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Loss of epigenetic information as a cause of mammalian aging

Authors
Jae-Hyun Yang,Motoshi Hayano
Patrick T. Griffin,João A. Amorim,Michael S. Bonkowski,John K. Apostolides,Elias L. Salfati,Marco Blanchette,Elizabeth M. Munding,Mital Bhakta,Yap Ching Chew,Wei Guo,Xiaojing Yang,Sun Maybury-Lewis,Xiao Tian,Jaime M. Ross,Giuseppe Coppotelli,Margarita V. Meer,Ryan Rogers-Hammond,Daniel L. Vera,Yuancheng Ryan Lu,Jeffrey W. Pippin,Michael L. Creswell,Zhixun Dou,Caiyue Xu,Sarah J. Mitchell,Abhirup Das,Brendan L. O’Connell,Sachin Thakur,Alice E. Kane,Qiao Su,Yasuaki Mohri,Emi K. Nishimura,Laura Schaevitz,Neha Garg,Ana-Maria Balta,Meghan A. Rego,Meredith Gregory-Ksander,Tatjana C. Jakobs,Lei Zhong,Hiroko Wakimoto,Jihad El Andari,Dirk Grimm,Raul Mostoslavsky,Amy J. Wagers,Kazuo Tsubota,Stephen J. Bonasera,Carlos M. Palmeira,Jonathan G. Seidman,Christine E. Seidman,Norman S. Wolf,Jill A. Kreiling,John M. Sedivy,George F. Murphy,Richard E. Green,Benjamin A. Garcia,Shelley L. Berger,Philipp Oberdoerffer,Stuart J. Shankland,Vadim N. Gladyshev,Bruce R. Ksander,Andreas R. Pfenning,Luis A. Rajman,David A. Sinclair,Patrick Griffin,Jaime Ross,Stephen Bonasera,Carlos Palmeira,Benjamin García,Shelley Berger,Andreas Pfenning,João Amorim,Michael Bonkowski,John Apostolides,Elias Salfati,Elizabeth Munding,Yap Chew,Sun Kim,Margarita Meer,Daniel Vera,Yuancheng Lu,Jeffrey Pippin,Michael Creswell,Sarah Mitchell,Brendan O’Connell,Alice Kane,Emi Nishimura,Meghan Rego,Meredith Gregory‐Ksander,Tatjana Jakobs,Jihad Andari,Raúl Mostoslavsky,Amy Wagers,Jonathan Seidman,Christine Seidman,Jill Kreiling,John Sedivy,Gëorge Murphy,Edward Green,Stuart Shankland,Vadim Gladyshev,Bruce Ksander,Luis Rajman,Norman Wolf
+102 authors
,David Sinclair
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Published
Jan 1, 2023
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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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