Since the industrial revolution, the level of physical activity drastically declined while the amount of ingested calories increased and those of essential omega-3 fatty acids (w3) decreased. Physical activity, caloric intake and w3 are beneficial for health and survival. However, no study tried to identify the interactions between these parameters, and given their importance, we hypothesize that a strong synergistic effect may exist between them. We thus propose to test the effects of a multi-modal intervention combining chronic caloric restriction (CR), physical activity (ACT) and optimal w3 levels on longevity and brain ageing in a primate (Microcebus murinus). The three interventions will be applied either individually (ACT, CR, w3) or in interaction (ACT/CR/w3, ACT/w3, ACT/CR, CR/w3). The project will focus on age-related neurodegeneration in link with cognitive functions and metabolic disorders. For the first time in mouse lemur, we will use non-invasive methods to evaluate biomarkers of central nervous system alterations, based on retina study, through the emerging concept of “the eye as a window to the brain”. A lower rate of age-related pathologies and extended lifespan are expected in the group receiving the three treatments. This synergistic approach represents new avenues to an optimal longevity.