Examining age-dependent DNA methylation patterns and gene expression in the male and female mouse hippocampus

DNA methylation is a well-characterized epigenetic modification involved in numerous molecular and cellular functions. Methylation patterns have also been associated with aging mechanisms. However, how DNA methylation patterns change within key brain regions involved in memory formation in an age-and sex-specific manner remains unclear. Here, we performed reduced representation bisulfite sequencing (RRBS) from mouse dorsal hippocampus – which is necessary for the formation and consolidation of specific types of memories – in young and aging mice of both sexes. Overall, our findings demonstrate that methylation levels within the dorsal hippocampus are divergent between sexes during aging in genomic features correlating to mRNA functionality, transcription factor binding sites, and gene regulatory elements. These results define age-related changes in the methylome across genomic features and build a foundation for investigating potential target genes regulated by DNA methylation in an age- and sex-specific manner.