Research Paper|Volume 12, Issue 24|pp 26080—26094

Postprandial triglyceride-rich lipoproteins-induced premature senescence of adipose-derived mesenchymal stem cells via the SIRT1/p53/Ac-p53/p21 axis through oxidative mechanism

Qun-yan Xiang^1,^2,^3,^4,⁵, Feng Tian^1,^2,^3,^4,⁶, Xiao Du^1,^2,^3,⁴, Jin Xu^1,^2,^3,⁴, Li-yuan Zhu^1,^2,^3,⁴, Li-ling Guo^1,^2,^3,⁴, Tie Wen^7,⁸, You-shuo Liu⁵, Ling Liu^1,^2,^3,⁴

¹Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China
²Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha 410011, Hunan, PR China
³Modern Cardiovascular Disease Clinical Technology Research Center of Hunan Province, Changsha 410011, Hunan, PR China
⁴Cardiovascular Disease Research Center of Hunan Province, Changsha 410011, Hunan, PR China
⁵Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China
⁶Department of Geriatric Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, PR China
⁷Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China
⁸Emergency Medicine and Difficult Disease Institute, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China

Received: January 9, 2020Accepted: November 6, 2020Published: December 9, 2020

https://doi.org/10.18632/aging.202298

Copyright: © 2020 Xiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The accumulation of senescent adipose-derived mesenchymal stem cells (AMSCs) in subcutaneous white adipose tissue (WAT) is the main cause for the deterioration of WAT and the subsequent age-related disorders in obesity. The number of AMSCs staining positively for senescence-associated-β-galactosidase (SA-β-Gal) increased significantly after incubation with postprandial triglyceride-rich lipoproteins (TRL), accompanied by an impaired cell proliferation capacity and increased expression of inflammatory factors. Besides, the expression of anti-aging protein, silent mating-type information regulation 2 homolog 1 (SIRT1), was downregulated significantly, while those of acetylated p53 (Ac-p53), total p53, and p21 proteins were upregulated significantly during postprandial TRL-induced premature senescence of AMSCs. Furthermore, the production of intracellular reactive oxygen species (ROS) in the TRL group increased significantly, while pretreatment with the ROS scavenger N-acetyl-L-cysteine effectively attenuated the premature senescence of AMSCs by decreasing ROS production and upregulating SIRT1 level. Thus, postprandial TRL induced premature senescence of AMSCs through the SIRT1/p53/Ac-p53/p21 axis, partly through increased oxidative stress.