BACKGROUND: Visible light, in particular blue light, has been identified as an additional contributor to cutaneous photoageing. However, clinical studies demonstrating the clear effect of blue light on photoageing are still scarce, and so far, most studies have focused on broad-spectrum visible light. Although there is evidence for increased skin pigmentation, the underlying mechanisms of photoageing in vivo are still unclear. Furthermore, there is still a need for active ingredients to significantly protect against blue light-induced hyperpigmentation in vivo. Our study had two aims: to detect visible changes in skin pigmentation following repeated irradiation of the skin with LED-based blue light and to reduce pigmentation using suitable active ingredients. METHOD: We conducted a randomized, double-blind and placebocontrolled clinical study on 33 female volunteers with skin phototypes III and IV. We used a repetitive blue light (4 9 60 J cm À2 , 450 nm) irradiation protocol on the volunteers' inner forearms. Using hyperspectral imaging, we assessed chromophore status. In addition, we took chromameter measurements and photographs to assess visible hyperpigmentation. RESULTS: We measured significant changes in chromophore status (P < 0.001 vs baseline), that is of melanin, haemoglobin and oxygen saturation, immediately after blue light irradiation. In addition, we found visible skin colour changes which were expressed by a significant decrease in ITA°values (delta ITA°= À16.89, P < 0.001 vs baseline for the placebo group) and an increase in a* (delta a* = +3.37, P < 0.001 vs baseline for the placebo group) 24 h post-irradiation. Hyperpigmentation and skin reddening were mitigated by both a formulation containing 3% of a microalgal product and a formulation containing 3% niacinamide. CONCLUSION: Our study sets out an efficient and robust protocol for investigating both blue light-induced cutaneous alterations, such as changes in skin chromophores, and signs of photoageing, such as hyperpigmentation. Moreover, we have shown evidence that both an extract of the microalga Scenedesmus rubescens and niacinamide (vitamin B3) have the potential to protect against blue light-induced hyperpigmentation.

The human skin microbiome has recently become a focus for both the dermatological and cosmetic fields. Understanding the skin microbiota, that is the collection of vital microorganisms living on our skin, and how to maintain its delicate balance is an essential step to gain insight into the mechanisms responsible for healthy skin and its appearance. Imbalances in the skin microbiota composition (dysbiosis) are associated with several skin conditions, either pathological such as eczema, acne, allergies or dandruff or non‐pathological such as sensitive skin, irritated skin or dry skin. Therefore, the development of approaches which preserve or restore the natural, individual balance of the microbiota represents a novel target not only for dermatologists but also for skincare applications. This review gives an overview on the current knowledge on the skin microbiome, the currently available sampling and analysis techniques as well as a description of current approaches undertaken in the skincare segment to help restoring and balancing the structure and functionality of the skin microbiota.

Background: Facial wrinkles, pores, and uneven skin tone are major beauty concerns. There is differential manifestation of aging signs in different ethnic groups. In this regard, studies on Black Africans from the African continent are scarce.Objective: To investigate facial wrinkles, pores, and skin tone in Black African women from Mauritius Island and elucidate the differences to Caucasian women from France.Methods: Facial images were taken using the imaging system ColorFace ® . Wrinkles and pores were measured by their length, depth, surface, volume, and number; for skin tone, we measured L*a*b* and calculated ITA, IWA Newtone , and color homogeneity. Results:We found good correlations of wrinkle and pore scores with expert ranking done on ColorFace ® images for Caucasians (Spearman's rho = 0.78 and 0.72) andBlack Africans (Spearman's rho = 0.86 and 0.65). Caucasians showed more advanced facial signs of aging than Black Africans. Exceptions were vertical lines on upper lip and the depth of pores which were greatest for the Black African subjects. Black Africans had higher heterogeneity scores indicative for uneven skin tone. Luminance (L*) was significantly higher in Caucasians but a* and b* values were significantly higher in the Black African subjects. ITA and IWA Newtone were significantly higher for Caucasians. Conclusions:The high correlation between expert ranking and wrinkle and pore measurements prove ColorFace ® a valid imaging system to study skin aging. Our results show that Africans from the African continent show delayed signs of aging compared to Caucasians. Some exceptions suggest that ethnic differences in facial aging are a complex phenomenon. K E Y W O R D Santi-aging, Black African skin, Caucasian skin, ColorFace®, Ethnic, facial imaging, pores, skin tone, wrinkles

