Aging and obesity changes the central and peripheral chemical sensory perception in African turquoise killifish.

Morphophysiological changes in the chemical senses are well investigated in research in human elderly, as well as considered key factors in the development of obesity [1]. Key biological mechanisms underlying these changes have been largely hypothesized and not completely understood. The aims of our research are to broaden knowledge on the interplay of chemical senses in the metabolic control via nutrient-sensing mechanism under two different physiologically altered metabolic conditions, aging and overfeeding. At this aim, we carried out our study in the model Nothobranchius furzeri, the shortest-lived vertebrate that can be bred in captivity [2], coupling behavioral observations, western blot and immunohistochemical analyses. In vivo observations confirmed a remarkable difference in the food selection: old and obese fish did not discriminate among different types of food, while young and normal fed subjects demonstrated a clear selectivity. For ex vivo analyses, we mainly focused on the brain and taste buds in oral cavity, respectively involved in the central and peripheral chemical sensory perception, and we collected samples of animals at 16 weeks old (normal fed and overfed) and 52 weeks (old animals). We investigated key chemoattractant-mediated signal transduction (i.e. PLCB2, TRPM5) and NPY, an appetite-related neuropeptide with functional role in aging [3-4] and obesity . At central level, mainly in the hypothalamus, we observed occurrence of a) TRPM5 in all experimental groups; b) PLCB2 in adults and obese, and drastic reduction in old fish; c) NPY in all brain samples with a sharp increase in the old. In the taste buds, we observed a homogeneous distribution of TRPM5 and PLCB2 without evident differences among groups, and a decrease of NPY in old animals. Our results suggest i) a physiological age-related decrease of taste receptors at central level, in line with the behavioral observations of low food selectivity; ii) an increase of PLCB2 at central level supporting the hypothesis that overfeeding continuously activates receptors, while we suppose that the peripheral perception of taste is reduced likely due to a lack of satiety feedback, which leads animals to feed continuously; iii) the age-related different central and peripheral regulation of NPY which prompts for a clear role of NPY in the peripheral sensorineural decline. Altogether, these preliminary data may have many implications for translational research into nutrition, aging and obesity.