TY - JOUR T1 - Universal DNA methylation age across mammalian tissues JF - bioRxiv DO - 10.1101/2021.01.18.426733 SP - 2021.01.18.426733 AU - MAMMALIAN METHYLATION CONSORTIUM AU - Ake T. Lu AU - Zhe Fei AU - Amin Haghani AU - Todd R. Robeck AU - Joseph A. Zoller AU - Caesar Z. Li AU - Joshua Zhang AU - Julia Ablaeva AU - Danielle M. Adams AU - Javier Almunia AU - Reza Ardehali AU - Adriana Arneson AU - C. Scott Baker AU - Katherine Belov AU - Pete Black AU - Daniel T. Blumstein AU - Eleanor K. Bors AU - Charles E. Breeze AU - Robert T. Brooke AU - Janine L. Brown AU - Alex Caulton AU - Julie M. Cavin AU - Ioulia Chatzistamou AU - Hao Chen AU - Priscila Chiavellini AU - Oi-Wa Choi AU - Shannon Clarke AU - Joseph DeYoung AU - Christopher Dold AU - Candice K. Emmons AU - Stephan Emmrich AU - Chris G. Faulkes AU - Steven H. Ferguson AU - Carrie J. Finno AU - Jean-Michel Gaillard AU - Eva Garde AU - Vadim N. Gladyshev AU - Vera Gorbunova AU - Rodolfo G. Goya AU - Matthew J Grant AU - Erin N. Hales AU - M. Bradley Hanson AU - Martin Haulena AU - Andrew N. Hogan AU - Carolyn J. Hogg AU - Timothy A. Hore AU - Anna J. Jasinska AU - Gareth Jones AU - Eve Jourdain AU - Olga Kashpur AU - Harold Katcher AU - Etsuko Katsumata AU - Vimala Kaza AU - Hippokratis Kiaris AU - Michael S. Kobor AU - Pawel Kordowitzki AU - William R. Koski AU - Brenda Larison AU - Sang-Goo Lee AU - Ye C. Lee AU - Marianne Lehmann AU - Jean-Francois Lemaitre AU - Andrew J. Levine AU - Cun Li AU - Xinmin Li AU - David TS Lin AU - Nicholas Macoretta AU - Dewey Maddox AU - Craig O. Matkin AU - Julie A. Mattison AU - June Mergl AU - Jennifer J. Meudt AU - Khyobeni Mozhui AU - Asieh Naderi AU - Martina Nagy AU - Pritika Narayan AU - Peter W. Nathanielsz AU - Ngoc B. Nguyen AU - Christof Niehrs AU - Alexander G. Ophir AU - Elaine A. Ostrander AU - Perrie O’Tierney Ginn AU - Kim M. Parsons AU - Kimberly C. Paul AU - Matteo Pellegrini AU - Gabriela M. Pinho AU - Jocelyn Plassais AU - Natalia A. Prado AU - Benjamin Rey AU - Beate R. Ritz AU - Jooke Robbins AU - Magdalena Rodriguez AU - Jennifer Russell AU - Elena Rydkina AU - Lindsay L. Sailer AU - Adam B. Salmon AU - Akshay Sanghavi AU - Kyle M. Schachtschneider AU - Dennis Schmitt AU - Todd Schmitt AU - Lars Schomacher AU - Lawrence B. Schook AU - Karen E. Sears AU - Andrei Seluanov AU - Dhanansayan Shanmuganayagam AU - Anastasia Shindyapina AU - Kavita Singh AU - Ishani Sinha AU - Russel G. Snell AU - Elham Soltanmaohammadi AU - Matthew L. Spangler AU - Lydia Staggs AU - Karen J. Steinman AU - Victoria J. Sugrue AU - Balazs Szladovits AU - Masaki Takasugi AU - Emma C. Teeling AU - Michael J. Thompson AU - Bill Van Bonn AU - Sonja C. Vernes AU - Diego Villar AU - Harry V. Vinters AU - Mary C. Wallingford AU - Nan Wang AU - Robert K. Wayne AU - Gerald S. Wilkinson AU - Christopher K. Williams AU - Robert W. Williams AU - X. William Yang AU - Brent G. Young AU - Bohan Zhang AU - Zhihui Zhang AU - Peng Zhao AU - Yang Zhao AU - Joerg Zimmermann AU - Wanding Zhou AU - Jason Ernst AU - Ken Raj AU - Steve Horvath Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/19/2021.01.18.426733.abstract N2 - Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of 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, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials. The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations 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 and compelling evidence.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, JE, AA as inventors. The other authors declare no conflicts of interest. ER -