ArticleInternational journal of molecular sciences2023
Melatonin Exerts Prominent, Differential Epidermal and Dermal Anti-Aging Properties in Aged Human Eyelid Skin Ex Vivo.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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
16 citing papers in PubMed, 26 citations in OpenAlex.
- Innovative HPMC/PVP K90 Dissolving Microneedles Incorporating Tacrolimus-Loaded Cubosomes: A Novel Strategy for Managing Allergic Conjunctivitis.Pharmaceutics · 2026Article
- Next-Generation Minimally Invasive Anti-Aging Therapy: Incorporation of Resveratrol-Nicotinamide Cerosomes into PLGA Microneedles for Enhanced Skin Permeation.Pharmaceutics · 2026Article
- The systemic wrinkled skin phenotype involves aberrant expression and variation of genes related to the oxidative stress and extracellular matrix in Xiang pigs.BMC genomics · 2025Article
- Skinspan: A Holistic Roadmap for Extending Skin Longevity With Evidence-Based Interventions.Journal of cosmetic dermatology · 2025Review
- IL-15 Promotes the Survival of Anti-Inflammatory (M2), Immunoinhibitory (IL-10+) Dermal Macrophages in Human Eyelid Skin Under IFNγ-Dominated Inflammatory Conditions.International journal of molecular sciences · 2025Article
- Protective Effect of Melatonin Against Bisphenol A Toxicity.International journal of molecular sciences · 2025Review
- Preclinical Evidence That Mesoglycan Unfolds Complex Anti-Aging Effects in Photoaged Female Facial Skin.International journal of molecular sciences · 2025Article
- Comparative Analysis of Melatonin and Polydeoxyribonucleotide: Possible Benefits of Co-Treatment Effects and Potential Synergistic Applicability.International journal of molecular sciences · 2025Review
- Melatonin and the Skin: Current Progress and Perspectives for Human Health.The Journal of investigative dermatology · 2025Review
- Regulation of dermal circadian pathways by a novel topical formulation.International journal of cosmetic science · 2025Article
- Potential Targets Related to Skin Aging: Based on eQTL and GWAS Datasets.Clinical, cosmetic and investigational dermatology · 2025Article
- Review of sensory systems deployed by epidermal keratinocytes.Frontiers in cell and developmental biology · 2025Review
- Longevity cosmeceuticals as the next frontier in cosmetic innovation: a scientific framework for substantiating product claims.Frontiers in aging · 2025Review
- Review
- Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach.Aging and disease · 2024Review
- Melatonin in animal husbandry: functions and applications.Frontiers in veterinary science · 2024Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human skin aging is associated with functional deterioration on multiple levels of physiology, necessitating the development of effective skin senotherapeutics. The well-tolerated neurohormone melatonin unfolds anti-aging properties in vitro and in vivo, but it remains unclear whether these effects translate to aged human skin ex vivo. We tested this in organ-cultured, full-thickness human eyelid skin (5-6 donors; 49-77 years) by adding melatonin to the culture medium, followed by the assessment of core aging biomarkers via quantitative immunohistochemistry. Over 6 days, 200 µM melatonin significantly downregulated the intraepidermal activity of the aging-promoting mTORC1 pathway (as visualized by reduced S6 phosphorylation) and MMP-1 protein expression in the epidermis compared to vehicle-treated control skin. Conversely, the transmembrane collagen 17A1, a key stem cell niche matrix molecule that declines with aging, and mitochondrial markers (e.g., TFAM, MTCO-1, and VDAC/porin) were significantly upregulated. Interestingly, 100 µM melatonin also significantly increased the epidermal expression of VEGF-A protein, which is required and sufficient for inducing human skin rejuvenation. In aged human dermis, melatonin significantly increased fibrillin-1 protein expression and improved fibrillin structural organization, indicating an improved collagen and elastic fiber network. In contrast, other key aging biomarkers (SIRT-1, lamin-B1, p16INK4, collagen I) remained unchanged. This ex vivo study provides proof of principle that melatonin indeed exerts long-suspected but never conclusively demonstrated and surprisingly differential anti-aging effects in aged human epidermis and dermis.
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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.