, and G2 phase was significantly increased in A2780cis, PEO1 and MDA-MB-231 treated cells (p?≤?0.05)."	MGAT5//ST3GAL4	Upregulation//Upregulation	RT-qPCR	"Consistent with increases in highly branched and sialylated glycans, the expression of MGAT5 and ST4GAL3, glycosyltransferases responsible for branching and sialylation, was also increased in chemosensitive cell lines A2780 and PEO1 post-5-AZA-dC treatment."	--	--	--	--	HL	apoptosis	33579350
Sen_E_756	EGT	Chemical compounds	"Keratinocytes,fibroblasts"	--	Photoaging	Prevent	SA-β-gal activity assay	"SA-β-gal-positive staining was markedly increased in the vehicle-treated group following irradiation compared to the control group. With higher concentrations of EGT, SA-β-gal staining decreased."	HSP70	Upregulation	Western blot	"Following UVB irradiation, the expression of HSP70 was drastically decreased in the vehicle-treated groups compared to the negative control. HSP70 expression was significantly increased in all EGT-treated groups."	Nrf2-HO-1	Activation	Western blot	"In the vehicle-treated group, expression of Nrf2 was significantly decreased in keratinocytes following UVB irradiation compared to the negative control. However, EGT treatment prevented the decrease in Nrf2 expression following UVB irradiation. HO-1 expression showed a similar pattern in keratinocytes following UVB irradiation."	L	apoptosis	33577831
Sen_E_757	IR	Other	CD4+T	--	Aging	Accelerate	SA-β-gal activity assay	"IR induced SA-β-gal activity in CCR6 +Th17, CCR6 neg Th and Treg, but SA-β-gal activity dose-response was significantly higher for CCR6 +Th17 compared to CCR6 neg Th and Treg.Interestingly, irradiated CCR6 +Th17 secreted larger amounts of VEGF-A and IL-8 compared to irradiated CCR6 neg Th."	H2A.J	Upregulation	γH2AX staining//qRT-PCR//Immunofluorescence	"We thus investigated DSB repair by enumerating γH2AX foci in sorted, resting CCR6 +Th17, CCR6 neg Th and Treg lymphocytes at different time points after 2Gy IR. IR-induced γH2AX foci peaked around 15-30 min post-IR in the three T-lymphocyte subsets which showed similar repair kinetics, but the number of γH2AX foci at 30min after 2Gy IR was higher in CCR6 +Th17 compared to CCR6 neg Th and Treg. H2A.J expression increased 72 hours after a 2Gy IR of CCR6 +Th17 and CCR6 neg Th, but this increased expression was higher in CCR6 +Th17."	ROS-MAPKs-mTOR	Activation	qRT-PCR	"Pretreatment with NAC, rapamycin, and the three MAPKinase pathway inhibitors prevented the IR-induced upregulation of p16 Ink4a expression and SA-β-Gal activity in both CCR6 +Th17 and CCR6 neg Th, whereas pretreatment with the ATM inhibitor did not. Conversely, IR-induced H2A.J expression was not prevented by pretreatment with NAC, rapamycin and p38-MAPK inhibitor, whereas pretreatment with the ATM inhibitor or MEK1/2 and JNK inhibitors did prevent its expression."	L	delay aging	31689464
Sen_E_758	CPBMF65	Chemical compounds	"HepG2,PBMC"	--	HCC	Accelerate	NMA analysis//Flow cytometry	"We also investigated whether treatment with CPBMF65 would induce senescence, another mechanism that may be involved in decreasing cell proliferation. A significant senescence increase of 9% in HepG2 cells treated with CPBMF65 was observed, while the positive control group (treated with H2O2, 150 μM) presented a 16% senescence increase. In order to explore if the Urd treatment was also capable of inducing senescence, the NMA assay was performed. Results demonstrated that 5 and 10 mM of Urd, as well as 150 μM of H2O2 (positive control), induced an increase of senescence in HepG2 cells."	--	--	--	--	--	--	--	--	L	apoptosis	32367200
Sen_E_759	Hypoxia	Other	--	Synovial tissue	Osteoarthritis	Accelerate	SA-β-gal activity assay//Immunofluorescence//Western blot//ELISA//qRT-PCR	"It was determined that the expression level SA-β-gal in FLS increased with H/R intervention compared to the control group. Furthermore, in the H/R + TNF-α group, the expression level of SA-β-gal was further increased compared with the control group, H/R group and TNF-α group, which indicated a larger proportion of senescent cells.  IL-1β and IL-6 levels in FLS were assessed using ELISA, and HMGB1, Casp8, p16, p21, MMP-3 and MMP-13 proteins were detected by western blotting. In addition, RT-qPCR was used to detect the mRNA expression levels of HMGB1, Casp8, p16, p21, MMP-3, MMP-13, IL-1β and IL-6. The results indicated that the protein and mRNA expression levels of HMGB1, Casp8, p16, p21, MMP-3, MMP-13, IL-1β and IL-6 were significantly increased in the H/R environment compared with the control. Moreover, the expression levels of all these factors were further significantly increased after pre-incubation with TNF-α before 24 h of H/R compared with the control group, H/R group and TNF-α group."	--	--	--	--	JNK	Activation	qRT-PCR//Western blot	"Western blotting was used to assess the protein expression levels of JNK, p53, Bcl-2 and Bax. In addition, the mRNA expression levels of JNK, p53, Bax and Bcl-2 were detected by RT-qPCR. It was demonstrated that, compared with the control group, H/R intervention decreased the expression level of Bcl-2, and enhanced the expression levels of JNK, p53 and Bax. Therefore, the present results indicated that H/R may be important in activating the JNK signaling pathway to promote senescence."	L	cellular senescence	32377698
Sen_E_760	Reoxygenation	Other	--	Synovial tissue	Osteoarthritis	Accelerate	SA-β-gal activity assay//Immunofluorescence//Western blot//ELISA//qRT-PCR	"It was determined that the expression level SA-β-gal in FLS increased with H/R intervention compared to the control group. Furthermore, in the H/R + TNF-α group, the expression level of SA-β-gal was further increased compared with the control group, H/R group and TNF-α group, which indicated a larger proportion of senescent cells.  IL-1β and IL-6 levels in FLS were assessed using ELISA, and HMGB1, Casp8, p16, p21, MMP-3 and MMP-13 proteins were detected by western blotting. In addition, RT-qPCR was used to detect the mRNA expression levels of HMGB1, Casp8, p16, p21, MMP-3, MMP-13, IL-1β and IL-6. The results indicated that the protein and mRNA expression levels of HMGB1, Casp8, p16, p21, MMP-3, MMP-13, IL-1β and IL-6 were significantly increased in the H/R environment compared with the control. Moreover, the expression levels of all these factors were further significantly increased after pre-incubation with TNF-α before 25 h of H/R compared with the control group, H/R group and TNF-α group."	--	--	--	--	JNK	Activation	qRT-PCR//Western blot	"Western blotting was used to assess the protein expression levels of JNK, p53, Bcl-2 and Bax. In addition, the mRNA expression levels of JNK, p53, Bax and Bcl-2 were detected by RT-qPCR. It was demonstrated that, compared with the control group, H/R intervention decreased the expression level of Bcl-2, and enhanced the expression levels of JNK, p54 and Bax. Therefore, the present results indicated that H/R may be important in activating the JNK signaling pathway to promote senescence."	L	cellular senescence	32377699
