老年性疾病通过cGAS-STING通路调控衰老相关分泌表型

Senile disease regulates aging-related secretion phenotype through cGAS-STING pathway

老龄化是癌症、心血管疾病、糖尿病和神经退行性疾病等人类疾病最主要的风险因素之一,而许多衰老性疾病都与细胞衰老相关。细胞在衰老过程中表现出明显的表型变化,这是由代谢、染色质组织和转录活性的改变所驱动的。衰老的一个明显特征是炎症介质的分泌,包括各种细胞因子、趋化因子、细胞外基质蛋白和生长因子,统称为衰老相关分泌表型(senescence-associated secretory phenotype,SASP)。衰老细胞通过分泌SASP,对许多生物学过程产生重要影响,包括伤口愈合、组织修复、肿瘤形成或体内重组等。此外,与SASP相关的炎症反应被认为是衰老相关疾病的基础,从而发现衰老效应反应的新靶点是至关重要的。最近的科学进展表明,先天免疫应答特别是涉及cGAS-STING途径的免疫应答,会在衰老细胞中触发SASP。该文综述了老龄化疾病衰老细胞中cGAS-STING信号通路对SASP的调控作用。

Aging is one of the most important risk factors for human diseases such as cancer,cardiovascular diseases,diabetes and neurodegenerative diseases,and many aging diseases are related to cellular aging.Cells show profound phenotypic changes during aging,which are driven by changes in metabolism,chromatin organizationand transcriptional activity.A significant feature of aging is the secretion of inflammatory mediators,including various cytokines,chemokines,extracellular matrix proteins and growth factors,collectively known as the aging-related secreted phenotype(SASP).By secreting SASP,senescent cells have important effects on many biological processes,such as wound healing,tissue repair,tumor formation,or in vivo reorganization.In addition,the inflammatory response associated with SASP is considered to be the basis of aging-related diseases,and the discovery of new targets to control the response of aging effects is crucial.Recent scientific advances have shown that innate immune responses,particularly those involving the cGAS-STING pathway,trigger SASP.In this article,we review the biological function and regulatory mechanism of SASP through the cGAS-STING signaling pathway in aging diseases.