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Background Melanism is more frequent in animals living in polluted areas at urban-industrial sites. Given that a growing part of the human population is exposed to elevated air pollution levels, we wondered if environmental pollutants might affect melanogenesis in human skin likewise. Epidemiological studies in Caucasians and East Asians indeed showed that exposure to traffic-related air pollutants such as Diesel Exhaust Particles (DEP) is associated with more clinical signs of hyperpigmentation. Mechanistic evidence linking DEP exposure with pigmentation, however, has been elusive. Objectives to develop an ex vivo skin model allowing topical repetitive application of ambient relevant DEP and proof-of-concept in humans. Methods Measurement of skin pigmentation, melanin and pigmentation associated gene expression and evaluation of oxidative stress. Results Repetitive exposure of ex vivo skin to DEP at non-toxic concentrations increased pigmentation. This increase was visible by the naked eye, time-dependent, associated with an increase in melanin content and transcription of genes involved in melanin de novo synthesis. In healthy subjects (n=76) repetitive topical application of DEP at non-toxic concentrations increased skin pigmentation similarly. DEP-induced pigmentation was mediated by an oxidative stress response, because after DEP application (i) epidermal antioxidants were depleted, (ii) lipid peroxidation and oxidative DNA damage were enhanced, and (iii) in a vehicle-controlled, double-blinded, clinical study DEP-induced pigmentation was prevented by topical application of an antioxidant mixture. Conclusion Similar to solar radiation, air pollutants cause skin tanning. Since eumelanin is an antioxidant, we propose that this response serves to protect human skin against air pollution-induced oxidative stress.

Introduction: Skin ageing involves senescent fibroblast accumulation, disturbance in extracellular matrix (ECM) homeostasis, and decreased collagen synthesis. Objective: to assess a cell therapy product for aged skin (RCS-01; verum) consisting of ~25 × 106 cultured, autologous cells derived from anagen hair follicle non-bulbar dermal sheath (NBDS). Methods: For each subject in the verum group, 4 areas of buttock skin were injected intradermally 1 or 3 times at monthly intervals with RCS-01, cryomedium, or needle penetration without injection; in the placebo group RCS-01 was replaced by cryomedium. The primary endpoint was assessment of local adverse event profiles. As secondary endpoints, expression of genes related to ECM homeostasis was assessed in biopsies from randomly selected volunteers in the RCS-01 group taken 4 weeks after the last injection. ­Results: Injections were well tolerated with no severe adverse events reported 1 year after the first injection. When compared with placebo-treated skin, a single treatment with RCS-01 resulted in a significant upregulation of TGFβ1, CTGF, COL1A1, COL1A2, COL3A1, and lumican mRNA expression. Limitations: The cohort size was insufficient for dose ­ranging evaluation and subgroup analyses of efficacy. Conclusions: RCS-01 therapy is well tolerated and associated with a gene expression response consistent with an improvement of ECM homeostasis.

SummaryBackground Increasing evidence suggests photo-protection by oral supplementation with s-carotene and lycopene. Objectives We examined the capacity of lycopene rich tomato nutrient complex (TNC) and lutein, to protect against UVA/B- and UVA1 radiation at a molecular level. Methods In a placebo-controlled, double blinded, randomized cross over study two actives containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 radiation-inducible genes including heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-1 (MMP-1). 65 healthy volunteers were allocated to 4 treatment groups and subjected to a 2-weeks wash-out phase, followed by two 12-weeks treatment phases separated by another 2-weeks wash-out. Volunteers started either with active and switched then to placebo or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 hours later biopsies were taken from untreated, UVB/A- and UVA1 irradiated skin for subsequent RT-PCR analysis of gene expression. Moreover, blood samples were taken after the wash out and the treatment phases for assessment of carotenoids. Results TNC completely inhibited UVA1 as well as UVA/B induced upregulation of HO-1, ICAM-1 and MMP1 mRNA no matter of sequence (ANOVA, p

Nutritional strategies to benefit skin health are of growing importance. Current approaches mainly involve nutritional supplements containing antioxidants which were initially designed to protect human skin against ultraviolet radiation-induced damage. Within recent years, however, a growing number of studies suggests that the beneficial effects of these products clearly extend beyond photoprotection. In this review we take the nutritional supplement Pycnogenol®, which is based on an extract prepared from French marine pine bark extract, as an example to illustrate this development. Accordingly, the existing data provide compelling evidence that Pycnogenol® intake does not only provide photoprotection, but may be used to (i) reduce hyperpigmentation of human skin and (ii) improve skin barrier function and extracellular matrix homeostasis.

