cGAS-STING通路与老龄化疾病的研究进展

Research Progress on the relationship between cGAS-STING pathway and ageing-related diseases

关键词:  衰老  cGAS-STING通路  衰老相关分泌表型

Key words:  aging  cGAS-STING pathway  senescence-associated secretory phenotype

摘要:

衰老是指随着年龄的增长生物体在分子、细胞、组织和系统水平上损伤的积累和功能的减退，逐渐趋向死亡的一种现象。衰老是导致年龄相关性疾病（aging-related diseases, ARDs）发生、发展和死亡的重要危险因素。衰老具有的特征有基因组不稳定、端粒损耗、表观遗传改变、蛋白质稳态丧失、大自噬失能、营养感应失调、线粒体功能障碍、细胞衰老、干细胞耗竭、细胞间通讯改变、慢性炎症和生态失调等。其中，细胞衰老主要由端粒缩短、DNA损伤、氧化应激以及细胞周期阻滞等因素所引起。DNA损伤-累积导致促炎因子的过表达，包括各种细胞因子、趋化因子，统称为衰老相关分泌表型(senescence-associated secretory phenotype, SASP)。最近诸多科学研究表明，cGAS-STING通路会在衰老细胞中激活，从而进一步触发SASP表型。本文将对cGAS与细胞衰老的关系、SASP的调控以及相关老龄化疾病的影响进行综述。

Abstract:

Aging is a phenomenon that with the increase of age the accumulation of damage and the decline of function of organisms at the molecular, cellular, tissue and system levels, gradually tend to death. Aging is an important risk factor for the occurrence and development of aging-related diseases(ARDs). Aging is characterized by genomic instability, telomere loss, epigenetic changes, loss of protein homeostasis, macroautophagy dysfunction, nutritional induction disorders, mitochondrial dysfunction, cell senescence, stem cell depletion, intercellular communication changes, chronic inflammation, and ecological disorders, etc. Among them, cell senescence is mainly caused by telomere shortening, DNA damage, oxidative stress, and cell cycle arrest. The accumulation of DNA damage leads to the overexpression of pro-inflammatory factors, including various cytokines and chemokines, collectively referred to as senescence-associated secretory phenotype(SASP). Recently, many studies have shown that the cGAS-STING pathway is activated in senescent cells, which further triggers the SASP phenotype. This article will discuss the relationship between cGAS and cell senescence, the regulation of SASP, and its effects on aging-related diseases.