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
- 1 Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China
- 2 Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha 410011, Hunan, PR China
- 3 Modern Cardiovascular Disease Clinical Technology Research Center of Hunan Province, Changsha 410011, Hunan, PR China
- 4 Cardiovascular Disease Research Center of Hunan Province, Changsha 410011, Hunan, PR China
- 5 Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China
- 6 Department of Geriatric Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, PR China
- 7 Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China
- 8 Emergency Medicine and Difficult Disease Institute, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China
Received: January 9, 2020 Accepted: November 6, 2020 Published: December 9, 2020
https://doi.org/10.18632/aging.202298How to Cite
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.