Restoring neuropetide Y levels in the hypothalamus ameliorates premature aging phenotype in mice
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<sup>-/-</sup> 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.
Authors
- Joana Pereira (ORCID: https://orcid.org/0000-0002-0020-2417)
- Sara Carmo‐Silva (ORCID: https://orcid.org/0000-0001-6124-0428)
- Mariana Botelho (ORCID: https://orcid.org/0000-0002-5197-7159)
- Cláudia Cavadas (ORCID: https://orcid.org/0000-0001-8020-9266)
- Célia A. Aveleira (ORCID: https://orcid.org/0000-0002-2191-0682)
- Luís Pereira de Almeida (ORCID: https://orcid.org/0000-0001-5831-3307)
- Clévio Nóbrega (ORCID: https://orcid.org/0000-0002-8312-5292)
- Carlos López-Otı́n (ORCID: https://orcid.org/0000-0001-6964-1904)
- Marisa Ferreira‐Marques (ORCID: https://orcid.org/0000-0002-8740-6411)
Institutions
- Inserm (FR)
- Universidad de Oviedo (ES)
- Instituto Politécnico de Leiria (PT)
- Polytechnic Institute of Coimbra (PT)
- Universidad Nebrija (ES)
- Sorbonne Université (FR)
- Centre de Recherche des Cordeliers (FR)
- Algarve Biomedical Center (PT)
- University of Algarve (PT)
- University of Coimbra (PT)
Publication Details
- Journal
- GeroScience
- Published
- 2025-02-26
- DOI
- https://doi.org/10.1007/s11357-025-01574-0
- Citations
- 2
- Primary Topic
- Regulation of Appetite and Obesity
- Type
- article
- Field-Weighted Citation Impact
- 1.83
Funders
- Progeria Research Foundation
- Ministerio de Ciencia e Innovación
- Universidade de Coimbra
- Fundação para a Ciência e a Tecnologia
- European Regional Development Fund
- H2020 Spreading Excellence and Widening Participation
- HORIZON EUROPE European Research Council