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.

DNA 甲基化是一种充分表征的表观遗传修饰，涉及多种分子和细胞功能。甲基化模式也与衰老机制有关。然而，DNA 甲基化模式如何在参与记忆形成的关键大脑区域以年龄和性别特异性方式发生变化仍不清楚。在这里，我们对年轻和年老小鼠的小鼠背海马进行了还原代表性亚硫酸氢盐测序（RRBS）——这对于特定类型记忆的形成和巩固是必要的。总体而言，我们的研究结果表明，在衰老过程中，背侧海马内的甲基化水平在与 mRNA 功能、转录因子结合位点和基因调控元件相关的基因组特征方面存在性别差异。这些结果定义了跨基因组特征的甲基化组与年龄相关的变化，并为研究以年龄和性别特异性方式受 DNA 甲基化调节的潜在靶基因奠定了基础。