细胞衰老相关分子机制及鉴定的研究进展

Research progress in the molecular mechanisms and identification of cellular senescence

细胞衰老指的是细胞发生稳定的、不可逆的细胞周期停滞现象, 是导致机体衰老的基本机制之一。最近的研究表明, 细胞衰老代表了一系列广泛, 动态且具有高度异质性的细胞状态, 发生衰老的细胞具有独特的表型改变。细胞衰老的主要原因是细胞损伤引起的抑癌基因如p16, p21或p53的激活, 从而导致细胞周期的停滞。发生衰老的细胞通过激活NF-κB通路和C/EBP家族通路可以向细胞外分泌细胞因子, 即衰老相关的分泌表型(SASP);其中SASP因子如转化生长因子-β(TGF-β)、胰岛素样生长因子结合蛋白1(IGFBP-1)以及白细胞介素-1α(IL-1α)、白细胞介素-6(IL-6)等炎性因子会以自分泌或旁分泌的方式维持或诱导更多衰老细胞的产生, 而SASP的不断累积也会促进组织的崩解和重构, 从而影响器官功能。衰老细胞与老年性疾病的关系是当今的研究热点, 研究表明, 清除衰老细胞可以延长寿命并延缓心血管、大脑和骨骼退行性疾病的进展。虽然相关研究已取得一定的进展, 但由于衰老细胞的鉴定和分离尚存在困难, 故研究成果需进一步证实。而对细胞衰老的发生机制及鉴定进行综述, 有利于进一步了解细胞衰老的分子机制, 为从细胞衰老的角度理解老年退行性疾病提供理论基础和思路。

Cellular senescence refers to the stable and irreversible cell cycle arrest and is one of the basic mechanisms leading to aging condition.Recent studies have shown that cellular senescence represents a wide range of dynamic and highly heterogeneous cell states,and that senescent cells have unique phenotypic changes.The main cause of senescence is the activation of tumor suppressor genes such as p16,p21 or p53 caused by cell damage,which leads to the arrest of the cell cycle.Senescent cells can also secrete cytokines after activation of the NF-κB pathway and the C/EBP family pathway,initiating the senescence-associated secretory phenotype(SASP).SASP factors such as TGF-β,IGFBP-1 and IL-1α,IL-6 and other inflammatory factors will maintain or induce the production of senescent cells in an autocrine or paracrine manner,and the accumulation of SASP will also promote the disintegration and reconstruction of tissues,thereby affecting organ homeostasis.The relationship between senescent cells and senile diseases is a research hotspot today.Studies have shown that killing senescent cells in vivo can prolong lifespan and delay the progression of cardiovascular,brain and bone degenerative diseases.Although some progress has been made in related research,there is technical problems identifying and separating senescent cells,so the results of the research need to be further confirmed.A review of the mechanisms and identification of cellular senescence is useful to further understand the molecular mechanism of cellular senescence and provide theoretical basis and ideas for understanding degenerative diseases in aging.