A combination of three antioxidants decreases the impact of rural particulate pollution in Normal human keratinocytes.

OBJECTIVE: It is well established that exposure of human skin to airborne pollution, particularly in the form of particulate matter sized 2.5 µm (PM2.5 ), is associated with oxidative stress, DNA damage and inflammation, leading to premature signs of skin aging. Because much of the damage results from oxidative stress, we examined the effects of a topical composition containing three antioxidants in an in vitro model system to assess the potential for amelioration of premature aging. The use of multiple antioxidants was of interest based on the typical composition of therapeutic skincare products. It is important to determine the efficacy of multiple antioxidants together and develop a short-term assay for larger scale efficacy testing. METHODS: Normal human epidermal keratinocytes were exposed to a rural-derived source of PM2.5 in the presence and absence of an antioxidant mixture of resveratrol, niacinamide and GHK peptide. Endpoints related to inflammation, premature aging and carcinogenicity were monitored after 5 h of exposure and included IL-6, CXCL10, MMP-1 and NRF2. Differentially expressed genes were monitored by RNA-seq. RESULTS: Pre-treatment of keratinocytes with the antioxidant preparation in the absence of PM2.5 reduced baseline levels of MMP-1, IL-6 and CYP1A1 and reduced PM2.5 -induced increases in all four endpoints, MMP-1, IL-6, CXCL10 and CYP1A1. Antioxidants significantly increased NRF2 protein in the presence of PM2.5 , indicating a protective response. RNA-seq interrogation of antioxidant-treated cells further showed increased expression of NRF2 inducible genes. The expression of CYP1A1 and genes related to aryl hydrocarbon activation were induced by PM2.5 and suppressed by antioxidants. CONCLUSIONS: Specific signalling pathways known to be correlated with skin inflammation and aging were examined based on their suitability for use in efficacy testing for the prevention of skin damage due to ambient hydrocarbon pollution. Endpoints examined after only 5 h of exposure provide a useful method amenable to high through-put screening. The results obtained reinforce the concept that a multiple antioxidant preparation, topically applied, may reduce pro-inflammatory signalling and cellular damage and thereby reduce premature skin aging due to exposure to rural-derived airborne pollution.

OBJECTIF: Il est bien établi que l'exposition de la peau humaine à la pollution atmosphérique, en particulier sous forme de particules d'une taille de 2,5 µm (PM2,5 ), est associée à un stress oxydatif, à des dommages à l'ADN et à une inflammation entraînant des signes prématurés de vieillissement cutané. Étant donné que la plupart des dommages résultent du stress oxydatif, nous avons examiné les effets d'une composition topique contenant trois antioxydants dans un système de modèle in vitro afin d'évaluer le potentiel d'amélioration du vieillissement prématuré. L'utilisation de plusieurs antioxydants a été intéressante en raison de la composition typique des produits thérapeutiques de soin de la peau. Il est important de déterminer l'efficacité de plusieurs antioxydants combinés et de développer un test à court terme pour des tests d'efficacité à plus grande échelle. MÉTHODES: Des kératinocytes épidermiques humains normaux ont été exposés à une source de PM2,5 rurale en présence et en l'absence d'un mélange antioxydant de resvératrol, de niacinamide et de peptide GHK. Les critères d'évaluation liés à l'inflammation, au vieillissement prématuré et à la carcinogénicité ont été surveillés après 5 heures d'exposition et comprenaient l'IL-6, CXCL10, MMP-1 et le NRF2. Les gènes exprimés de manière différentielle ont été surveillés par séquençage de l'ARN. RÉSULTATS: Le prétraitement des kératinocytes par la préparation antioxydante en l'absence de PM2,5 a réduit les taux initiaux de MMP-1, IL-6 et de CYP1A1 et a réduit les augmentations induites par les PM2,5 dans les quatre critères d'évaluation, MMP-1, IL-6, CXCL10 et CYP1A1. Les antioxydants ont significativement augmenté la protéine NRF2 en présence de PM2,5 , ce qui indique une réponse protectrice. L'interrogation des séquences d'ARN des cellules traitées par antioxydants a également montré une expression accrue des gènes inductibles par NRF2. L'expression du CYP1A1 et des gènes liés à l'activation des hydrocarbures aryles a été induite par les PM2,5 et supprimée par les antioxydants. CONCLUSIONS: Les voies de signalisation spécifiques connues pour être corrélées à l'inflammation cutanée et au vieillissement ont été examinées en fonction de leur adéquation à l'utilisation dans les tests d'efficacité pour la prévention des lésions cutanées dues à la pollution des hydrocarbures ambiants. Les critères d'évaluation examinés après seulement 5 heures d'exposition fournissent une méthode utile pouvant être utilisée pour un dépistage à haut débit. Les résultats obtenus renforcent le principe selon lequel une préparation antioxydante multiple, appliquée par voie topique, peut réduire la signalisation pro-inflammatoire et les dommages cellulaires et ainsi réduire le vieillissement prématuré de la peau résultant de l'exposition à la pollution atmosphérique d'origine rurale.

