1 State Key Discipline of Infectious Diseases and Chemical Biology Laboratory for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
2 Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China.
Cell Transplant. 2017 Sep;26(9):1483-1495. doi: 10.1177/0963689717735407.
Stem cell aging is a process in which stem cells progressively lose their ability to self-renew or differentiate, succumb to senescence or apoptosis, and eventually become functionally depleted. Unresolved oxidative stress and concomitant oxidative damages of cellular macromolecules including nucleic acids, proteins, lipids, and carbohydrates have been recognized to contribute to stem cell aging. Excessive production of reactive oxygen species and insufficient cellular antioxidant reserves compromise cell repair and metabolic homeostasis, which serves as a mechanistic switch for a variety of aging-related pathways. Understanding the molecular trigger, regulation, and outcomes of those signaling networks is critical for developing novel therapies for aging-related diseases by targeting stem cell aging. Here we explore the key features of stem cell aging biology, with an emphasis on the roles of oxidative stress in the aging process at the molecular level. As a concept of cytoprotection of stem cells in transplantation, we also discuss how systematic enhancement of endogenous antioxidant capacity before or during graft into tissues can potentially raise the efficacy of clinical therapy. Finally, future directions for elucidating the control of oxidative stress and developing preventive/curative strategies against stem cell aging are discussed.
干细胞衰老是一个渐进的过程,在此过程中,干细胞逐渐丧失自我更新或分化的能力,走向衰老或凋亡,最终功能耗竭。未解决的氧化应激以及细胞大分子(包括核酸、蛋白质、脂质和碳水化合物)的伴随氧化损伤,被认为是导致干细胞衰老的原因。活性氧的过度产生和细胞抗氧化储备的不足会损害细胞修复和代谢平衡,这是多种与衰老相关途径的机制开关。了解这些信号网络的分子触发、调节和结果,对于通过靶向干细胞衰老来开发与衰老相关疾病的新疗法至关重要。在这里,我们探讨了干细胞衰老生物学的关键特征,重点关注氧化应激在分子水平上对衰老过程的作用。作为移植中干细胞细胞保护的一个概念,我们还讨论了在组织内移植前或移植期间系统增强内源性抗氧化能力如何潜在地提高临床治疗的效果。最后,讨论了阐明氧化应激控制和开发针对干细胞衰老的预防/治疗策略的未来方向。