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Epigenetic clock and DNA methylation studies of roe deer in the wild

By Jean-François Lemaître, Benjamin Rey, Jean-Michel Gaillard, Corinne Régis, Emmanuelle Gilot-Fromont, Maryline Pellerin, Amin Haghani, Joseph Alan Zoller, Caesar Z Li, Steve Horvath

Posted 22 Sep 2020
bioRxiv DOI: 10.1101/2020.09.21.306613

DNA methylation-based biomarkers of aging (epigenetic clocks) promise to lead to new insights in the evolutionary biology of ageing. Relatively little is known about how the natural environment affects epigenetic aging effects in wild species. In this study, we took advantage of a unique long-term (>40 years) longitudinal monitoring of individual roe deer ( Capreolus capreolus ) living in two wild populations (Chizé and Trois Fontaines, France) facing different ecological contexts to investigate the relationship between chronological age and levels of DNA methylation (DNAm). We generated novel DNA methylation data from n=90 blood samples using a custom methylation array (HorvathMammalMethylChip40). We present three DNA methylation-based estimators of age (DNAm or epigenetic age), which were trained in males, females, and both sexes combined. We investigated how sex differences influenced the relationship between DNAm age and chronological age through the use of sex-specific epigenetic clocks. Our results highlight that both populations and sex influence the epigenetic age, with the bias toward a stronger male average age acceleration (i.e. differences between epigenetic age and chronological ages) particularly pronounced in the population facing harsh environmental conditions. Further, we identify the main sites of epigenetic alteration that have distinct aging patterns across the two sexes. These findings open the door to promising avenues of research at the crossroad of evolutionary biology and biogerontology. ### Competing Interest Statement SH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several of his patents from his employer UC Regents. The other authors declare no conflicts of interest.

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