Despite the active research in this field, molecular mechanisms underlying exercise-induced beneficial effects on brain function are still matter of debate, especially with regard to those concerning the onset and progression of hippocampal aging in individuals unfamiliar with exercise. Since such effects seem to be mediated by changes in antioxidative, antiglycative and metabolic status within the brain, a possible exercise-induced coordinated response involving redox, methylglyoxal- and sirtuin-related molecular networks may be hypothesized.

 Our findings suggested that the 4-mo regular running lowered the chance of dicarbonyl and oxidative stress, activated mitochondrial catabolism and preserved sirtuin1-related neuroprotection, yet the same cellular pathways were negatively affected by the first 2 months of exercise, thus showing an interesting exercise-induced biphasic response.

This research revealed important details of the interaction between exercise and mammal hippocampus during the transition from mature to middle age, and this may help to develop non-pharmacological approaches aimed at retarding brain senescence, even in individuals unfamiliar with physical activity.