Neuropeptide Y NPY system as a new target to delay aging

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Restoring neuropetide Y levels in the hypothalamus ameliorates premature aging phenotype in mice

Publication . Ferreira-Marques, Marisa; Carmo Silva, Sara; Pereira, Joana; Botelho, Mariana; Nóbrega, Clévio; López‐Otín, Carlos; Almeida, Luís Pereira de; Aveleira, Célia A.; Cavadas, Cláudia

The 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.

2025-02-27Journal article

Open access