Global DNA Hypomethylation as a Biomarker of Accelerated Epigenetic Ageing in Primates

IntroductionEpigenetic clocks based on DNA methylation patterns provide a powerful tool for measuring biological ageing, but requiring genome-wide methylation data and high costs limits their broad application across species and populations. MethodsWe investigated whether simply quantifying global DNA methylation levels could serve as an inexpensive proxy for epigenetic ageing, using a captive colony of owl monkeys (Aotus nancymaae) using a colorimetric ELISA assay to measure proportional content of levels of blood and brain 5-methylcytosine (5-mC) across the genome, comparing owl monkeys with known exposures to ageing accelerators and controls. Resultswe found that global 5-mC declined significantly with chronological age in blood, and in the brain of parents. Notably, this age-related blood hypomethylation in individuals experiencing early life maternal rejection was accelerated. Parenting experience also accelerated DNA methylation loss with age, but this effect was specific to the brain and not seen in blood. Infection history did not impact blood 5-mC trajectories. Although multiple regression models did not replicate all findings, likely due to sample size constraints, our results demonstrate that global DNA hypomethylation tracks biological ageing in blood. DiscussionThis simple metric successfully detected accelerated epigenetic ageing induced by early adversity, as well as distinct patterns relating to reproductive investment in the brain - phenotypes typically identified by sophisticated epigenetic clocks. Quantifying global methylation thus provides a cost-effective alternative approach to assessing susceptibility to environmentally-driven accelerated ageing across primate species and populations where DNA methylation arrays or sequencing are impractical.