DNA Methylation of Synaptic Genes in the Prefrontal Cortex is Associated with Aging and Age-Related Cognitive Impairment

This study investigated the epigenetic mark of DNA methylation in the medial prefrontal cortex (mPFC) as a function of age and cognition. Young and aged F344 rats were characterized in a cognitive flexibility task, set shifting, and whole-genome bisulfite sequencing was performed in an Illumina system.The results indicate that differential methylation was linked to the expression of genes within functional categories which may mediate impaired cognition in aging. Differences in aging included hypermethylation of genes linked to synaptic function and GTPase activity. Further, age-related cognitive flexibility impairment was correlated to hypermethylation of synaptic, postsynaptic density and ion channel activity genes.

本研究以年龄与认知为关联变量，针对内侧前额叶皮层（medial prefrontal cortex, mPFC）的DNA甲基化表观遗传标记展开系统性分析。研究选取年轻及老年F344大鼠，通过认知灵活性任务（含定势转换范式）完成行为表型表征，并采用Illumina测序平台开展全基因组亚硫酸氢盐测序（whole-genome bisulfite sequencing）。结果表明，差异甲基化水平与特定功能类别的基因表达存在显著关联，此类基因或可介导衰老过程中的认知损伤。衰老相关的甲基化差异包括与突触功能及GTP酶活性相关基因的高甲基化。进一步研究发现，年龄相关性认知灵活性损伤与突触、突触后致密物及离子通道活性相关基因的高甲基化呈显著相关。