Universal DNA methylation age across mammalian tissues
Aimei Lu(University of California, Los Angeles), Zhe Fei(University of California, Los Angeles), Amin Haghani(University of California, Los Angeles), Todd R. Robeck(SeaWorld Entertainment), Joseph A. Zoller(University of California, Los Angeles), Chengzhang Li(University of California, Los Angeles), Robert Lowe(University of California, Los Angeles), Qi Yan(University of Auckland), Joshua Zhang(University of California, Los Angeles), Hoang‐Giang Vu(University of California, Los Angeles), Julia Ablaeva(University of Rochester), Victoria A. Acosta-Rodríguez(University of Rochester), Denise M. Adams(University of Maryland, College Park), Javier Almunia(Fundación A LA PAR), Ajoy Aloysius, Reza Ardehali(University of California, Los Angeles), A Arneson(University of California, Los Angeles), C. Scott Baker(Oregon State University), Gareth Banks(University of California, Los Angeles), Katherine Belov(The University of Sydney), Nigel C. Bennett(AgResearch), Peter McL. Black, Daniel T. Blumstein(University of California, Los Angeles), Eleanor K. Bors(Oregon State University), Charles E. Breeze(Altius Institute for Biomedical Sciences), Robert T. Brooke, Janine L. Brown(Smithsonian Conservation Biology Institute), G. Carter(University of California, Los Angeles), Alex Caulton(AgResearch), Julie M. Cavin, Lisa Chakrabarti(Queen Mary University of London), Ioulia Chatzistamou(University of South Carolina), Hao Chen(University of Tennessee Health Science Center), Kai Cheng(Queen Mary University of London), Priscila Chiavellini(Biochemistry Research Institute of La Plata), Oi‐Wa Choi(University of California, Los Angeles), Shannon Clarke(AgResearch), Lisa Noelle Cooper, Marie‐Laurence Cossette, Joanna Day(University of Auckland), Joseph DeYoung(University of California, Los Angeles), Stacy DiRocco(NOAA National Marine Fisheries Service), Christopher Dold(SeaWorld Entertainment), Erin E. Ehmke(Brigham and Women's Hospital), Candice K. Emmons(NOAA National Marine Fisheries Service), Stephan Emmrich(University of Rochester), Ebru Erbay(University of Otago), Claire Erlacher‐Reid(The University of Sydney), Christopher G. Faulkes(Queen Mary University of London), Steven H. Ferguson(Fisheries and Oceans Canada), Carrie J. Finno(University of California, Davis), Jennifer E. Flower(Université Claude Bernard Lyon 1), Jean‐Michel Gaillard(Université Claude Bernard Lyon 1), Eva Garde(Grønlands Naturinstitut), Livia Gerber(BC Children's Hospital), Vadim N. Gladyshev(Brigham and Women's Hospital), Vera Gorbunova(University of Rochester), Rodolfo G. Goya(Biochemistry Research Institute of La Plata), Maria J. Grant(University of Auckland), C.B. Green(University of California, Los Angeles), Erin N. Hales(University of California, Davis), M. Bradley Hanson(NOAA National Marine Fisheries Service), Daniel W. Hart, Martin Haulena(Vancouver Aquarium), K. Herrick, Andrew N. Hogan(National Institutes of Health), Carolyn J. Hogg(The University of Sydney), T.A. Hore(University of Otago), Taosheng Huang, Juan Carlos Izpisúa Belmonte, Anna J. Jasinska(University of California, Los Angeles), Gareth Jones(University of Bristol), Eve Jourdain, Olga Kashpur(Tufts Medical Center), Harold L. Katcher, Etsuko Katsumata, Vimala Kaza(University of South Carolina), Hippokratis Kiaris(University of South Carolina), Michael S. Kobor(BC Children's Hospital), Paweł Kordowitzki(InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences), William R. Koski(LGL (Canada)), Michael Kruetzen(NOAA National Marine Fisheries Service), Soon‐Bae Kwon, Brenda Larison(University of California, Los Angeles), Sang‐Goo Lee(University of California, Los Angeles), Marina Lehmann(Biochemistry Research Institute of La Plata), Jean‐François Lemaître(Université Claude Bernard Lyon 1), Andrew J. Levine(University of California, Los Angeles), Chengzhang Li(Texas Biomedical Research Institute), X. Li(University of California, Los Angeles), A. Lim, David Lin(BC Children's Hospital), D. Lindemann, Tom J. Little, Nicholas Macoretta(University of Rochester), Debra Maddox, Craig O. Matkin, Julie A. Mattison(National Institutes of Health), Mélanie McClure(Missouri State University), June Mergl, J.J. Meudt(University of Wisconsin–Madison), Gisele Montano(University of Wisconsin–Madison), Khyobeni Mozhui(University of Tennessee Health Science Center), Jason Munshi‐South(SeaWorld Entertainment), Asieh Naderi(University of South Carolina), Martina Nagy(Museum für Naturkunde), Pritika Narayan(University of Auckland), Peter W. Nathanielsz(Texas Biomedical Research Institute), Ngọc Bích Nguỹên(University of California, Los Angeles), Christof Niehrs(Institute of Molecular Biology), Justine K. O’Brien, Perrie O’Tierney-Ginn(Tufts Medical Center), Duncan T. Odom(University of Wisconsin–Madison), Alexander G. Ophir(Cornell University), S. B. Osborn(Royal Veterinary College), Elaine