Keratinocytic Malfunction as a Trigger for the Development of Solar Lentigines

Introduction: Solar lentigines (SL) affect chronically UV-radiated skin. Treatment is often refractory. Deeper knowledge on its pathogenesis might improve therapeutic effects. Material and Methods: Morphological characterization of 190 SL was performed and epidermal thickness, pigment distribution, dendricity, and cornification grade were measured. Immunoreactivity was investigated using Melan A, Tyrosinase, MITF, p53, and CD20, as well as Notch1 using immunofluorescence. Results: We found 2 groups of histological patterns, i.e., either acanthotic or atrophic epidermis. Lesions with basket-woven cornification and atrophic epidermis were observed in 6 out of 9 and 14 out of 16 cases from the face, respectively. Consistency of areas with a high pigmentation was observed in 96–97% of the cases. Hyperpigmentation grade and acanthosis or cornification disorders correlated positively in 88.5% of the cases. Overexpressed of p53 was found in 19 out of 20 lesions, presenting in a scattered distribution. A significant correlation of p53 and acanthosis (p = 0.003) and cornification grade (p = 0.0008) was observed. Notch1 was expressed in all SL, with the highest immunoreactivity in atrophic facial lesions. Lesions from the hands expressed Notch1 mainly in acanthotic areas with elongated rete ridges and less compact cornification. Discussion: We suggest that Notch1-dependent keratinocytic malfunction causes the development of SL. Consequently, hyperpigmentation would be a result and not the primary cause of the pathogenesis. Confirmation of these findings might have clinical implications as hitherto treatment has mainly focused on melanocytes and pigmentation and not on the proliferation/differentiation balance of keratinocytes

RGCCA for the analysis of Microbiome data

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A chronic pro-inflammatory environment contributes to the physiopathology of actinic lentigines

Abstract Actinic lentigines (AL) or age spots, are skin hyperpigmented lesions associated with age and chronic sun exposure. To better understand the physiopathology of AL, we have characterized the inflammation response in AL of European and Japanese volunteers. Gene expression profile showed that in both populations, 10% of the modulated genes in AL versus adjacent non lesional skin (NL), i.e. 31 genes, are associated with inflammation/immune process. A pro-inflammatory environment in AL is strongly suggested by the activation of the arachidonic acid cascade and the plasmin pathway leading to prostaglandin production, along with the decrease of anti-inflammatory cytokines and the identification of inflammatory upstream regulators. Furthermore, in line with the over-expression of genes associated with the recruitment and activation of immune cells, immunostaining on skin sections revealed a significant infiltration of CD68+ macrophages and CD4+ T-cells in the dermis of AL. Strikingly, investigation of infiltrated macrophage subsets evidenced a significant increase of pro-inflammatory CD80+/CD68+ M1 macrophages in AL compared to NL. In conclusion, a chronic inflammation, sustained by pro-inflammatory mediators and infiltration of immune cells, particularly pro-inflammatory M1 macrophages, takes place in AL. This pro-inflammatory loop should be thus broken to normalize skin and improve the efficacy of age spot treatment

Age-related changes of the cutaneous microcirculation in vivo.

International audienceBACKGROUND: The architectural frameworks of the skin microcirculation are rather complex and change continuously with aging. But these changes are yet poorly documented in vivo. OBJECTIVES: Using non-invasive methods belonging to the field of biometrology, the study aimed to investigate quantitatively the changes of the cutaneous microvasculature in different anatomic sites with age. METHODS: Measurements were performed on crow's feet, forehead, volar forearm and dorsum of hand in 50 women (aged 20-74 years who consisted of 10 probands in each live decades). The superficial vascular plexus was scanned by videocapillaroscopy and assessed with the software Capilab Toolbox. The subpapillary vascular plexus was explored with laser Doppler flowmetry. The skin color a* was analyzed by chromametry. RESULTS: A marked site and age effect on the skin microcirculation has been demonstrated. The density of capillary loops in the eldest group decreased by about 40-70% compared with the youngest group whereas the vascular length increased by 35-156%. The capillary density in the back of the hand was 4 times higher than in the crow's feet. The vascular length in the crow's feet was 3 times longer than in the back of the hand. Both blood flow and skin redness (a*) increased also with age. CONCLUSION: Both morphology and quantification of the cutaneous microvasculature showed changes with site and age. Videocapillaroscopy associated to an image processing and laser Doppler flowmetry revealed different vascular layers. So the combination of both instruments offers an easy way to observe the architectural frameworks in vivo

Age-related changes in skin topography and microcirculation

International audienceAbstract Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20–74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging