Loss of epigenetic information as a cause of mammalian aging
Loss of epigenetic information as a cause of mammalian aging
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DOI：
10.1016/j.cell.2022.12.027
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发表时间：
2023-01-19
期刊：
影响因子：
64.5
通讯作者：
Sinclair, David A.
中科院分区：
文献类型：
--
作者：
Yang, Jae-Hyun;Hayano, Motoshi;Sinclair, David A.
所有生物都经历熵的增加，表现为遗传和表观遗传信息的丢失。在酵母中，由于染色质修饰蛋白重新定位到DNA断裂处，表观遗传信息随着时间的推移而丢失，导致细胞失去其身份，这是酵母老化的标志。使用一种称为“ICE”（表观基因组的可诱导变化）的系统，我们发现忠实的DNA修复行为在生理，认知和分子水平上促进衰老，包括表观遗传景观的侵蚀，细胞外分化，衰老和DNA甲基化时钟的进步，这可以通过OSK介导的复兴来逆转。这些数据与衰老的信息理论是一致的，该理论指出，遗传信息的丢失是衰老的可逆原因。
All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE"(induc-ible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epige-netic information is a reversible cause of aging.