Photoprotection of human skin by means of sunscreens or daily skin-care products is traditionally centered around the prevention of acute (e.g. sunburn) and chronic (e.g. skin cancer and photoaging) skin damage that may result from exposure to ultraviolet rays (UVB and UVA). Within the last decade, however, it has been appreciated that wavelengths beyond the ultraviolet spectrum, in particular visible light and infrared radiation, contribute to skin damage in general and photoaging of human skin in particular. As a consequence, attempts have been made to develop skin care/sunscreen products that not only protect against UVB or UVA radiation but provide photoprotection against visible light and infrared radiation as well. In this article, we will briefly review the current knowledge about the mechanisms responsible for visible light/infrared radiation-induced skin damage and then, based on this information, discuss strategies that have been successfully used or may be employed in the future to achieve photoprotection of human skin beyond ultraviolet radiation. In this regard we will particularly focus on the use of topical antioxidants and the challenges that result from the task of showing their efficacy.

Introduction and Objectives: In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. Materials and Methods: For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. Results: Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. Conclusions: This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.

The efficacy of sunscreens to protect against ultraviolet (UV) A radiation is usually assessed by measuring erythema formation and pigmentation. The biological relevance of these endpoints for UVA-induced skin damage, however, is not known. We therefore carried out two complementary studies to determine UVA protection provided by a broad-spectrum sunscreen product at a molecular level by studying UVA radiation-induced gene expression. One study was performed on human reconstructed skin in vitro with a semi-global gene expression analysis of 227 genes in fibroblasts and 244 in keratinocytes. The second one was conducted in vivo in human volunteers and focused on genes involved in oxidative stress response and photo-ageing (haeme oxygenase-1, superoxide dismutase-2, glutathione peroxidase, catalase, matrix metalloproteinase-1). In-vitro UVA radiation induced modulation of genes involved in extracellular matrix homeostasis, oxidative stress, heat shock responses, cell growth, inflammation and epidermal differentiation. Sunscreen pre-application abrogated or significantly reduced these effects, as underlined by unsupervised clustering analysis. The in vivo study confirmed that the sunscreen prevented UVA radiation-induced transcriptional expression of the five studied genes. These findings indicate the high efficacy of a broad-spectrum sunscreen in protecting human skin against UVA-induced gene responses and suggest that this approach is a biologically relevant complement to existing methods.

Infrared A radiation (IRA) from solar sunlight contributes to photoaging of human skin, e.g. by upregulating MMP-1 expression in dermal fibroblasts, indicating the need for photoprotection of human skin against IRA. Up to now, however, there has been no controlled study to show that effective protection of human skin against IRA radiation is possible. Here, we have conducted a randomized, controlled, double-blinded prospective study in 30 healthy volunteers to assess the capacity of an SPF 30 sunscreen versus the same sunscreen supplemented with an antioxidant cocktail containing grape seed extract, vitamin E, ubiquinone and vitamin C to protect human skin against IRA radiation-induced MMP-1 upregulation. As expected, exposure to IRA radiation significantly upregulated MMP-1 expression, as compared to unirradiated skin, and this response was significantly reduced, if the SPF30 sunscreen plus the antioxidant cocktail had been applied prior to IRA radiation. In contrast, treatment of human skin with the SPF30 sunscreen alone did not provide significant protection. These results indicate that topically applied antioxidants effectively protect human skin against IRA radiation and that regular sunscreens need to be supplemented with specific antioxidants in order to achieve IRA photoprotection.