应激颗粒在细胞衰老中的作用

The role of stress granules in cellular senescenece

细胞衰老是当不断增殖的细胞受到氧化应激、DNA损伤和癌基因活化等内源或外源压力时,诱发的细胞周期永久停滞的一种状态,被认为是一种保护机体以免获得不必要损害的细胞防御机制.研究表明,细胞衰老对胚胎发育、组织重塑、伤口愈合和肿瘤抑制等有益.作为机体衰老的重要特征,细胞衰老也会引发生理机能衰退和衰老相关疾病,如神经性退行性疾病、心血管疾病和癌症等.很多压力同样可以诱导应激颗粒的形成,这是一种在真核细胞胞浆中组装形成、主要包含mRNA-蛋白质复合体的生物分子凝聚体.近年来研究发现,应激颗粒通过招募衰老相关因子调控了细胞衰老过程,而衰老过程中细胞内环境也导致了应激颗粒组成及其动态的异常,这些异常应激颗粒组成反过来又促进衰老及其相关疾病.主要对应激颗粒在细胞衰老过程中的作用作简要概述和探讨.

Cellular senescence was usually regarded as a state of permanent cell cycle arrest that occured in proliferating cells in response to a variety of endogenous and exogenous stress,including oxidative stress,DNA damage and activation of oncogenes.Cellular senescence was also often considered as a cellular defense mechanism that minimized unnecessary damage to the organisms.Studies had showed that cellular senescence exerted beneficial influences on embryonic development,tissue remodeling,wound healing and tumor suppression.Meanwhile,as a hallmark of aging,cellular senescence also triggered organ dysfunction and aging-related diseases,such as neurodegenerative diseases,cardiovascular diseases and cancers.Many types of stress could also induce stress granules(SGs)which were biomolecular condensates of mRNA-protein complexes assembled in the cytoplasm of eukaryotic cells.Recent findings showed that SGs regulate cellular senescence via recruitment of senescence associated proteins,while senescence-induced changes of intracellular environment also led to aberrant composition and dynamics of SGs,which in turn accelerated the process of aging and aging-related diseases.Based on these viewpoint of facts,it was briefly summarized and discussed the role of SGs in cellular senescence.