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Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span
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Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span
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Journal Article
Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span
2015
Overview
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 flavincontaining 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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - metabolism
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - metabolism
/ Caenorhabditis elegans - physiology
/ Caenorhabditis elegans Proteins - chemistry
/ Caenorhabditis elegans Proteins - genetics
/ Caenorhabditis elegans Proteins - metabolism
/ Caenorhabditis elegans Proteins - physiology
/ Diet
/ Enzymes
/ Health
/ Hypoxia
/ Mice
/ Receptors, Serotonin - metabolism
/ Transcription Factors - chemistry
