细胞衰老相关分泌表型因子及其分子调控机制研究进展  

Senescence-associated secretory phenotype and its complex regulation networks: a review of molecular mechanisms

作　　者：王瑜[1] 朱振新[1] 蔡清萍[1] WANG Yu;ZHU Zhen-xin;CAI Qing-ping(Department of General Surgery(Ⅱ),Changzheng Hospital,Navy Medical University(Second Military Medical University),Shanghai 200003,China)

机构地区：[1]海军军医大学(第二军医大学)长征医院普外二科,上海200003

出　　处：《第二军医大学学报》2018年第4期422-427,共6页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(8137260;81100629)~~

摘　　要：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 factorκB(NF-κB)and CCAAT/enhancer-binding proteinβ(C/EBPβ),epigenetic alterations of SASP gene,posttranscriptional 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 agerelated 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.

关 键 词：细胞衰老 衰老相关分泌表型 DNA损伤 P38蛋白 核因子ΚB CCAAT/增强子结合蛋白β 表观遗传学 自噬 

分 类 号：R364.3[医药卫生—病理学]