Sen_E_761	NPs	Chemical compounds	IMR-90	--	Aging	Prevent	SA-β-gal activity assay//ELISA	"The chiral effect of CuxCoyS NPs on the viability of senescent IMR-90 cells (induced by 0.1 μM doxorubicin (Dox) for 7 day) was studied. The successful construction of senescent cells was confirmed by the high expression of senescence-associated β-galactosidase and up-regulated levels of P16ink4a. Moreover, the high secretion levels of SASP factors such as IL 6 and IL 1, quantified by enzyme-linked immunosorbent assay (ELISA), further proved the presence of senescent cells The chiral effect of CuxCoyS NPs on the activities of senescent cells was investigated by incubating the NPs (L-, D-, and DL-CuxCoyS NPs) with senescent cells at different concentrations. The viability of senescent cells displayed an obvious decrease when incubated at the concentration greater than 60 nM, and the cells incubated with D-NPs showed poorest viability compared with the cells incubated with DL-NPs or L-NPs."	--	--	--	--	--	--	--	--	L	apoptosis	32400008
Sen_E_762	ABT-263	Chemical compounds	"SK-BR-7,U2OS,A549,HCC712,MDA-MB-175,MCF-7"	--	Aging	Prevent	Western blot//Immunoblotting//Immunofluorescence//Microscopy//Gene editing	"Treatment with appropriate senolytic drugs induced strong activation of caspase 3, as detected by immunofluorescence staining and immunoblot, but only in senescent cells.Time course microscopy confirmed doxorubicin-induced senescent 4226 and MDA-MB-175 cells underwent rapid and near-synchronous cell death when treated with ABT-263 or ABT-263/S63845. To verify the role of BCL-XL and MCL1 in survival of senescent MCF-7 A/S-sensitive cells, we infected with CRISPR/Cas9 lentivirus and guide RNAs targeting either BCL2L1 (BCL-XL) or MCL1, and hypothesized edited cells would die when treated with only the MCL1 inhibitor S63845 or ABT-263, respectively. This hypothesis was supported as the number of senescent MCF-7 BCL2L1-sg cells was significantly reduced with S63845 alone, and senescent MCF-7 MCL1-sg cell number was reduced by treatment with ABT-263 alone."	--	--	--	--	--	--	--	--	L	apoptosis	32457483
Sen_E_763	SFN	Chemical compounds	"TE-1,ECA-109,HEEpiC"	--	Esophageal cancer	Accelerate	CCK-8//EdU assay//SA-β-gal activity assay//Flow cytometry//ROS Assay	"Cell viability was analyzed by CCK-8 kit. EdU staining assay was performed, and nuclei of all cells were stained with blue while nuclei of cells with high DNA replication activities were stained with green simultaneously. SFN increased SA-β-gal activity. The cells treated with SFN for 24 h were stained with PI and analyzed by FACS assay. SFN-treated ECA-109 cells were stained with DAPI to show SAHFs. SFN disrupts the GSH/GSSG balance to promote ROS production."	--	--	--	--	--	--	--	--	HL	delay aging	32476238
Sen_E_764	Exosome	Chemical compounds	"UMSC,OMSC"	--	Aging	Prevent	TEM//SA-β-gal activity assay//Western blot//Flow cytometry	"Western blot analysis confirmed that the isolated particles expressed exosome-specific markers: CD63, CD9, and Alixs. The particle size of ExoUMSCs was around 60–150nm as shown by dynamic light scattering (DLS). After OMSCs were incubated with Dil-labeled ExoUMSCs for 48h, fluorescence was detected inside the cells, indicating that ExoUMSCs?were efficiently internalized into the target cells. A number of β-gal-positive cells were significantly reduced in OMSCs after treated with ExoUMSCs. Expression of aging-related factors p53, p21, and p16 was also markedly reduced, and the level of Sirt1 was increased in the ExoUMSCs-treated OMSCs. The growth rate of OMSCs was significantly increased, and more OMSCs entered into S phase of cell cycle after treatment with ExoUMSCs. The numbers of EdU-positive OMSCs were significantly higher in the ExoUMSCs-treated OMSCs than the untreated cells."	miRNA-136	Upregulation	qRT-PCR//Western blot	"Among these miRNAs, miR-136 was the most abundant in UMSCs, as compared with OMSCs, and was increased more than 20-fold in OMSCs after cultured with ExoUMSCs, whereas no significant difference was observed for other miRNAs such as miR-106a, miR-155, and miR-29C among these groups. Moreover, the level of miRNA-136 in ExoUMSCs was also higher than that in ExoOMSCs. Next, we examined the role of miR-136 in regulating OMSC senescence and biological function. The mRNA and protein levels of senescent-associated markers p53, p21 and p16, as well as the β-gal+?cells, were markedly reduced in OMSCs after transfected with miR-136 mimics."	--	--	--	--	L	apoptosis	32641103
Sen_E_765	ABT-263	Chemical compounds	"NCI-A549,MDA-MB-231"	--	Tumor	Prevent	SA-β-gal activity assay	"ABT‐263 treatment resulted in robust elimination of senescent, but not proliferating, A549 cells. Likewise, a single 48‐h exposure to 2μm ABT‐263 significantly reduced viable cell number in senescent Eto‐, Dox‐, or IR‐treated cells, but not in untreated controls. ABT‐263 markedly reduced the number of SA‐β‐gal‐positive cells, resulting in a population with minimal or no X‐Gal staining; furthermore, the capacity of ABT‐263 to drive the Eto‐treated A549 cells toward cell death diminished over time as the cells recovered from senescence."	--	--	--	--	BCL-X L-BAX	Downregulation	Western blot//Knockdown//Co-IP	"Western blot analysis of these anti‐apoptotic proteins demonstrated that BCL‐XL expression was consistently high in both MDA‐MB‐231 and A549 cells. In contrast, BCL‐2 expression was gradually decreased in MDA‐MB‐231 cells or undetectable in A549 cells. We further substantiated the effects of BCL‐XL inhibition with shRNA knockdown. MDA‐MB‐231 cells were stably transduced with shC (scrambled sequence) or shBCL‐XL, and then exposed to Dox. shC cells responded similarly to nontransduced cells following treatment with Dox, while shBCL‐XL cells underwent a dramatic decrease in viability, following senescence induction at day 4. A549 cells could not survive a stable transduction of shBCL‐XL (data not shown), and as such, A549 cells were first induced into senescence by Eto and then transduced with shC or shBCL‐XL. As with MDA‐MB‐231 cells, shBCL‐XL caused a decline in cell viability compared to shC in senescent conditions only. BCL‐XL has previously been shown to bind BAX directly, and this interaction should be disrupted by ABT‐263. Co‐immunoprecipitation assays confirmed that in the nonsenescent and senescent states, BAX co‐precipitates with BCL‐XL. Addition of ABT‐263 decreased co‐precipitation of BAX, suggesting disruption of its binding to BCL‐XL. Taken together, these data demonstrate that ABT‐263‐induced apoptosis in senescent cells specifically occurs via the disruption of the BAX/BCL‐XL complex."	L	apoptosis	32652830
