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

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.

journal_name

Nature

journal_title

Nature

authors

Zhang G,Li J,Purkayastha S,Tang Y,Zhang H,Yin Y,Li B,Liu G,Cai D

doi

10.1038/nature12143

subject

Has Abstract

pub_date

2013-05-09 00:00:00

pages

211-6

issue

7448

eissn

0028-0836

issn

1476-4687

pii

nature12143

journal_volume

497

pub_type

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