Senescent melanocytes signaling impairs skin barrier function

Summary: Abstract Body: Melanocyte senescence primarily occurs in the skin of middle-aged and older individuals, progressively increasing with age. The senescent melanocytes may propagate aging signals to neighboring cells. Our findings reveal that senescent melanocytes contribute to skin barrier dysfunction. Senescent melanocytes-derived conditioned medium downregulated the expression of barrier-associated genes and differentiation markers in keratinocytes and ex vivo skin, thereby impairing skin barrier function. The senescent cells showed different secretomes and inhibition of these signaling pathways mitigated skin barrier damage induced by senescent melanocytes. These findings highlight senescent melanocytes and their secretome as promising therapeutic targets for age-related skin barrier disruption. Tae Jun Park^{3, 2}, Jin Cheol Kim^{1, 2}, Yul Hee Kim¹, Yeongeun Kim^{1, 2}, Seongcheon Lee⁴, Agnes Tessier⁴, Gaelle Gendronneau⁴, Youcef Ben Khalifa⁴, 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). 4. Innovation Research and Development, Chanel Parfums Beauté, Pantin, France. Epidermal Structure and Barrier Function