作为哺乳动物衰老原因的表观遗传信息丢失。
Loss of epigenetic information as a cause of mammalian aging.
机构信息
Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA; Department of Ophthalmology, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
出版信息
Cell. 2023 Jan 19;186(2):305-326.e27. doi: 10.1016/j.cell.2022.12.027. Epub 2023 Jan 12.
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" (inducible 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 epigenetic information is a reversible cause of aging.
所有生物都会经历熵的增加，表现为遗传和表观遗传信息的丧失。在酵母中，由于染色质修饰蛋白重新定位到 DNA 断裂处，表观遗传信息会随着时间的推移而丢失，导致细胞失去身份，这是酵母衰老的一个标志。使用一种称为“ICE”（诱导表观基因组变化）的系统，我们发现忠实的 DNA 修复行为会加速生理、认知和分子水平的衰老，包括表观遗传景观的侵蚀、细胞去分化、衰老和 DNA 甲基化时钟的推进，这可以通过 OSK 介导的年轻化来逆转。这些数据与衰老的信息理论一致，该理论指出，表观遗传信息的丧失是衰老的一个可逆原因。
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