FROM OVERNUTRITION TO BRAIN-GUT ALTERATIONS DURING AGING IN NOTHOBRANCHIUS FURZERI

Overnutrition is associated with chronic inflammation and alterations involving both the central nervous system and the intestine. Hypercaloric diets can induce cognitive impairment through mechanisms including gut microbiota dysbiosis and activation of inflammatory pathways along the gut–brain axis. Several of these changes overlap with hallmarks of aging, suggesting that prolonged caloric excess may promote aging-like features. In this context, Nothobranchius furzeri, a short-lived vertebrate model, represents an ideal system to investigate the long-term effects of overnutrition on the gut–brain axis during aging. In a previous pilot study, we tested different overnutrition conditions and identified the one inducing the most marked central alterations in adult animals (20 weeks post hatching, wph). Based on these findings, in the second phase of the study we maintained this condition up to 27 wph, corresponding to the onset of aging in this species, to assess its long-term effects on brain and gut homeostasis.