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      DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging

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          SUMMARY

          There are numerous hallmarks of aging in mammals, but no unifying cause has been identified. In budding yeast, aging is associated with a loss of epigenetic information that occurs in response to genome instability, particularly DNA double-strand breaks (DSBs). Mammals also undergo predictable epigenetic changes with age, including alterations to DNA methylation patterns that serve as epigenetic “age” clocks, but what drives these changes is not known. Using a transgenic mouse system called “ICE” (for inducible changes to the epigenome), we show that a tissue’s response to non-mutagenic DSBs reorganizes the epigenome and accelerates physiological, cognitive, and molecular changes normally seen in older mice, including advancement of the epigenetic clock. These findings implicate DSB-induced epigenetic drift as a conserved cause of aging from yeast to mammals.

          One Sentence Summary

          DNA breaks induce epigenomic changes that accelerate the aging clock in mammals

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          Author and article information

          Journal
          bioRxiv
          October 21 2019
          Article
          10.1101/808659
          © 2019
          Product

          Molecular biology

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