Sen_E_766	PTE	Chemical compounds	"PC-12,A375,H9C2"	--	Aging	Accelerate	SA-β-gal activity assay//flow cytometry//scanning electron microscope//ROS Assay	"The effect of PTE and its main components on SA-β-gal staining on AAPH or H2O2 induced cells. Effect of PTE on AAPH-induced morphological changes in PC-12 using scanning electron microscope (6000 ×) . Cell cycle, mitochondrial membrane potential, and apoptosis detected by flow cytometry. Intracellular ROS production was performed with the Reactive Oxygen Species Assay Kit."	--	--	--	--	--	--	--	--	L	apoptosis	32659678
Sen_E_767	PTE	Chemical compounds	"PC-12,A375,H9C2"	--	Aging	Prevent	SA-β-gal activity assay//ELISA//Fluorescence//Flow cytometry	"Taking advantage of cellular senescence models, we tested the possible effect of PTE and its main components on SA-β-gal staining. SA-β-gal-positive cells significantly increased in AAPH and H2O2 groups, while control, PTE, succinic acid, and adenosine groups were relatively low."	SIRT1//Foxo3a//Bcl-2//AROS//HuR//Bax//p53//DBC1	Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Downregulation//Downregulation//Downregulation	qRT-PCR//Western blot	"Compared with the AAPH group, the levels of Bcl-2 and Foxo3a mRNA expression significantly increased in control and PTE groups (10, 20, 40 μg/mL) (P<0.01), and the Bax level significantly decreased in those groups (P<0.01) (Fig. 6). Furthermore, compared with the H2O2 group, the levels of SIRT1, Bcl-2, and Foxo3a mRNA expression significantly increased in control, four batches of PTE, succinic acid, and adenosine groups, and the Bax level significantly decreased in those groups (P<0.01). We performed western blot assays to find out the effect of PTE on the protein levels of p53, HuR, AROS, and DBC1 in AAPH-induced cells. SIRT1 can regulate the expressionof FOXO3a and p53, and be regulated by DBC1 (known as KIAA1967), AROS (known as RPS19BP1) and the tumor suppressor HuR (known as ELA VL1)."	--	--	--	--	L	cellular senescence	32659678
Sen_E_768	Wogonin	Chemical compounds	MDA-MB-231	--	TNBC	Accelerate	SA-β-gal activity assay//RT-qPCR//Western blot//ROS Assay//Immunofluorescence	"Compared with control cells, more wogonin-treated cells were positively stained in theβ-galactosidase staining assay. Consistent with this, RT-qPCR results showed that the transcription of P16 and P21 were both up-regulated, but not that of P27. The protein levels of P16 and P21 were also increased by wogonin. Flow cytometry analysis confirmed that wogonin upregulated ROS level in MDA-MB-231 cells. Immuno-fluorescent staining and western blots showed that wogonin increased γH2AX levels in MDA-MB-231 cells."	TXNRD2	Downregulation	RT-qPCR//Western blot//Ch-IP-qPCR	RT-qPCR assay showed that wogonin downregulated mRNA level of TXNRD2 significantly. Protein abundance of TXNRD2 and H3K9Ac was measured by western blot. Reduction of H3K9Ac at the regulatory region of TXNRD2 after wogonin treatment was shown by ChIP-qPCR.	--	--	--	--	HL	cellular senescence	32671444
Sen_E_769	TBHP	Chemical compounds	HFF-1	--	Aging	Accelerate	SA-β-gal activity assay//RT-qPCR//Western blot	"tBHP treated and control cells were stained for SA-β-galactosidase activity on D9 of the experiment. RT-qPCR was performed to check for p21 mRNA levels. Protein expression of phosphorylated pRB, p53, p-p53 (Serin15) and p21 was measured by Westernblot on D4 and D9 of the experiment."	--	--	--	--	p53	Upregulation	Western blot	"Protein expression of phosphorylated pRB, p53, p-p53 (Serin15) and p21 was measured by Westernblot on D4 and D9 of the experiment."	HL	cellular senescence	32710895
Sen_E_770	UA	Chemical compounds	HLE-B3	--	Cateract	Accelerate	SA-β-gal activity assay	"Assay for the senescence marker, SA-β-gal, showed the presence of blue labels for SA-β-gal in the cytoplasm of UA-treated cells. Such staining was not detected in cells treated without UA in the controls. The percentage of SA-β-gal positive cells were 5.27 ± 0.97% in cells treated with 50 μM UA, 17.22 ± 2.67% in 100 μM group, and 23.04 ± 7.42% in 200 μM group, showing a dose dependent increase in senescent cells after UA treatment."	--	--	--	--	--	--	--	--	L	apoptosis	32713071
Sen_E_771	Resveratrol	Chemical compounds	INS-1	--	Aging	Prevent	SA-β-gal activity assay//Immunohistochemistry//Immunofluorescence	"On the other hand, in comparison with the ethanol treatment, the resveratrol treatment obviously increased the level of SIRT1 (increased by 62%, P < 0.05) and the number of Ki67 positive β-cells in islets from the Eth+Res group. Meanwhile, resveratrol decreased the levels of p-p38MAPK and p16 in β-cells and the percentage of SA-β-gal positive area in islets."	SIRT1	Upregulation	Western blot//SA-β-gal activity assay	"Moreover, compared with the ethanol+resveratrol group, Ex527 completely abolished the anti-senescence effects of resveratrol by increasing the percentage of SA-β-gal-positive cells (P < 0.001) and activating the p38MAPK/p16 pathway (P < 0.01, P < 0.01) in the Ex527+Res+ethanol group, which further suggested that SIRT1 activation is indeed necessary for the anti-senescence effect of resveratrol."	p38MAPK-p16	Downregulation	Western blot//SA-β-gal activity assay	"As shown in Figure 4, supplementation with SB203580 protected INS-1 cells from ethanol-induced senescence by significantly reducing the percentage of SA-β-gal-positive cells (17.4% vs. 28.2%, P < 0.01) and elevating the expression of the proliferation markers PCNA and Ki67 (P < 0.05). Moreover, several studies have established a critical role for the polycomb group protein Bmi1 in the p38-MAPK/p16 pathway, in which Bmi1 is downregulated by p38MAPK which further activates p16 to induce β-cell senescence. In comparison with ethanol-treated cells, SB203580-treated cells had significantly decreased ethanol-stimulated expression of p16 (decreased by 25%, P < 0.05) but recovered Bmi1 and cyclin D2 levels (increased by 40%, P < 0.05; 125%, P < 0.05, respectively), which indicated that activation of p38MAPK/p16 pathway largely contributed to the ethanol-induced β-cell senescence."	L	cellular senescence	33326842
