One of the least-understood aspects of ageing is its coordinated and stereotyped progression in all organ systems. In this paper, Zhang and colleagues document the integration of inflammatory responses with systemic control of ageing by the hypothalamus. The hypothalamus is important for the development of whole-body ageing in mice, and involves hypothalamic immunity mediated by IκB kinase-β (IKK-β), nuclear factor κB (NF-κB) and related microglia–neuron immune signaling. Ageing retardation and lifespan extension are achieved in mice by preventing ageing-related hypothalamic or brain IKK-β and NF-κB activation. Mechanistic studies further revealed that IKK-β and NF-κB inhibit gonadotropin-releasing hormone (GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing. The authors concluded that the hypothalamus has a programmatic role in ageing development via immune–neuroendocrine integration. Immune inhibition or GnRH restoration in the hypothalamus may represent strategies for optimizing lifespan and combating ageing-related health problems.

Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G, Cai D: Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature doi:10.1038/nature12143  [Epub May 1, 2013].

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