Activity and selectivity assessment of new bi-aryl amide 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11β-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11β-HSD1 over 11β-HSD2, 17β-HSD1 and 17β-HSD2. These inhibitors also potently inhibited 11β-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme and in intact primary human keratinocytes expressing endogenous 11β-HSD1. Moreover, compounds 2b, 3e and 12e were tested for their activity in human skin biopsies. They were able to prevent, at least in part, both the cortisone- and the UV-mediated decreases in collagen content. Thus, inhibition of 11β-HSD1 by these compounds can be further investigated to delay or prevent UV-mediated skin damage and skin aging.

One of the first lines of cutaneous defense against photoaging is (a) the synthesis of melanin and (b) the initiation of an oxidative stress response to protect skin against the harmful effects of solar radiation. Safe and selective means to stimulate epidermal pigmentation associated with oxidative stress defense are; however, scarce. Activation of the melanocortin-1 receptor (MC1R) on epidermal melanocytes represents a key step in cutaneous pigmentation initiation and, additionally, it regulates cellular defense mechanisms like oxidative stress and DNA-repair. Thus, making the activation of MC1R an attractive strategy for modulating skin pigmentation and oxidative stress. In this context, we designed and synthesized pentapeptides that act as MC1R agonists. These peptides bound, with high potency, to MC1R and activated cAMP synthesis in CHO cells expressing human MC1R. Using one lead pentapeptide, we could show that this activation of MC1R was specific as testing the activation of other G-protein coupled receptors, including the MC-receptor family, was negative. In vitro efficacy on mouse melanoma cells showed similar potency as for the synthetic MC1R agonist alpha-melanocyte stimulating hormone (NDP-alpha-MSH). Moreover, we could reproduce this activity in human skin tissue culture. The lead pentapeptide was able to induce ex-vivo protein expression of key melanogenesis markers melanocyte inducing transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP-1). Concerning oxidative stress response, we found that the pentapeptide enhanced the activation of Nrf2 after UVA-irradiation. Our results make this pentapeptide an ideal candidate as a skin pigmentation enhancer that mimics alpha-MSH and may also have anti-photoaging effects on the skin.

Determining hitherto uninvestigated and safe targets to halt the aging process is important in our aging society. Graying is a hallmark of the aging process and may be used to identify aging tissue for comparative analysis. Here we analyzed differential gene expressions between pigmented, gray, and white human scalp skin hair follicles (HFs) from identical donors. Forming intersections between five donors identified 194/192 downregulated and 186/177 upregulated genes in gray/white HFs. These included melanogenesis (tyrosinase; tyrosinase-related protein 1)- and melanosome structure (Melan-A; Pmel17)-associated genes and regulation of melanocyte relevant tyrosine kinases. Alongside these expected changes, regulated genes included nonmelanocyte-related genes associated with aging as well as nonaging-related genes associated with melanocytes. Intriguingly, among them, genes associated with energy metabolism (i.e., glutaminase) and axon guidance (plexin C1) were altered. These results were reflected by pathway analysis and exemplarily confirmed by PCR and immunohistochemical studies. Supplementing cultured HFs with glutamine or plexin C1 revealed biological relevance and pharmacointerventional potential of these microarray results in altering the HF aging process. Together, we present intriguing data obtained from intra-individual sample comparison that suggest the graying HF to be a valid aging model and a promising target for testing therapeutic interventions.

