Mesoglycan exerts prominent anti-aging effects in photoaged human facial skin

Summary: Abstract Body: Novel senotherapeutics are needed to counteract aging-related skin decline. Mesoglycan, a glycosaminoglycan mix that enhances perfusion, angiogenesis, and reduces inflammation, warrants exploration for its synergy with VEGF-A. This pilot study aimed to evaluate the senotherapeutic potential of mesoglycan to inhibit skin aging in old, photoaged human facial skin ex vivo, using an organ culture model of accelerated aging. Full-thickness facial skin from 7 women (mean age 72 ± 5 years) was organ-cultured under serum-free conditions for 6 days and treated with topical or systemic mesoglycan (100–300 mg/mL). Skin aging biomarkers were assessed via quantitative immunohistomorphometry. Mesoglycan treatment significantly improved aging biomarkers in old, photoaged female facial skin ex vivo. In the epidermis, it counteracted aging-associated changes by enhancing Ki-67, melanin content, gp100+, c-KIT+, and MITF+ cells. Mesoglycan reduced p16INK4A and p-S6 levels while increasing SIRT1, Lamin B1, filaggrin, collagen 17A1, and laminin, indicating improved senescence regulation, nuclear integrity, and epidermal barrier and dermal-epidermal junction function. It also enhanced mitochondrial function by upregulating MTCO-1, PGC1α, and VDAC/Porin, demonstrating efficacy against mitochondrial aging. Mesoglycan boosted skin antioxidant defenses by upregulating NRF-2, HO-1, glutathione reductase, and PRDX. It improved dermal markers, including collagen I and III, fibrillin-1, and CD31+ endothelial cells, and significantly increased VEGF-A expression. As expected, systemic delivery showed greater efficacy than topical application in reducing aging biomarkers, consistent with mesoglycan’s limited skin penetration. Our ex vivo study demonstrates that both topical and systemic mesoglycan are promising senotherapeutics with significant anti-aging potential for photoaged human facial skin. Aviad Keren¹, Assaf Zeltzer¹, Ralf Paus^{2, 3}, Amos Gilhar¹ 1. Technion Israel Institute of Technology, Haifa, Haifa District, Israel. 2. University of Miami Miller School of Medicine, Miami, FL, United States. 3. CUTANEON, Hamburg, Germany. Stem Cell Biology, Tissue Regeneration and Wound Healing