Ferreira-Marques, MarisaCarmo-Silva, SaraPereira, JoanaBotelho, MarianaNóbrega, ClévioLópez‐Otín, CarlosAlmeida, Luís Pereira deAveleira, Célia A.Cavadas, Cláudia2026-04-082026-04-082025-02-272509-2723http://hdl.handle.net/10400.1/28620The hypothalamus has been recognized as a regulator of whole-body aging. Neuropeptide Y (NPY), highly abundant in the central nervous system and produced by the hypothalamus, enhances autophagy in this brain region and mediates autophagy triggered by caloric restriction, suggesting a potential role as a caloric restriction mimetic and an aging regulator. Considering that hypothalamic NPY levels decline during aging, we investigated if reestablishment of NPY levels mitigate aging phenotype, using a mouse model of premature aging – Zmpste24−/− mouse. The results show that reestablishing hypothalamic NPY levels delayed aging-associated features, including lipodystrophy, alopecia, and memory. Moreover, these results suggest that strategies that promote maintenance of hypothalamic NPY levels might be relevant to counteract aging progression and age-related deteriorations.engBiology of agingBrain agingHypothalamusNeuropeptide Yjournal article10.1007/s11357-025-01574-0