Sex‐Chromosome‐Dependent Ageing in Female Heterogametic Methylomes

Recent research in humans and both model and non‐model animals has shown that DNA methylation (DNAm), an epigenetic modification, is one of the mechanisms underlying the ageing process. DNAm‐based indices predict mortality and provide valuable insights into biological ageing mechanisms. Although sex‐dependent differences in lifespan are ubiquitous and sex chromosomes are thought to play an important role in sex‐specific ageing, they have been largely ignored in epigenetic ageing studies. We characterised the genome‐wide distribution of age‐related CpG (Cytosine‐phosphate‐Guanine) sites from longitudinal samples in two avian species (zebra finch and jackdaw), including for the first time the avian sex chromosomes (Z and the female‐specific, haploid W). In both species, we find a small fraction of the CpG sites to show age‐related changes in DNAm with the majority of them being located on the haploid, female‐specific W chromosome, where DNAm levels predominantly decrease with age. Age‐related CpG sites were over‐represented on the zebra finch but under‐represented on the jackdaw Z chromosome. Our results highlight distinct age‐related changes in sex chromosome DNAm compared to the rest of the genome in two avian species, suggesting this previously understudied feature of sex chromosomes may be instrumental in sex‐dependent ageing. Moreover, studying the DNAm of sex chromosomes might be particularly useful in ageing research, facilitating the identification of shared (sex‐dependent) age‐related pathways and processes between phylogenetically diverse organisms.