O22 Potential biomarkers of photoageing relate to pigmentation, DNA repair and the immune response

Abstract Introduction and aims Ultraviolet radiation (UVR) is a major environmental contributor to skin ageing that induces changes in DNA methylation (DNAm); this regulates gene expression to enhance cellular resilience to stress, but can potentially silence critical genes and lead to genomic dysregulation, accelerated ageing, and increased cancer risk. While DNAm has been characterized in habitually photoexposed skin, this has not been related to changes in DNAm that occur following acute UVR exposure of photoprotected skin. Methods Significant differentially methylated positions (DMPs) (Padj ≤ 0.05, Δβ ≥ ± 0.05) in the photoprotected epidermis following acute, solar-simulated UVR (80% sunburn threshold; daily for 5 days) were compared with published data (GSE51954) examining photoexposed skin. Studies included healthy, White, older (acute: > 65 years, n = 12; photoexposed: > 60 years, n = 10) and younger (acute: 18–30 years, n = 12; photoexposed: < 35 years, n = 10) individuals. Data were analysed with limma and related Kyoto Encyclopedia of Genes and Genomes pathways and gene ontology (GO) terms identified using missMethyl. Results Compared with photoprotected skin, acute UVR-exposed skin had fewer significant DMPs (older = 3946; younger = 948) than photoexposed skin (older = 78 593; younger = 29 510). A portion of significant DMPs overlapped following both acute and habitual photoexposure in the younger (70 DMPs) and older (589 DMPs) epidermis. Of these overlapping DMPs, 45 showed significant hypomethylation across age groups. The extent of hypomethylation at these 45 DMPs correlated with age and UVR levels, with old, photoexposed samples showing the greatest loss of methylation (P < 0.001). Associated pathways included citrate cycle (P = 0.037) and antifolate resistance (P = 0.047); both important in facilitating nucleotide synthesis for DNA repair and maintaining cellular function under stress. Significant GO terms included pigment accumulation (P < 0.001) and regulation of CD8+ T-cell activation (P < 0.001). Conclusions A panel of 45 DMPs identified following acute UVR exposure of photoprotected skin were also present in younger and older photoexposed skin. Extent of hypomethylation at these DMPs may be potential biomarkers for the progression of photoageing.