细胞衰老与抗衰老药物senolytics的研究进展

Current Advances in Cellular Senescence and Senolytics

细胞衰老是一种稳定的增殖抑制并伴有衰老相关的分泌表型(SASP)。其发生主要是由于细胞在复制过程中端粒酶的消耗以及外界衰老相关刺激如癌基因激活、活性氧积聚、DNA损伤等。短期内衰老细胞的产生有助于机体胚胎发育、损伤修复和肿瘤抑制等;而机体内长期积聚衰老的细胞会导致肿瘤的发生、机体老化和老化相关的疾病。近年来研究发现,特异性清除体内衰老细胞有助于延缓机体老化、重塑身体机能等;这再次将衰老相关的研究推向了一个新的高度。该文将从细胞衰老的主要特征、生理学功能、发生机制及抗衰老药物senolytics的发展等方面进行讨论,并结合相关研究的最新进展,为衰老及相关疾病的防治提供理论依据。

Cellular senescence is mainly described as a stable cell cycle arrest and SASP (senescence-associated secretory phenotype).Theoretically,senescence is mainly induced by diverse stimuli including telomere shortening,oncogene activation,oxidative stress and DNA damage.It has been demonstrated that time dependent short-term induction of cellular senescence plays beneficial roles in terms of embryonic development,wound healing and tumor suppression;whereas long-term accumulation of senescent cells in tissues is harmful and may contribute to cancer progression,aging or age-associated disorders.Recent studies have demonstrated that selectively killing senescent cells can extend healthy lifespan and restore physical function,which bring the senescence field to an even higher interesting grade than ever before.Here,the review will discuss the characters,functions and mechanisms of cellular senescence,together with the development of senolytics,thus aiming to provide theoretical targets for aging and age-related diseases.