Evidence map›Paper›PMID 41792330›Full record

ArticleNature aging2026

The glycolytic metabolite phosphoenolpyruvate restricts cGAS-driven inflammation to promote healthy aging.

Zengqing Song, Huaibin Hu, Wanpeng Zhang, Xincheng Zheng, Liyun Liang, Bing Zhao, Guangping Song, Jianing Li, Sen Li, Yuqi Wen and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

19 authors.

Zengqing Song *Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China. zqsong@xmail.ncba.ac.cn.ORCID http://orcid.org/0009-0005-5638-4714
Huaibin Hu *Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Wanpeng Zhang *Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Xincheng Zheng *Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Liyun LiangNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Bing ZhaoNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Guangping SongNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Jianing LiNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Sen LiNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Yuqi WenNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Biyu ZhangNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Wen WangNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Guozhen DengDepartment of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Cunjin ZhangDepartment of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.ORCID http://orcid.org/0000-0001-7996-7246
Hua JiangDepartment of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Supei HuNingbo No. 2 Hospital, Ningbo, China.
Haiqing TuNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Min WuNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China.
Huiyan LiNanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, formerly known as National Center of Biomedical Analysis (NCBA), Beijing, China. hyli@ncba.ac.cn.ORCID http://orcid.org/0000-0002-6394-7205

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32341003
6 · The paper itself

Abstract

Aging involves multiple detrimental changes in the systemic milieu, leading to functional deterioration and age-related diseases. However, the potential self-protective adaptive alterations during aging remain underexplored. Here we show that phosphoenolpyruvate (PEP), a glycolytic metabolite, acts as a protective factor against age-related chronic inflammation. Longitudinal analyses in mice and humans reveal a biphasic PEP trajectory, characterized by initial accumulation followed by progressive decline. Blocking PEP accumulation exacerbates inflammation and accelerates aging phenotypes, whereas PEP administration before its decline promotes healthy aging in mice. In aged humans, high PEP levels strongly correlate with lower inflammation and healthier traits. Mechanistically, PEP acts as an endogenous inhibitor of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway by competitively binding to cGAS. Moreover, PEP alleviates neuroinflammation and improves cognitive function in an Alzheimer's disease mouse model. Thus, our findings define PEP accumulation as an evolutionarily conserved geroprotective mechanism, positioning PEP as a promising intervention for aging and associated diseases.

Indexed as

Healthy AgingInflammationNucleotidyltransferasesPhosphoenolpyruvateAgingAlzheimer DiseaseAnimalscGAS-STING Signaling PathwayCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDisease Models, AnimalFemaleGlycolysisHumansMaleMembrane ProteinsMicecGAS protein, humancGAS protein, mouseCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMembrane ProteinsNucleotidyltransferasesPhosphoenolpyruvateSTING Protein

Identifiers

PMID41792330

What OpenQuestion holds

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Registered trials

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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.