ArticleNutrients2022
Leucine Supplementation in Middle-Aged Male Mice Improved Aging-Induced Vascular Remodeling and Dysfunction via Activating the Sirt1-Foxo1 Axis.
Article in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Glucose and Lipid Metabolic Mechanisms in Vascular Aging and Related Therapeutic Strategies.Reviews in cardiovascular medicine · 2026Review
- Preventive and Ameliorative Effects of Alanine Supplementation on High-Fat Diet-Induced Obesity and Metabolic Dysfunction via the Gut-Liver-Adipose Axis in C57BL/6J Mice.Foods (Basel, Switzerland) · 2026Article
- Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis.Cell death discovery · 2025Review
- L-Glutamate enables the EGFR-MEK-ERK-mTFB2 axis to enhance mitochondrial biogenesis in intestinal stem cells.Stem cell research & therapy · 2025Article
- The Mechanism and Potential Therapeutic Strategies of Vascular Aging.Aging medicine (Milton (N.S.W)) · 2025Review
- Can Sirtuin 1 Serve as a Therapeutic Target in Pulmonary Arterial Hypertension? A Comprehensive Review.Molecules (Basel, Switzerland) · 2025Review
- Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging.Biogerontology · 2025Review
- Comparative metabolomic analysis of mouse plasma in response to different dietary conditions.Food science and biotechnology · 2024Article
- Protein Intake Is Associated with Blood Pressure and Cholesterol Levels in Italian Older Adults: A Cross-Sectional Study.Metabolites · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular aging is associated with metabolic remodeling, and most studies focused on fatty acid and glucose metabolism. Based on our metabolomic data, leucine was significantly reduced in the aortas of aged mice. Whether leucine supplementation can reverse aging-induced vascular remodeling remains unknown. To investigate the effectiveness of leucine, male mice at 15 or 18 months were supplemented with leucine (1.5%) for 3 months. All the aged mice, with or without leucine, were sacrificed at 21 months. Blood pressure and vascular relaxation were measured. H&E, Masson's trichrome, and Elastica van Gieson staining were used to assess aortic morphology. Vascular inflammation, reactive oxidative stress (ROS), and vascular smooth muscle cell (VSMC) phenotype were also measured in mouse aortas. Compared with the 21-month-old mice without leucine, leucine supplementation from 15 months significantly improved vascular relaxation, maintained the contractile phenotype of VSMCs, and repressed vascular inflammation and ROS levels. These benefits were not observed in the mice supplemented with leucine starting from 18 months, which was likely due to the reduction in leucine transporters Slc3a2 or Slc7a5 at 18 months. Furthermore, we found benefits from leucine via activating the Sirt1-induced Foxo1 deacetylation. Our findings indicated that leucine supplementation in middle-aged mice improved aging-induced vascular remodeling and dysfunction.
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