Abstract
The orexinergic system is anatomically and functionally conserved in almost all vertebrates, and the role in healthy ageing and age-associated diseases has been studied in mammals. Here, we review the main findings on the age-related regulation of orexinergic system in mammals, including human patients and highlights how the fish Nothobranchius furzeri serves as an exceptional model to spearhead research and unravel the intricate mechanisms underlying orexinergic regulation during ageing. The ageing brain of this teleost is characterized by the presence of neurodegenerative processes similar to those associated with human pathologies rather than those of healthy ageing. We present an in-depth summary and discussion on the groundbreaking advances in understanding the neuroanatomical organization of the orexinergic system, its pivotal role in mammalian and fish models, and its profound involvement in healthy ageing and age-associated diseases.