Fig. 1

Whole-genome analysis of age-related differential methylation in males and females. a Heatmap of age-related differentially methylated regions, age-DMR (Fisher Exact Test with FDR < 0.05, n = 3/group) across all groups. Dot plot showing changes in methylation with aging relative to baseline methylation in young animals in males (b) and females (c). d Overlap between age-DMRs in males and in females and the directionality of methylation changes of common age-DMRs. Pathway enrichment of genes containing age-DMR within their gene body in females (e) and in males (f). Significant enrichment was determined by hypergeometric test (p < 0.05). g, h Over- and under-representation of age-DMRs in genic regions, CpG islands, and regulatory elements in the brain divided by their activation state, and regulatory elements annotated by specific histone marks in males and females. Over- and under-representation were determined using hypergeometric test (p < 0.05)