Абстракт

Objectives: 1. Capture the epigenetic response of skin to 1 week (acute) low dose solar-simulated UV exposure. 2. Compare the acute UV response with epigenetic photo-ageing changes. 3. Compare the acute UV response with epigenetic intrinsic ageing changes. 4. Investigate if intrinsic epigenetic changes with age are present in laboratory grown keratinocytes from donors of differing ages. 5. Highlight how epigenetics can be utilised in the laboratory and beyond for diagnostics and anti-ageing products. Introduction: Epigenetics relates to how skin cells regulate gene expression (how genes are activated from DNA) which drive skin’s function such as producing melanin. Studying one type of epigenetic modification in cells – the methylation of DNA – has uncovered how methylation changes to DNA at certain positions are very good biomarkers of skin ageing. Why is this epigenetic modification to our DNA such a good measure of the rate of human ageing and how can this field help both further ageing research and drive new anti-ageing products? Materials / method: We have carried out an observation study involving 12 young and 12 old volunteers to better understand DNA methylation changes in the epidermis with age, and their response to acute UV exposure. We next examined if the acute UV response was reflective of photo-ageing and intrinsic ageing; the epigenetic intrinsic ageing changes were also tested for their presence in cultured keratinocyte cells in the laboratory. Furthermore, we reviewed the latest epigenetic modification techniques that are helping drive further understanding in this field. Results: The acute UV response was dominated by loss of methylation, was reflective of 5 months and 30 years of photo-ageing but was opposite to the gain of methylation occurring at the same sites with intrinsic ageing. Young to old epidermal intrinsic ageing differences were mainly present in laboratory grown keratinocytes and CRISPR/Cas9 technology can now be used for their study. Finally, ageing epigenetic changes are being used as a measure of rejuvenation technology efficacy, and for identifying anti-ageing routes for future technologies. Conclusion: Differences in intrinsic and photo-ageing ageing are highlighted by the acute UV epigenetic response being reflective of 5 months and 30 years of photo-ageing but opposite to that of intrinsic skin ageing. The ability to now edit DNA methylation levels in laboratory grown skin cells offers a route to study the drivers and consequences of these changes. In addition, epigenetics is enabling preventative and rejuvenation technologies to be tested for their anti-ageing benefits and for highlighting ways to rejuvenate skin cells, adding value beyond research for this exciting field.