Pan-primate DNA methylation clocks

ABSTRACT DNA methylation data have been successfully used to develop highly accurate estimators of age (“epigenetic clocks”) in many mammalian species. With a view of extending such epigenetic clocks to all primate species, we analyzed DNA methylation profiles of 2400 tissues derived from 37 primate species including 11 haplorhine species (baboons, marmosets, vervets, rhesus macaque, chimpanzees, gorillas, orangutan, humans) and 26 strepsirrhine species (suborders Lemuriformes and Lorisiformes). From these we present here, pan-primate epigenetic clocks which are highly accurate for all primates including humans (age correlation R=0.98). We also carried out in-depth analysis of baboon DNA methylation profiles and generated five epigenetic clocks for baboons (Olive-yellow baboon hybrid), one of which, the pan-tissue epigenetic clock, was trained on seven tissue types (fetal cerebral cortex, adult cerebral cortex, cerebellum, adipose, heart, liver, and skeletal muscle) with ages ranging from late fetal life to 22.8 years of age. To facilitate translation of findings in baboons to humans, we further constructed two dual-species, human-baboon clocks. We also identified and present here, epigenetic predictors of sex that apply to all primate species. Low overlap can be observed between age- and sex-related CpGs. Overall, this study advances our understanding of conserved age- and sex-related epigenetic changes in primates, and provides biomarkers to study the aging of all primate species with the facility to readily translate any findings between primate species. Competing Interest Statement SH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents. All of these patents list SH as inventor. One of the patents also lists JE as inventor. The other authors declare no conflicts of interest. Footnotes ↵# co-first authorship Emails: ahaghani{at}g.ucla.edu jaz18{at}g.ucla.edu akekaikailu{at}gmail.com jason.ernst{at}ucla.edu matteop{at}mcdb.ucla.edu ankajasinska{at}gmail.com Julie.mattison{at}nih.gov salmona{at}uthscsa.edu ken.raj{at}phe.gov.uk markushorvath{at}hotmail.com kimberlyc.paul{at}gmail.com britz{at}g.ucla.edu todd.robeck{at}seaworld.com Maria.Spriggs{at}buschgardens.com erin.ehmke{at}duke.edu sjenki13{at}uwyo.edu cli5{at}uwyo.edu We added more species and more array data. We updated our original analysis.