Universal DNA methylation age across mammalian tissues
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
Abstract
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.