Epigenetics of brain aging

The complexity of human aging and longevity results from a combination of genetic, epigenetic, and environmental factors. Epigenetic mechanisms, including DNA methylation, chromatin structure, and RNA interference, regulate gene expression and control the main metabolic pathways throughout life. This strict epigenetic management becomes progressively defective with age, which increases the risk for the onset of age-related pathologies. This chapter reviews the main alterations of the epigenetic machinery throughout life, with special focus on those affecting the aging brain, as well as the epigenetic control of life span by regulating telomere length and mitochondrial function, with special emphasis on the epigenetic interplay between nuclear and mitochondrial DNA. The last section summarizes the main epigenetic aberrations involving the most prevalent form of pathologic brain deterioration in elderly individuals, Alzheimer's disease, and novel potential epigenetic-based treatments.