Universal DNA methylation age across mammalian tissues

作者：Aimei Lu, Zhe Fei, Amin Haghani, Todd R. Robeck, Joseph A. Zoller, Chengzhang Li, Robert Lowe, Qi Yan, Joshua Zhang, Hoang‐Giang Vu, Julia Ablaeva, Victoria A. Acosta-Rodríguez, Denise M. Adams, Javier Almunia, Ajoy Aloysius, Reza Ardehali, A Arneson, C. Scott Baker, Gareth Banks, Katherine Belov, Nigel C. Bennett, Peter McL. Black, Daniel T. Blumstein, Eleanor K. Bors, Charles E. Breeze, Robert T. Brooke, Janine L. Brown, G. Carter, Alex Caulton, Julie M. Cavin, Lisa Chakrabarti, Ioulia Chatzistamou, Hao Chen, Kai Cheng, Priscila Chiavellini, Oi‐Wa Choi, Shannon Clarke, Lisa Noelle Cooper, Marie‐Laurence Cossette, Joanna Day, Joseph DeYoung, Stacy DiRocco, Christopher Dold, Erin E. Ehmke, Candice K. Emmons, Stephan Emmrich, Ebru Erbay, Claire Erlacher‐Reid, Christopher G. Faulkes, Steven H. Ferguson, Carrie J. Finno, Jennifer E. Flower, Jean‐Michel Gaillard, Eva Garde, Livia Gerber, Vadim N. Gladyshev, Vera Gorbunova, Rodolfo G. Goya, Maria J. Grant, C.B. Green, Erin N. Hales, M. Bradley Hanson, Daniel W. Hart, Martin Haulena, K. Herrick, Andrew N. Hogan, Carolyn J. Hogg, T.A. Hore, Taosheng Huang, Juan Carlos Izpisúa Belmonte, Anna J. Jasinska, Gareth Jones, Eve Jourdain, Olga Kashpur, Harold L. Katcher, Etsuko Katsumata, Vimala Kaza, Hippokratis Kiaris, Michael S. Kobor, Paweł Kordowitzki, William R. Koski, Michael Kruetzen, Soon‐Bae Kwon, Brenda Larison, Sang‐Goo Lee, Marina Lehmann, Jean‐François Lemaître, Andrew J. Levine, Chengzhang Li, X. Li, A. Lim, David Lin, D. Lindemann, Tom J. Little, Nicholas Macoretta, Debra Maddox, Craig O. Matkin, Julie A. Mattison, Mélanie McClure, June Mergl, J.J. Meudt, Gisele Montano, Khyobeni Mozhui, Jason Munshi‐South, Asieh Naderi, Martina Nagy, Pritika Narayan, Peter W. Nathanielsz, Ngọc Bích Nguỹên, Christof Niehrs, Justine K. O’Brien, Perrie O’Tierney-Ginn, Duncan T. Odom, Alexander G. Ophir, S. B. Osborn, Elaine A. Ostrander, Kim M. Parsons, Kaninika Paul, Matteo Pellegrini, Klaus Peters, Amy B. Pedersen, Jessica L. Petersen, Darren W. Pietersen, Gabriela Medeiros de Pinho, Jocelyn Plassais, Jesse R. Poganik, Natalia A. Prado, Pradeep Reddy, Benjamin Rey, Beate Ritz, Jooke Robbins, Magdalena Rodríguez, Jennifer Russell, Elena Rydkina, Lindsay L. Sailer, Adam B. Salmon, Akshay Sanghavi, Kyle M. Schachtschneider, Dennis Schmitt, Todd L. Schmitt, Lars Schomacher, Lawrence B. Schook, Karen E. Sears, Ashley W. Seifert, Andrei Seluanov, Aaron B. A. Shafer, Dhanansayan Shanmuganayagam, Anastasia V. Shindyapina, M. Simmons, Kavita Singh, Indranil Sinha, Jesse Slone, Russell G. Snell, E. Soltanmaohammadi, Matthew L Spangler, Maria Spriggs, Lydia Staggs, Nicole Stedman, Karen J. Steinman, Donald T. Stewart, Victoria J Sugrue, Balázs Szladovits, Joseph S. Takahashi, M. Takasugi, Emma C. Teeling, Michael J. Thompson, B. Van Bonn, Sonja C. Vernes, Diego Villar, Harry V. Vinters, Mary C. Wallingford, Nan Wang, Robert K. Wayne, Gerald S. Wilkinson, CK Williams, Robert W. Williams, X. William Yang, M. Yao, B. G. Young, Bohan Zhang, Zhihui Zhang, Peng Zhao, Yang Zhao, Wei Zhou, Jörg Zimmermann, Jason Ernst, K. Raj, Steve Horvath · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2021 · DOI：10.1101/2021.01.18.426733 · 被引用次数：150 · 研究领域：Epigenetics and DNA Methylation、Genetics and Neurodevelopmental Disorders、Identity, Memory, and Therapy

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 agi...