Evidence map›Paper›PMID 38787463›Full record

ArticleGeroScience2024

Fmo induction as a tool to screen for pro-longevity drugs.

Shijiao Huang, Rebecca L Cox, Angela Tuckowski, Safa Beydoun, Ajay Bhat, Marshall B Howington, Marjana Sarker, Hillary Miller, Ethan Ruwe, Emily Wang and 8 more

Abstract read
In one paragraph

Article in GeroScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. The Fourth Annual Symposium of the Midwest Aging Consortium.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Shijiao HuangMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA. shijiaoh@ksu.edu.
Rebecca L CoxMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Angela TuckowskiCell and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109, USA.
Safa BeydounMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Ajay BhatMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Marshall B HowingtonCell and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109, USA.
Marjana SarkerMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Hillary MillerMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Ethan RuweMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Emily WangMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Xinna LiDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 316048109-2200, USA.
Emily A GardeaDepartment of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA.
Destiny DeNicolaDepartment of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA.
William PetersonDepartment of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA.
Jeffrey M CarrierDepartment of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA.
Richard A MillerDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 316048109-2200, USA.
George L SutphinDepartment of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA.
Scott F LeiserMolecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA. leiser@umich.edu.ORCID 0000-0002-8003-2955

Funding

Laboratory for Anti-Geric Testing, Evaluation and ResearchU01AG022303 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RICHARD A MILLER · 2003 to 2026
$25.4M
Flavin-containing monooxygenases in endogenous metabolism and agingR01AG075061 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT F LEISER · 2022 to 2026
$2.1M
NIA NIH HHS R01 AG075061NIH HHS R01AG075061
6 · The paper itself

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.

Indexed as

Caenorhabditis elegansLongevityAnimalsCaenorhabditis elegans ProteinsCaloric RestrictionDrug Evaluation, PreclinicalFibroblastsMiceOxygenasesCaenorhabditis elegans Proteinsdimethylaniline monooxygenase (N-oxide forming)OxygenasesC. elegansDietary restrictionDrugsFlavin-containing monooxygenasesFmo-2 inductionHypoxiaLongevity

Identifiers

PMID38787463
PMCPMC11335711

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.