Sen_E_772	Osalmid	Chemical compounds	KYSE150	--	Esophageal cancer	Accelerate	SA-β-gal activity assay//Western blot	"Next, we detected senescence-associated SA-β-gal activity in KYSE150 and KYSE150R and found SA-β-gal positive cells were significantly increased in the Osalmid and IR combination group. Furthermore, as demonstrated by the levels of p53, p21, p16, and retinoblastoma expression, Osamid combined with IR enhanced the emergence of senescence."	--	--	--	--	--	--	--	--	L	apoptosis	32763454
Sen_E_773	AgNP	Chemical compounds	MRC5	Lung	Aging	Accelerate	SA-β-gal activity assay//SAHF//SASP//Western blot//Confocal microscopy//flow cytometry	"SA-β-gal staining was performed and senescent cells were stained with blue color, the ratio of SA-β-gal positive cells was calculated per group. Fluorescence microscopy images of SAHF formation. Heatmap depiction of SASP factor. Immunoblotting of γ-H2AX, p21, p-H3S10, H3K4-m3, and total of H3.β-Actin was used as loading control. Alexa Fluor 488-labeled antibodies (green) and Cy3-labeled Tel C telomere probe were used to identifyγ-H2AX and telomere, respectively. Cell cycle analysis using flow cytometry."	COX2	Upregulation	Western blot//Immunofluorescence	NULL	COX2-PGE2	Upregulation	ELISA	"The PGE2 levels in the culture medium was detected after treatment with AgNPs at 3rd, 7th and 10th day. The addition of COX2 inhibitor led to the decrease of PGE2 level in the culture medium."	HL	apoptosis	32763567
Sen_E_774	TEF	Chemical compounds	PC-3	--	Prostate cancer	Accelerate	NMA analysis//SA-β-gal activity assay	"The morphometric analyses of nuclei size and irregularity showed that TEF at 2xIC50 increased the percentages of large and regular nuclei, which is characteristic of senescence. TEF at 2xIC50 significantly increased the number of β-gal-positive cells. At this concentration, an increase in larger regular nuclei was also observed; the cells turned out to be flat, increased their volume, and displayed a vacuole-rich cytoplasm, which are characteristics of senescence."	--	--	--	--	--	--	--	--	L	apoptosis	32768881
Sen_E_775	TSG	Chemical compounds	HUVEC	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"The results revealed that TSG pretreatment could reduce the percentage of senescence-associated-β-galactosidase (SA-β-gal) positive cells, and decrease the expression levels of the cellular senescence biomarkers, p53 and PAI-1 proteins."	SIRT1	Upregulation	Western blot	Representative images of WB analysis and the semi‐quantification of SIRT1 and E2F1 in HUVECs.	--	--	--	--	L	delay aging	32898442
Sen_E_776	Hinokitiol	Chemical compounds	HeLa	--	Cervical cancer	Accelerate	SA-β-gal activity assay	SA-β-gal assay results showed that ?hinokitiol treatment obviously increased β-galactosidase activity as ?compared with control.	cyclin D1//cyclin E	Downregulation//Downregulation	Western blot	Results of western ?blotting showed that the protein levels of cyclin D1 and cyclin E ?were significantly downregulated in cells treated with hinokitiol in ?a dose-dependent manner.	p53-p21	Activation	Western blot	An increase in both p21 and p53 level was ?observed in hinokitiol-treated cells. 	L	apoptosis	32917321
Sen_E_777	"6,4′-Dihydroxy-7-methoxyflavanone"	Chemical compounds	Human dermal fibroblasts	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"Pretreatment with DMF (20–80?μM, 12?h) resulted in decreased ac-p53, p21Cip1/WAF1, and p16Ink4α expression. In contrast, pRb and cyclin D1 levels increased. We found that DMF pretreatment of cells reduced cytosolic positive stain for senescence (blue) and SA-β-gal positive cells percentage, concentration-dependently."	SIRT1	Upregulation	Western blot	"DMF up-regulated SIRT1 expression and activity, concentration-dependently. Optimum SIRT1 induction was achieved at 80?μM DMF. Treating cells with DMF (80?μM) increased SIRT1 expression and activity, time-dependently. SIRT1 induction by DMF occurred within 3?h, reached maximum at 12?h, and then decreased at 24?h post treatment."	PI3K-Akt	Downregulation	Western blot//SA-β-gal activity assay	"Pretreatment of the cells with LY294002 and PD98059 inhibited Akt and ERK phosphorylation, respectively, we found that selective PI3 K inhibition by LY294002 dramatically reduced SA-β-gal positive cells percentage after H2O2 exposure, whereas no reduction was detected in PD98059-pretreated cells. Moreover, 80?μM DMF (15%) showed more effective protection than 20?μM LY294002 (53%). To further investigate DMF inhibition effect on Akt activation, HDFs were pretreated with LY294002 (as a positive control) and DMF prior to 3?h of incubation with H2O2. We found that DMF pretreatment of cells significantly inhibited Akt phosphorylation."	L	cellular senescence	33111210
Sen_E_778	HIV infection	Other	SupT1	--	HIV	Accelerate	Confocal microscopy	"To determine telomeric DDR in HIV-infected SupT1 and primary CD4 T cells, we compared the number of TIFs by examining the co-localization of 53BP1 and TRF1 using confocal microscopy."	ATM	Downregulation	Western blot	"Western blot analysis of p24, ATM, CHK2, AKT, PARP-1, and γH2AX expressions in SupT1 cells at day 6 of HIV infection."	PI3K-ATM	Downregulation	Western blot	"Western blot analysis of p24, ATM, CHK2, AKT, PARP-1, and γH2AX expressions in SupT1 cells at day 6 of HIV infection. B) Western blot analysis of p24, ATM, CHK2, AKT, PARP-1, andγH2AX expressions in primary CD4 cells at day 5 of HIV infection."	L	apoptosis	32907975
