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

Research output: Contribution to journalArticle

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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 - 2013

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Gonadotropin-Releasing Hormone
Hypothalamus
Pituitary Hormone-Releasing Hormones
Neurogenesis
Brain
Microglia
Immunity
Phosphotransferases
Neurons
Health

ASJC Scopus subject areas

  • General

Cite this

Zhang, G., Li, J., Purkayastha, S., Tang, Y., Zhang, H., Yin, Y., ... 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

Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. / Zhang, Guo; Li, Juxue; Purkayastha, Sudarshana; Tang, Yizhe; Zhang, Hai; Yin, Ye; Li, Bo; Liu, Gang; Cai, Dongsheng.

In: Nature, Vol. 497, No. 7448, 2013, p. 211-216.

Research output: Contribution to journalArticle

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, vol. 497, no. 7448, pp. 211-216. https://doi.org/10.1038/nature12143
Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature. 2013;497(7448):211-216. https://doi.org/10.1038/nature12143
Zhang, Guo ; Li, Juxue ; Purkayastha, Sudarshana ; Tang, Yizhe ; Zhang, Hai ; Yin, Ye ; Li, Bo ; Liu, Gang ; Cai, Dongsheng. / Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. In: Nature. 2013 ; Vol. 497, No. 7448. pp. 211-216.
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