DNA methylation-based age prediction and sex-specific epigenetic aging in a lizard with female-biased longevity

Sex differences in lifespan are widespread across animal taxa, but their causes remain unresolved. Alterations to the epigenome are hypothesized to contribute to vertebrate aging, and DNA methylation-based aging clocks allow for quantitative estimation of biological aging trajectories. Here, we investigate the influence of age, sex, and their interaction on genome-wide DNA methylation patterns in the brown anole (Anolis sagrei), a lizard with pronounced female-biased survival and longevity. We develop a series of age predictor models and find that, contrary to our predictions, rates of epigenetic aging were not slower in female lizards. However, methylation states at loci acquiring age-associated changes appear to be more “youthful” in young females, suggesting that female DNA methylomes are preemptively fortified in early life in opposition to the direction of age-related drift. Collectively, our findings provide insights into epigenetic aging in reptiles and suggest that early-life epigenetic profiles may be more informative than rates of change over time for predicting sex biases in longevity. Genome-wide enzymatic methylation sequencing data from 40 individual Anolis sagrei were sequenced to a target coverage depth on 5x. Sampled individuals included representation from both sexes across six distinct ages, ranging from one month to five years. The resuting methylation data was used to examine how age and sex interact to pattern the sagrei methylome.