ArticleJournal of physiology and biochemistry2021
Metformin reverses the effects of high glucose on human dermal fibroblasts of aged skin via downregulating RELA/p65 expression.
Article in Journal of physiology and biochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Potential Utilisation of Secretome from Ascorbic Acid-Supplemented Stem Cells in Combating Skin Aging: Systematic Review of A Novel Idea.Cell journal · 2023Pooled it
- Skin Aging: From Molecular Mechanisms to Therapeutic and Technological Innovations.Journal of cellular and molecular medicine · 2026Review
- Skin aging: mechanisms, evaluation, and rejuvenation.The EMBO journal · 2026Review
- Lawsone modulates oxidative stress, apoptosis, and enhances growth factor expression in human dermal fibroblasts under hyperglycemic conditions.Molecular biology reports · 2026Article
- Metformin in skin diseases: the role of gut microbiota and immune response.Pharmacological reports : PR · 2026Review
- Major Common Hallmarks and Potential Epigenetic Drivers of Wound Chronicity and Recurrence: Hypothesis and Reflections.International journal of molecular sciences · 2025Review
- Skinspan: A Holistic Roadmap for Extending Skin Longevity With Evidence-Based Interventions.Journal of cosmetic dermatology · 2025Review
- Flavonoids in Lotus Stamen Extract Inhibit High Glucose-Induced Intracellular Glycation in Fibroblasts by Upregulating the Expression of Glyoxalase 1 and Alleviating Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Metformin represses the carcinogenesis potentially induced by 50 Hz magnetic fields in aged mouse fibroblasts via inhibition of NF-kB.Journal of cellular and molecular medicine · 2024Article
- Analysis of Biogenic Amines and Small Molecule Metabolites in Human Diabetic Wound Ulcer Exudate.ACS pharmacology & translational science · 2024Article
- Skin Aging and the Upcoming Role of Ferroptosis in Geroscience.International journal of molecular sciences · 2024Review
- Research Progress in Skin Aging, Metabolism, and Related Products.International journal of molecular sciences · 2023Review
- Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections.International journal of molecular sciences · 2023Review
- Τhe Endless Beauty of Metformin: Does It Also Protect from Skin Aging? A Narrative Review.Advances in therapy · 2023Review
- Review
- The Effects of Nutrient Signaling Regulators in Combination with Phytocannabinoids on the Senescence-Associated Phenotype in Human Dermal Fibroblasts.International journal of molecular sciences · 2022Article
- Modeling of the Senescence-Associated Phenotype in Human Skin Fibroblasts.International journal of molecular sciences · 2022Article
- Glucose/ROS cascade-responsive ceria nanozymes for diabetic wound healing.Materials today. Bio · 2022Article
- Evaluation of Skin Biophysical Parameters and Angiogenesis Using CD34 as a Biomarker in Older Diabetic Women Treated with Radiofrequency.Clinical, cosmetic and investigational dermatology · 2022Article
- Adhesive, injectable, and ROS-responsive hybrid polyvinyl alcohol (PVA) hydrogel co-delivers metformin and fibroblast growth factor 21 (FGF21) for enhanced diabetic wound repair.Frontiers in bioengineering and biotechnology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Metformin has been successfully used as an anti-aging agent but exact molecular mechanisms of metformin in anti-aging remain unknown. Hyperglycemia during skin aging not only causes oxidative damage to cellular macromolecules, like dermal collagen, but also modulates the activation of transcription factor nuclear factor kappa B (NF-kB). We aimed to investigate in vitro effects of high glucose (HG) and metformin treatment on proliferation and apoptosis of human primary dermal fibroblasts (HDFs), and the expression of COL1A1, COL3A1, and RELA/p65 genes. Effects of normal glucose (5.5 mM) and HG concentration (50 mM HG) on HDFs, with two doses of metformin (50 μM and 500 μM), were investigated by immunostaining. Apoptotic levels were analyzed by flow cytometry. Expression of COL1A1, COL3A1, and RELA/p65 genes was measured by quantitative real-time PCR. The proliferation of HDFs was decreased significantly (P < 0.01) and expression of COL1A1 was downregulated by HG without metformin, whereas proliferation was elevated and expression was upregulated with 500 μM metformin + HG compared to 5.5 mM glucose (P < 0.05). The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis). Metformin not only significantly downregulated RELA/p65 expression, but also inhibited the apoptosis of HDFs from aged human skin at toxic glucose concentrations which could be inversely mediated via COL1A1 and COL3A1 expression.
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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.