Shi Changyou, Wang Lin, Sen Payel
Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Transl Med Aging. 2020;4:121-131. doi: 10.1016/j.tma.2020.08.002. Epub 2020 Aug 17.
Adult stem cells undergo both replicative and chronological aging in their niches, with catastrophic declines in regenerative potential with age. Due to repeated environmental insults during aging, the chromatin landscape of stem cells erodes, with changes in both DNA and histone modifications, accumulation of damage, and altered transcriptional response. A body of work has shown that altered chromatin is a driver of cell fate changes and a regulator of self-renewal in stem cells and therefore a prime target for juvenescence therapeutics. This review focuses on chromatin changes in stem cell aging and provides a composite view of both common and unique epigenetic themes apparent from the studies of multiple stem cell types.
成体干细胞在其生态位中会经历复制性衰老和自然衰老，随着年龄增长，其再生潜力会急剧下降。由于衰老过程中反复受到环境损伤，干细胞的染色质景观受到侵蚀，DNA和组蛋白修饰均发生变化，损伤积累，转录反应改变。大量研究表明，染色质改变是细胞命运变化的驱动因素，也是干细胞自我更新的调节因子，因此是年轻化治疗的主要靶点。本综述聚焦于干细胞衰老过程中的染色质变化，并综合呈现了从多种干细胞类型研究中得出的常见和独特的表观遗传主题。