Sen_E_779	JQ1	Chemical compounds	KYSE450	--	Oesophageal cancer	Prevent	SA-β-gal activity assay//qPCR//Western blot//CCK-8 assay	"KYSE450 cells were treated with JQ1 for 144 hours, and cellular senescence was monitored by SA-β-gal staining. mRNA levels of p21, p27 in KYSE450 cells treated with JQ1 for 72 hours using qPCR. Immunoblotting for BRD4 and p21 in KYSE450 after treatment with vehicle or JQ1 for 48, 72, 96 and 144 hours. GAPDH served as a loading control. Four oesophageal cancer cell lines were treated with indicated JQ1 for 72 hours. The cell viability was assayed by CCK-8."	BRD4	Downregulation	RT-PCR//Western blot	"Expression levels of BRD2, BRD3 and BRD4 in oesophageal cancer cell lines using real-time PCR. Protein levels of BRD4 in various oesophageal cancer cell lines using immunoblotting."	--	--	--	--	L	apoptosis	32954665
Sen_E_780	GSC	Chemical compounds	HAEC	--	Aging	Prevent	SA-β-gal activity assay//Western blot//Confocal microscopy//CCK-8 assay	Cell viability as determined by CCK-8 assay. SA-β-gal were detected in HAECs. Western blot analysis of the expression of p16 and p21 in HAECs. Confocal images to show γ-H2AX focus expression in HAECs after 48 h.	--	--	--	--	AMPK	--	--	--	L	delay aging	32963699
Sen_E_781	Icariin (ICA)	Chemical compounds	fibroblast	--	Aging	Prevent	SA-β-gal activity assay//Western blot//MTT assay//flow cytometry	"Senescence of iMr-90 cells was assessed by senescenc e-associated-β-galactosidase (Sa-β-Gal) staining assay. cell viability, and the expression levels of p53/p21, sirtuin (SirT) 1/6 and p50/p65 were determined via the MTT assay and western blotting respectively. The changes in cell cycle arrest of IMR?90 cells were assessed via flow cytometric analysis."	--	--	--	--	SIRT1-NF-κB	Upregulation	Western blot	"The ratio of p-p53/p53 and p-p21/p21, and protein levels of cav-1, SirT1 and SirT6 were determined via western blotting.  The effects of D?gal and ICA on the ratio of of p?p53/p53 and p?p21/p21, and protein levels of cav?1 determined via western blotting were semi?quantified. The effects of D?gal and ICA on the protein levels of SIRT1 and SIRT6 determined via western blotting were semi?quantified."	L	delay aging	33000191
Sen_E_782	HIV	Other	SupT1	--	AIDS	Accelerate	Flow cytometry analysis	"HIV infection increased ?the number of early apoptotic and late apoptotic cells thereafter (days 4 to 6). SupT1 cells with HIV infection cultured for 3 to 6?days displayed significantly shortened telomeres compared to uninfected cells, especially at day 6. "	p24	Upregulation	Western blot	Western blot ?analysis revealed HIV dose-dependent changes in p24 expression in SupT1 cells.	PI3K-ATM	Downregulation	Western blot	"Intriguingly, compared to the uninfected controls (lane ?1), HIV-infected cells (lane 2) exhibited a slight decrease in total ATM but an increase in ?pATM, likely reflecting HIV-induced DDR. In parallel, levels of total CHK2 and AKT ?proteins were decreased, but levels of pCHK2 and pAKT were significantly increased by ?HIV infection, along with elevation of the DDR-mediated apoptotic markers H2AX and ?PARP1."	L	apoptosis	32907975
Sen_E_783	Trans-anethole	Chemical compounds	HepG2	--	Non-alcoholic fatty liver disease	Prevent	Flow cytometry	"When exposed to 100 and 500 μg/mL of TAO, the senescence was estimated to be 0.40 and 0.37 times greater than those of the control, respectively. Although the difference in cellular senescence between the two concentrations was not significant (p < 0.07), senescence dramatically decreased by 0.14 times at 1000 μg/mL"	--	--	--	--	--	--	--	--	L	cellular senescence	33114589
Sen_E_784	Benzo[a]pyrene	Chemical compounds	MCF7	--	Aging	Accelerate	SA-β-gal activity assay	"To analyse whether B[a]P-induced proliferation arrest is associated with senescence, we measured the induction of senescence. Both microscopical detection of ?-Gal stained cells and flow cytometry-based detection of C12FDG-positive cells showed up to 40% senescent cells. Notably, 120 h (5 days) after B[a]P exposure seems to be an early stage in the development of the senescence phenotype, reaching 30–40% ?-Gal positivity. Already 7 days after B[a]P treatment, the amount of senescent MCF7 cells further increased up to ?80% (Figure ?(Figure7A,7A, left panel), whereas no signs of toxicity or alterations in the cell cycle distribution were observed."	p21	Upregulation	Western blot//RT-qPCR	"To analyse whether this repression is caused by the p21-DREAM pathway, B[a]P-induced transcriptional repression of E2F1 was analysed upon pharmacological inhibition of p21 and by siRNA-mediated knockdown. Both strategies efficiently rescued the expression of E2F1 mRNA. p21 inhibition also abolished E2F1 protein repression, further highlighting a critical role of p21."	E2F1	Downregulation	RT-qPCR	"Repression of MSH2, MSH6, EXO1 and RAD51 as well as induction of p21 were still observed two weeks after B[a]P exposure, indicating that this feature is maintained in senescent cells."	L	cellular senescence	33166399
Sen_E_785	JH-RE-06	Chemical compounds	MEFs	--	Aging	Accelerate	Immunofluorescence//SA-β-gal activity assay//qRT-PCR	"Examination of the tissue sections from the combination treatment  revealed  lipofuscin accumulation and positive staining for senescence associated β-galactosidase activity. Two other hallmarks of senescence, increased micronuclei formation and reduced Lamin B1 expression.    We observed an increase in SA-β-Gal activity in combination versus cisplatin monotherapy-treated cells; H2O2 was used as a control senescence-inducing agent.  The induction of senescence hallmarks by cisplatin/JH-RE-06 treatment was maximal for 48 h, after which the cells lost plasma membrane integrity, as demonstrated by the ability of membrane-impermeable 7-AAD to label the nucleus and exhibited decreased colony survival. Indeed, by 72 h following combination treatment, we observed a complete elimination of SA-β-Gal positive cells."	--	--	--	--	--	--	--	--	L	apoptosis	33168727
Sen_E_786	Rosi	Chemical compounds	C57BL/6J(未做细胞实验）	--	Aging	Prevent	Histological staining	"Immuno‐histochemical analysis using Sirius Red staining and an F4/80 antibody of WAT revealed, respectively, diminished fibrosis and decreased macrophage infiltration in the Rosi‐treated group. Furthermore, treated mice showed decreased hepatic inflammation and diminished islet degeneration. Given the known role of Rosi in regulating mitochondrial function in muscle, we compared muscle fiber size and number and mitochondrial morphology of muscle obtained from control and treated mice. As shown in Figure ?Figure2e,2e, SDH staining revealed increased oxidative fibers and electron microscopy analysis showed elevation in mitochondrial density in muscle of Rosi‐treated mice."	--	--	--	--	--	--	--	--	HL	cellular senescence	33219735