A. Ostrander(National Institutes of Health), Kim M. Parsons(NOAA National Marine Fisheries Service), Kaninika Paul(University of California, Los Angeles), Matteo Pellegrini(University of California, Los Angeles), Klaus Peters, Amy B. Pedersen(University of California, Los Angeles), Jessica L. Petersen(University of California, Los Angeles), Darren W. Pietersen, Gabriela Medeiros de Pinho(University of California, Los Angeles), Jocelyn Plassais(National Institutes of Health), Jesse R. Poganik, Natalia A. Prado(Smithsonian Conservation Biology Institute), Pradeep Reddy(University of California, Los Angeles), Benjamin Rey(Université Claude Bernard Lyon 1), Beate Ritz(UCLA Health), Jooke Robbins(Center for Coastal Studies), Magdalena Rodríguez, Jennifer Russell(SeaWorld Entertainment), Elena Rydkina(University of Rochester), Lindsay L. Sailer(Cornell University), Adam B. Salmon(Geriatric Research Education and Clinical Center), Akshay Sanghavi, Kyle M. Schachtschneider(University of Illinois Chicago), Dennis Schmitt(SeaWorld Entertainment), Todd L. Schmitt(SeaWorld Entertainment), Lars Schomacher(Institute of Molecular Biology), Lawrence B. Schook(University of Illinois Chicago), Karen E. Sears(University of California, Los Angeles), Ashley W. Seifert(University of Illinois Chicago), Andrei Seluanov(University of Rochester), Aaron B. A. Shafer, Dhanansayan Shanmuganayagam(University of Wisconsin–Madison), Anastasia V. Shindyapina(Brigham and Women's Hospital), M. Simmons(University of Bonn), Kavita Singh(Narsee Monjee Institute of Management Studies), Indranil Sinha(University of California, Los Angeles), Jesse Slone(Public Health England), Russell G. Snell(University of Auckland), E. Soltanmaohammadi(University of South Carolina), Matthew L Spangler(University of Nebraska–Lincoln), Maria Spriggs, Lydia Staggs(SeaWorld Entertainment), Nicole Stedman(Public Health England), Karen J. Steinman(SeaWorld Entertainment), Donald T. Stewart(University of Wisconsin–Madison), Victoria J Sugrue(University of Otago), Balázs Szladovits(Royal Veterinary College), Joseph S. Takahashi(University of Otago), M. Takasugi(University of Rochester), Emma C. Teeling(University College Dublin), Michael J. Thompson(University of California, Los Angeles), B. Van Bonn(Shedd Aquarium), Sonja C. Vernes(University of St Andrews), Diego Villar(Queen Mary University of London), Harry V. Vinters(University of California, Los Angeles), Mary C. Wallingford(Tufts Medical Center), Nan Wang(University of California, Los Angeles), Robert K. Wayne(University of California, Los Angeles), Gerald S. Wilkinson(University of Maryland, College Park), CK Williams(University of Tennessee Health Science Center), Robert W. Williams(University of Tennessee Health Science Center), X. William Yang(University of California, Los Angeles), M. Yao(University of Bonn), B. G. Young(Fisheries and Oceans Canada), Bohan Zhang(Brigham and Women's Hospital), Zhihui Zhang(University of Rochester), Peng Zhao(University of California, Los Angeles), Yang Zhao(University of Rochester), Wei Zhou(Children's Hospital of Philadelphia), Jörg Zimmermann(University of Bonn), Jason Ernst(University of California, Los Angeles), K. Raj(Public Health England), Steve Horvath(University of California, Los Angeles)
Cited by 149Open Access
Abstract
ABSTRACT Aging is often perceived as a degenerative process resulting from random accrual of cellular damage over time. Despite this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, we hypothesized that one can build pan-mammalian clocks that measure age in all mammalian species. To address this, we generated data using 11,754 methylation arrays, each profiling up to 36 thousand cytosines in highly-conserved stretches of DNA, from 59 tissue-types derived from 185 mammalian species. From these methylation profiles, we constructed three age predictors, each with a single mathematical formula, termed universal pan-mammalian clocks that are accurate in estimating the age (r>0.96) of any mammalian tissue. Deviations between epigenetic age and chronological age relate to mortality risk in humans, mutations that affect the somatotropic axis in mice, and caloric restriction. We characterized specific cytosines, whose methylation levels change with age across most mammalian species. These cytosines are greatly enriched in polycomb repressive complex 2-binding sites, are located in regions that gradually lose chromatin accessibility with age and are proximal to genes that play a role in mammalian development, cancer, human obesity, and human longevity. Collectively, these results support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new compelling evidence. SUMMARY This study identifies and characterizes evolutionarily conserved cytosines implicated in the aging process across mammals and establishes pan mammalian epigenetic clocks.
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