Aging is a gradual process during which molecular and cellular processes deteriorate progressively, often leading to such pathological conditions as vascular and metabolic disorders and cognitive decline. Although the mechanisms of aging are not yet fully understood, inflammation, oxidative damage, mitochondrial dysfunction, functional alterations in specific neuronal circuits and a restricted degree of apoptosis are involved. Physical exercise improves the efficiency of the capillary system and increases the oxygen supply to the brain, thus enhancing metabolic activity and oxygen intake in neurons, and increases neurotrophin levels and resistance to stress. Regular exercise and an active lifestyle during adulthood have been associated with reduced risk and protective effects for mild cognitive impairment and Alzheimer's disease. Similarly, studies in animal models show that physical activity has positive physiological and cognitive effects that correlate with changes in transcriptional profiles. According to numerous studies, epigenetic events that include changes in DNA methylation patterns, histone modification and alterations in microRNA profiles seem to be a signature of aging. Hence, insight into the epigenetic mechanisms involved in the aging process and their modulation through lifestyle interventions such as physical exercise might open new avenues for the development of preventive and therapeutic strategies to treat aging-related diseases. © 2011 Elsevier B.V.