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The human skin is a complex organ, and its aging is a complicated process involving both the passage of time (chronological aging) and environmental exposure, especially to UV light (photoaging). This aging phenomenon works through various cellular mechanisms, including changes in apoptosis, alterations in cellular signaling, and an increased genetic instability. In this study, we investigated changes of human epidermal proteins with a proteomic analysis of human sun-protected vs sun-exposed epithelium. Epidermal samples from sun-protected vs sun-exposed areas of the skin were collected using D-Squame discs.A barocycler was employed to enhance high-pressure shearing of skin cells and removal from discs, without any detergents or organic chemicals which might release adhesives from the tape.Technical replicates were ran for each of the conditions (exposed and sun-protected) using LC-MS/MS, and both ANOVA and Bays factor (QSPEC) analysis were utilized to determine up- and down-regulation of epidermal proteins.Some previous studies have shown higher levels of proteases in sun-damaged epithelium, while other studies have shown diminished proteosome components in aged skin.Initial results from this study revealed some proteases to be up-regulated in the sun-protected relative to sun-exposed skin, as well as other enzymes involved in catalysis such as histidine ammonia lyase. Initial results also showed higher levels of proteosome components in sun-protected skin, and also higher levels of two serpins, which inhibit serine proteases, suggesting complex regulation of protein catalysis. Overall, these results suggest that UVA and UVB influence the complex regulation of proteins in healthy human epidermis.