Epigenetics of Brain Aging

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