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Updated: Aug 14, 2025

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
Published on: September 7, 2021
Loss of epigenetic information as a cause of mammalian aging
Jae-Hyun Yang1, Motoshi Hayano2, Patrick T Griffin1
1Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Abstract:
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.
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