Vitamin D Update.

Purpose: The goal of this review is to provide an update in the field of vitamin D, in particular, the role of vitamin D in non-skeletal health, the complexity of providing patient guidance regarding obtaining sufficient vitamin D, and the possible involvement of vitamin D in morbidity and mortality due to SARS-CoV-2 (COVID-19). Recent Findings: In addition to bone health, vitamin D may play a role in innate immunity, cardiovascular disease, and asthma. Although rickets is often regarded as an historical disease of the early twentieth century, it appears to be making a comeback worldwide, including "first-world" countries. Broad-spectrum sunscreens (with high UVA filters) that prevent erythema are unlikely to compromise vitamin D status in healthy populations. Summary: New attention is now focused on the role of vitamin D in a variety of diseases, and more individualized patient recommendation schemes are being considered that take into account more realistic and achievable goals for achieving sufficient vitamin D through diet, supplements, and sun behavior.

Trichloroacetic acid model to accurately capture the efficacy of treatments for postinflammatory hyperpigmentation.

Postinflammatory hyperpigmentation (PIH) occurs following cutaneous injury and is common following resolution of acne especially in patients with skin of color. The objective of this study was to further validate a trichloroacetic acid (TCA)-induced PIH model and compare it to acne-induced PIH using topical bakuchiol, a botanical extract that has been shown to have antimicrobial, anti-inflammatory, antioxidant, and antiacne properties. A prospective, non-randomized clinical trial was conducted on subjects with skin phototypes IV-VI with a history of acne-induced PIH. Subjects applied bakuchiol or vehicle cream twice daily to 2 acne-induced and 2 TCA-induced PIH lesions for 28 days with a third lesion serving as a control in each group. Degree of improvement was defined as the change in the Investigator Global Assessment (IGA) score over 28 days of treatment. Twenty subjects (6 males, 14 females) completed the study. For TCA-induced PIH sites, there was a statistically significant (p < 0.05) degree of improvement with bakuchiol treatment (- 0.50 ± 0.18) compared to vehicle (0.05 ± 0.15) and control (- 0.06 ± 0.17). For acne-induced PIH, there was a greater degree of improvement for bakuchiol (- 1.06 ± 0.23) when compared to vehicle (- 0.56 ± 0.16) and control (- 0.69 ± 0.18); however, statistical significance was not reached (p > 0.05). TCA-induced PIH sites were uniform in size and pigment intensity thereby allowing better comparison among sites. This emphasizes the relevance of using this model for PIH which may help reduce the barriers in clinical trials and help improve access to treatments for patients who suffer from PIH. The results suggest that topical bakuchiol may decrease the severity of PIH.

Indoor PM2.5 exposure affects skin aging manifestation in a Chinese population.

Traffic-related air pollution is known to be associated with skin aging manifestations. We previously found that the use of fossil fuels was associated with skin aging, but no direct link between indoor air pollutants and skin aging manifestations has ever been shown. Here we directly measured the indoor PM2.5 exposure in 30 households in Taizhou, China. Based on the directly measured PM2.5 exposure and questionnaire data of indoor pollution sources, we built a regression model to predict the PM2.5 exposure in larger datasets including an initial examination group (N = 874) and a second examination group (N = 1003). We then estimated the association between the PM2.5 exposure and skin aging manifestations by linear regression. In the initial examination group, we showed that the indoor PM2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead (12.5% more spots per increase of IQR, P-value 0.0371), and wrinkle on upper lip (7.7% more wrinkle on upper lip per increase of IQR, P-value 0.0218). The results were replicated in the second examination group as well as in the pooled dataset. Our study provided evidence that the indoor PM2.5 exposure is associated with skin aging manifestation in a Chinese population.

