Ageing is closely associated with both nutrition and inflammation, and certain neurons can mediate environmental influences on ageing in Caenorhabditis elegans and Drosophila. This study focuses on the hypothalamus, a brain region that is critical for the neuroendocrine interaction between the central nervous system and the periphery. Guo Zhang et al. show that activation of IKK-β and NF-κB in the hypothalamus of mice accelerates the ageing process and shortens lifespan. Inhibition of IKK-β and NF-κB, mediators of metabolic inflammation, delays ageing and extends lifespan. NF-κB activation results in a decline of gonadotropin-releasing hormone (GnRH) levels and suppresses neurogenesis. GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing. These results suggest that NF-κB-mediated inhibition of GnRH may shut down reproduction and ensure the quality of the species, but it initiates systemic ageing at the same time.
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