Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix.

BACKGROUND: Actinic lentigos (AL) are benign hyperpigmented skin lesions associated with photoageing. Despite their high prevalence, biological mechanisms driving their formation remain unclear. OBJECTIVES: To provide new insights about the physiopathology of AL through a comprehensive description of their histological and molecular features. METHODS: Quantitative analysis of dermoscopic images was used to select AL containing elongated patterns, predicted to display a highly deformed dermal-epidermal junction (DEJ), on the back of the hands of 15 Caucasian women. Biopsies from lesional and adjacent nonlesional (NL) areas were processed for histological analysis or gene expression profiling. RESULTS: Histological staining confirmed a drastic deformation of the DEJ in AL, with deep epidermal invaginations into the dermis. Although the melanin content was significantly higher in AL compared with NL epidermis, the distribution of melanocytes along the DEJ was unchanged. Transcriptomic analysis revealed a signature of 529 genes differently expressed in AL vs. NL skin. Alteration of epidermal homeostasis was confirmed by the dysregulation of keratinocyte proliferation and differentiation markers. Surprisingly, canonical genes involved in melanogenesis were not significantly modulated in AL. A striking finding was the overexpression of a large group of genes involved in dermal extracellular matrix organization and remodelling. Dermal alterations were confirmed by immunolabellings on AL and NL sections. CONCLUSIONS: Drastic disorganization of the cutaneous structure in AL is accompanied by a specific molecular signature revealing alterations in both epidermal and dermal compartments. In particular, our results suggest that local modifications of the dermal extracellular matrix might contribute to hyperpigmentation in AL.

Clinical vs. chronological skin age: exploring determinants and stratum corneum protein markers of differential skin ageing in 351 healthy women.

Apparent skin age can be determined by several clinical measurements and may differ from chronological age, hence defining age acceleration/deceleration (Age A/D). Using data from 360 women with dermatological scoring of 21 clinical signs, we defined 3 well-separated co-occurring classes capturing the dryness, the elasticity and the oily nature of the skin. We related the risk of each clinical signs to the stratum corneum levels of 5 pre-selected proteins, we identified specific chronological age-adjusted signatures of each clinical sign. Using variable selection approaches, we identified 6 (of the 21) clinical signs which were jointly predictive of chronological age and used to define the clinical skin age, and subsequently age A/D. Applying univariate and multivariate approaches we found that stratum corneum levels of insulin degrading enzyme (IDE) was protective against (ß = - 1.74, p = 3.3 × 10-6; selection proportion > 90%) accelerated skin ageing. In conclusion, our results support the fact that molecular markers found in the stratum corneum could predict skin ageing acceleration/deceleration.