Adult Stem Cell Research Center College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Gerontology. 2013;59(6):557-63. doi: 10.1159/000353857. Epub 2013 Aug 17.
Adult stem cells in mammalian organs play pivotal roles in the maintenance and repair of these organs throughout the life of the adult and maintain the proper homeostasis of a tissue or organ. Among the adult stem cells described to date, mesenchymal stem cells (MSCs) are highlighted for clinical applications because MSCs have many advantages for cell therapy, including multilineage differentiation, homing, immune modulation and wound-healing effects. However, as the aging of MSCs leads to an age-associated decline in their number and function, it is important to clarify the age-associated factors and regulatory mechanism associated with the MSC aging process. In this review, we amass and discuss the recent data related to age-associated genes in MSCs. In particular, the activities of epigenetic regulatory factors, including histone acetylase and DNA methyltransferase, modulate gene expression and crosstalk with each other during the MSC senescence process. p16(INK4A) and high-mobility group A2 play important age-associated roles in the regulation of MSC stemness, and lamin A- and prelamin A-dependent nuclear abnormalities have significant biological relevance in MSC aging. Taken together, the information described here, including the epigenetic regulatory factors, transcription factors and cell signaling, could be used toward the development of treatments for MSC aging and related defects.
哺乳动物器官中的成体干细胞在成年期维持和修复这些器官方面发挥着关键作用，并维持组织或器官的适当稳态。在迄今为止描述的成体干细胞中，间充质干细胞（MSCs）因其在细胞治疗方面具有许多优势而备受关注，包括多能分化、归巢、免疫调节和伤口愈合作用。然而，随着 MSCs 的老化，其数量和功能会出现与年龄相关的下降，因此阐明与 MSC 老化过程相关的与年龄相关的因素和调节机制非常重要。在这篇综述中，我们汇集并讨论了与 MSCs 中与年龄相关的基因相关的最新数据。特别是，表观遗传调节因子（包括组蛋白乙酰转移酶和 DNA 甲基转移酶）的活性在 MSC 衰老过程中调节基因表达并相互交流。p16(INK4A)和高迁移率族蛋白 A2 在调节 MSC 干性方面起着重要的与年龄相关的作用，核纤层 A 和前核纤层 A 依赖性核异常在 MSC 衰老中具有重要的生物学相关性。总之，这里描述的信息，包括表观遗传调节因子、转录因子和细胞信号，可用于开发针对 MSC 衰老和相关缺陷的治疗方法。
