Senescence in Post-Mitotic Cells: A Driver of Aging?

被引:113
作者
von Zglinicki, Thomas [1 ,2 ]
Wan, Tengfei [1 ]
Miwa, Satomi [1 ]
机构
[1] Newcastle Univ, Fac Med Sci, Biosci Inst, Ageing Res Labs, Campus Ageing & Vital, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England
[2] Near East Univ, Arts & Sci Fac, Mol Biol & Genet, Nicosia, Turkey
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
aging; senescence; post-mitotic; DIFFERENT FIBER TYPES; SKELETAL-MUSCLE; DNA-DAMAGE; CELLULAR SENESCENCE; SECRETORY PHENOTYPE; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; TUMOR-SUPPRESSOR; VASTUS LATERALIS; LIFE-SPAN;
D O I
10.1089/ars.2020.8048
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Significance: Cell senescence was originally defined by an acute loss of replicative capacity and thus believed to be restricted to proliferation-competent cells. More recently, senescence has been recognized as a cellular stress and damage response encompassing multiple pathways or senescence domains, namely DNA damage response, cell cycle arrest, senescence-associated secretory phenotype, senescence-associated mitochondrial dysfunction, autophagy/mitophagy dysfunction, nutrient and stress signaling, and epigenetic reprogramming. Each of these domains is activated during senescence, and all appear to interact with each other. Cell senescence has been identified as an important driver of mammalian aging. Recent Advances: Activation of all these senescence domains has now also been observed in a wide range of post-mitotic cells, suggesting that senescence as a stress response can occur in nondividing cells temporally uncoupled from cell cycle arrest. Here, we review recent evidence for post-mitotic cell senescence and speculate about its possible relevance for mammalian aging. Critical Issues: Although a majority of senescence domains has been found to be activated in a range of post-mitotic cells during aging, independent confirmation of these results is still lacking for most of them. Future Directions: To define whether post-mitotic senescence plays a significant role as a driver of aging phenotypes in tissues such as brain, muscle, heart, and others.
引用
收藏
页码:308 / 323
页数:16
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