Evidence map›Paper›PMID 42135577›Full record

ArticleNature aging2026

Glutamine-driven reductive TCA cycle metabolism supports aged muscle stem cell function via de novo lipogenesis.

David E Lee, Lauren K McKay, Akshay Bareja, JiaCheng Yang, Wentao He, Demitrius A Hill, James R Bain, Shihuan Kuang, Guo-Fang Zhang, Christopher B Newgard and 1 more

Abstract read
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. Article
  2. Article
  3. 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

11 authors.

David E LeeSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
Lauren K McKaySarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
Akshay BarejaSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
JiaCheng YangDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA.
Wentao HeSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
Demitrius A HillSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
James R BainSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
Shihuan KuangDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA.
Guo-Fang ZhangSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-3484-5864
Christopher B NewgardSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-1293-691X
James P WhiteSarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA. james.white@duke.edu.ORCID http://orcid.org/0000-0003-2667-0806

Funding

Resource Core 3 - Metabolomics CoreP30AG028716 · NIA · DUKE UNIVERSITY · PI Virginia B Kraus · 2006 to 2026
$24.6M
Pilot & Feasibility ProgramP30DK124723 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Morgana Lee Mongraw-Chaffin · 2020 to 2026
$11.0M
TRANSFUSION MEDICINE AND RELATED AREAST32HL007057 · NHLBI · DUKE UNIVERSITY · PI Gowthami M Arepally · 1985 to 2026
$10.6M
Metabolic regulation of muscle satellite cell homeostasisR01DK132819 · NIDDK · PURDUE UNIVERSITY · PI Shihuan Kuang · 2023 to 2026
$2.0M
Myogenic Mechanisms of Craniofacial Skeletal Muscle RegenerationK08DE031029 · NIDCR · VIRGINIA COMMONWEALTH UNIVERSITY · PI MCKAY, LAUREN KATZ · 2021 to 2025
$904k
Fibro/Adipogenic Progenitor Metabolic Reprogramming for Age-Related Muscle FibrosisK01AG088232 · NIA · DUKE UNIVERSITY · PI David E. Lee · 2024 to 2026
$489k
Assessing healthspan and epigenetics in aged mice after prolonged exposure to young circulationR21AG065943 · NIA · DUKE UNIVERSITY · PI WHITE, JAMES P. · 2020 to 2021
$443k
NIA NIH HHS K01 AG088232U.S. Department of Health & Human Services | National Institutes of Health (NIH) DK046092U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) T32HL007057U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR) K08DE031029U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) P30DK124723U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK132819U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) K01ag088232U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P30AG028716U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R21AG065943
6 · The paper itself

Abstract

Sarcopenia and the age-related decline in muscular strength and regenerative capacity contribute directly to loss of autonomy, greater risk for hospitalization and healthcare utilization. One contributing cellular phenotype associated with skeletal muscle aging is a loss in the function and number of resident muscle stem cells (MuSCs) or satellite cells. MuSC activation leads to dramatic changes in cellular architecture and metabolic reprogramming, including both mitochondrial biogenesis and increased glycolysis. Despite these changes to increase energy production, high energy demands may not be fully met during periods of MuSC activation. Here we used in vitro and in vivo approaches in mice to demonstrate the function of glutaminase for age-related changes in MuSC function. By combining fluorescence-activated cell sorting (FACS) isolation with metabolomics and stable isotope tracing, we show an age-related decline in reductive (counterclockwise) flux of glutamine through the tricarboxylic acid (TCA) cycle, a pathway by which MuSCs build cellular fatty acid stores as necessary biomass for MuSC function.

Indexed as

AgingCitric Acid CycleGlutamineLipogenesisMuscle, SkeletalSatellite Cells, Skeletal MuscleStem CellsAnimalsGlutaminaseMetabolic ReprogrammingMiceSarcopeniaGlutaminaseGlutamine

Identifiers

PMID42135577
PMCPMC13284908

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.