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DNA 稳态和衰老:裸鼹鼠的启示。

DNA Homeostasis and Senescence: Lessons from the Naked Mole Rat.

机构信息

The Healthy Lifespan Institute and the Institute of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK.

The Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, UK.

出版信息

Int J Mol Sci. 2021 Jun 2;22(11):6011. doi: 10.3390/ijms22116011.

Abstract

As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations. The naked mole rats (NMR) are from eastern Africa and can live for over three decades in chronically hypoxic environments. Despite their long lifespan, NMRs show little to no biological decline, neurodegeneration, or senescence. Here, we discuss molecular pathways and adaptations that NMRs employ to maintain genome integrity and combat the physiological and pathological decline in organismal function.

摘要

随着年龄的增长,我们的身体会积累 DNA 突变造成的损伤。这些突变导致产生次优的蛋白质,从而导致细胞内环境失衡和衰老。衰老细胞的积累会对局部细胞微环境产生负面影响,并导致与衰老相关的疾病,包括神经退行性疾病。因此,限制 DNA 损伤的积累对于健康的神经元群体至关重要。裸鼹鼠(NMR)来自东非,可以在长期缺氧的环境中生活超过三十年。尽管它们的寿命很长,但 NMR 几乎没有表现出生物衰退、神经退行性变或衰老。在这里,我们讨论了 NMR 用来维持基因组完整性和对抗机体功能的生理和病理衰退的分子途径和适应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6d3/8199619/49ff5a306412/ijms-22-06011-g001.jpg

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