Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, 400013, China.
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, China.
Int J Biol Sci. 2021 Sep 21;17(14):3923-3935. doi: 10.7150/ijbs.64953. eCollection 2021.
A common feature of aging is the accumulation of genetic damage throughout life. DNA damage can lead to genomic instability. Many diseases associated with premature aging are a result of increased accumulation of DNA damage. In order to minimize these damages, organisms have evolved a complex network of DNA repair mechanisms, including mismatch repair (MMR). In this review, we detail the effects of MMR on genomic instability and its role in aging emphasizing on the association between MMR and the other hallmarks of aging, serving to drive or amplify these mechanisms. These hallmarks include telomere attrition, epigenetic alterations, mitochondrial dysfunction, altered nutrient sensing and cell senescence. The close relationship between MMR and these markers may provide prevention and treatment strategies, to reduce the incidence of age-related diseases and promote the healthy aging of human beings.
衰老的一个共同特征是一生中遗传损伤的积累。DNA 损伤可导致基因组不稳定。许多与早衰相关的疾病是由于 DNA 损伤的积累增加所致。为了最小化这些损伤，生物体进化出了一个复杂的 DNA 修复机制网络，包括错配修复（MMR）。在这篇综述中，我们详细描述了 MMR 对基因组不稳定性的影响及其在衰老中的作用，强调了 MMR 与衰老的其他标志之间的关联，这些关联有助于驱动或放大这些机制。这些标志包括端粒磨损、表观遗传改变、线粒体功能障碍、营养感应改变和细胞衰老。MMR 与这些标志物之间的密切关系可能为预防和治疗策略提供依据，以降低与年龄相关的疾病的发病率，促进人类健康衰老。
