Authors: Zhang G; Li J; Purkayastha S; Tang Y; Zhang H; Yin Y; Li B; Liu G; Cai D
Abstract: Ageing is a result of gradual and overall functional deteriorations across the body; however, it is unknown whether an individual tissue primarily works to mediate the ageing progress and control lifespan. Here we show that the hypothalamus is important for the development of whole-body ageing in mice, and that the underlying basis involves hypothalamic immunity mediated by IkappaB kinase-beta (IKK-beta), nuclear factor kappaB (NF-kappaB) and related microglia-neuron immune crosstalk. Several interventional models were developed showing that ageing retardation and lifespan extension are achieved in mice by preventing ageing-related hypothalamic or brain IKK-beta and NF-kappaB activation. Mechanistic studies further revealed that IKK-beta and NF-kappaB inhibit gonadotropin-releasing hormone (GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing. In conclusion, the hypothalamus has a programmatic role in ageing development via immune-neuroendocrine integration, and immune inhibition or GnRH restoration in the hypothalamus/brain represent two potential strategies for optimizing lifespan and combating ageing-related health problems.
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Journal: Nature Date: May 3, 2013 PMID: 23636330 |
Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G, Cai D (2013) Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature.
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