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<p>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 – <i>Zmpste24</i><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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月27日

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

摘要

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.