| 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。 |
| 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 |
| DOI：10.16781/j.0258-879x.2018.04.0422 |
| 投稿时间：2017-08-21修订日期：2017-12-25 |
| 基金项目:国家自然科学基金（8137260，81100629）. |
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| Senescence-associated secretory phenotype and its complex regulation networks: a review of molecular mechanisms |
| 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
*Corresponding author) |
| Abstract: |
| 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. |
| Key words: cell senescence senescence-associated secretory phenotype DNA damage p38 protein nuclear factor κB CCAAT/enhancer-binding protein β epigenetics autophagy |
