Evidence map›Paper›PMID 41417787›Full record

ArticlePLoS biology2025

Aging-related peroxisomal dysregulation disrupts intestinal stem cell differentiation through alterations of very long-chain fatty acid oxidation.

Xiaoxin Guo, Gang Du, Juanyu Zhou, Fang Fu, Yu Yuan, Xingzhu Liu, Haiou Chen, Qianyi Wan, Bo Gong, Haiyang Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

10 authors.

Xiaoxin GuoWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Gang DuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
Juanyu ZhouWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Fang FuWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yu YuanWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xingzhu LiuWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Haiou ChenWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Qianyi WanWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Bo GongGenetic Diseases Key Laboratory of Sichuan Province, Department of Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Haiyang ChenWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID 0000-0001-8305-4060

Funding

National Key R&D Program of ChinaNational Natural Science Foundation of ChinaSichuan Provincial Natural Science FoundationSichuan Science and Technology ProgramThe Project of China Postdoctoral Science Foundation
6 · The paper itself

Abstract

Aging disrupts intestinal stem cell (ISC) lineage fidelity, impairing epithelial barrier function and then promoting systemic health decline. In this study, we identify peroxisomal dysfunction as a critical driver of age-associated ISC mis-differentiation. Using Drosophila and mouse colonic organoids, we demonstrate that reduced PEX5 expression in aged ISCs impairs peroxisomal matrix protein import, leading to very long-chain fatty acids (VLCFAs) accumulation. In addition, we found that RAB7-dependent late endosome maturation and SOX21A were downstream of the peroxisome in controlling aged ISC differentiation. Aspirin, a classic anti-inflammatory drug, restores ISC lineage fidelity by enhancing PEX5-mediated peroxisomal β-oxidation of VLCFAs. Taken together, these findings highlight peroxisomal dysfunction and VLCFA metabolism as pivotal regulators of ISC aging and suggest new therapeutic strategies for combating age-related intestinal decline.

Indexed as

AgingCell DifferentiationFatty AcidsIntestinesPeroxisomesStem CellsAnimalsDrosophila melanogasterDrosophila ProteinsIntestinal MucosaMiceOxidation-ReductionDrosophila ProteinsFatty Acids

Identifiers

PMID41417787
PMCPMC12716710

What OpenQuestion holds

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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.