ArticleNature aging2021
Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice.
Article in Nature aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 3 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
173 citing papers in PubMed, 3 syntheses or guidelines pooled it, 253 citations in OpenAlex.
- Interplay between frailty and cardiometabolic disorders: from pathophysiology to clinical implications.Cardiovascular diabetology · 2025Pooled it
- Soy Consumption and the Risk of Type 2 Diabetes and Cardiovascular Diseases: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- Meta-analysis links dietary branched-chain amino acids to metabolic health in rodents.BMC biology · 2022Pooled it
- Trial
- 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
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- The Dietary Protein Source Modulates Obesity Development and Induces Distinct Plasma Lipid Profiles and Transcriptome Profiles in Liver and Adipose Tissue.Molecular nutrition & food research · 2026Article
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Amino acid and appendicular skeletal muscle mass insufficiency are associated to cognitive decline in Chinese population.GeroScience · 2026Article
- Article
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Sex differences in response to longevity interventions.Ageing research reviews · 2026Review
- Amino acid-based biological age clock and its implications for human health and aging.Nature communications · 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
113 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
Protein restricted (PR) diets promote health and longevity in many species. While the precise components of a PR diet that mediate the beneficial effects to longevity have not been defined, we recently showed that many metabolic effects of PR can be attributed to reduced dietary levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. Here, we demonstrate that restricting dietary BCAAs increases the survival of two different progeroid mouse models, delays frailty and promotes the metabolic health of wild-type C57BL/6J mice when started in midlife, and leads to a 30% increase in lifespan and a reduction in frailty in male, but not female, wild-type mice when fed lifelong. Our results demonstrate that restricting dietary BCAAs can increase healthspan and longevity in mice, and suggest that reducing dietary BCAAs may hold potential as a translatable intervention to promote healthy aging.
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Registered trials
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.