Central and Peripheral NPY Age-Related Regulation: A Comparative Analysis in Fish Translational Models

NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the age-related regulation of NPY in the brain and foregut of the shortest- and longest-lived fish species, Nothobranchius furzeri and Danio rerio, respectively. These two research models, despite some similarities, display profound biological differences making them attractive vertebrates to elucidate the mechanisms underlying the regulation of neuropeptide synthesis and function. It is noteworthy that in both fish species only Npya has been identified, while in the other teleosts two classes of NPY (Npya and Npyb) have been annotated. Our findings document that in both species: (i) NPY is centrally regulated; (ii) NPY levels increase in the brain during aging; (iii) NPY is localized in the enteroendocrine cells as well as in the myenteric plexus and drastically decreases in old animals. According to our data, the age-related regulation in the gut resembles that described in other vertebrate species while the increased levels in the brain offer the unique possibility to explore the role of NPY in model organisms to develop future experimental and translatable approaches.