Sen_E_787	Quercetin	Chemical compounds	Dermal fibroblasts	Skin	Skin	Prevent	SA-β-gal activity assay//Clonal expansion assay	"Lastly, quercetin delayed cellular senescence not only in UV-irradiated primary human dermal fibroblasts but also in HES1-deficient human primary dermal fibroblasts"	--	--	--	--	--	--	--	--	HL	cellular senescence	33238152
Sen_E_788	KML001	Chemical compounds	CD4+T	--	Aging	Accelerate	Flow cytometry	"Indeed, as shown in Fig.1A, following exposure to KML001, CD4 T cells showed an increased mean fluorescence intensity (MFI) of MG from day 1 to day 7 compared to control, indicating an increased mitochondrial mass or mitochondrial swelling in aging T cells induced by the KML001 treatment."	--	--	--	--	--	--	--	--	HL	cellular senescence	33268822
Sen_E_789	Methoxyeugenol 	Chemical compounds	Ishikawa cells	--	Endometrial cancer	Accelerate	Western blot//Flow cytometry	"According to the median fluorescence intensity(MFI), methoxyeugenol-treated cells did not show an increase in the enzymatic activity of β-galactosidase. As expected, the positive control H2O2 (500 μM) confirmed the SA-β-gal induction. Representative flow cytometric plots are shown."	--	--	--	--	p53-p21	Activation	PCR	p53 expression increase in response to treatments with MET and CPPD. There was no difference in the expression levels of p16 in response to the treatment. MET treatment (60 μM) also raised the expression389 levels of p21 and yet decreased the expression levels of CDK4. and CDK6.	L	apoptosis	33271245
Sen_E_790	Alpha-lipoic acid	Chemical compounds	MDA-MB-231	--	Aging	Accelerate	Western blot//RT-qPCR	"Moreover, expression levels of p53 and activation of p38 mitogen-activated protein kinase (MAPK) and NF-κB were significantly increased in the ALA+RT group compared to the control. The expression levels of IL-6, IL-8, and Cxcl1 (the senescence-associated cytokine and chemokines were measured by qPCR to additionally examine the effect of ALA on cellular senescence in irradiated cells. Increased levels of the corresponding mRNAs were observed in the ALA+RT group compared to all groups."	--	--	--	--	--	--	--	--	L	cellular senescence	33321563
Sen_E_791	ALA	Chemical compounds	MDA-MB-231 cancer cells	--	Breast cancer	Accelerate	Western blot//PCR	"Cytosolic expression of HMGB1 was increased in the ALA and ALA+RT groups, whereas nuclear expression levels of HMGB1 were decreased in these groups compared to the control. Moreover, expression levels of p53 and activation of p38 mitogen-activated protein kinase (MAPK) and NF- κB were significantly increased in the ALA+RT group compared to the control. The expres- sion levels of IL-6, IL-8, and Cxcl1 were measured by qPCR to additionally examine the effect of ALA on cellular senes - cence in irradiated cells. Increased levels of the correspond- ing mRNAs were observed in the ALA+RT group compared to all groups. The expression of p21, a cyclin- dependent kinase (Cdk) inhibitor that induces senescence through cell cycle arrest, was significantly increased in the ALA+RT group compared to the other groups."	HMGB1	Downregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation	Western blot	"Cytosolic expression of HMGB1 was increased in the ALA and ALA+RT groups, whereas nuclear expression levels of HMGB1 were decreased in these groups compared to the control."	--	--	--	--	L	apoptosis	33321563
Sen_E_792	"SHEAD-CM,HGF,SCF"	Other	HBMSC	--	Aging	Prevent	SA-β-gal activity assay//ROS Assay//Mitochondrial membrane potential assay//RT-qPCR	"The passage 3 (P3) to passage 8 (P8) hBMSCs were cultured in the conditioned medium from SHED (SHED-CM). The percentage of senescent cells was evaluated by β-galactosidase staining.  The effects of HGF and SCF on mitochondrial function were assessed by measuring the ROS and mitochondrial membrane potential levels. Relative mRNA expression levels of p16, p21, Nanog, and OCT4 in passage 3 (P3) and passage 8 (P8) hBMSCs cultured in SHED-CM (P8-SHED-CM) and treated with 100 ng/ml HGF (P8-HGF 100), 10 ng/ml SCF (P8-SCF 10), and the combination of 100 ng/ml HGF and 10 ng/ml SCF (P8-H+S)."	--	--	--	--	PI3K-ERK-STAT3 	Upregulation	Western blot	"Western blot results of the expression of mitochondrial-relative proteins (Mfn1, Mfn2, SOD2, and Catalase) and the PI3K/AKT, Erk1/2, and STAT3 signaling pathway-related proteins in passage 3 (P3) and passage 8 (P8) hBMSCs cultured in SHED-CM (P8-SHED-CM) and treated with 100 ng/ml (P8-HGF 100), 10 ng/ml SCF (P8-SCF 10), and the combination of 100 ng/ml HGF and 10 ng/ml SCF (P8-H+S)."	L	delay aging	32736659
Sen_E_793	Size of MSCs	Other	UCB-MSC	--	Aging	Prevent	SA-β-gal activity assay//Western blot	"SA β-gal-positive cells were considerably greater in both groups by P13. However, SA β-gal activity in small cells (8 ± 3%) was significantly lower than that in control cells (25 ± 6%). In both groups, cells became flattened and enlarged, especially the control cells, most of which exhibited these morphological changes. In parallel, Western blot analysis revealed enhanced expression of p16, p21, phosphorylated p38 (P-p38), and phosphorylated p53 (P-p53) in control cells when compared to small cells at P13."	GROa//IL-8	Downregulation	Cytokine array//ELISA	"Notably, both GROa and IL-8 secretion were significantly low in small cells. The secretion of GROa or IL-8 gradually increased with subsequent passages in both groups. Interestingly, cells of the two groups could be distinguished based on the concentration and rate of increase in GROa and IL-8 secretion with passaging. The increase in SASP-related secretion (GROa and IL-8) with cell passaging was markedly lower in small cells. "	--	--	--	--	HL	cellular senescence	33401590
Sen_E_794	Apremilast	Chemical compounds	ATDC5	--	Osteoarthritis	Prevent	SA-β-gal activity assay	"IL-17 stimulation induced a 3.7-fold increase of SA-β-gal activity, while 1 ?M apremilast reduced its activity to only 2.1-fold"	SIRT1	Upregulation	RT-qPCR//Western blot	"Compared to the non-treated cells, IL-17 reduced the mRNA level of SIRT1 to 53%, which was recovered to 92%, close to the baseline, in the presence of 1 ?M apremilast. It was also confirmed that apremilast rescued the protein level of SIRT1 which had been significantly reduced by IL-17. As revealed in Fig. 7A, in normal SIRT-expressing cells, apremilast significantly suppressed cellular senescence, however, its effect was almost abolished in SIRT1-silenced cells. The results from western blot analysis in Fig. 7B and C revealed that the inhibitory effect of apremilast on PAI-1 and p21 was abolished by the silencing of SIRT1."	--	--	--	--	L	cellular senescence	33448323
