AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells

Zhan,Jun‑Kun; Wang,Yan‑Jiao; Li,Shuang; Wang,Yi; Tan,Pan; He,Je‑Yu; Chen,Yi‑Yin; Deng,Hui‑Qian; Huang,Wu; Lin,Xiao; Liu,You‑Shuo

doi:10.3892/etm.2018.6767

December-2018 Volume 16 Issue 6

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December-2018 Volume 16 Issue 6

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Article

AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells

Authors:
- Jun‑Kun Zhan
- Yan‑Jiao Wang
- Shuang Li
- Yi Wang
- Pan Tan
- Je‑Yu He
- Yi‑Yin Chen
- Hui‑Qian Deng
- Wu Huang
- Xiao Lin
- You‑Shuo Liu
View Affiliations / Copyright

Affiliations: Geriatric Department, The Second Xiangya Hospital, Institute of Aging and Geriatrics, Central South University, Changsha, Hunan 410011, P.R. China
Pages: 4853-4858
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Published online on: September 19, 2018

https://doi.org/10.3892/etm.2018.6767
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells

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