RT Journal Article
SR Electronic
T1 Epigenetic predictors of maximum lifespan and other life history traits in mammals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.16.444078
DO 10.1101/2021.05.16.444078
A1 C.Z. Li
A1 A. Haghani
A1 T.R. Robeck
A1 D. Villar
A1 A.T. Lu
A1 J. Zhang
A1 C.G. Faulkes
A1 H. Vu
A1 J. Ablaeva
A1 D.M. Adams
A1 R. Ardehali
A1 A. Arneson
A1 C.S. Baker
A1 K. Belov
A1 D.T. Blumstein
A1 E.K. Bors
A1 C.E. Breeze
A1 R.T. Brooke
A1 J.L. Brown
A1 A. Caulton
A1 J.M. Cavin
A1 I. Chatzistamou
A1 H. Chen
A1 P. Chiavellini
A1 O.W. Choi
A1 S. Clarke
A1 J. DeYoung
A1 C.K. Emmons
A1 S. Emmrich
A1 Z. Fei
A1 S.H. Ferguson
A1 C.J. Finno
A1 J.E. Flower
A1 J.M. Gaillard
A1 E. Garde
A1 V.N. Gladyshev
A1 R.G. Goya
A1 M.B. Hanson
A1 M. Haulena
A1 K. Herrick
A1 A.N. Hogan
A1 C.J. Hogg
A1 T.A. Hore
A1 A.J. Jasinska
A1 G. Jones
A1 E. Jourdain
A1 O. Kashpur
A1 H. Katcher
A1 E. Katsumata
A1 V. Kaza
A1 H. Kiaris
A1 M.S. Kobor
A1 P. Kordowitzki
A1 W.R. Koski
A1 B. Larison
A1 S.G. Lee
A1 M. Lehmann
A1 J.F. Lemaitre
A1 A.J. Levine
A1 C. Li
A1 X. Li
A1 D.T.S. Lin
A1 D.M. Lindemann
A1 N. Macoretta
A1 D. Maddox
A1 C.O. Matkin
A1 J.A. Mattison
A1 J. Mergl
A1 J.J. Meudt
A1 G.A. Montano
A1 K. Mozhui
A1 A. Naderi
A1 M. Nagy
A1 P. Narayan
A1 P.W. Nathanielsz
A1 N.B. Nguyen
A1 C. Niehrs
A1 D.T. Odom
A1 A.G. Ophir
A1 E.A. Ostrander
A1 P. O’Tierney Ginn
A1 K.M. Parsons
A1 K.C. Paul
A1 M. Pellegrini
A1 G.M. Pinho
A1 J. Plassais
A1 N.A. Prado
A1 B. Rey
A1 B.R. Ritz
A1 J. Robbins
A1 M. Rodriguez
A1 J. Russell
A1 E. Rydkina
A1 L.L. Sailer
A1 A.B. Salmon
A1 A. Sanghavi
A1 K.M. Schachtschneider
A1 D. Schmitt
A1 L. Schomacher
A1 L.B. Schook
A1 K.E. Sears
A1 A.W. Seifert
A1 A.V. Shindyapina
A1 K. Singh
A1 I. Sinha
A1 R.G. Snell
A1 E. Soltanmohammadi
A1 M.L. Spangler
A1 M. Spriggs
A1 K.J. Steinman
A1 V.J. Sugrue
A1 B. Szladovits
A1 M. Takasugi
A1 E.C. Teeling
A1 B. Van Bonn
A1 S.C. Vernes
A1 H.V. Vinters
A1 M.C. Wallingford
A1 N. Wang
A1 G.S. Wilkinson
A1 R.W. Williams
A1 X.W. Yang
A1 B.G. Young
A1 B. Zhang
A1 Z. Zhang
A1 P. Zhao
A1 Y. Zhao
A1 W. Zhou
A1 J.A. Zoller
A1 J. Ernst
A1 A. Seluanov
A1 K. Raj
A1 V. Gorbunova
A1 S. Horvath
A1 MAMMALIAN METHYLATION CONSORTIUM
YR 2021
UL http://biorxiv.org/content/early/2021/05/18/2021.05.16.444078.abstract
AB Maximum lifespan of a species is the oldest that individuals can survive, reflecting the genetic limit of longevity in an ideal environment. Here we report methylation-based models that accurately predict maximum lifespan (r=0.89), gestational time (r=0.96), and age at sexual maturity (r=0.87), using cytosine methylation patterns collected from over 12,000 samples derived from 192 mammalian species. Our epigenetic maximum lifespan predictor corroborated the extended lifespan in growth hormone receptor knockout mice and rapamycin treated mice. Across dog breeds, epigenetic maximum lifespan correlates positively with breed lifespan but negatively with breed size. Lifespan-related cytosines are located in transcriptional regulatory regions, such as bivalent chromatin promoters and polycomb-repressed regions, which were hypomethylated in long-lived species. The epigenetic estimators of maximum lifespan and other life history traits will be useful for characterizing understudied species and for identifying interventions that extend lifespan.Competing Interest StatementSH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents. These patents list SH, AA, and JE as inventors. Robert T. Brooke is the Executive Director of the Epigenetic Clock Development Foundation. The other authors declare no conflicts of interest.