DNA methylation and hydroxymethylation dynamics in the aging brain and its impact on ischemic stroke

DNA methylation and hydroxymethylation patterns at the 5th carbon of cytosine (5mC and 5hmC) in CpG dinucleotides tightly regulate gene transcription in normal physiology, aging, and associated diseases, including ischemic stroke. Resilience to ischemic brain injury depends on the interplay of diverse neural and non-neural cell types, whose gene expression and identity are predominantly regulated by brain-enriched epigenetic mechanisms, particularly the dynamics of 5mC and 5hmC in response to changing transcriptional demands under ischemic stress. In this review, we discussed the role of 5mC and 5hmC in aging and the pathophysiology of stroke. Given the high degree of inter-individual variability in stroke studies and its multifactorial etiology, we emphasize the need for personalized, temporally controlled, epigenome-based therapies to improve stroke outcomes.