造血干细胞老化与mTOR信号通路

Senescence of Hematopoietic Stem Cells and mTOR Signaling Pathway

衰老是一个生命的自然过程,也是世界性的健康问题,目前并无有效延缓衰老的对策。细胞老化可能在哺乳动物衰老发生、发展方面起关键作用,特别是成人干细胞的老化现象。该综述主要回顾了生理和病理环境条件下造血干细胞老化的证据。近年来,随着研究的深入,对细胞老化的理解及其机制有了新的认识,不仅包括传统的p53/p21途径和p16/Rb途径,而且G-CSF/STAT3/BATF通路和衰老相关分泌表型(senescence-associated secretory phenotype,SASP)也引起学者们的重视。有效清除体外和体内老化细胞已经成为可能。最近有研究表明,mTOR(mammalian target of rapamycin)信号通路激活后参与细胞老化的发生、发展过程。在细胞老化机制深入研究基础上,这为进一步探索预防老化细胞产生或有效消除老化细胞的方法提供了新思路。

Aging is a process in life but becomes a worldwide health issue with unresolved strategies to extend lifespan. Recent studies have shown that cellular senescence might play crucial roles in mammalian aging, specifically in adult stem cell senescence. We presently reviewed the evidence of hematopoietic stem cell senescence in physiological and pathological contexts. Understanding mechanisms of senescence have been made significant improvement including p53/p21 pathway, p16/Rb pathway, G-CSF/STAT3/BATF pathway and SASP. Depletion of senescent cells has become possible in vitro and in vivo. Activation of m TOR signaling pathway may be involved in the initiation and development of cellular senescence. These remarkable findings will provide us new opportunities for developing the mechanism-based strategies to prevent and/or deplete senescent cells in near future.