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

Abstract

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 (Chize 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 several 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.

Epigenetic predictors of maximum lifespan and other life history traits in mammals

“…In line with a recent analysis of age-and sex-specific mortality trajectories across mammals 23,24 , the frequency of species for which females outlive males is about twice as high as for species where the opposite pattern is observed (Extended Data Table 1.3). Indeed, females are predicted to have a longer maximum lifespan than males for humans (p=1.E-37, two sample T-test), naked mole rat (p=6.1E-11), vervet monkey (p=0.00012), brown rat (p=0.001), domestic pig (p=0.00014), noctule (p=0.00026), and wapiti elk (p=0.00073).…”

“…However, we report several species where one sex is predicted to live a longer life than the other sex. Some of these predictions could already be validated based on the existing literature 23 . While we focused on maximum lifespan, we also present results for correlated life history traits: gestation time and age at sexual maturity.…”

Development of DNA methylation-based epigenetic age predictors in loblolly pine (Pinus taeda)

“…amplicon sequencing, bait capture techniques) are likely needed if measures of epigenetic age are to be scaled to stand and population applications (Meek & Larson, 2019). Due to the age distributions of our sampled trees, age predictions for our individuals older than 55 years of age were poor, which may have contributed to the greater MAE from our clocks compared to those predicting ages for many vertebrate species (Bertucci et al, 2021;Bors et al, 2021;Lemaître et al, 2020;Meer, Podolskiy, Tyshkovskiy, & Gladyshev, 2018;Stubbs et al, 2017). As we initially removed sites not present in at least 80% of our individuals and many of our trees were within stand ages (Cunningham, n.d.;Li et al, 1999;Stiff & Stansfield, 2003), additional sampling of older trees could allow for retention of higher numbers of cytosine sites whose methylation status remains dynamic in later life, allowing for more accurate age predictions of older trees in further clock studies.…”