OBJECTIVE: There are methods to evaluate skin colour on defined areas over the face but no approach automatically and accurately evaluates skin colour variations on large facial areas, comparing subjects, treatments and/or time points. We propose such an image-based approach to visualize quickly the outcome of clinical studies on colour variations. METHODS: Among 54 Asian women, one group applied a vehicle twice daily, during 28 days, and the other group an anti-ageing emulsion, taking facial images at baseline and after treatment. Changes in L*a*b* values were studied on four pre-selected facial regions. We also reconstructed average facial images from which the L*a*b* parameters were extracted for every pixel, computing relevance (DE) and significance data. Using colour gradients, we mapped these results onto the average facial images. RESULTS: After treatment, L*a*b* parameters show no statistically relevant colour changes in the vehicle group. In the 'active' group, skin was lighter at the upper cheek and, overall, redness decreased. Relevance and significance maps confirmed no visible colour changes in the vehicle group. In the 'active' group, the mapping approach revealed colour changes and their location. Skin became lighter below the eye, cheek and forehead. It was less red below the eyes, on the cheek, jawline and forehead, and generally more yellow. CONCLUSION: Our image-based mapping approach proves to be powerful. It enables us to identify precise facial regions of relevant and statistically significant colour changes after a topical treatment, regions that would have otherwise been undetected. R esum e OBJECTIF: Il existe des m ethodes pour evaluer la couleur de la peau sur des zones pr e-d efinies du visage mais aucune approche n' evalue de mani ere automatique et pr ecise les variations de couleur de peaux sur de large r egions du visage, en comparant les sujets, les traitements et/ou les temps d'analyse. Nous proposons une telle m ethode bas ee sur l'analyse d'images pour visualiser de mani ere rapide les r esultats des etudes cliniques portant sur des variations colorim etriques. M ETHODES: Parmi 54 femmes d'origine asiatique, un premier groupe a appliqu e un v ehicule deux fois par jour, pendant 28 jours. Un deuxi eme groupe a, lui, appliqu e une emulsion anti-âge. Des images de visage ont et e r ealis ees avant et apr es traitement. Les variations des valeurs L*a*b* ont et e etudi ees sur quatre r egions du visage pr e-s electionn ees. Nous avons egalement reconstruit des images de visages moyens pour lesquelles les param etres L*a*b* ont et e extraits pour chaque pixel. Pour ces mêmes pixels, les valeurs de pertinence (delta E) et significativit e ont et e calcul ees. A l'aide d'un gradient de couleur, nous avons repr esent e ces r esultats sur les images de visages moyens. RESULTATS: Apr es traitement, les param etres L*a*b* n'ont montr e aucun r esultat significativement pertinent pour le groupe ayant appliqu e le v ehicule. Pour le groupe "actif", la peau est devenue plus claire sur la part...

Aging of skin manifests in loss of volume and firming due to degradation of extracellular matrix components such as collagen and hyaluronic acid leading to wrinkling and sagging. To counteract loss of facial volume and regain firmness, fillers like hyaluronic acid (HA) are commonplace in cosmetic dermatology. We developed a synthetic tripeptide tetradecyl aminobutyroylvalylaminobutyric acid urea trifluoroacetate with proven hyaluronic acid stimulating activity in vitro. This study investigated the filling and firming activity of the tripeptide. In vitro: Microtissue technology was used to construct spherical 3D-skin equivalents. These were exposed to a tripeptide solution and content of hyaluronic acid and its receptor CD44 were assessed using histological techniques. Skin tissue culture was used to assess HA expression ex vivo. A placebo controlled, randomized, in parallel groups study to assess the firming, filling, and moisturizing activity of the peptide product was designed. We recruited 30 female Caucasian volunteers age 40 to 60 per group. Product application was twice daily for 29 days. Skin volume, deformation and moisturization were measured. HA and CD44 content in skin were increased in vitro and ex vivo. In vivo, skin firming was improved by a significant decrease in cheek deformation, a significantly restored skin volume below the eyes, and significantly improved skin hydration as measured on the cheekbone. We show evidence that the tripeptide tetradecyl-diaminobutyroylvalyldiaminobutyric urea trifluoroacetate restores facial skin volume by stimulating HA synthesis. These results underline the anti-aging activity of this synthetic tripeptide.