| First Author | Zhang G | Year | 2013 |
| Journal | Nature | Volume | 497 |
| Issue | 7448 | Pages | 211-6 |
| PubMed ID | 23636330 | Mgi Jnum | J:198750 |
| Mgi Id | MGI:5499075 | Doi | 10.1038/nature12143 |
| Citation | Zhang G, et al. (2013) Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature 497(7448):211-6 |
| abstractText | 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. |