Sen_E_795	t-BHP	Chemical compounds	NPSCs	--	Intervertebral disk	Accelerate	SA-β-gal activity assay	"We conducted SA-β-Gal staining to label senescent NPSCs. The results showed that treatment with t-BHP resulted in a significant increase in the percentage and the staining intensity of SA-β-Gal-positive NPSCs in a dose-dependent manner. However, HSP70 activation significantly decreased the SA-β-Gal-positive rate, indicating that HSP70 impeded the process of t-BHP-induced senescence."	HSP70	Upregulation//Upregulation	Western blot	"12 h treatment of t-BHP significantly decreased NPSC viability in a dose-dependent manner in all groups except 1 μM t-BHP-treated group com- pared with the control group. In addition, time-dependent cell viability loss was also observed after treating with 120 μM t-BHP for 3 h, 6 h, 9 h, 12 h, 18 h, or 24 h compared with the control group. Furthermore, we performed western blot analysis to investigate the promoting effects of t-BHP on HSP70 expres- sion in NPSCs. Our data indicated that t-BHP significantly stimulated the expression of HSP70 in human NPSCs in all doses except 200 μM group compared with the control group. In addition, treatment with t-BHP for 3 h, 6 h, 12 h, 18 h, or 24 h increased the expression of HSP70 compared with the control group. However, the expression of HSP70 partially declined after treatment with t-BHP for 24 h, indicating a HSP70 fluctuation in a time-dependent manner."	p53-p21//JNK-C-Jun	Activation//Activation	Western blot//Western blot	T-BHP treatment elevated the expression levels of p53 and p21. The protein expression of the p53/p21 pathway was determined by western blot analysis. T-BHP treatment elevated the expression levels of p53 and p21 compared with the control group. We also found that the activation of HSP70 significantly decreased the protein levels of p53 and p21.//T-BHP treatment elevated the levels of p-JNK/JNK ratio and p–c-Jun/c-Jun ratio in a dose-dependent manner.	L	apoptosis	33511552
Sen_E_796	Daturataturin A	Chemical compounds	HaCaT	--	Aging	Accelerate	Western blot//SA-β-gal activity assay	"We found that senescence-related molecules p21, p53 (Ser392), and p53 (Ser15) were activated by DTA and inhibited in the presence of the autophagy inhibitor 3-MA, suggesting that autophagy induced by DTA was closely related to senescence activation. β-Galactosidase (SA-β-Gal) staining confirmed the relationship between HaCaT autophagy and senescence. DTA at 30 μM showed a significant role in inducing senescence (p < .01), with inhibition observed in the presence of 3-MA (p < .05)"	NF-κB	Downregulation	Western blot//ELISA	"DTA 7.5, 15, and 30 μM inhibited the nuclear expression of NF-κB and its downstream PCNA in a dose-dependent manner. IL-6, IL-8, and TNF-α secretion were measured by ELISA, and 30 μM DTA displayed excellent anti-inflammatory effects."	PI3K-Akt-mTOR-IL17//p53-p21	Downregulation//Activation	Cell scratch assay//Western blot	"In the cell migration experiment, DTA inhibited IL-17-induced accelerated migration in a dose- dependent manner. DTA inhibits the phosphorylation of downstream Akt and mTOR (mammalian target of rapamycin, mTOR).//We found that senescence-related molecules p21,p53 (Ser392) ,and p53 (Ser15) were activated by DTA."	L	apoptosis	33560581
Sen_E_797	Silymarin	Chemical compounds	Chondrocyte	Cartilaginous tissues	Osteoarthritis	Prevent	SA-β-gal activity assay	"Moreover, supplementation with 25 μM SMN ameliorated GAG production, cell survival and β-gal expression in IL-1β-injured chondrocytes"	--	--	--	--	--	--	--	--	L	cellular senescence	33610183
Sen_E_798	Synthetic glucocorticoids	Chemical compounds	"Osteoblasts,ostecytes,endothelial cells"	--	Aging	Accelerate	Flow cytometry//SA-β-gal activity assay//In situ assay//qRT-PCR	Flow cytometry indicates high-level activation of the p16INK4a promoter.Flow cytometry analysis showed that the total number of βGal+ cells and the percentage of SA-βGal-expressing endothelial cells increased.We found an increase in the number of SA-βGal +cells in primary and secondary spongiosa regions.Co-staining of bone tissue sections with SA-βGal and Emcn also showed markedly increased percentage of SA-βGal-expressing blood vessels in metaphysis in MPS-treated mice.The femoral bone tissue sections revealed a much greater number of tdTom+ cells in both primary and secondary spongiosa regions in MPS-treated mice.QRT-PCR analysis revealed that CD144+ cells from MPS-treated mice had reduced expression of cell proliferative marker Ki67.	ANG//Ki67//p16//p53//HMGB1	Downregulation//Downregulation//Upregulation//Upregulation//Upregulation	Flow cytometry//In situ assay//qRT-PCR	QRT-PCR analysis revealed that CD144+ cells from MPS-treated mice had reduced expression of cell proliferative marker Ki67 and much higher expression of p16INK4a and p53.HMGB1 and Ki67 signal were reduced or completely lost in cells from MPS-treated mice.The absolute numbers of RANK+ and TRAP+ cells expressing ANG were significantly reduced in response to MPS treatment.	ANG-PLXNB2	Downregulation	DNA FISH	"Intense positive signal of Rrna transcription was detected in Emcn+ blood vessel cells in metaphysis of vehicle-treated mice,whereas much less positive signal was detected in blood vessels of MPS-treated mice."	L	cellular senescence	33758201
Sen_E_799	SRT1720	Chemical compounds	Dermal fibroblasts	--	Aging	Prevent	SA-β-gal activity assay//Western blot//Confocal microscopy	"After treatment with SRT1720, cellular senescence was examined by SA-β-gal staining (senescent cells were stained blue) and examined by bright-field microscopy (original magnification ×200). Scale bar, 50 μM. Percentages of blue cells per 50 cells were calculated. HDFs were also exposed to SRT1720 (10 μM) for 1 h and then protein levels were analyzed by immunoblotting."	SIRT1	Upregulation	Western blot	HDFs were exposed to SRT1720 (10 μM) for 1 h and then protein levels were analyzed by immunoblotting.	SIRT1-NF-κB	Upregulation	Western blot	"HDFs were subjected to immunoprecipitation analysis using SIRT1 antibody or control IgG, and then blotted with antibodies-recognizing ac-NF-κB, LC3, and Beclin-1."	L	delay aging	33965557