Transcription factors and stress response gene alterations in human keratinocytes following Solar Simulated Ultra Violet Radiation.

Ultraviolet radiation (UVR) from sunlight is the major effector for skin aging and carcinogenesis. However, genes and pathways altered by solar-simulated UVR (ssUVR), a mixture of UVA and UVB, are not well characterized. Here we report global changes in gene expression as well as associated pathways and upstream transcription factors in human keratinocytes exposed to ssUVR. Human HaCaT keratinocytes were exposed to either a single dose or 5 repetitive doses of ssUVR. Comprehensive analyses of gene expression profiles as well as functional annotation were performed at 24 hours post irradiation. Our results revealed that ssUVR modulated genes with diverse cellular functions changed in a dose-dependent manner. Gene expression in cells exposed to a single dose of ssUVR differed significantly from those that underwent repetitive exposures. While single ssUVR caused a significant inhibition in genes involved in cell cycle progression, especially G2/M checkpoint and mitotic regulation, repetitive ssUVR led to extensive changes in genes related to cell signaling and metabolism. We have also identified a panel of ssUVR target genes that exhibited persistent changes in gene expression even at 1 week after irradiation. These results revealed a complex network of transcriptional regulators and pathways that orchestrate the cellular response to ssUVR.

Genetic variants associated with skin aging in the Chinese Han population.

BACKGROUND: The progression and manifestation of human skin aging has a strong genetic basis; however, most of the supporting evidence has been gathered in Caucasian populations. The genetic contribution to the variation in skin aging in non-Caucasian populations is poorly understood. OBJECTIVE: To investigate the genetic risk factors of relevance for skin aging in East Asians, we conducted the first candidate gene study for signs of skin aging in Han Chinese. METHODS: We collected skin aging and genotype data in 502 female Han Chinese from the Taizhou cohort. We evaluated skin aging by the validated skin aging score SCINEXA™. Confounding factors were assessed through a questionnaire. We obtained the genotype data for 21 candidate SNPs and for a further 509 SNPs from 16 related candidate genes. Associations were tested by linear and logistic regression analyses and adjusted for potential confounders. RESULTS: Our candidate study found a significant association between SNP rs2066853 in exon 10 of the aryl hydrocarbon receptor gene AHR and crow's feet. In addition, we found a significant association between SNP rs10733310 in intron 5 of BNC2 and pigment spots on the arms, and between SNP rs11979919, 3kb downstream of COL1A2, and laxity of eyelids. CONCLUSIONS: Our results identified genetic risk factors for signs of skin aging (pigmentation, wrinkles or laxity) in Han Chinese. We also found that the manifestation of skin aging is further modified by anatomical site. Together with previous work, our results also suggest that different genetic variants could be responsible for distinct skin aging signs characteristic of Caucasians compared to East Asians.

Extrinsic skin ageing in German, Chinese and Japanese women manifests differently in all three groups depending on ethnic background, age and anatomical site.

