PT  - JOURNAL ARTICLE
AU  - Motoshi Hayano
AU  - Jae-Hyun Yang
AU  - Michael S. Bonkowski
AU  - Joao A. Amorim
AU  - Jaime M. Ross
AU  - Giuseppe Coppotelli
AU  - Patrick T. Griffin
AU  - Yap Ching Chew
AU  - Wei Guo
AU  - Xiaojing Yang
AU  - Daniel L. Vera
AU  - Elias L. Salfati
AU  - Abhirup Das
AU  - Sachin Thakur
AU  - Alice E. Kane
AU  - Sarah J. Mitchell
AU  - Yasuaki Mohri
AU  - Emi K. Nishimura
AU  - Laura Schaevitz
AU  - Neha Garg
AU  - Ana-Maria Balta
AU  - Meghan A. Rego
AU  - Meredith Gregory-Ksander
AU  - Tatjana C. Jakobs
AU  - Lei Zhong
AU  - Hiroko Wakimoto
AU  - Raul Mostoslavsky
AU  - Amy J. Wagers
AU  - Kazuo Tsubota
AU  - Stephen J. Bonasera
AU  - Carlos M. Palmeira
AU  - Jonathan G. Seidman
AU  - Christine E. Seidman
AU  - Norman S. Wolf
AU  - Jill A. Kreiling
AU  - John M. Sedivy
AU  - George F. Murphy
AU  - Philipp Oberdoerffer
AU  - Bruce R. Ksander
AU  - Luis A. Rajman
AU  - David A. Sinclair
TI  - DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging
AID  - 10.1101/808659
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 808659
4099  - http://biorxiv.org/content/early/2019/10/21/808659.short
4100  - http://biorxiv.org/content/early/2019/10/21/808659.full
AB  - 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