O25 Compared to sun-protected skin, the circadian transcriptome in sun-exposed skin demonstrates dampened, phase-advanced rhythms with fewer cycling genes

Abstract Introduction and aims Daily molecular rhythms modulate skin physiology. However, the effects of chronic sunlight exposure on these rhythms remain unstudied. Methods Twenty women aged 50–65 years who exhibited moderate-to-severe photoageing of the dorsal forearm were recruited. Skin biopsies (3 mm) were taken from upper buttock and dorsal forearm of each individual at noon, 18.00 h, 00.00 h, and 06.00 h, across one 24-h cycle. Skin biopsies were analysed by RNA sequencing. Cosinor analysis was used to identify cycling genes along with their amplitudes and peak expression phases. Nested models identified significant differences between photoprotected and photoexposed samples. Phase set and gene set enrichment analyses identified pathways under circadian control. Results In photoprotected buttock skin 1546 (12%) genes met criteria for cycling. In photoexposed forearm skin the number was reduced to 959 (8%). Overall, 1076 transcripts cycled exclusively in the buttock and 489 exclusively in the forearm. The peak expression times for individual cycling transcripts were clustered in the early morning and mid-afternoon. Focusing on transcripts that cycled in both sites revealed that cycling in the buttock was of overall higher amplitude (P < 2.2e−16). For these transcripts, distributions of peak times were significantly different between forearm and buttock skin (P < 0.001), with peak times advanced in forearm skin. Genes involved in the unfolded protein response, DNA repair, and Myc targets were enriched among those that cycled exclusively in buttock skin. Inflammatory response and epithelial–mesenchymal transition pathway genes were enriched among those that cycled exclusively in forearm skin. Tumour necrosis factor-α signalling pathway genes and Myc targets were also enriched among genes that cycled in both skin sites. Conclusions Altered cycling patterns and a reduced number of cycling genes in photoexposed compared with photoprotected skin, suggest that chronic UV exposure may reprogram circadian output rhythms in anticipation of daily environmental stressors, which may in turn compromise the optimal functioning of other biological processes.