BACKGROUND: It has been suggested that extrinsic skin ageing manifests differently in Caucasians versus East Asians. In particular, from previous studies it was concluded that Caucasians are more prone to develop wrinkles, whereas pigment spot formation is the hallmark of extrinsic skin ageing in East Asians. However, these assumptions are based on a very limited number of studies which did not include different East Asian populations. OBJECTIVE: We here compare the manifestation of extrinsic skin ageing signs in German, Japanese and Chinese women by specifically elucidating the age and anatomical site dependence of any potential ethnic difference. METHODS: In the present study, we assessed skin ageing in N=902 German, N=165 Japanese and N=1260 Chinese women ranging from 30 to 90 years by means of SCINEXA™. Linear regression analysis was used to test for ethnic differences and their age and site dependence adjusted for educational level, sun exposure, smoking and sun protection behaviours. RESULTS: Pigment spots and wrinkles on the face were present among all three ethnic groups and differences were influenced by age and anatomical sites independently of further influencing factors. Pigment spots on the forehead were most pronounced over the whole age range in Chinese and German women and least developed in Japanese. Pigment spots on cheeks were a typical extrinsic skin an ageing sign in the two East Asian populations in all age groups. However, in older German women they reach the same level as observed in the two East Asian populations. In contrast, pigment spots on arms and hands were significantly more pronounced in German women ≥45years of age. Wrinkles were not exclusively a skin an ageing sign of German women, but were also very pronounced in Chinese women on forehead, between the eyebrows and in the crow's feet area. CONCLUSION: These results corroborate the previous notion that the occurrence of pigments spots and wrinkles is different between Caucasians and East Asians. In addition, this study shows that this difference depends on age and anatomical site and that it also differs between different ethnic groups from East Asia.

Biological Rhythms in the Skin.

Circadian rhythms, ≈24 h oscillations in behavior and physiology, are reflected in all cells of the body and function to optimize cellular functions and meet environmental challenges associated with the solar day. This multi-oscillatory network is entrained by the master pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which directs an organism's rhythmic expression of physiological functions and behavior via a hierarchical system. This system has been highly conserved throughout evolution and uses transcriptional-translational autoregulatory loops. This master clock, following environmental cues, regulates an organism's sleep pattern, body temperature, cardiac activity and blood pressure, hormone secretion, oxygen consumption and metabolic rate. Mammalian peripheral clocks and clock gene expression have recently been discovered and are present in all nucleated cells in our body. Like other essential organ of the body, the skin also has cycles that are informed by this master regulator. In addition, skin cells have peripheral clocks that can function autonomously. First described in 2000 for skin, this review summarizes some important aspects of a rapidly growing body of research in circadian and ultradian (an oscillation that repeats multiple times during a 24 h period) cutaneous rhythms, including clock mechanisms, functional manifestations, and stimuli that entrain or disrupt normal cycling. Some specific relationships between disrupted clock signaling and consequences to skin health are discussed in more depth in the other invited articles in this IJMS issue on Sleep, Circadian Rhythm and Skin.

Solar Simulated Ultraviolet Radiation Induces Global Histone Hypoacetylation in Human Keratinocytes.

Ultraviolet radiation (UVR) from sunlight is the primary effector of skin DNA damage. Chromatin remodeling and histone post-translational modification (PTM) are critical factors in repairing DNA damage and maintaining genomic integrity, however, the dynamic changes of histone marks in response to solar UVR are not well characterized. Here we report global changes in histone PTMs induced by solar simulated UVR (ssUVR). A decrease in lysine acetylation of histones H3 and H4, particularly at positions of H3 lysine 9, lysine 56, H4 lysine 5, and lysine 16, was found in human keratinocytes exposed to ssUVR. These acetylation changes were highly associated with ssUVR in a dose-dependent and time-specific manner. Interestingly, H4K16ac, a mark that is crucial for higher order chromatin structure, exhibited a persistent reduction by ssUVR that was transmitted through multiple cell divisions. In addition, the enzymatic activities of histone acetyltransferases were significantly reduced in irradiated cells, which may account for decreased global acetylation. Moreover, depletion of histone deacetylase SIRT1 in keratinocytes rescued ssUVR-induced H4K16 hypoacetylation. These results indicate that ssUVR affects both HDAC and HAT activities, leading to reduced histone acetylation.

Physiological and lifestyle factors contributing to risk and severity of peri-orbital dark circles in the Brazilian population.

