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Updated: Jun 24, 2026
A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans
Published on: March 20, 2018
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.
Abstract:
Dietary restriction (DR) and hypoxia (low oxygen) extend lifespan in Caenorhabditis elegans through the induction of a convergent downstream longevity gene, fmo-2. Flavin-containing monooxygenases (FMOs) are highly conserved xenobiotic-metabolizing enzymes with a clear role in promoting longevity in nematodes and a plausible similar role in mammals. This makes them an attractive potential target of small molecule drugs to stimulate the health-promoting effects of longevity pathways. Here, we utilize an fmo-2 fluorescent transcriptional reporter in C. elegans to screen a set of 80 compounds previously shown to improve stress resistance in mouse fibroblasts. Our data show that 19 compounds significantly induce fmo-2, and 10 of the compounds induce fmo-2 more than twofold. Interestingly, 9 of the 10 high fmo-2 inducers also extend lifespan in C. elegans. Two of these drugs, mitochondrial respiration chain complex inhibitors, interact with the hypoxia pathway to induce fmo-2, whereas two dopamine receptor type 2 (DRD2) antagonists interact with the DR pathway to induce fmo-2, indicating that dopamine signaling is involved in DR-mediated fmo-2 induction. Together, our data identify nine drugs that each (1) increase stress resistance in mouse fibroblasts, (2) induce fmo-2 in C. elegans, and (3) extend nematode lifespan, some through known longevity pathways. These results define fmo-2 induction as a viable approach to identifying and understanding mechanisms of putative longevity compounds.
Insights
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.
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.
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