Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH

Guo Zhang, Juxue Li, Sudarshana Purkayastha, Yizhe Tang, Hai Zhang, Ye Yin, Bo Li, Gang Liu, Dongsheng Cai

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441 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)211-216
Number of pages6
JournalNature
Volume497
Issue number7448
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

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    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, 497(7448), 211-216. https://doi.org/10.1038/nature12143