Ferreira-Marques, MarisaCarmo Silva, SaraPereira, JoanaBotelho, MarianaNóbrega, ClévioLópez‐Otín, CarlosAlmeida, Luís Pereira deAveleira, Célia A.Cavadas, Cláudia2025-09-302025-09-302025-02-27Ferreira-Marques, M., Carmo-Silva, S., Pereira, J. et al. Restoring neuropetide Y levels in the hypothalamus ameliorates premature aging phenotype in mice. GeroScience (2025). https://doi.org/10.1007/s11357-025-01574-0http://hdl.handle.net/10400.8/14161The 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/s11357-025-01574-02509-2723