Epigenetic mechanisms in brain aging and their role in cognitive decline and mental health disorders.

The aging brain accumulates increased variability of gene expression over time, in part due to environmental and lifestyle factors that influence an individual's biologic processes underlying healthy and diseased age-related pathology. Targeted by such external factors is the epigenome, a collection of chemical marks on DNA and histone proteins that can change dynamically in response to stimuli and can alter transcriptional machinery to regulate gene expression and protein synthesis. Recent work has revealed epigenetic mechanisms - such as DNA methylation, histone posttranslational modifications, and chromatin remodeling complexes - as key drivers of variation across the genomic landscape in aging. Epigenetic mechanisms integral to cognitive performance and behavior are both permissive and repressive, allowing for either the facilitation or negative regulation of gene expression that enables memory encoding and recall. The epigenome is modified by a large number of molecular processes utilized during the lifespan, which lends itself to exploration of aberrant genetic events accumulated in aging that may contribute to disease. This chapter synthesizes current knowledge in neuroepigenetics as specifically related to age-dependent cognitive processes and discusses new avenues as potential therapeutic or predictive markers for age-related diseases.