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Related Experiment Video

Updated: Jun 24, 2026

A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans
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Fmo induction as a tool to screen for pro-longevity drugs.

Shijiao Huang1, Rebecca L Cox2, Angela Tuckowski3

  • 1Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA. shijiaoh@ksu.edu.

Geroscience
|May 24, 2024
PubMed
Summary

Dietary restriction and hypoxia extend lifespan by inducing the longevity gene fmo-2. A screen identified nine compounds that induce fmo-2, enhance stress resistance, and extend lifespan in C. elegans.

Keywords:
C. elegansFmo-2 inductionDietary restrictionDrugsFlavin-containing monooxygenasesHypoxiaLongevity

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Area of Science:

  • Biochemistry
  • Genetics
  • Gerontology

Background:

  • Dietary restriction (DR) and hypoxia are known longevity pathways in C. elegans.
  • These pathways converge on the induction of the flavin-containing monooxygenase gene, fmo-2.
  • FMOs are conserved enzymes with potential roles in mammalian longevity.

Purpose of the Study:

  • To screen compounds for their ability to induce fmo-2 expression.
  • To identify small molecules that activate longevity pathways.
  • To investigate the mechanisms of DR- and hypoxia-mediated fmo-2 induction.

Main Methods:

  • Utilized an fmo-2 fluorescent transcriptional reporter in C. elegans.
  • Screened 80 compounds known to improve stress resistance in mouse fibroblasts.
  • Assessed compound effects on fmo-2 induction and C. elegans lifespan.

Main Results:

  • 19 out of 80 compounds significantly induced fmo-2 expression.
  • 10 compounds induced fmo-2 more than twofold.
  • 9 of these compounds also extended lifespan in C. elegans.
  • Mitochondrial inhibitors and DRD2 antagonists were identified as inducers of fmo-2, revealing links to hypoxia and dopamine signaling pathways.

Conclusions:

  • fmo-2 induction is a viable strategy for identifying potential longevity compounds.
  • Nine identified drugs enhance stress resistance, induce fmo-2, and extend lifespan.
  • Dopamine signaling plays a role in DR-mediated fmo-2 induction.