Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Oxid Med Cell Longev. 2022 Apr 1;2022:2713483. doi: 10.1155/2022/2713483. eCollection 2022.
There is a hot topic in stem cell research to investigate the process of hematopoietic stem cell (HSC) aging characterized by decreased self-renewal ability, myeloid-biased differentiation, impaired homing, and other abnormalities related to hematopoietic repair function. It is of crucial importance that HSCs preserve self-renewal and differentiation ability to maintain hematopoiesis under homeostatic states over time. Although HSC numbers increase with age in both mice and humans, this cannot compensate for functional defects of aged HSCs. The underlying mechanisms regarding HSC aging have been studied from various perspectives, but the exact molecular events remain unclear. Several cell-intrinsic and cell-extrinsic factors contribute to HSC aging including DNA damage responses, reactive oxygen species (ROS), altered epigenetic profiling, polarity, metabolic alterations, impaired autophagy, Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, nuclear factor- (NF-) B pathway, mTOR pathway, transforming growth factor-beta (TGF-) pathway, and wingless-related integration site (Wnt) pathway. To determine how deficient HSCs develop during aging, we provide an overview of different hallmarks, age-related signaling pathways, and epigenetic modifications in young and aged HSCs. Knowing how such changes occur and progress will help researchers to develop medications and promote the quality of life for the elderly and possibly alleviate age-associated hematopoietic disorders. The present review is aimed at discussing the latest advancements of HSC aging and the role of HSC-intrinsic factors and related events of a bone marrow niche during HSC aging.
干细胞研究中有一个热门话题，即研究造血干细胞（HSC）衰老的过程，其特征是自我更新能力下降、向髓系分化、归巢受损以及与造血修复功能相关的其他异常。HSC 保持自我更新和分化能力以在体内平衡状态下随着时间的推移维持造血功能至关重要。尽管在小鼠和人类中，HSC 的数量随年龄增长而增加，但这并不能弥补衰老 HSC 的功能缺陷。人们从多个角度研究了 HSC 衰老的潜在机制，但确切的分子事件仍不清楚。几个细胞内和细胞外因素导致 HSC 衰老，包括 DNA 损伤反应、活性氧（ROS）、表观遗传谱改变、极性、代谢改变、自噬受损、Janus 激酶/信号转导和转录激活因子（JAK/STAT）途径、核因子-（NF-）B 途径、mTOR 途径、转化生长因子-β（TGF-）途径和 Wnt 相关整合位点（Wnt）途径。为了确定在衰老过程中缺陷 HSC 是如何发展的，我们概述了年轻和衰老 HSC 中的不同特征、与年龄相关的信号通路和表观遗传修饰。了解这些变化是如何发生和进展的，将有助于研究人员开发药物，提高老年人的生活质量，并可能缓解与年龄相关的造血障碍。本综述旨在讨论 HSC 衰老的最新进展，以及 HSC 内在因素和 HSC 衰老过程中骨髓龛相关事件的作用。
