Epigenetic changes differentiate between endogenous ageing and photoageing in skin and can detect sun-protection factor cream effects in a 5-month interventional study.

Epigenetics is a rapidly expanding field in ageing research. This is partly because changes in DNA methylation are excellent indicators of overall tissue ageing. Here, in a cross-sectional observational study, methylation levels were compared in upper-inner (sun-protected) and lower-outer (sun-exposed) arm skin biopsies of young (21-30 years, n = 24) and older (45-65 years, n = 24) participants of either European or Chinese ancestry. In young sun-protected skin, there were 69 significantly differentially methylated sites (DMSs) between those of Chinese and European ancestry. In a comparison between young and older sun-protected skin (endogenous ageing) there were 3545 pan-ethnic DMSs with a preference for hypermethylation and enrichment at the RNF32, FOXG1, NEFM, and ZIC1 gene loci. For photoageing, 2208 pan-ethnic photoageing DMS were identified with a preference for hypomethylation and enrichment at the HOXB1-3, TWIST1, and TBX20 gene loci. From the photoageing DMSs, 156 CpG sites were selected that consistently differentiated photo-exposed from protected skin even in the young participants. The mean degree of change for these 156 CpG sites was subsequently measured over 5-months in an interventional study on participants' lower outer-arm skin (n = 42). Participants had regular sun-protection factor (SPF) use on one arm and normal free-living conditions on the contralateral arm. The free-living arm demonstrated greater skin darkening and a significantly larger mean change in methylation compared with the SPF-treated arm. Overall, the results highlight endogenous and photoageing methylation differences in skin and suggest that specific DNA methylation sites can track short-term sun-exposure and its attenuation by SPF use.