Evidence map›Paper›PMID 40163476›Full record

ArticlePLoS genetics2025

Doxifluridine promotes host longevity through bacterial metabolism.

Rui Wei, Yuling Peng, Yamei Luo, Xinyuan Wang, Zhenzhong Pan, Ran Zhou, Huan Yang, Zongyao Huang, Yaojia Liu, Lunzhi Dai and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

12 authors.

Rui WeiState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yuling PengState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yamei LuoState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xinyuan WangProteomics-Metabolomics Platform of Core Facilities, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0003-3621-8151
Zhenzhong PanState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Ran ZhouState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0002-8175-2508
Huan YangState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Zongyao HuangState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yaojia LiuState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Lunzhi DaiState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yuan WangState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0002-6324-6134
Yan ZhangState Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0002-6041-4454

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aging is associated with alternative splicing (AS) defects that have broad implications on aging-associated disorders. However, which drug(s) can rescue age-related AS defects and extend lifespan has not been systematically explored. We performed large-scale compound screening in C. elegans using a dual-fluorescent splicing reporter system. Among the top hits, doxifluridine, a fluoropyrimidine derivative, rescues age-associated AS defects and extends lifespan. Combining bacterial DNA sequencing, proteomics, metabolomics and the three-way screen system, we further revealed that bacterial ribonucleotide metabolism plays an essential role in doxifluridine conversion and efficacy. Furthermore, doxifluridine increases production of bacterial metabolites, such as linoleic acid and agmatine, to prolong host lifespan. Together, our results identify doxifluridine as a potent lead compound for rescuing aging-associated AS defects and extending lifespan, and elucidate drug's functions through complex interplay among drug, bacteria and host.

Indexed as

BacteriaCaenorhabditis elegansFloxuridineLongevityAgingAlternative SplicingAnimalsFloxuridine

Identifiers

PMID40163476
PMCPMC11977963

What OpenQuestion holds

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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.