National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing 100053, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell Metab. 2017 Sep 5;26(3):460-474. doi: 10.1016/j.cmet.2017.07.019. Epub 2017 Aug 17.
Stem cell aging and exhaustion are considered important drivers of organismal aging. Age-associated declines in stem cell function are characterized by metabolic and epigenetic changes. Understanding the mechanisms underlying these changes will likely reveal novel therapeutic targets for ameliorating age-associated phenotypes and for prolonging human healthspan. Recent studies have shown that metabolism plays an important role in regulating epigenetic modifications and that this regulation dramatically affects the aging process. This review focuses on current knowledge regarding the mechanisms of stem cell aging, and the links between cellular metabolism and epigenetic regulation. In addition, we discuss how these interactions sense and respond to environmental stress in order to maintain stem cell homeostasis, and how environmental stimuli regulate stem cell function. Additionally, we highlight recent advances in the development of therapeutic strategies to rejuvenate dysfunctional aged stem cells.
干细胞衰老和衰竭被认为是机体衰老的重要驱动因素。与年龄相关的干细胞功能下降的特征是代谢和表观遗传变化。了解这些变化的机制可能会揭示改善与年龄相关表型和延长人类健康寿命的新的治疗靶点。最近的研究表明，代谢在调节表观遗传修饰中起着重要作用，这种调节对衰老过程有显著影响。这篇综述重点介绍了目前关于干细胞衰老机制以及细胞代谢和表观遗传调控之间联系的知识。此外，我们还讨论了这些相互作用如何感知和响应环境应激以维持干细胞的内稳态，以及环境刺激如何调节干细胞功能。此外，我们强调了最近在开发治疗策略以恢复功能失调的衰老干细胞方面的进展。
