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DNA methylation study of age and sex in baboons and four other primates

By Steve Horvath, Amin Haghani, Joseph Alan Zoller, Jason Ernst, Matteo Pellegrini, Anna J. Jasinska, Julie A. Mattison, Ken Raj, Adam B Salmon, Susan Jenkins, Cun Li, Peter W. Nathanielsz

Posted 30 Nov 2020
bioRxiv DOI: 10.1101/2020.11.29.402891

DNA methylation data have been successfully used to develop highly accurate estimators of age ("epigenetic clocks") in several mammalian species. With a view of extending epigenetic clocks to primates, we analyzed DNA methylation profiles from five primate species; Papio hamadryas (baboons), Callithrix jacchus (common marmoset), Chlorocebus sabaeus (vervet monkey), Macaca mulatta (rhesus macaque), and Homo sapiens (human). From these we present here, a highly accurate primate epigenetic clock. This clock is based on methylation profiles of CpGs that are highly conserved and are located on a custom methylation array (HorvathMammalMethylChip40). Furthermore, we carried out in-depth analysis of the baboon, as it is evolutionarily the closest primate to humans that can be employed in biomedical research. We present 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 translational capability, we constructed two dual-species, human-baboon clocks, whereby one measures ages of both species in units of years, while the other reports ages relative to the maximum lifespan of the species. Although the primate clock applies to all five primate species, the baboon-specific clocks exhibit only moderate age correlations with other primates. We also provide detailed gene and pathway analyses of individual CpGs that relate to age and sex across different primate species. Ten out of 739 sex related CpGs in primate species are located near 9 autosomal genes (including FAM217A, CDYL, POU3F2, and UHRF2). Overall, this study sheds light on epigenetic aging mechanisms in primates, and the potential influence of sex.

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