Universal DNA methylation age across mammalian tissues.
Ake T LuZ FeiAmin HaghaniT R RobeckJoseph Alan ZollerCaesar Z LiR LoweQ YanJoshua ZhangH VuJ AblaevaVictoria América Acosta-RodríguezDanielle M AdamsJavier AlmuniaAjoy AloysiusR ArdehaliA ArnesonCharles Scott BakerG BanksK BelovN C BennettP BlackDaniel T BlumsteinE K BorsCharles E BreezeR T BrookeJ L BrownG G CarterA CaultonJ M CavinL ChakrabartiI ChatzistamouH ChenK ChengP ChiavelliniO W ChoiShannon M ClarkeLisa Noelle CooperMarie-Laurence CossetteJoanna DayJ DeYoungS DiRoccoC DoldE E EhmkeCandice K EmmonsStephan EmmrichE ErbayC Erlacher-ReidChris G FaulkesSteven H FergusonC J FinnoJ E FlowerJ M GaillardE GardeL GerberVadim N GladyshevVera GorbunovaRodolfo G GoyaM J GrantC B GreenE N HalesM B HansonDaniel William HartM HaulenaK HerrickA N HoganCarolyn J HoggTimothy Alexander HoreTaosheng HuangJ C Izpisua BelmonteAnna J JasinskaGareth JonesE JourdainO KashpurH KatcherE KatsumataV KazaHippokratis KiarisM S KoborPaweł KordowitzkiWilliam R KoskiMichael KrützenS B KwonB LarisonS G LeeM LehmannJean-François LemaitreA J LevineC LiX LiA R LimD T S LinD M LindemannT J LittleN MacorettaD MaddoxC O MatkinJ A MattisonM McClureJ MerglJ J MeudtG A MontanoKhyobeni MozhuiJ Munshi-SouthAsieh NaderiMartina NagyPritika NarayanP W NathanielszN B NguyenC NiehrsJ K O'BrienPerrie O'Tierney GinnD T OdomAlexander G OphirS OsbornElaine A OstranderK M ParsonsK C PaulM PellegriniKatharina J PetersA B PedersenJessica L PetersenDarren W PietersenGabriela M PinhoJocelyn PlassaisJesse R PoganikN A PradoP ReddyBenjamin ReyBeate R RitzJooke RobbinsM RodriguezJennifer RussellE RydkinaLindsay L SailerAdam B SalmonAkshay SanghaviK M SchachtschneiderDennis SchmittT SchmittLars SchomacherLawrence B SchookKaren E SearsA W SeifertAndrei SeluanovA B A ShaferDhanansayan ShanmuganayagamA V ShindyapinaM SimmonsK SinghI SinhaJ SloneRussell Grant SnellE SoltanmaohammadiMatthew L SpanglerM C SpriggsL StaggsN StedmanK J SteinmanD T StewartV J SugrueBalazs SzladovitsJoseph S TakahashiM TakasugiEmma C TeelingMichael J ThompsonB Van BonnS C VernesDiego VillarH V VintersM C WallingfordN WangR K WayneGerald S WilkinsonC K WilliamsR W WilliamsXiangdong William YangM YaoBrent G YoungB ZhangZ ZhangPeng ZhaoY ZhaoW ZhouJörg ZimmermannJason ErnstKenneth RajSteve HorvathPublished in: Nature aging (2023)
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.