Comparative circadian transcriptome analysis reveals dampened and phase-advanced rhythms in sun-exposed human skin

Daily molecular rhythms modulate skin physiology. However, the effects of chronic sun exposure on these rhythms remain unstudied. This study aimed to identify and compare rhythmic genes and pathways in photoprotected and chronically photoexposed human skin in vivo. Skin biopsies were taken from photoprotected (upper buttock) and photoexposed (dorsal forearm) skin of 20 subjects at noon, 6 PM, midnight, and 6 AM across a 24-hour cycle, and gene expression was quantified using RNA sequencing. Cosinor analysis identified cycling genes along with their amplitudes and peak expression phases. We found that fewer genes met the criteria for cycling in photoexposed skin than in photoprotected skin, and transcripts that cycled in both sites had lower amplitudes and advanced peak times in photoexposed skin than in photoprotected skin. We identified 480 genes with significantly different rhythmic properties between the skin sites. Genes involved in DNA repair, MYC targets, E2F, and G2M checkpoint pathways were enriched among those that showed higher amplitude oscillations in photoprotected skin. Genes involved in epithelial-mesenchymal transition and apical junction pathways showed higher amplitude oscillations in photoexposed skin. These results suggest that chronic UV exposure may disrupt and/or reprogram circadian output rhythms to further alter skin physiology.