Skin differences based on age and chronicity of ultraviolet exposure: results from a gene expression profiling study

Skin ageing represents an inevitable physiological consequence of getting older but the impact on personal health and wellbeing can be significant, and therefore considerable efforts have been made to understand the biology and pathophysiology of skin ageing to try to identify new targets that might offer therapeutic intervention and prevention.

This study was designed to identify differences at the gene expression level between young and old, sun-exposed and sun-protected skin.

We generated transcriptomic data from young and old skin from sun-exposed and sun-protected sites (10 samples of each) using HG-U133 Plus 2.0 Affymetrix GeneChips. The data were analysed using hierarchical clustering, theme analysis and interaction mapping to identify regulated pathways, processes and potential targets for therapy.

With 54,613 probe sets on the GeneChip, 2731 significant differences would be expected by chance (at P = 0·05), but we noted that 13,640 probe sets were significantly different comparing young arm skin vs. older arm skin (photoageing), and 7215 probe sets were significant for the young buttock vs. older buttock comparison (intrinsic ageing). In both types of ageing there was reduced expression of many genes implicated in lipid biosynthesis and epidermal differentiation with functional relevance to skin barrier integrity and maintenance. Increased expression of genes contributing to oxidative stress and decreased expression of antioxidant defences were also common to both types of ageing. Differences between intrinsic ageing and photoageing were mainly noted in extracellular matrix gene expression with reduced expression of interstitial collagen genes in intrinsic ageing and increased expression of elastic tissue genes in photoageing.

Collectively, the data identified new biomarkers of aged skin, particularly involving abnormalities of proteases, matrix proteins and inflammation. These findings offer the prospect of new and more specific targets for therapeutic development based on an improved understanding of the biology of skin ageing.