文章：

生活在中断中：细胞衰老作为DNA损伤反应

Living on a break: cellular senescence as a DNA-damage response

原文发布日期：2008-07-01

DOI: 10.1038/nrc2440

类型: Review Article

开放获取: 否

要点：

1. Cells respond to the perception of DNA damage by arresting cell-cycle progression and attempting repair: collectively these actions are known as the DNA-damage response (DDR). In mammals, proliferation is not resumed until DNA damage is fixed.
2. Cellular senescence is a condition in which cells, despite being alive, are unable to proliferate further. This is a stress response, and therefore is different from quiescence or terminal differentiation.
3. Replicative senescence limits the proliferation of normal human cells. Proliferation that is associated with progressive telomere shortening leads to senescence establishment when critically short telomeres are recognized as DNA damage and trigger a DDR.
4. Mammalian ageing is associated with the progressive accumulation of senescent cells and DDR accumulation in stem or progenitor cells and more differentiated cells. In the skin of primates, DDR markers associate with the telomeres.
5. Oncogene activation also causes DDR activation and cellular senescence. Oncogene-induced DNA damage is caused by altered DNA replication, and oncogene-induced senescence is a barrier to cancer. Senescent cells can be observed in vivo in preneoplastic lesions.
6. Collectively, mounting evidence indicates that senescence, triggered by different stimuli, is the outcome of a protracted DDR.

要点翻译：

1. 细胞通过停滞细胞周期进程并尝试修复来应对DNA损伤的感知：这些行动统称为DNA损伤反应（DDR）。在哺乳动物中，除非DNA损伤被修复，否则增殖不会恢复。
2. 细胞衰老是指细胞尽管存活，却无法进一步增殖的状态。这是一种应激反应，因此与静止状态或终末分化有所不同。
3. 复制性衰老限制了正常人类细胞的增殖。与端粒逐渐缩短相关的增殖会导致衰老的确立，当关键性短的端粒被识别为DNA损伤并触发DDR时。
4. 哺乳动物的衰老与衰老细胞的逐渐积累以及DDR在干细胞或祖细胞和更分化细胞中的积累有关。在灵长类动物的皮肤中，DDR标记物与端粒相关联。
5. 癌基因的激活也会引起DDR激活和细胞衰老。癌基因诱导的DNA损伤是由DNA复制的改变引起的，而癌基因诱导的衰老是癌症的一道屏障。在肿瘤前病变中可以观察到衰老细胞的存在。
6. 总的来说，越来越多的证据表明，由不同刺激触发的衰老是持久DDR的结果。

英文摘要：

Cellular senescence is associated with ageing and cancer in vivo and has a proven tumour-suppressive function. Common to both ageing and cancer is the generation of DNA damage and the engagement of the DNA-damage response pathways. In this Review, the diverse mechanisms that lead to DNA-damage generation and the activation of DNA-damage-response signalling pathways are discussed, together with the evidence for their contribution to the establishment and maintenance of cellular senescence in the context of organismal ageing and cancer development.

摘要翻译： 

细胞衰老与体内的衰老和癌症相关，并具有明确的抑瘤功能。衰老和癌症的共同点是DNA损伤的产生以及DNA损伤应答通路的激活。本综述讨论了导致DNA损伤产生的多种机制以及DNA损伤应答信号通路的激活，以及它们在机体衰老和癌症发展过程中对细胞衰老的建立和维持的贡献证据。

原文链接：

Living on a break: cellular senescence as a DNA-damage response