| External factors: | 6,4′-Dihydroxy-7-methoxyflavanone |
| Aging type: | Prevent |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Aging |
| Experiment: | SA-β-gal activity assay//Western blot |
| Description: | 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. |
| Target gene: | SIRT1 |
| R-EF-Target gene: | Upregulation |
| Official symbol(s): | SIRT1 |
| Target gene experiment: | Western blot |
| Target gene description: | 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. |
| Regulatory pathway: | PI3K-Akt |
| R-EF-Pathway: | Downregulation |
| Official symbol(s): | PIK3CB-AKT |
| Pathway experiment: | Western blot//SA-β-gal activity assay |
| Pathway description: | 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. |
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