The lifestyle affects all organisms and organs, including the brain, and cognition is affected as well. Although many of these effects occur through epigenetic mechanisms, they are not the only ones, but the most studied and potentially useful, as modifying them can lead to significant benefits. Today, we will focus on the effects of physical exercise on cognition in mice, analyzing both microRNAs and the microbiota, mitochondria, as well as their inter- and transgenerational transmission. Specifically, we will analyze the attempt to find brain region-specific microRNA signatures of either sedentary or exercised lifestyle, the features of the hormetic profile of exercise-induced effects on cognition and its potential molecular mechanisms, the involvement of some specific families of bacteria, and whether the exercise effects can be transgenerationally transmitted. The effects of the amount and intensity of exercise on the brain have been scarcely analyzed, and together with the transgenerational potential, all together points to a list of mechanisms of exercise influences as long as promising in the field of lifestyle and health.

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