Epigenetic Clocks in Skin Aging: From Exposome Drivers to Biomarkers and Therapeutic Interventions

Alejandra DelaO-Escamilla,1 Samar Khalil,2 Hassan Galadari,3 Stefania Guida4 1Department of Dermatology, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico; 2Department of Dermatology, Skin and Scalpel Clinic, Beirut, Lebanon; 3Department of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 4School of Medicine, Vita-Salute San Raffaele University, Dermatology Clinic, IRCCS San Raffaele Hospital, Milan, ItalyCorrespondence: Hassan Galadari, Department of Medicine and Health Sciences, United Arab Emirates University, Khalifa Bin Zayed Street, P.O. Box 15551, Tawam, Al Ain, United Arab Emirates, Tel +971-03-7137571, Email [email protected]: Skin aging is a multifactorial process driven by a combination of intrinsic genetic programming and extrinsic environmental exposures. Recent advances in epigenetics have illuminated how changes in DNA methylation, histone modifications, and non-coding RNAs regulate skin aging, with the epigenetic clock emerging as a powerful tool to quantify biological age. This review aims to synthesize current evidence on how environmental and lifestyle factors – particularly ultraviolet radiation, pollution, smoking, diet, and stress – accelerate skin aging through epigenetic mechanisms, while also evaluating the potential of skin-specific epigenetic clocks as biomarkers for early detection of premature aging and for guiding therapeutic interventions. We further discuss the expanding field of epigenetic-targeted therapies in dermatology, encompassing topical agents, energy-based devices, and systemic approaches that may reverse or delay visible signs of cutaneous aging. By integrating insights from molecular biology, environmental science, and clinical dermatology, this review positions skin aging not as an irreversible outcome but as a modifiable, biologically regulated process with promising avenues for personalized prevention and rejuvenation.Keywords: epigenetic aging, skin rejuvenation, environmental exposome, DNA methylation, therapeutic interventions