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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Intestines / enzymology*
  • Longevity / genetics
  • Longevity / physiology*
  • Mice
  • Neurons / metabolism*
  • Oxygenases / genetics
  • Oxygenases / physiology*
  • Protein Stability
  • RNA Interference
  • Receptors, Serotonin / metabolism
  • Signal Transduction
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Tryptophan Hydroxylase / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • HIF-1 protein, C elegans
  • HLH-30 protein, C elegans
  • Receptors, Serotonin
  • Transcription Factors
  • serotonin 7 receptor
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • Tryptophan Hydroxylase