BACKGROUND: Peri-orbital dark circles are a cosmetic concern worldwide, and have been attributed to hyperpigmentation from allergy or atopic dermatitis, blood stasis, structural shadowing effects, and a thin epidermis/dermis under the eye. It is of interest to better understand lifestyle and demographic risk factors and the relative impact of melanin, blood and epidermal/dermal factors on the severity of Peri-orbital dark circles. OBJECTIVE: To compare by non-invasive imaging the impact of biological factors to a visual grading scale for Peri-orbital dark circles, and test the correlation of various demographic factors with Peri-orbital dark circles. METHODS: Subjects completed a lifestyle and health survey, and Peri-orbital dark circles severity was evaluated using standardized photographs. Hyperspectral image analysis was used to assess the contributions of melanin, blood volume, degree of blood oxygen saturation, and dermal scattering. RESULTS: Family history was the most significant risk factor for Peri-orbital dark circles. The average age of onset was 24 years, and earlier onset correlated with higher severity scores. Asthma was significantly associated with Peri-orbital dark circles scores, but self-reported allergy was not. In this study, sleep was not correlated with Peri-orbital dark circles scores. Hyperspectral imaging indicated that melanin was the dominant correlate for Peri-orbital dark circles severity, while oxygen saturation was secondary. The difference between under-eye and cheek measurements for ΔL*and ΔE* were the most significant instrumental parameters correlated with visual assessment of Peri-orbital dark circles severity. CONCLUSION: Although typically associated with lack of sleep, risk of Peri-orbital dark circles is primarily hereditary. The main factors contributing to the appearance of Peri-orbital dark circles are melanin and (deoxygenated) blood.

Physiological and lifestyle factors contributing to risk and severity of peri-orbital dark circles in the Brazilian population

AbstractBACKGROUND:Peri-orbital dark circles are a cosmetic concern worldwide, and have been attributed to hyperpigmentation from allergy or atopic dermatitis, blood stasis, structural shadowing effects, and a thin epidermis/dermis under the eye. It is of interest to better understand lifestyle and demographic risk factors and the relative impact of melanin, blood and epidermal/dermal factors on the severity of Peri-orbital dark circles.OBJECTIVE:To compare by non-invasive imaging the impact of biological factors to a visual grading scale for Peri-orbital dark circles, and test the correlation of various demographic factors with Peri-orbital dark circles.METHODS:Subjects completed a lifestyle and health survey, and Peri-orbital dark circles severity was evaluated using standardized photographs. Hyperspectral image analysis was used to assess the contributions of melanin, blood volume, degree of blood oxygen saturation, and dermal scattering.RESULTS:Family history was the most significant risk factor for Peri-orbital dark circles. The average age of onset was 24 years, and earlier onset correlated with higher severity scores. Asthma was significantly associated with Peri-orbital dark circles scores, but self-reported allergy was not. In this study, sleep was not correlated with Peri-orbital dark circles scores. Hyperspectral imaging indicated that melanin was the dominant correlate for Peri-orbital dark circles severity, while oxygen saturation was secondary. The difference between under-eye and cheek measurements for ΔL*and ΔE* were the most significant instrumental parameters correlated with visual assessment of Peri-orbital dark circles severity.CONCLUSION:Although typically associated with lack of sleep, risk of Peri-orbital dark circles is primarily hereditary. The main factors contributing to the appearance of Peri-orbital dark circles are melanin and (deoxygenated) blood.

Epidemiological evidence that indoor air pollution from cooking with solid fuels accelerates skin aging in Chinese women.

BACKGROUND: Recently, we showed that outdoor air pollution exposure from traffic and industry is associated with an increased risk of skin aging in Caucasian women. In China, indoor air pollution exposure caused by the use of solid fuels like coal is a major health problem and might also increase the risk of skin aging in Chinese women. OBJECTIVE: As cooking with solid fuels is a major source of indoor air pollution exposure in China, we aimed to test if cooking with solid fuels is associated with more pronounced skin aging in Chinese women. METHODS: We conducted two cross-sectional studies in China to assess the association between cooking with solid fuels and signs of skin aging. In Pingding (in northern China) we assessed N=405 and in Taizhou (in southern China) N=857 women between 30 and 90 years of age. Skin aging was evaluated by the SCINEXA score. Indoor air pollution exposure, sun exposure, smoking and other confounders were assessed by questionnaires. Associations were then tested by linear and logistic regression analyses adjusted for further confounders. RESULTS: The analysis showed that cooking with solid fuels was significantly associated with a 5-8% more severe wrinkle appearance on face and an 74% increased risk of having fine wrinkles on back of hands in both studies combined, independent of age and other influences on skin aging. CONCLUSION: The present studies thus corroborate our previous finding that air pollution is associated with skin aging and extend it by showing that indoor air pollution might be another risk factor for skin aging.

