ArticleAging cell2017
Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.
Article in Aging cell, 2017. 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 113 papers, 2 of them syntheses that pooled it.
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
113 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Topical metformin in wound healing: a comprehensive systematic review of therapeutic outcomes.Archives of dermatological research · 2025Pooled it
- The impact of resveratrol on skin wound healing, scarring, and aging.International wound journal · 2022Pooled it
- Skin aging: mechanisms, evaluation, and rejuvenation.The EMBO journal · 2026Review
- Dysregulated Repair in Aging and Disease: Extracellular Vesicles as an Emerging Protective Strategy.Cells · 2026Review
- Metformin in skin diseases: the role of gut microbiota and immune response.Pharmacological reports : PR · 2026Review
- Effect of resveratrol on the renal cell morphology in acute restraint stress-induced male adult Wistar albino rat model, a pilot study.International urology and nephrology · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Inflammaging and Senescence-Associated Secretory Phenotype (SASP) in Psoriasis - A Narrative Review of Potential Mechanisms and Anti-Inflammaging Strategies.Psoriasis (Auckland, N.Z.) · 2026Review
- Metformin and butyrate attenuate chronic radiation proctitis by alleviating inflammation and macrophage senescence.Frontiers in immunology · 2026Article
- The therapeutic value of antidiabetic drugs in lung cancer treatment: from clinical evidence to possible mechanisms.Frontiers in immunology · 2026Review
- Highly expressed TRIM32 promoted traumatic wound healing by mediating ubiquitination of PIAS1.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Metformin promotes wound healing in senescent fibroblasts by regulating SIRT1 and FAP-α.Histochemistry and cell biology · 2025Article
- L-Tryptophan Produced by Bifidobacterium pseudocatenulatum NCU-08 Delays Aging in SAMP8 Mice by Activating the Sirt1/P53/P21/Rb Signaling Pathway.Aging cell · 2025Article
- From bench to bedside: the research status and application opportunity of extracellular vesicles and their engineering strategies in the treatment of skin defects.Journal of nanobiotechnology · 2025Review
- Mitochondria in cutaneous health, disease, ageing and rejuvenation-the 3PM-guided mitochondria-centric dermatology.The EPMA journal · 2025Article
- Autophagy in Tissue Repair and Regeneration.Cells · 2025Review
- CB-MNCs@ CS/HEC/GP promote wound healing in aged murine pressure ulcer model.Stem cell research & therapy · 2025Article
- Films Based on Chitosan/Konjac Glucomannan Blend Containing Resveratrol for Potential Skin Application.Materials (Basel, Switzerland) · 2025Article
- Development and Evaluation of Trans-Resveratrol-Loaded Transfersomes: Role of Cholesterol in Formulation Design for Dermal Delivery.Nanotechnology, science and applications · 2025Article
- Exosomes derived from minor salivary gland mesenchymal stem cells: a promising novel exosome exhibiting pro-angiogenic and wound healing effects similar to those of adipose-derived stem cell exosomes.Stem cell research & therapy · 2024Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.
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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.