Muller Michael
Centre for Education and Research on Ageing, ANZAC Research Institute, University of Sydney, Concord RG Hospital, Concord, Sydney, Australia.
Antioxid Redox Signal. 2009 Jan;11(1):59-98. doi: 10.1089/ars.2008.2104.
Cellular senescence is recognized as a critical cellular response to prolonged rounds of replication and environmental stresses. Its defining characteristics are arrested cell-cycle progression and the development of aberrant gene expression with proinflammatory behavior. Whereas the mechanistic events associated with senescence are generally well understood at the molecular level, the impact of senescence in vivo remains to be fully determined. In addition to the role of senescence as an antitumor mechanism, this review examines cellular senescence as a factor in organismal aging and age-related diseases, with particular emphasis on aberrant gene expression and abnormal paracrine signaling. Senescence as an emerging factor in tissue remodeling, wound repair, and infection is considered. In addition, the role of oxidative stress as a major mediator of senescence and the role of NAD(P)H oxidases and changes to intracellular GSH/GSSG status are reviewed. Recent findings indicate that senescence and the behavior of senescent cells are amenable to therapeutic intervention. As the in vivo significance of senescence becomes clearer, the challenge will be to modulate the adverse effects of senescence without increasing the risks of other diseases, such as cancer. The uncoupled relation between cell-cycle arrest and the senescent phenotype suggests that this is an achievable outcome.
细胞衰老被认为是细胞对长时间复制轮次和环境应激的一种关键反应。其定义特征是细胞周期进程停滞以及具有促炎行为的异常基因表达的发展。虽然与衰老相关的机制事件在分子水平上通常已被充分理解，但衰老在体内的影响仍有待全面确定。除了衰老作为一种抗肿瘤机制的作用外，本综述还探讨了细胞衰老作为机体衰老和与年龄相关疾病的一个因素，特别强调异常基因表达和异常旁分泌信号传导。衰老作为组织重塑、伤口修复和感染中的一个新兴因素也被考虑在内。此外，还综述了氧化应激作为衰老的主要介质的作用以及NAD(P)H氧化酶的作用和细胞内谷胱甘肽/氧化型谷胱甘肽状态的变化。最近的研究结果表明，衰老和衰老细胞的行为适合进行治疗干预。随着衰老在体内的重要性变得更加清晰，挑战将是在不增加其他疾病（如癌症）风险的情况下调节衰老的不利影响。细胞周期停滞与衰老表型之间的非耦合关系表明这是一个可以实现的结果。