Solar-simulated ultraviolet radiation induces histone 3 methylation changes in the gene promoters of matrix metalloproteinases 1 and 3 in primary human dermal fibroblasts.

Molecular signalling pathways delineating the induction of matrix metalloproteinases (MMPs) by ultraviolet radiation (UVR) are currently well-defined; however, the effects of UVR on epigenetic mechanisms of MMP induction are not as well understood. In this study, we examined solar-simulated UVR (ssUVR)-induced gene expression changes and alterations to histone methylation in the promoters of MMP1 and MMP3 in primary human dermal fibroblasts (HDF). Gene expression changes, including the increased expression of MMP1 and MMP3, were observed using Affymetrix GeneChip arrays and confirmed by qRT-PCR. Using ChIP-PCR, we showed for the first time that in HDF irradiated with 12 J/cm(2) ssUVR, the H3K4me3 transcriptional activating mark increased and the H3K9me2 transcriptional silencing mark decreased in abundance in promoters, correlating with the observed elevation of MMP1 and MMP3 mRNA levels following ssUVR exposure. Changes in mRNA levels due to a single exposure were transient and decreased 5 days after exposure.

MMP-1 and -3 promoter variants are indicative of a common susceptibility for skin and lung aging: results from a cohort of elderly women (SALIA).

Studies have indicated that there may be a smoking-dependent association between skin wrinkling and airflow obstruction of the lung. It was suggested that this association might be because of an underlying susceptibility in genes responsible for extracellular matrix (ECM) remodeling. Our purpose was to confirm the association between skin wrinkling and airflow obstruction and to identify genetic polymorphisms indicative of an underlying susceptibility. In 697 elderly women, we assessed skin wrinkles by SCINEXA (SCore for INtrinsic and EXtrinsic skin Aging) and airflow obstruction by spirometry, using the ratio of forced expiratory volume in 1 second (FEV1) to forced volume capacity (FVC). For association analysis, we used multiple regression and found that the FEV1/FVC ratio decreased 1.2% per 6-point increase in the wrinkle severity score after accounting for age, education, body mass index, skin type, and sun exposure. This association was significant and independent of smoking or air pollution. Most interestingly, this association occurred only in carriers of the matrix metalloproteinase-1 (MMP-1) 2G (rs1799750) or the MMP-3 6A (rs3025058) allele but not in homozygous carriers of the 1G or 5A allele. Thus, skin and lung aging are linked in carriers of the 2G or 6A allele. These alleles appear to be indicative of a common genetic susceptibility.

Omeprazole, a gastric proton pump inhibitor, inhibits melanogenesis by blocking ATP7A trafficking.

Omeprazole is a proton pump inhibitor used in the treatment of peptic ulcer disease and gastrosophageal reflux disease and acts by irreversibly blocking ATP4A, a P-type H+/K+ ATPase in gastric parietal cells. We found that omeprazole and its closely related congeners inhibited melanogenesis at micromolar concentrations in B16 mouse melanoma cells, normal human epidermal melanocytes, and in a reconstructed human skin model. Omeprazole topically applied to the skin of UV-irradiated human subjects significantly reduced pigment levels after 3 weeks compared with untreated controls. Omeprazole had no significant inhibitory effect on the activities of purified human tyrosinase or on the mRNA levels of tyrosinase, dopachrome tautomerase, Pmel17, or MITF mRNA levels. Although melanocytes do not express ATP4A, they do express ATP7A, a copper transporting P-type ATPase in the trans-Golgi network that is required for copper acquisition by tyrosinase. ATP7A relocalization from the trans-Golgi network to the plasma membrane in response to elevated copper concentrations in melanocytes was inhibited by omeprazole. Omeprazole treatment increased the proportion of EndoH sensitive tyrosinase, indicating that tyrosinase maturation was impaired. In addition, omeprazole reduced tyrosinase protein abundance in the presence of cycloheximide, suggestive of increased degradation. Our findings are consistent with the hypothesis that omeprazole reduces melanogenesis by inhibiting ATP7A and by enhancing degradation of tyrosinase.

