ArticleJournal of advanced research2022
Metformin suppresses vascular smooth muscle cell senescence by promoting autophagic flux.
Article in Journal of advanced research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers.
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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.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Endothelial PARP1 orchestrates endothelial-to-mesenchymal transition via the PARylation of FHL2 in ischaemic heart failure.Acta pharmacologica Sinica · 2026Article
- Metformin Ameliorates Diabetes-Associated Cognitive Dysfunction via p53/Parkin-Mediated Mitophagy.Diabetes, obesity & metabolism · 2026Article
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
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- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Cardiotoxicity induced by multiple myeloma therapies: mechanistic convergence across proteasome inhibitors, CAR-T, and bispecific antibodies.Blood cancer journal · 2026Review
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Senotherapeutics for metabolic disease and diabetic complications.Journal of internal medicine · 2026Review
- Endothelial senescence of the vertebral artery in the context of cervical degeneration: biomechanically driven remodeling of the hemodynamic environment.Frontiers in cell and developmental biology · 2026Review
- Metformin and butyrate attenuate chronic radiation proctitis by alleviating inflammation and macrophage senescence.Frontiers in immunology · 2026Article
- Decoding Vascular Senescence: Cellular Insights and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Targeting Aging and Diseases Associated with Ferroptosis and Senescence Through Modulation of Iron, Oxidative Stress and Lipid Peroxidation.Antioxidants (Basel, Switzerland) · 2025Review
- KDM4A-induced tumor senescence enhances the efficacy of immunotherapy by inhibiting AGT-PHB1 axis-mediated mitophagy in colorectal cancer.Autophagy · 2025Article
- Article
- Neutrophil membrane-camouflaged SiRNA nanoplatform targeting IL-33 attenuates osteoarthritis through autophagy-dependent senescence regulation.Journal of nanobiotechnology · 2025Article
- SOX6 enhances vascular smooth muscle cell phenotypic switching and elevates blood pressure by activating autophagy.Animal models and experimental medicine · 2025Article
- Machine learning models to identify lead compound and substitution optimization to have derived energetics and conformational stability through docking and MD simulations for sphingosine kinase 1.Molecular diversity · 2025Article
- Roadmap for alleviating the manifestations of ageing in the cardiovascular system.Nature reviews. Cardiology · 2025Review
- Spatio-temporal processes in autophagosome-lysosome fusion.Medical review (2021) · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionVascular smooth muscle cell (VSMC) senescence in the vasculature results in vascular aging as well as age-related diseases, while metformin improves the inflamm-aging profile by enhancing autophagy. However, metformin's impact on VSMC senescence is largely undefined.
objectivesTo test the hypothesis that metformin exerts an anti-senescence role by restoring autophagic activity in VSMCs and vascular tissues.
methodsAnimal models established by angiotensin II (Ang II) induction and physiological aging and senescent primary VSMCs from the aortas of elderly patients were treated with metformin. Cellular and vascular senescence were assessed by measuring the amounts of senescence-associated β-galactosidase and senescence markers, including p21 and p53. Autophagy levels were assessed by autophagy-related protein expression, transmission electron microscope, and autolysosome staining. In order to explore the underlying mechanism of the anti-senescence effects of metformin, 4D label-free quantitative proteomics and bioinformatic analyses were conducted, with subsequent experiments validating these findings.
resultsAng II-dependent senescence was suppressed by metformin in VSMCs and vascular tissues. Metformin also significantly improved arterial stiffness and alleviated structural changes in aged arteries, reduced senescence-associated secretory phenotype (SASP), and improved proliferation and migration of senescent VSMCs. Mechanistically, the proteomic analysis indicated that autophagy might contribute to metformin's anti-senescence effects. Reduced autophagic flux was observed in Ang II-induced cellular and vascular senescence; this reduction was reversed by metformin. Specifically, metformin enhanced the autophagic flux at the autophagosome-lysosome fusion level, whereas blockade of autophagosome-lysosome fusion inhibited the anti-senescence effects of metformin.
conclusionsMetformin prevents VSMC and vascular senescence by promoting autolysosome formation.
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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.