RT Journal Article
SR Electronic
T1 Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 808642
DO 10.1101/808642
A1 Jae-Hyun Yang
A1 Patrick T. Griffin
A1 Daniel L. Vera
A1 John K. Apostolides
A1 Motoshi Hayano
A1 Margarita V. Meer
A1 Elias L. Salfati
A1 Qiao Su
A1 Elizabeth M. Munding
A1 Marco Blanchette
A1 Mital Bhakta
A1 Zhixun Dou
A1 Caiyue Xu
A1 Jeffrey W. Pippin
A1 Michael L. Creswell
A1 Brendan L. O’Connell
A1 Richard E. Green
A1 Benjamin A. Garcia
A1 Shelley L. Berger
A1 Philipp Oberdoerffer
A1 Stuart J. Shankland
A1 Vadim N. Gladyshev
A1 Luis A. Rajman
A1 Andreas R. Pfenning
A1 David A. Sinclair
YR 2019
UL http://biorxiv.org/content/early/2019/10/19/808642.abstract
AB All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Here we show that the transient induction of genomic instability, in the form of a low number of non-mutagenic DNA breaks, accelerates many of the chromatin and tissue changes seen during aging, including the erosion of the epigenetic landscape, a loss of cellular identity, advancement of the DNA methylation clock and cellular senescence. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.One Sentence Summary The act of repairing DNA breaks induces chromatin reorganization and a loss of cell identity that may contribute to mammalian aging