Sen_E_800	LEE011	Chemical compounds	"BxPC-3,PANC-1,MiaPaCa-2"	--	Pancreatic ductal adenocarcinoma	Accelerate	SA-β-gal activity assay//Cell cycle analysis	"Cell cycle analysis of BxPC-3, Panc-1, and MiaPaCa-2 cells following 48 hours of treatment with DMSO, LEE011 (1μM), MEK162 (5μM), or combination shows a reduction in S-phase fraction following combination treatment with a concomitant increase in G0/G1 fraction, suggesting cell cycle arrest at G1/S checkpoint in all cell lines. Treated cells were stained for β-galactosidase, a surrogate marker for cell senescence, and analyzed using brightfield microscopy."	Rb	Downregulation	Western blot	"All cell lines were then exposed to increasing dosages of ribociclib (LEE011), a highly selective small molecule inhibitor of CDK4/6, which demonstrated significantly decreased pRb in a concentration and time-dependent fashion."	--	--	--	--	L	apoptosis	34001634
Sen_E_801	MEK162	Chemical compounds	"BxPC-3,PANC-1,MiaPaCa-2"	--	Pancreatic ductal adenocarcinoma	Accelerate	SA-β-gal activity assay//Cell cycle analysis	"Cell cycle analysis of BxPC-3, Panc-1, and MiaPaCa-2 cells following 48 hours of treatment with DMSO, LEE011 (1μM), MEK162 (5μM), or combination shows a reduction in S-phase fraction following combination treatment with a concomitant increase in G0/G1 fraction, suggesting cell cycle arrest at G1/S checkpoint in all cell lines. Treated cells were stained for β-galactosidase, a surrogate marker for cell senescence, and analyzed using brightfield microscopy."	ERK	Downregulation	Western blot	"After treating all cell lines with escalating doses of MEK162, we observed reduced phosphorylated ERK (pERK) levels at all doses and in a time-dependent manner."	--	--	--	--	L	apoptosis	34001634
Sen_E_802	Sargahydroquinoic acid	Chemical compounds	HUVEC	--	Aging	Prevent	Western blot//SA-β-gal activity assay//Cell viability assay	"Short-term exposure to low doseH2O2 elevated protein expression of three senescence biomarkers, p53, p21, and p16, whose levels were suppressed by SHQA in a dose-dependentmanner.Whereas,SHQA suppressed the SA-β-Gal positive cell abundance at all three tested concentrations. The SA-β-Gal positive cell percentages were around 24%, 18% and 12% when pretreated with 0.5, 1.0, or 2.0 μM SHQA, respectively. Culturing and passaging HUVECs in growth medium supplemented with 2.0 μM SHQA remarkably delayed the cellular growth arrest. When cultured in normal medium supplemented with DMSO, the growth of HUVECs was arrested at 23.9 PDL (population doubling), whereas the supplementation of SHQA extended the cell growth to 26.3 PDL.The SA-β-Gal positive cells were significantly lower in cells supplemented with SHQA at PDL24 (24%), compared to cells cultured with DMSO at PDL23 (51%). SHQA treatment also reduced the protein expression levels of p53, p21, and p16 in senescent cells. "	Akt//mTOR	Downregulation	Western blot	"However, the H2O2-induced hyperphosphorylation of Akt and mTOR was suppressed by SHQA at 1.0 μM and 2.0 μM.SHQA inhibited the phosphoryla tion of Akt, mTOR at all three concentrations tested."	Akt-mTOR	Downregulation	Western blot	"However, the H2O2-induced hyperphosphorylation of Akt and mTOR was suppressed by SHQA at 1.0 μM and 2.0 μM.SHQA inhibited the phosphoryla tion of Akt, mTOR at all three concentrations tested."	L	delay aging	34022274
Sen_E_803	Apigenin	Chemical compounds	WI-38	Lung	Aging	Prevent	SA-β-gal activity assay//Cell viability assay//Western blot	"Senescent cells were stained blue due to SA-β-gal activity, while only ~46%, and 23% of cells displayed SA-β-gal activity after pre-treatment with 10 and 20 μM apigenin, respectively.Apigenin pre-treatment also ameliorated H2O2-induced growth arrest and did not affect the normal growth speed of cells.Apigenin pre-treatment downregulated protein levels of ac-p53, p21Waf1/Cip1, and p16Ink4a and upregulated protein levels of p-Rb and cyclin D1.Interestingly, apigenin pre-treatment also significantly reduced cytosolic positive stain (blue) and abrogated DOXO-induced cell enlargement and flattened morphology.The percentage of SA-β-gal activity were ~48% and 19% at 10 and 20 μM apigenin treatment, respectively. Meanwhile, the decreases in ac-p53, p21Cip1/WAF1, and p16Ink4a and the increases in p-Rb and cyclin D1 were observed."	SIRT1//CD38	Upregulation//Downregulation	RT-qPCR//Western blot	"Apigenin induced expression of the SIRT1 protein and mRNA in a concentration- and time-dependent manner. Subsequently, SIRT1 activity was examined and were found to increase with apigenin concentration and time. Apigenin increased NAD+ and NAD+/NADH activity in a concentrationdependent manner, while it attenuated CD38 activity. Next, we examined whether the apigenin-induced reduction in CD38 activation altered levels of SIRT1. As shown in Figs. 5D and 5E, apigenin and CD38 siRNA inhibited CD38 expression and modulated SIRT1 levels."	p53-p21Cip1/WAF1//p16Ink4a-Rb	Downregulation	Western blot	"Apigenin pre-treatment downregulated protein levels of ac-p53, p21Waf1/Cip1, and p16Ink4a and upregulated protein levels of p-Rb and cyclin D1.SIRT1 siRNA treatment decreased SIRT1 levels and the modulatory role of apigenin on ac-p53, p21Waf1/Cip1, p16Ink4a, p-Rb, and cyclin D1 was abolished."	L	delay aging	34049472
Sen_E_804	CNF1	Chemical compounds	HCT116	--	Aging	Accelerate	SA-β-gal activity assay//Western blot	"70% of HCT-116 cells showed increased SA-β-gal activity after exposure to CNF1 for 72 h, whereas less than 9% of untreated and polyploid cell-derived daughter cells were positive for SA-β-gal activity.To confirm CNF1-induced senescent arrest, we analysed the expression of cell-cycle checkpoints proteins and observed that the expression of p53, p21 and p16 in HCT-116 cells were significantly increased after 24 h exposure to CNF1, and further increased after prolonged exposure during 72 h as compared with untreated control cells."	--	--	--	--	p53//p21//p16	Upregulation//Upregulation//Upregulation	Western blot	"To confirm CNF1-induced senescent arrest, we analysed the expression of cell-cycle checkpoints proteins and observed that the expression of p53, p21 and p16 in HCT-116 cells were significantly increased after 24 h exposure to CNF1, and further increased after prolonged exposure during 72 h as compared with untreated control cells."	L	genomic instability	30542142