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• W2890636926 abstract "Age‑associated diseases, including vascular diseases, are on the rise with the increase in the aging population. However, the mechanisms of aging and age‑associated vascular dysfunction remain to be fully elucidated. Replicative senescence of vascular smooth muscle cells (VSMCs) contributes to aging as well as age‑associated vascular diseases. Rapamycin may delay aging‑associated diseases via inhibition of the mammalian target of rapamycin (mTOR), but its role in VSMC aging has remained elusive. The present study investigated the involvement of mTOR signaling in replicative senescence of VSMCs. Replicative senescence was induced in human VSMCs by extended passages and identified by assessing the cell morphology, senescence‑associated β‑galactosidase activity, and p53 and p21 protein expression. Protein expression and phosphorylation were determined by western blot analysis. Significant senescence of VSMCs was observed in cells subjected to extended passaging (until passage 15). Significant decreases in adenosine monophosphate‑activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) phosphorylation, but significant increases in mTOR/ribosomal protein S6 kinase 1 (S6K1) phosphorylation, were observed in cells with replicative senescence compared with those in young cells. Pre‑treatment of VSMCs with AMPK activator and mTOR inhibitor delayed replicative senescence and reversed changes in AMPKα, TSC2, mTOR and S6K1 phosphorylation in senescent VSMCs. The AMPK/TSC2/mTOR/S6K1 signaling axis was found to have an important role in regulating replicative senescence of human VSMCs." @default.
• W2890636926 created "2018-09-27" @default.
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• W2890636926 date "2018-09-19" @default.
• W2890636926 modified "2023-10-18" @default.
• W2890636926 title "AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells" @default.
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• W2890636926 doi "https://doi.org/10.3892/etm.2018.6767" @default.
• W2890636926 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6257130" @default.
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