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Sex differences in life span 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 for predicting sex biases in longevity.
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This content will become publicly available on May 15, 2026
Sex differences in DNA methylation in bats
Sex-biased longevity is observed across a wide range of animal taxa, including bats, for reasons not well understood. Patterns of cytosine methylation vary predictably with age in many organisms, offering a valuable means to investigate differences in patterns of aging at the molecular level. We tested sex differences in cytosine methylation across 14 bat species and compared patterns of age-associated variation. Sex differences were overrepresented on the X chromosome, showing a strong pattern of female hypermethylation within promoter regions. Sex and age-associated differences in methylation were non-randomly distributed with respect to proximity to putative sex hormone receptor binding sites, with sites hypermethylated in males and females tending to be underrepresented near androgen and estrogen receptor binding sites, respectively. Across species, we observed the relative steepness of male versus female slopes of age-associated variation was associated with the strength of precopulatory sexual selection, with especially strong trends towards male-biased age-associated slopes in two harem-polygynous species that exhibit female-biased longevity. Our results offer insights into how patterns of methylation differ across sexes and ages, and raise intriguing questions for future research, such as whether sex differences in molecular aging reflect sex-biased longevity, for which records in bats are sparse.
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- Award ID(s):
- 2213824
- PAR ID:
- 10592626
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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