Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unre-paired damaged DNA,which leads to neuronal death. In this way,DNA damage has been implicated in the pathogenesis of neurological disorders,cancer,and aging. Lifestyle factors,such as physical exercise,are neuroprotective and increase brain function by improving cognition,leing,and memory,in addition to regulating the cellular redox milieu. Several mechanisms are associated with the effects of exercise in the brain,such as reduced production of oxidants,up-regulation of antioxidant capacity,and a consequent decrease in nuclear DNA damage. Furthermore,physical exercise is a potential strategy for further DNA damage repair. However,the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown. In this review,we discuss the influence of exercise on DNA damage and adjacent mech-anisms in the brain. We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage.