1. DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging
- Author
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Lei Zhong, Amy J. Wagers, Elias L. Salfati, Michael Bonkowski, Sarah J. Mitchell, Daniel L. Vera, Giuseppe Coppotelli, Patrick Griffin, Meredith S Gregory-Ksander, Xiaojing Yang, Wei Guo, Jonathan G. Seidman, Alice E. Kane, Yap Ching Chew, Jaime M. Ross, Tatjana C. Jakobs, Yasuaki Mohri, Carlos M. Palmeira, Laura Schaevitz, Emi K. Nishimura, Jae-Hyun Yang, David A. Sinclair, George F. Murphy, Abhirup Das, Luis A. Rajman, Sachin Thakur, Motoshi Hayano, Raul Mostoslavsky, Stephen J. Bonasera, Neha Garg, Christine E. Seidman, Hiroko Wakimoto, Philipp Oberdoerffer, Kazuo Tsubota, John M. Sedivy, Ana-Maria Balta, Jill A. Kreiling, Meghan A. Rego, Norman S. Wolf, João A. Amorim, and Bruce R. Ksander
- Subjects
Genome instability ,0303 health sciences ,biology ,DNA damage ,fungi ,Epigenome ,Cell biology ,Chromatin ,chemistry.chemical_compound ,03 medical and health sciences ,Histone ,0302 clinical medicine ,chemistry ,DNA methylation ,biology.protein ,sense organs ,Epigenetics ,DNA ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
SUMMARYThere 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 induciblechanges to theepigenome), 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 SummaryDNA breaks induce epigenomic changes that accelerate the aging clock in mammals
- Published
- 2019
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