Evidence map›Paper›PMID 41062862›Full record

ArticleNature aging2025

The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan.

Motohiro Sekiya, Kenta Kainoh, Wanpei Chen, Daichi Yamazaki, Tomomi Tsuyuzaki, Yuto Kobari, Ayumi Nakata, Kenji Saito, Nao Aono-Soma, Ali Majid and 10 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature aging, 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. Article
  2. Obesity Disrupts CtBP2-Mediated Maintenance of Transcriptional Equilibrium in Hypothalamic Feeding Circuitry.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    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

20 authors.

Motohiro SekiyaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan. msekiya@md.tsukuba.ac.jp.ORCID http://orcid.org/0000-0002-5170-9699
Kenta KainohDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Wanpei ChenDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Daichi YamazakiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Tomomi TsuyuzakiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Yuto KobariDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Ayumi NakataDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Kenji SaitoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Nao Aono-SomaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Ali MajidDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Hiroshi OhnoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Takafumi MiyamotoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Takashi MatsuzakaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.ORCID http://orcid.org/0000-0002-5898-3463
Rikako NakajimaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Takaaki MatsudaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.ORCID http://orcid.org/0009-0000-8780-8536
Yuki MurayamaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Yoko SuganoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Yoshinori OsakiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.ORCID http://orcid.org/0000-0003-1425-7790
Hitoshi IwasakiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Hitoshi ShimanoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.ORCID http://orcid.org/0000-0002-5562-5572

Funding

Japan Agency for Medical Research and Development (AMED) JP18gm5910007Japan Agency for Medical Research and Development (AMED) JP22ek0210175Japan Agency for Medical Research and Development (AMED) JP25gm6710004MEXT | Japan Society for the Promotion of Science (JSPS) 20K08855MEXT | Japan Society for the Promotion of Science (JSPS) 23K18270
6 · The paper itself

Abstract

Within each cell, metabolite-sensing factors respond to coordinate metabolic homeostasis. How metabolic homeostasis is regulated intercellularly and how this may become dysregulated with age, however, remains underexplored. Here we describe a system regulated by a metabolite sensor, CtBP2. CtBP2 is secreted via exosomes in response to reductive metabolism, which is suppressed by oxidative stress. Exosomal CtBP2 administration extends lifespan in aged mice and improves healthspan in particular by reducing frailty. Mechanistically, we identify activation of CYB5R3 and AMPK downstream of exosomal CtBP2. Consistently, serum CtBP2 levels decrease with age and are negatively associated with cardiovascular disease incidence in humans yet are elevated in individuals from families with a history of longevity. Together our findings define a CtBP2-mediated metabolic system with potential for future clinical applications.

Indexed as

Alcohol OxidoreductasesCo-Repressor ProteinsHealthy AgingLongevityAnimalsCardiovascular DiseasesFemaleHumansMaleMiceMice, Inbred C57BLOxidative StressAlcohol OxidoreductasesCo-Repressor ProteinsCTBP2 protein, humanCtbp2 protein, mouse

Identifiers

PMID41062862

What OpenQuestion holds

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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.