Role of miR-214 and miR-382 in regulating key molecular pathways involved in skin aging

Summary: Abstract Body: Skin aging is a complex process that is influenced by intrinsic and extrinsic factors, leading to structural and functional skin changes. This study investigated aging-associated microRNAs (miRNAs) and their roles in regulating the molecular pathways involved in skin aging, including epigenetic regulation, mitochondrial function, and extracellular matrix degradation. We performed miRNA-seq and RNA-seq analyses on human skin tissue from young (18–30 years) and aged (>70 years) individuals, identifying miR-214 and miR-382 as significantly altered with age. Human dermal fibroblasts were transfected with miR-214 and miR-382 mimics and inhibitors to validate their roles. Functional assays revealed that these miRNAs significantly affected the expression of histone deacetylases (HDACs), Sirtuins (SIRTs), PINK1, PARKIN, MMP-1, and procollagen, which are critical regulators of histone deacetylation, mitochondrial health, extracellular matrix integrity, and collagen synthesis. Dysregulation of HDACs and SIRTs, which are key players in epigenetic modifications and stress responses, may disrupt cellular homeostasis and accelerate aging. These findings suggest that miR-214 and miR-382 contribute to skin aging by modulating epigenetic regulation, mitochondrial function, and extracellular matrix dynamics, highlighting their potential as therapeutic targets for mitigating age-related skin changes. Kyeong-No Yoon^{1, 2, 3}, Min-Kyoung Kim^{1, 2, 3}, Yidan Cui^{1, 2, 3}, Dong Hun Lee^{1, 2, 3} 1. Department of Dermatology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea, Seoul, None Selected, Korea (the Republic of). 2. Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea, Seoul, None Selected, Korea (the Republic of). 3. Institute of Human-Environmental Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea, Seoul, None Selected, Korea (the Republic of). Genetic Disease, Gene Regulation, Gene Therapy & Epigenetics