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. The study contains 10 young and 20 aged rats utilized to investigate the epigenetic alterations in the mPFC associated to aging and executive function.