Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB

William Mair, Ianessa Morantte, Ana P. C. Rodrigues, Gerard Manning, Marc Montminy, Reuben J. Shaw () and Andrew Dillin ()
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William Mair: The Salk Institute for Biological Studies
Ianessa Morantte: The Salk Institute for Biological Studies
Ana P. C. Rodrigues: The Salk Institute for Biological Studies
Gerard Manning: The Salk Institute for Biological Studies
Marc Montminy: The Salk Institute for Biological Studies
Reuben J. Shaw: The Salk Institute for Biological Studies
Andrew Dillin: The Salk Institute for Biological Studies

Nature, 2011, vol. 470, issue 7334, 404-408

Abstract: CTRCs as ageing mediators Ageing is slowed, and lifespan extended, in the nematode Caenorhabditis elegans by the activation of the enzyme AMPK (5′ adenosine monophosphate-activated protein kinase) or by inactivation of the protein phosphatase calcineurin. The nature of the related molecular pathways involved has remained unclear, but here it is shown that inhibition of CRTC-1, the sole CREB-regulated transcriptional activator in C. elegans, is required for these life-extending effects. Eliminating the crtc-1 gene increases lifespan in a crh-1 dependent manner, as does elimination of crh-1 (the gene for CREB homologue 1) alone. Downregulation of components in the CRTC/CREB pathway has been shown to confer health benefits to mice, complementing their lifespan effects in worms, and it will be interesting to discover whether CTRCs act as ageing modulators more generally in mammals.

Date: 2011
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DOI: 10.1038/nature09706

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