Universal DNA methylation age across mammalian tissues

Authors: Ake T. Lu, Zhe Fei, Amin Haghani, Todd R. Robeck, Joseph A. Zoller, Caesar Z. Li, Robert Lowe, Qi Yan, Joshua Zhang, Hoang‐Giang Vu, Julia Ablaeva, Victoria A. Acosta-Rodríguez, Danielle M. Adams, Javier Almunia, Ajoy Aloysius, Reza Ardehali, A Arneson, C. Scott Baker, Gareth Banks, Katherine Belov, Nigel C. Bennett, Peter C. Black, Daniel T. Blumstein, Eleanor K. Bors, Charles E. Breeze, Robert T. Brooke, Janine L. Brown, Gerald 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, Chris 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, Myles J.A. Grant, C. B. Green, Erin N. Hales, M. Bradley Hanson, Daniel W. Hart, Martin Haulena, K. Herrick, Andrew N. Hogan, Carolyn J. Hogg, Timothy 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 Krützen, Soon‐Bae Kwon, Brenda Larison, Sang‐Goo Lee, Marina Lehmann, Jean‐François Lemaître, Arnold J. Levine, Chunquan Li, X. Li, A. R. Lim, David Lin, D. Lindemann, Tom J. Little, Nicholas Macoretta, Debra Maddox, Craig O. Matkin, Julie A. Mattison, Mélanie McClure, June Mergl, Jennifer 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, Katharina J. 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, A. 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, M. C. 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, Christopher K. Williams, Robert W. Williams, X. William Yang, M. Yao, Brent G. Young, Bohan Zhang, Zhihui Zhang, P. Zhao, Yang Zhao, Wanding Zhou, Jörg Zimmermann, Jason Ernst, Ken Raj, Steve Horvath - Nature Aging 2023 cited by 387

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.