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Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH.
|Title||Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G, Cai D|
|Date Published||2013 May 9|
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 IκB kinase-β (IKK-β), nuclear factor κB (NF-κB) 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-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. 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.