Skin Aging, Cellular Senescence and Natural Polyphenols.

The skin, being the barrier organ of the body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found to accumulate with age and may contribute to age-related skin changes and pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on skin aging. By affecting molecular pathways of senescence, polyphenols are able to prevent or delay the senescence formation and, consequently, avoid or ameliorate aging and age-associated pathologies of the skin. This review aims to provide an overview of the current state of knowledge in skin aging and cellular senescence, and to summarize the recent in vitro studies related to the anti-senescent mechanisms of natural polyphenols carried out on keratinocytes, melanocytes and fibroblasts. Aged skin in the context of the COVID-19 pandemic will be also discussed.

Dietary Collagen Hydrolysates Ameliorate Furrowed and Parched Skin Caused by Photoaging in Hairless Mice.

Collagen hydrolysates have been suggested as a favorable antiaging modality in skin photoaged by persistent exposure to ultraviolet radiation (UV). The current study evaluated the beneficial effect of collagen hydrolysates (fsCH) extracted from Pangasius hypophthalmus fish skin on wrinkle formation and moisture preservation in dorsal skin of hairless mice challenged with UV-B. Inter-comparative experiments were conducted for anti-photoaging among fsCH, retinoic acid (RA), N-acetyl-D-glucosamine (NAG), and glycine-proline-hydroxyproline (GPH). Treating human HaCaT keratinocytes with 100-200 µg/mL fsCH reciprocally ameliorated the expression of aquaporin 3 (AQP3) and CD44 deranged by UV-B. The UV-B-induced deep furrows and skin thickening were improved in parched dorsal skin of mice supplemented with 206-412 mg/kg fsCH as well as RA and GPH. The UV-B irradiation enhanced collagen fiber loss in the dorsal dermis, which was attenuated by fsCH through enhancing procollagen conversion to collagen. The matrix metalloproteinase expression by UV-B in dorsal skin was diminished by fsCH, similar to RA and GPH, via blockade of collagen degradation. Supplementing fsCH to UV-B-irradiated mice decreased transepidermal water loss in dorsal skin with reduced AQP3 level and restored keratinocyte expression of filaggrin. The expression of hyaluronic acid synthase 2 and hyaluronidase 1 by UV-B was remarkably ameliorated with increased production of hyaluronic acid by treating fsCH to photoaged mice. Taken together, fsCH attenuated photoaging typical of deep wrinkles, epidermal thickening, and skin water loss, like NAG, RA, or GPH, through inhibiting collagen destruction and epidermal barrier impairment.

Trends in the Use of Botanicals in Anti-Aging Cosmetics.

Botanical ingredients have been used for thousands of years in skincare for their convenience as well as the diversity and abundance in compounds with biological activity. Among these, polyphenols and especially flavonoids have gained increasing prominence due to their antioxidant and anti-inflammatory properties. In this study, the most used botanical preparations in anti-aging products marketed in 2011 were determined. The analysis was repeated in 2018 for new and reformulated products. The scientific evidence for their application as active ingredients in anti-aging cosmetics and their flavonoid content was also compiled by searching in online scientific databases. Overall, in 2018, there was a noticeable increase in the use of botanical preparations in anti-aging cosmetics. However, the top three botanical species in both years were Vitis vinifera, Butyrospermum parkii, and Glycine soja, which is consistent with the greater amount of scientific evidence supporting their efficacy. Regarding the function of botanical preparations, there is a clear preference for DNA-protecting ingredients. The most prevalent flavonoids were flavan-3-ols, proanthocyanidins, and anthocyanins. This study provided an updated overview of the market trends regarding the use of botanicals in anti-aging products and documented the state of the art of scientific evidence for the most used plants.

Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging.

Skin is the largest and most complex organ in the human body comprised of multiple layers with different types of cells. Different kinds of environmental stressors, for example, ultraviolet radiation (UVR), temperature, air pollutants, smoking, and diet, accelerate skin aging by stimulating inflammatory molecules. Skin aging caused by UVR is characterized by loss of elasticity, fine lines, wrinkles, reduced epidermal and dermal components, increased epidermal permeability, delayed wound healing, and approximately 90% of skin aging. These external factors can cause aging through reactive oxygen species (ROS)-mediated inflammation, as well as aged skin is a source of circulatory inflammatory molecules which accelerate skin aging and cause aging-related diseases. This review article focuses on the inflammatory pathways associated with UVR-mediated skin aging.

A Validated Photonumeric Scale for the Evaluation of Neck Skin Laxity.

BACKGROUND: Neck aging is usually evaluated together with the lower face. To date, a skin laxity scale for the neck as an independent anatomical district is lacking. OBJECTIVE: To create and validate a proposed photonumeric neck skin laxity (NSL) scale. MATERIALS AND METHODS: Frontal neck photographic images of 110 subjects were collected. Each standardized neck image was evaluated twice by 3 independent doctors, 1 week apart. A 4-point photonumeric NSL scale was developed (0 = absence of skin laxity and 4 = severe skin laxity) and validated in terms of intraobserver and interobserver correlation and internal consistency. RESULTS: The intraobserver reliability analysis of the 2 assessments performed by each observer revealed excellent correlation and consistency of the severity grading, independently of the time of evaluation (from 0.96 to 0.99, p < .01). Furthermore, the interobserver reliability analysis revealed an excellent agreement between the evaluators and an internal consistency independent of the evaluator (0.97, p < .01). CONCLUSION: The newly developed NSL scale is a reliable and reproducible scoring system for the aesthetic evaluation of skin laxity of the neck.

