Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Mech Ageing Dev. 2018 Mar;170:13-21. doi: 10.1016/j.mad.2017.08.004. Epub 2017 Aug 16.
Cellular senescence is a fundamental trait of many eukaryotic organisms. Senescent cells participate both in the developmental program and in normal ageing and age-related diseases. Senescence of proliferation-prone cells is a state of permanent cell cycle arrest accompanied by metabolic activity manifested by high secretion levels of numerous factors, including pro-inflammatory ones. It seems that cell senescence is a stress response. There are many intrinsic and extrinsic stress inducers which can elicit cell senescence. Generally accepted are those causing DNA double strand breaks (DSBs), which trigger permanent activation of DNA damage response (DDR) considered as a hallmark and a cause of cell senescence. In this review we discuss the possibility that cell senescence can be acquired in the absence of DDR or following DDR in the absence of DNA damage. Any scenario seems possible, based on data obtained by many researchers including ourselves, but it should be emphasized that unrepaired DSBs are a well-recognized trigger of senescence.
细胞衰老（Cellular senescence）是许多真核生物的基本特征。衰老细胞既参与发育过程，也参与正常衰老和与年龄相关的疾病。增殖活跃细胞的衰老（Progression to senescence）是一种永久性细胞周期停滞的状态，伴随着代谢活性，表现为许多因子（包括促炎因子）的高水平分泌。细胞衰老似乎是一种应激反应。有许多内在和外在的应激诱导物可以引发细胞衰老。目前普遍认为，能引发细胞衰老的是导致 DNA 双链断裂（Double-strand breaks, DSBs）的因素，它会引发永久性的 DNA 损伤反应（DNA damage response, DDR）的激活，而 DDR 被认为是细胞衰老的一个标志和原因。在这篇综述中，我们讨论了在没有 DDR 的情况下或在没有 DNA 损伤的情况下通过 DDR 获得细胞衰老的可能性。基于包括我们在内的许多研究人员获得的数据，任何情况似乎都是可能的，但应该强调的是，未修复的 DSB 是衰老的一个公认诱因。
