1. Universal DNA methylation age across mammalian tissues.
- Author
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Lu AT, Fei Z, Haghani A, Robeck TR, Zoller JA, Li CZ, Lowe R, Yan Q, Zhang J, Vu H, Ablaeva J, Acosta-Rodriguez VA, Adams DM, Almunia J, Aloysius A, Ardehali R, Arneson A, Baker CS, Banks G, Belov K, Bennett NC, Black P, Blumstein DT, Bors EK, Breeze CE, Brooke RT, Brown JL, Carter GG, Caulton A, Cavin JM, Chakrabarti L, Chatzistamou I, Chen H, Cheng K, Chiavellini P, Choi OW, Clarke SM, Cooper LN, Cossette ML, Day J, DeYoung J, DiRocco S, Dold C, Ehmke EE, Emmons CK, Emmrich S, Erbay E, Erlacher-Reid C, Faulkes CG, Ferguson SH, Finno CJ, Flower JE, Gaillard JM, Garde E, Gerber L, Gladyshev VN, Gorbunova V, Goya RG, Grant MJ, Green CB, Hales EN, Hanson MB, Hart DW, Haulena M, Herrick K, Hogan AN, Hogg CJ, Hore TA, Huang T, Izpisua Belmonte JC, Jasinska AJ, Jones G, Jourdain E, Kashpur O, Katcher H, Katsumata E, Kaza V, Kiaris H, Kobor MS, Kordowitzki P, Koski WR, Krützen M, Kwon SB, Larison B, Lee SG, Lehmann M, Lemaitre JF, Levine AJ, Li C, Li X, Lim AR, Lin DTS, Lindemann DM, Little TJ, Macoretta N, Maddox D, Matkin CO, Mattison JA, McClure M, Mergl J, Meudt JJ, Montano GA, Mozhui K, Munshi-South J, Naderi A, Nagy M, Narayan P, Nathanielsz PW, Nguyen NB, Niehrs C, O'Brien JK, O'Tierney Ginn P, Odom DT, Ophir AG, Osborn S, Ostrander EA, Parsons KM, Paul KC, Pellegrini M, Peters KJ, Pedersen AB, Petersen JL, Pietersen DW, Pinho GM, Plassais J, Poganik JR, Prado NA, Reddy P, Rey B, Ritz BR, Robbins J, Rodriguez M, Russell J, Rydkina E, Sailer LL, Salmon AB, Sanghavi A, Schachtschneider KM, Schmitt D, Schmitt T, Schomacher L, Schook LB, Sears KE, Seifert AW, Seluanov A, Shafer ABA, Shanmuganayagam D, Shindyapina AV, Simmons M, Singh K, Sinha I, Slone J, Snell RG, Soltanmaohammadi E, Spangler ML, Spriggs MC, Staggs L, Stedman N, Steinman KJ, Stewart DT, Sugrue VJ, Szladovits B, Takahashi JS, Takasugi M, Teeling EC, Thompson MJ, Van Bonn B, Vernes SC, Villar D, Vinters HV, Wallingford MC, Wang N, Wayne RK, Wilkinson GS, Williams CK, Williams RW, Yang XW, Yao M, Young BG, Zhang B, Zhang Z, Zhao P, Zhao Y, Zhou W, Zimmermann J, Ernst J, Raj K, and Horvath S
- Subjects
- Humans, Mice, Animals, Aging genetics, Longevity genetics, Mammals genetics, DNA Methylation genetics, Epigenesis, Genetic
- 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., (© 2023. The Author(s).)
- Published
- 2023
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