ArticleCell metabolism2023
Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07329088 (ISOLeucine Addition Treatment Effects), which is not on this map. Cited by 82 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
8.7field-weighted citation impact, top 1% of its field
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.
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.
ISOLeucine Addition Treatment Effects (ISOLATE) in a Controlled Diet Study
Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Efficacy of a High-Protein Diet to Lower Glycemic Levels in Type 2 Diabetes Mellitus: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Effect of henagliflozin on aging biomarkers in patients with type 2 diabetes: A multicenter, randomized, double-blind, placebo-controlled study.Cell reports. Medicine · 2025Trial
- Exercise intensity determines circulating levels of Lac-Phe and other exerkines: a randomized crossover trial.Metabolomics : Official journal of the Metabolomic Society · 2025Trial
- The gut-lung axis and viral pneumonia: Unrevealing the gut microbiota.Pharmaceutical science advances · 2026Review
- Macronutrient mixtures and interactions in health and disease.Nature reviews. Endocrinology · 2026Review
- Balancing essential amino acids in low-protein diets: Impacts on growth performance, amino acid transport, and cecal microbiota in yellow-feathered chickens.Poultry science · 2026Article
- Review
- Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions.Biogerontology · 2026Review
- Intermediate leucine catabolism is associated with longevity and sustained reproduction in grasshoppers.GeroScience · 2026Article
- Adipose FGF21 signalling mediates the anti-senescence effects of protein restriction.The Journal of physiology · 2026Article
- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- The association of frailty with age and lifespan in mice differs by strain and sex.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Sex differences in response to longevity interventions.Ageing research reviews · 2026Review
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Article
- Time-restricted feeding improves functional capacity of adipose-derived stem cells with activation of OSK-associated transcriptional programs.npj aging · 2026Article
- Restriction of Individual Branched-Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 1 country.
Cara L GreenDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Michaela E TrautmanDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Krittisak ChaiyakulDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53705, USA.
Raghav JainDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Yasmine H AlamDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Reji BabygirijaDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Heidi H PakDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Michelle M SonsallaDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Comparative Biomedical Sciences Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Mariah F CalubagDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Chung-Yang YehDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Anneliese BleicherDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Grace NovakDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Teresa T LiuGeorge M. O'Brien Center of Research Excellence, Department of Urology, University of Wisconsin, Madison, WI 93705, USA.
Sarah NewmanDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Will A RickeGeorge M. O'Brien Center of Research Excellence, Department of Urology, University of Wisconsin, Madison, WI 93705, USA.
Kristina A MatkowskyjWilliam S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA; University of Wisconsin Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53705, USA.
Irene M OngDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53705, USA; University of Wisconsin Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53705, USA; Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI 53705, USA.
Cholsoon JangDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Judith SimcoxDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA.
Dudley W LammingDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706, USA; Comparative Biomedical Sciences Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA; University of Wisconsin Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: dlamming@medicine.wisc.edu.
University of Wisconsin–Madison · USUniversity of California, Irvine · USHoward Hughes Medical Institute · US
Funding
UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Justine Yang Bruce · 1985 to 2026
$142.6MWU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1MRole of Beta-Catenin in Urinary DysfunctionU54DK104310 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI RICKE, WILLIAM A · 2014 to 2023
$12.8MProject 3: Modulation of the head and neck tumor immune microenvironment by targeting the TAM family of receptorsP50CA278595 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI David J Beebe · 2022 to 2026
$12.5MProject 4: Role of Receptor Tyrosine Kinase AXL in HNSCC Therapy ResistanceP50DE026787 · NIDCR · UNIVERSITY OF WISCONSIN-MADISON · PI HARARI, PAUL M · 2016 to 2020
$10.8MBiology of Aging and Age-Related Diseases Training GrantT32AG000213 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Rozalyn M. Anderson, Sanjay Asthana · 1991 to 2026
$9.9MThe regulation of health and longevity by branched-chain amino acidsR01AG056771 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Dudley William Lamming · 2018 to 2026
$3.1MUniversity of Wisconsin Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Scholars ProgramK12HD101368 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI BARROILHET, LISA M, BURNSIDE, ELIZABETH S · 2020 to 2023
$2.9MThe regulation of cancer and aging by methionineR01AG084156 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI VINCENT L. CRYNS, JOHN M DENU · 2023 to 2026
$2.5MElucidating hallmarks of aging in the development of lower urinary tract dysfunction (LUTD)R01DK131175 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI RICKE, WILLIAM A · 2021 to 2024
$2.3MThe regulation of health and longevity by branched-chain amino acidsRF1AG056771 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM · 2023 to 2023
$2.1MComparative analysis of geroprotective interventions in established and novel mouse models of Alzheimer's diseaseR01AG062328 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM, MERRINS, MATTHEW J. · 2018 to 2022
$2.0MBLRD VA I01 BX004031NCI NIH HHS P30 CA014520NCI NIH HHS P50 CA278595NIAAA NIH HHS R01 AA029124NIA NIH HHS F31 AG066311NIA NIH HHS F31 AG081115NIA NIH HHS F31 AG082504NIA NIH HHS F32 AG077916NIA NIH HHS K01 AG059899NIA NIH HHS R01 AG056771NIA NIH HHS R01 AG062328NIA NIH HHS R01 AG084156NIA NIH HHS R56 AG056771NIA NIH HHS RF1 AG056771NIA NIH HHS T32 AG000213NIA NIH HHS U01 AG081482NICHD NIH HHS K12 HD101368NIDCR NIH HHS P50 DE026787NIDDK NIH HHS P30 DK020579NIDDK NIH HHS R01 DK125859NIDDK NIH HHS R01 DK131175NIDDK NIH HHS R01 DK133479NIDDK NIH HHS U54 DK104310
Abstract
Low-protein diets promote health and longevity in diverse species. Restriction of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine recapitulates many of these benefits in young C57BL/6J mice. Restriction of dietary isoleucine (IleR) is sufficient to promote metabolic health and is required for many benefits of a low-protein diet in C57BL/6J males. Here, we test the hypothesis that IleR will promote healthy aging in genetically heterogeneous adult UM-HET3 mice. We find that IleR improves metabolic health in young and old HET3 mice, promoting leanness and glycemic control in both sexes, and reprograms hepatic metabolism in a sex-specific manner. IleR reduces frailty and extends the lifespan of male and female mice, but to a greater degree in males. Our results demonstrate that IleR increases healthspan and longevity in genetically diverse mice and suggests that IleR, or pharmaceuticals that mimic this effect, may have potential as a geroprotective intervention.
Indexed as
IsoleucineLongevityAmino Acids, Branched-ChainAnimalsFemaleHealth PromotionMaleMiceMice, Inbred C57BLAmino Acids, Branched-ChainIsoleucineagingbranched-chain amino acidsfrailtyisoleucinelifespanmetabolic healthmicenutritional interventionsprotein restriction
Identifiers
What Socratic holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT07329088ClinicalTrials.gov
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 Socratic graph.