Evidence map›Paper›PMID 40085390›Full record

ArticleGeroScience2025

Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans.

Iman Man Hu, Ana Serna, Stacia Everts, Lale Güngördü, Bauke V Schomakers, Ellen A A Nollen, Arwen W Gao, Riekelt H Houtkooper, Georges E Janssens

Abstract read
In one paragraph

Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Iman Man HuLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Ana SernaLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Stacia EvertsLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Lale GüngördüEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Bauke V SchomakersCore Facility Metabolomics, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Ellen A A NollenEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Arwen W GaoLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Riekelt H HoutkooperLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Georges E JanssensLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. g.e.janssens@amsterdamumc.nl.ORCID 0000-0003-2104-8145

Funding

Velux Stiftung (no. 1063)
6 · The paper itself

Abstract

Aging is a major risk factor for disease, and developing effective pharmaceutical interventions to improve healthspan and promote longevity has become a high priority for society. One of the molecular pathways related to longevity in various model organisms revolves around lowering AKT1 levels. This prompted our in silico drug screen for small molecules capable of mimicking the transcriptional effects of AKT1 knockdown. We found topoisomerase inhibitors as a top candidate longevity-drug class. Evaluating multiple compounds from this class in C. elegans revealed that the topoisomerase inhibitor amonafide has the greatest benefit on healthspan and lifespan. Intriguingly, the longevity effect of amonafide was not solely dependent on DAF-16/FOXO, the canonical pathway for lifespan extension via AKT1 inhibition. We performed RNA-seq on amonafide-treated worms and revealed a more youthful transcriptional signature, including the activation of diverse molecular and cellular defense pathways. We found the mitochondrial unfolded protein response (UPR

Indexed as

Caenorhabditis elegansLongevityTopoisomerase InhibitorsAnimalsCaenorhabditis elegans ProteinsProto-Oncogene Proteins c-aktUnfolded Protein ResponseCaenorhabditis elegans ProteinsProto-Oncogene Proteins c-aktTopoisomerase InhibitorsCaenorhabditis elegansLongevityTopoisomerase inhibitors

Identifiers

PMID40085390
PMCPMC12181488

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.