Metformin as an early intervention for melanocyte senescence via autophagy-redox balance

Summary: Abstract Body: Melanocyte senescence predominantly occurs in aging skin and represents a critical target for addressing skin aging and pigmentary disorders. Single-cell transcriptomics and time-course analyses revealed dynamic changes of autophagy regulation during early and late stages of UV-induced melanocyte senescence. A reduction in ATG7 was a key event preceding full melanocyte senescence. The ATG7 knockdown induced premature senescence, characterized by elevated reactive oxygen species (ROS) levels. In contrast, glycolysis pathways were significantly upregulated only in fully senescent cells. Metformin treatment restored autophagic activity, including ATG7 expression, and mitigated oxidative stress, thereby delaying senescence. These findings suggest that targeting the interplay between autophagy and oxidative stress could provide a novel early intervention strategy for melanocyte aging. Jin Cheol Kim^{1, 2}, Yeongeun Kim^{1, 2}, Tae Jun Park^{2, 3}, Hee Young Kang^{1, 2} 1. Dermatology, Ajou University School of Medicine, Suwon-si, Gyeonggi-do, Korea (the Republic of). 2. Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon-si, Gyeonggi-do, Korea (the Republic of). 3. Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon-si, Gyeonggi-do, Korea (the Republic of). Translational Studies: Cell and Molecular Biology