Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation.

摘要: Brain aging is marked by cognitive decline and susceptibility to neurodegeneration. Caloric-restriction (CR) increases neurogenesis, improves memory function, protects from age-associated neurological disorders. Epigenetic mechanisms, including DNA methylation, are vital normal CNS cellular functions, dysregulated with aging. The beneficial effects of CR have been proposed work through epigenetic processes, but this largely unexplored. We therefore tested whether life-long prevents age-related methylation changes in the brain. Hippocampal young (3 months) old (24 male mice fed ad libitum 24 month a 40% calorie-restricted diet 3 months age were examined genome-wide bisulfite sequencing measure base-specificity. Over 27 million CG CH (non-CG) sites examined. Of ~40,000 differentially methylated CGs (dmCGs) ~80,000 CHs (dmCHs) aging, >1/3 prevented found across genomic regulatory regions gene pathways. also caused alterations at not these CR-specific demonstrated different pattern element pathway enrichment than those affected DNMT1 TET3 promoter hypermethylation corresponded reduced expression. These findings demonstrate that attenuates hippocampal changes, combination may contribute neuroprotective CR. prevention consistent pro-longevity working an mechanism.