| External factors: | Bood flow |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Other |
| Phenotype: | Atherosclerosis |
| Experiment: | SA-β-gal activity assay |
| Description: | 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. |
| Target gene: | SIRT1 |
| R-EF-Target gene: | -- |
| Official symbol(s): | SIRT1 |
| Target gene experiment: | SA-β-gal activity assay//Immunofluorescence |
| Target gene description: | 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. |
| Regulatory pathway: | p53-p21 |
| R-EF-Pathway: | -- |
| Official symbol(s): | TP53-CDKN1A |
| Pathway experiment: | SA-β-gal activity assay//Immunofluorescence |
| Pathway description: | 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. |
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