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Science. 2015 Dec 11;350(6266):1375-1378. doi: 10.1126/science.aac9257. Epub 2015 Nov 19.

Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span.

Author information

1
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
2
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
#
Contributed equally

Abstract

Stabilization of the hypoxia-inducible factor 1 (HIF-1) increases life span and health span in nematodes through an unknown mechanism. We report that neuronal stabilization of HIF-1 mediates these effects in Caenorhabditis elegans through a cell nonautonomous signal to the intestine, which results in activation of the xenobiotic detoxification enzyme flavin-containing monooxygenase-2 (FMO-2). This prolongevity signal requires the serotonin biosynthetic enzyme TPH-1 in neurons and the serotonin receptor SER-7 in the intestine. Intestinal FMO-2 is also activated by dietary restriction (DR) and is necessary for DR-mediated life-span extension, which suggests that this enzyme represents a point of convergence for two distinct longevity pathways. FMOs are conserved in eukaryotes and induced by multiple life span-extending interventions in mice, which suggests that these enzymes may play a critical role in promoting health and longevity across phyla.

PMID:
26586189
PMCID:
PMC4801033
DOI:
10.1126/science.aac9257
[Indexed for MEDLINE]
Free PMC Article

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