Author:
,Lu Ake T.,Fei Zhe,Haghani Amin,Robeck Todd R.,Zoller Joseph A.,Li Caesar Z.,Zhang Joshua,Ablaeva Julia,Adams Danielle M.,Almunia Javier,Ardehali Reza,Arneson Adriana,Baker C. Scott,Belov Katherine,Black Pete,Blumstein Daniel T.,Bors Eleanor K.,Breeze Charles E.,Brooke Robert T.,Brown Janine L.,Caulton Alex,Cavin Julie M.,Chatzistamou Ioulia,Chen Hao,Chiavellini Priscila,Choi Oi-Wa,Clarke Shannon,DeYoung Joseph,Dold Christopher,Emmons Candice K.,Emmrich Stephan,Faulkes Chris G.,Ferguson Steven H.,Finno Carrie J.,Gaillard Jean-Michel,Garde Eva,Gladyshev Vadim N.,Gorbunova Vera,Goya Rodolfo G.,Grant Matthew J,Hales Erin N.,Hanson M. Bradley,Haulena Martin,Hogan Andrew N.,Hogg Carolyn J.,Hore Timothy A.,Jasinska Anna J.,Jones Gareth,Jourdain Eve,Kashpur Olga,Katcher Harold,Katsumata Etsuko,Kaza Vimala,Kiaris Hippokratis,Kobor Michael S.,Kordowitzki Pawel,Koski William R.,Larison Brenda,Lee Sang-Goo,Lee Ye C.,Lehmann Marianne,Lemaitre Jean-Francois,Levine Andrew J.,Li Cun,Li Xinmin,Lin David TS,Macoretta Nicholas,Maddox Dewey,Matkin Craig O.,Mattison Julie A.,Mergl June,Meudt Jennifer J.,Mozhui Khyobeni,Naderi Asieh,Nagy Martina,Narayan Pritika,Nathanielsz Peter W.,Nguyen Ngoc B.,Niehrs Christof,Ophir Alexander G.,Ostrander Elaine A.,O’Tierney Ginn Perrie,Parsons Kim M.,Paul Kimberly C.,Pellegrini Matteo,Pinho Gabriela M.,Plassais Jocelyn,Prado Natalia A.,Rey Benjamin,Ritz Beate R.,Robbins Jooke,Rodriguez Magdalena,Russell Jennifer,Rydkina Elena,Sailer Lindsay L.,Salmon Adam B.,Sanghavi Akshay,Schachtschneider Kyle M.,Schmitt Dennis,Schmitt Todd,Schomacher Lars,Schook Lawrence B.,Sears Karen E.,Seluanov Andrei,Shanmuganayagam Dhanansayan,Shindyapina Anastasia,Singh Kavita,Sinha Ishani,Snell Russel G.,Soltanmaohammadi Elham,Spangler Matthew L.,Staggs Lydia,Steinman Karen J.,Sugrue Victoria J.,Szladovits Balazs,Takasugi Masaki,Teeling Emma C.,Thompson Michael J.,Van Bonn Bill,Vernes Sonja C.,Villar Diego,Vinters Harry V.,Wallingford Mary C.,Wang Nan,Wayne Robert K.,Wilkinson Gerald S.,Williams Christopher K.,Williams Robert W.,Yang X. William,Young Brent G.,Zhang Bohan,Zhang Zhihui,Zhao Peng,Zhao Yang,Zimmermann Joerg,Zhou Wanding,Ernst Jason,Raj Ken,Horvath Steve
Abstract
ABSTRACTAging 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.