细胞衰老相关分泌表型因子及其分子调控机制研究进展

细胞衰老是增殖细胞脱离细胞周期呈永久性生长停滞的状态，其显著特点之一是分泌大量生物活性物质，即细胞衰老相关分泌表型（SASP）因子。SASP因子的分泌大致可分为DNA损伤快速旁分泌期、SASP早期、SASP成熟期3个阶段。SASP因子的分子调控机制复杂，涉及DNA损伤反应、p38丝裂原活化蛋白激酶（MAPK）信号通路、核因子κB（NF-κB）及CCAAT/增强子结合蛋白β（C/EBPβ）激活、SASP基因表观遗传学改变、基因转录后调控和自噬等。SASP因子能改变细胞微环境导致的多种病理状态的发生，已成为调节衰老效应的药物靶标，为肿瘤和年龄相关性疾病提供了新的治疗方向。基于此，本文对SASP因子进行了分类，总结了其在生物过程中的作用，并深入探讨其调控机制。
Cellular senescence is a state of permanent growth arrest characterized by an irreversible exit from the cell cycle and the secretion of senescence-associated secretory phenotype (SASP). The secretory process of SASP can be roughly divided into three steps:DNA damage response (DDR)-rapid paracrine, early and mature stages. The complex molecular regulation mechanisms of SASP involve DDR, p38 mitogen-activated protein kinase (MAPK) signal pathway, activation of nuclear factor κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), epigenetic alterations of SASP gene, post-transcriptional regulation of gene and autophagy. SASP regulates a variety of pathological states caused by microenvironment changes and has been a drug target to regulate the aging effect, which providing a new therapeutic method for tumor and age-related pathological states. In this paper, we classified the different types of SASP, reviewed the role of SASP in biological processes and discussed the related molecular mechanisms