ArticleScience advances2025
Citrulline regulates macrophage metabolism and inflammation to counter aging in mice.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed.
- Ternary mTOR-targeted conductive nanofibrous scaffolds with bioactive peptides orchestrate immune-metabolic-fibrotic balance for diabetic bone regeneration.Bioactive materials · 2026Article
- Genipin induces liver injury by disrupting the CPS1-regulated urea cycle and redox homeostasis.Journal of pharmaceutical analysis · 2026Article
- Review
- Bioadhesive Hydrogel With Polyphenol-Armored Nanogene Rejuvenates Chondrocyte Senescence for Aged Osteoarthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting PLD3 Reverses the Immunosuppressive Niche by Reprogramming Tumor-Associated Macrophages and Potentiates Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Citrulline drives age-related lipid deposition for healthspan.Nature communications · 2026Article
- L-Citrulline: Novel Pharmacotherapy to Improve Outcomes in Infants and Children at Risk of Systemic or Pulmonary Vascular Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Recent advances in nonprotein amino acids: insights from function to biosynthesis.Journal of animal science and biotechnology · 2026Review
- Article
- [Metabolomics study on anti-inflammatory effects of Guanjie Zhentong Babu plaster in collagen-induced arthritis rats].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- Osteolineage cells ablation promotes skin aging phenotypes via dysregulated bone marrow macrophages.iScience · 2026Article
- Acceleration of Lactate Uptake and Utilization Contributes to Neuroprotective Action of FGF21 Involved in Naturally Aging Mice.Aging cell · 2026Article
- Hyperglutaminolysis drives senescence and aging through arginine-mTORC1 axis activation.Signal transduction and targeted therapy · 2026Article
- GLP-1RA Liraglutide Attenuates Sepsis by Modulating Gut Microbiota and Associated Metabolites.Nutrients · 2026Article
- Review
- A Pseudo-Mytilus Edulis Foot Protein-Based Hydrogel Adhesive with Osteo-Vascular-Immune Coupling Effects for Osteoporotic Bone-Implant Integration.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Oral microbiome-SASP-aging axis: mechanisms and targeted intervention strategies for age-related diseases.Journal of oral microbiology · 2026Review
- Transferrin-modified liposomes enhance chemosensitivity in hepatocellular carcinoma by suppressing RDM1-mediated DNA repair.Frontiers in oncology · 2026Article
- Ethyl Acetate Extract ofCurrent issues in molecular biology · 2025Article
- Identification and Molecular Mechanism of Anti-Aging Low-Molecular-Weight Peptides from Quinoa Bran.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic dysregulation and altered metabolite concentrations are widely recognized as key characteristics of aging. Comprehensive exploration of endogenous metabolites that drive aging remains insufficient. Here, we conducted an untargeted metabolomics analysis of aging mice, revealing citrulline as a consistently down-regulated metabolite associated with aging. Systematic investigations demonstrated that citrulline exhibited antiaging effects by reducing cellular senescence, protecting against DNA damage, preventing cell cycle arrest, modulating macrophage metabolism, and mitigating inflammaging. Long-term citrulline supplementation in aged mice yielded beneficial effects and ameliorated age-associated phenotypes. We further elucidated that citrulline acts as an endogenous metabolite antagonist to inflammation, suppressing proinflammatory responses in macrophages. Mechanistically, citrulline served as a potential inhibitor of mammalian target of rapamycin (mTOR) activation in macrophage and regulated the mTOR-hypoxia-inducible factor 1α-glycolysis signaling pathway to counter inflammation and aging. These findings underscore the significance of citrulline deficiency as a driver of aging, highlighting citrulline supplementation as a promising therapeutic intervention to counteract aging-related changes.
Indexed as
Identifiers
What OpenQuestion holds
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.