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体细胞和生殖衰老中的基因组不稳定性和 DNA 修复。

Genome Instability and DNA Repair in Somatic and Reproductive Aging.

机构信息

Institute for Genome Stability in Aging and Disease and Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne and University Hospital of Cologne, Cologne, Germany; email:

Max Planck Institute for Biology of Ageing, Cologne, Germany.

出版信息

Annu Rev Pathol. 2024 Jan 24;19:261-290. doi: 10.1146/annurev-pathmechdis-051122-093128. Epub 2023 Oct 13.

Abstract

Genetic material is constantly subjected to genotoxic insults and is critically dependent on DNA repair. Genome maintenance mechanisms differ in somatic and germ cells as the soma only requires maintenance during an individual's lifespan, while the germline indefinitely perpetuates its genetic information. DNA lesions are recognized and repaired by mechanistically highly diverse repair machineries. The DNA damage response impinges on a vast array of homeostatic processes and can ultimately result in cell fate changes such as apoptosis or cellular senescence. DNA damage causally contributes to the aging process and aging-associated diseases, most prominently cancer. By causing mutations, DNA damage in germ cells can lead to genetic diseases and impact the evolutionary trajectory of a species. The mechanisms ensuring tight control of germline DNA repair could be highly instructive in defining strategies for improved somatic DNA repair. They may provide future interventions to maintain health and prevent disease during aging.

摘要

遗传物质不断受到遗传毒性的侵害,严重依赖于 DNA 修复。体细胞和生殖细胞中的基因组维持机制不同,因为体细胞只需要在个体的寿命内维持,而生殖细胞则无限期地延续其遗传信息。DNA 损伤由机制上高度多样化的修复机制识别和修复。DNA 损伤反应影响到大量的体内平衡过程,并最终导致细胞命运的改变,如细胞凋亡或细胞衰老。DNA 损伤是导致衰老过程和与衰老相关疾病的原因,其中最突出的是癌症。生殖细胞中的 DNA 损伤会导致遗传疾病,并影响物种的进化轨迹。确保生殖细胞 DNA 修复严格控制的机制,对于确定改善体细胞 DNA 修复的策略具有重要意义。它们可能为未来提供干预措施,以在衰老过程中保持健康和预防疾病。

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