Sunscreen application substantially mitigates molecular perturbations induced by repetitive UV exposure and maintains healthy skin.

Ultraviolet (UV) radiation is a key environmental factor contributing to photoaging, inflammation, and carcinogenesis. While sunscreen is known to prevent sunburn and lower cancer risk, its effectiveness in limiting UV-induced molecular alterations in human skin is not fully defined. In this study, 32 female volunteers belonging to four Fitzpatrick phototypes underwent repeated moderate UV exposures, with skin samples collected from three distinct treatment sites on each participant, including untreated, UV-exposed without protection, and UV-exposed with prior application of sunscreen. Comprehensive profiling revealed that UV exposure markedly altered gene expression and DNA methylation, impacting pathways involved in DNA repair, immune response, and cell cycle regulation. Mapping these molecular signatures to the Hallmarks of Health revealed broad disturbance of the skin's core functional attributes. The application of sunscreen effectively prevented most UV-driven disruptions, including the acceleration of epigenetic age, and maintained the stability of hallmark-associated pathways, with minor residual molecular changes remaining. This study demonstrates the importance of regular photoprotection in preventing visible skin damage and maintaining molecular skin health. By deepening our understanding of the mechanisms underlying photoprotection, these findings also indicate a new scope for further advancements in the efficacy of future sunscreen formulations.