The protein deacetylase SIRT3 prevents oxidative stress-induced keratinocyte differentiation.

Keratinocyte differentiation is a key process in the formation and maintenance of the protective skin barrier. Dysregulation in the balance of reactive oxygen species homeostasis may play a role in keratinocyte differentiation. We have identified the mitochondrial deacetylase SIRT3 as a key regulator of mitochondrial reactive oxygen species in keratinocytes. Our studies demonstrate that SIRT3 expression is down-regulated during keratinocyte differentiation, consistent with an increase in mitochondrial superoxide levels. Importantly, loss of SIRT3 expression in keratinocytes increased superoxide levels and promoted the expression of differentiation markers, whereas overexpression decreased superoxide levels and reduced the expression of differentiation markers. These findings identify a new role for SIRT3 in the suppression of epidermal differentiation via lowering oxidative stress.

Mitochondrial common deletion mutation and extrinsic skin ageing in German and Japanese women.

The mitochondrial common deletion (CD) mutation is induced by oxidative stress. One main source of oxidative stress is the error-prone process of the respiratory chain located in the mitochondria. Another important source is the exposure to environmental factors, which further induces oxidative stress in the cells. For human skin, the primary damaging environmental factor is ultraviolet (UV) radiation, which is able to induce CD mutations and the characteristic extrinsic skin ageing signs. Traditionally, levels of UV exposure differ between German and Japanese populations, as tanned skin represents beauty and health in Western cultures, whereas photo-protected skin is considered ideal in Asia. We hypothesize that (i) this cultural-related UV exposure pattern might be reflected by CD concentrations in environmentally exposed skin and (ii) CD concentrations in environmentally exposed areas might be associated with the manifestation of extrinsic skin ageing. In this study, we determined the concentration of CD in skin from the neck (environmentally exposed area) and the buttock (environmentally protected area) of 22 German and 46 Japanese women between 30 and 70 years of age. We evaluated skin ageing signs by a validated clinical score, and exposure to environmental factors, such as UV exposure and smoking, was assessed using a questionnaire-based interview. Higher levels of CD were detected in neck skin than in buttock skin in both German and Japanese women. CD also increased with age in the neck skin. German women had higher CD concentrations in the neck skin than Japanese women. The CD concentrations in the buttock skin samples were similar in both populations. These findings suggest higher environmental UV exposure resulted in higher levels of CD in the skin of German women compared with Japanese women. However, only in Japanese women were the signs of extrinsic skin ageing associated with higher CD concentrations in the neck skin, in agreement with the hypothesis (ii). In German women, we did not find this latter association, which might be due to reaching a maximum level of CD, beyond which cells undergo negative selection and are lost to the population samples. In conclusion, under some conditions, there seems to be an association between the CD mutation concentration and extrinsic skin ageing, but this may be modified by cellular and tissue processes which affect the sampling rate for CD mutation concentrations and prevent a statistical association with extrinsic skin ageing.

Sunburn protection as a function of sunscreen application thickness differs between high and low SPFs.

BACKGROUND: Sunscreens are an important component of healthy sun-protection behavior. To achieve satisfactory protection, sunscreens must be applied consistently, evenly and correctly. Consumers do not apply sunscreen properly and, therefore, do not achieve the protection indicated by the label 'sun protection factor' (SPF). The objective of the present study was to determine the actual sun(burn) protection given by a range of sunscreen application thickness levels for both low and high SPF formulas. SUBJECTS AND METHODS: Forty study subjects were recruited from each of three geographical regions in China. Sunscreens with label SPFs of 4, 15, 30, and 55 were tested at application levels of 0.5, 1.0, 1.5, and 2.0 mg/cm(2) in three laboratories using a standard SPF protocol. RESULTS: Sunscreens with lower SPFs (4 and 15) showed a linear dose-response relationship with application level, but higher SPF (30 and 55) product protection was exponentially related to application thickness. CONCLUSION: Sunscreen protection is not related in one uniform way to the amount of product applied to human skin. Consumers may achieve an even lower than expected sunburn protection from high SPF products than from low SPF sunscreens.