Li Yi, Wu Qiong, Wang Yujia, Li Li, Bu Hong, Bao Ji
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Int J Mol Med. 2017 Apr;39(4):775-782. doi: 10.3892/ijmm.2017.2912. Epub 2017 Mar 9.
Mesenchymal stem cells (MSCs) have been used in cell-based therapy for various diseases, due to their immunomodulatory and inflammatory effects. However, the function of MSCs is known to decline with age, a process that is called senescence. To date, the process of MSC senescence remains unknown as in-depth understanding of the mechanisms involved in cellular senescence is lacking. First, senescent MSCs are so heterogeneous that not all of them express the same phenotypic markers. In addition, the genes and signaling pathways which regulate this process in MSCs are still unknown. Thus, an understanding of the molecular processes controlling MSC senescence is crucial to determining the drivers and effectors of age-associated MSC dysfunction. Moreover, the proper use of MSCs for clinical application requires a general understanding of the MSC aging process. Furthermore, such knowledge is essential for the development of therapeutic interventions that can slow or reverse age-related degenerative changes to enhance repair processes and maintain healthy function in aging tissues. To further clarify the properties of senescent cells, as well as to present significant findings from studies on the mechanisms of cellular aging, we summarize these biological features in the senescence of MSCs in this scenario. This review summarizes recent advances in our understanding of the markers and differentiation potential indicating MSC senescence, as well as factors affecting MSC senescence with particular emphasis on the roles of oxidative stress, intrinsic changes in telomere shortening, histone deacetylase and DNA methyltransferase, genes and signaling pathways and immunological properties.
间充质干细胞（MSCs）因其免疫调节和抗炎作用，已被用于多种疾病的细胞治疗。然而，已知MSCs的功能会随着年龄增长而下降，这一过程称为衰老。迄今为止，由于缺乏对细胞衰老相关机制的深入了解，MSCs衰老的过程仍然未知。首先，衰老的MSCs具有高度异质性，并非所有细胞都表达相同的表型标志物。此外，调节MSCs这一过程的基因和信号通路仍不清楚。因此，了解控制MSCs衰老的分子过程对于确定与年龄相关的MSCs功能障碍的驱动因素和效应器至关重要。此外，正确使用MSCs进行临床应用需要对MSCs衰老过程有全面的了解。此外，这些知识对于开发能够减缓或逆转与年龄相关的退行性变化、增强修复过程并维持衰老组织健康功能的治疗干预措施至关重要。为了进一步阐明衰老细胞的特性，并呈现细胞衰老机制研究的重要发现，我们在此概述了MSCs衰老过程中的这些生物学特征。本综述总结了我们对指示MSCs衰老的标志物和分化潜能的最新认识，以及影响MSCs衰老的因素，特别强调了氧化应激、端粒缩短的内在变化、组蛋白去乙酰化酶和DNA甲基转移酶、基因和信号通路以及免疫学特性的作用。
