DNA damage, cellular senescence and organismal ageing: causal or correlative?
DNA damage, cellular senescence and organismal ageing: causal or correlative?
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DNA损伤，细胞衰老和生物衰老：因果还是相关？
DOI：
10.1093/nar/gkm681
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发表时间：
2007
影响因子：
14.9
通讯作者：
Ozanne, Susan E.
中科院分区：
文献类型：
--
作者：
Chen, Jian-Hua;Hales, C. Nicholes;Ozanne, Susan E.
细胞衰老长期以来一直被用作理解衰老过程机制的细胞模型。近年来获得的令人信服的证据表明，DNA损伤是由端粒缩短引发的复制性衰老和由各种应激因素如致癌应激和氧化应激诱导的细胞过早衰老的共同介质。广泛的观察表明，DNA损伤随着年龄的增长而积累，这可能是由于活性氧（ROS）的产生增加和DNA修复能力随着年龄的增长而下降。增加DNA损伤的基因突变或表达中断通常会导致过早衰老。相反，增强抗氧化应激和减轻DNA损伤的干预措施有助于长寿。这一证据表明，基因组的不稳定性在衰老过程中起着致病作用。然而，存在相互矛盾的发现，表明ROS的产生和大分子（包括DNA）的氧化损伤水平并不总是与模型动物的寿命相关。在这里，我们回顾了最近的进展，在解决细胞衰老和有机体衰老的DNA损伤的作用。
Cellular senescence has long been used as a cellular model for understanding mechanisms underlying the ageing process. Compelling evidence obtained in recent years demonstrate that DNA damage is a common mediator for both replicative senescence, which is triggered by telomere shortening, and premature cellular senescence induced by various stressors such as oncogenic stress and oxidative stress. Extensive observations suggest that DNA damage accumulates with age and that this may be due to an increase in production of reactive oxygen species (ROS) and a decline in DNA repair capacity with age. Mutation or disrupted expression of genes that increase DNA damage often result in premature ageing. In contrast, interventions that enhance resistance to oxidative stress and attenuate DNA damage contribute towards longevity. This evidence suggests that genomic instability plays a causative role in the ageing process. However, conflicting findings exist which indicate that ROS production and oxidative damage levels of macromolecules including DNA do not always correlate with lifespan in model animals. Here we review the recent advances in addressing the role of DNA damage in cellular senescence and organismal ageing.
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影响因子：
64.8
作者：
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通讯作者：
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