Melatonin Exerts Prominent, Differential Epidermal and Dermal Anti-Aging Properties in Aged Human Eyelid Skin Ex Vivo
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Published:2023-11-04
Issue:21
Volume:24
Page:15963
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Samra Tara1, Gomez-Gomez Tatiana1ORCID, Linowiecka Kinga12ORCID, Akhundlu Aysun1, Lopez de Mendoza Gabriella1, Gompels Matthew1, Lee Wendy W.3, Gherardini Jennifer1, Chéret Jérémy1ORCID, Paus Ralf145
Affiliation:
1. Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA 2. Department of Human Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1, 87-100 Torun, Poland 3. Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL 33125, USA 4. Monasterium Laboratory, 48149 Muenster, Germany 5. CUTANEON—Skin & Hair Innovations, 22335 Hamburg, Germany
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.
Funder
Monat Global CUTANEON Endowed Frost Scholarship from the Dept. of Dermatology, University of Miami
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference152 articles.
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