Skin ageing is a complex process involving the convergence of two distinct mechanisms: the subtle effects of time-dependent intrinsic ageing, and the changes brought to bear on our skin by its constant interaction with the external environment, predominantly chronic sun exposure. This photoaged skin has a distinctive clinical appearance, exhibiting coarse and fine wrinkles, a sallowness of complexion and reduced ability to recoil. One major dermal alteration is loss of fibrillin-rich microfibrils – key components of the dermal elastic fibre matrix – at the dermal-epidermal junction. Topical all-trans retinoic acid (RA) improves the clinical appearance of photoaged skin; however, the time period for improvements to occur may be up to 6-months.Targeting improvements in photoaged skin is a commercial focus for personal care companies; with a shift in public perception around the scientific background to product claims, we designed a short-term in vivo screening assay fibrillin-rich microfibrils as a marker for outcome of repair to provide additional confidence during product design prior to commercial launch. Clinically assessed, severely photoaged individuals were recruited to the study (n = 8) and were subject to an occluded patch test on their photoaged extensor forearm (0.025% RA (positive control); 5% sodium lauryl sulphate (SLS, as an irritant control) or vehicle alone); a fourth untreated control area was also occluded to assess baseline expression of the biomarker. After 4-days, 4 mm biopsies were taken and probed for the occurrence of fibrillin-rich microfibrils (immunohistochemistry and in situ hybridization). In this 4-day patch test assay, RA and SLS significantly increased fibrillin-rich microfibril protein content compared to control and vehicle groups (p<0.05), with RA treatment significantly increasing fibrillin content over that of SLS (p<0.001). This was also observed at the mRNA level; RA-treatment producing highly significant increases in fibrillin-1 mRNA in epidermal keratinocytes (p<0.001) over SLS-treatment (p<0.05). This study indicates that RA can significantly affect fibrillin-rich microfibril content in photoaged skin and can be used as a biomarker of repair in short-term assays for testing the utility of topical products targeting photoageing.
Experimental Models (Exeter, UK) (2018) Proc Physiol Soc 40, SA18
Research Symposium: Cutaneous photoageing: Systems for modelling repair of human skin
R. E. Watson1
1. Centre for Dermatology Research, University of Manchester, Manchester, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.