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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Science advances
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40053596/ |
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| _version_ | 1868266234551730177 |
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| author | Xie, Zhangdan Lin, Moubin Xing, Beizi Wang, Hongmiao Zhang, Haosong Cai, Zimu Mei, Xinyu Zhu, Zheng-Jiang |
| author_facet | Xie, Zhangdan Lin, Moubin Xing, Beizi Wang, Hongmiao Zhang, Haosong Cai, Zimu Mei, Xinyu Zhu, Zheng-Jiang Xie, Zhangdan Lin, Moubin Xing, Beizi Wang, Hongmiao Zhang, Haosong Cai, Zimu Mei, Xinyu Zhu, Zheng-Jiang |
| collection | PubMed - marine biology |
| contents | Citrulline regulates macrophage metabolism and inflammation to counter aging in mice. Xie, Zhangdan Lin, Moubin Xing, Beizi Wang, Hongmiao Zhang, Haosong Cai, Zimu Mei, Xinyu Zhu, Zheng-Jiang Animals Citrulline Macrophages Mice Aging Inflammation Metabolomics Signal Transduction TOR Serine-Threonine Kinases Cellular Senescence Hypoxia-Inducible Factor 1, alpha Subunit Male 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. |
| format | Artículo científico |
| id | pubmed_40053596 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Science advances |
| record_format | pubmed |
| spellingShingle | Citrulline regulates macrophage metabolism and inflammation to counter aging in mice. Xie, Zhangdan Lin, Moubin Xing, Beizi Wang, Hongmiao Zhang, Haosong Cai, Zimu Mei, Xinyu Zhu, Zheng-Jiang Animals Citrulline Macrophages Mice Aging Inflammation Metabolomics Signal Transduction TOR Serine-Threonine Kinases Cellular Senescence Hypoxia-Inducible Factor 1, alpha Subunit Male Citrulline regulates macrophage metabolism and inflammation to counter aging in mice. Xie, Zhangdan Lin, Moubin Xing, Beizi Wang, Hongmiao Zhang, Haosong Cai, Zimu Mei, Xinyu Zhu, Zheng-Jiang Animals Citrulline Macrophages Mice Aging Inflammation Metabolomics Signal Transduction TOR Serine-Threonine Kinases Cellular Senescence Hypoxia-Inducible Factor 1, alpha Subunit Male 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. |
| title | Citrulline regulates macrophage metabolism and inflammation to counter aging in mice. |
| topic | Animals Citrulline Macrophages Mice Aging Inflammation Metabolomics Signal Transduction TOR Serine-Threonine Kinases Cellular Senescence Hypoxia-Inducible Factor 1, alpha Subunit Male |
| url | https://pubmed.ncbi.nlm.nih.gov/40053596/ |