Inhibition of EGR-1-dependent MMP1 transcription by ethanol extract of Ageratum houstonianum in HaCaT keratinocytes.

Matrix metalloproteinase 1 (MMP-1) initiates the breakdown of matrix networks by cleaving fibrillar collagen during the pathophysiological progression of skin aging. Ageratum houstonianum ethanol extract (AHE) has been used as a traditional herbal medicine to treat external wounds and skin diseases. However, the mechanism of action underlying A. houstonianum-mediated modulation of skin aging has not been investigated. In this study, we evaluated the effect of AHE on MMP-1 expression in HaCaT keratinocytes. Gene expression was analyzed by Reverse transcription-PCR (RT-PCR), Quantitative real-time PCR (Q-PCR), gene promoter-reporter assay, and immunoblotting. We found that AHE abrogated TNFα-induced MMP1 expression at the transcriptional level via the suppression of ERK1/2 mitogen-activated protein kinase (MAPK)-mediated Early Growth Response 1 (EGR1) expression. We also demonstrated that ß-caryophyllene, a cannabinoid receptor 2 (CB2) agonist, is a functional component of the AHE that inhibits TNFα-induced EGR-1 and MMP1 expression. AHE exerts inhibitory activity on TNFα-induced MMP1 expression at the transcription level through EGR-1 downregulation in keratinocytes. ß-Caryophyllene is a bioactive ingredient of AHE that is responsible for the inhibition of TNFα-induced EGR1 expression. ß-Caryophyllene can be used as a potential agent to prevent inflammation-induced skin aging.

The association of photo-induced collagen degeneration and the development of telangiectasias in rosacea.

Rosacea is a chronic, often progressive disorder characterized by facial erythema, telangiectasias, papules, pustules, and/or rhinophyma. In this study, we investigated the tissue structure in rosacea compared to controls. We performed a case-control study between five patients with mild-to-moderate erythematotelangiectatic rosacea (ETR) and five matched controls. Facial biopsy samples from rosacea patients and controls were stained with picrosirius red for collagen and CD31 for microvessel identification. Mean collagen content was significantly greater in control samples (19.603% ±8.821%) compared to rosacea samples (16.812% ± 7.787%, p = 0.030). In contrast, mean microvessel density was significantly higher in rosacea patients (4.775 E-5 ± 1.493 E-5 µm-3 ) compared to controls (2.559 E-5 ± 8.732 E-6 µm-3 , p = 0.004). Mean microvessel lumen area was also significantly higher in rosacea patients (491.710 ± 610.188 µm2 ) compared to controls (347.879 ± 539.624 µm2 , p = 0.003). We identified a correlation between decreased collagen content and increased microvessel size and density in rosacea patients that was not observed in controls. These structural changes to the dermal matrix may contribute to the characteristic vessel growth and dilation in rosacea.

Pro-inflammatory cytokines suppress HYBID (hyaluronan (HA) -binding protein involved in HA depolymerization/KIAA1199/CEMIP) -mediated HA metabolism in human skin fibroblasts.

In the skin, the metabolism of hyaluronan (HA) is highly regulated. Aging leads to chronic low-grade inflammation, which is characterized by elevated levels of pro-inflammatory cytokines; however, the relationship between inflammation and HA metabolism is not clear. Herein, we investigated the effects of a mixture of pro-inflammatory cytokines containing TNF-α, IL-1ß, and IL-6 on HA metabolism in human skin fibroblasts. Treatment with the cytokine mixture for 24 h suppressed HA depolymerization via downregulation of HYBID (HA-binding protein involved in HA depolymerization/KIAA1199/CEMIP) and promoted HA synthesis via upregulation of HAS2 in human skin fibroblasts. Moreover, HAS2-dependent HA synthesis was driven mainly by IL-1ß with partial contribution from TNF-α. Transmembrane protein 2 (TMEM2/CEMIP2), which was previously reported as a candidate hyaluronidase, was upregulated by the cytokine mixture, suggesting that TMEM2 might not function as a hyaluronidase in human skin fibroblasts. Furthermore, the effects of the cytokine mixture on HA metabolism were observed in fibroblasts after 8 days of treatment with cytokines during three passages. Thus, we have shown that HYBID-mediated HA metabolism is negatively regulated by the pro-inflammatory cytokine mixture, providing novel insights into the relationship between inflammation and HA metabolism in the skin.

Lycium barbarum polysaccharide fraction associated with photobiomodulation protects from epithelium thickness and collagen fragmentation in a model of cutaneous photodamage.

Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The polysaccharide fraction (LBPF) isolated from Lycium Barbarum fruits (goji berry) contains several active ingredients with antioxidant, immune system modulation, and antitumor effects. In addition, the photobiomodulation (PBM) is widely applied in photoaging treatment. This study investigated the effects of LBPF and PBM against the UVR-induced photodamage in the skin of hairless mice. The mice were photoaged for 6 weeks in a chronic and cumulative exposure regimen using a 300-W incandescent lamp that simulates the UVR effects. From the third to the sixth week of photoaging induction, the animals received topical applications of LBPF and PBM, singly or combined, in different orders (first LBPF and then PBM and inversely), three times per week after each session of photoaging. After completion of experiments, the dorsal region skin was collected for the analysis of thickness, collagen content, and metalloproteinases (MMP) levels. A photoprotective potential against the increase of the epithelium thickness and the fragmentation of the collagen fibers was achieved in the skin of mice treated with LBPF or PBM singly, as well as their combination. All treatments maintained the skin collagen composition, except when PBM was applied after the LBPF. However, no treatment protected against the UVR-induced MMP increase. Taken together, we have shown that the LBPF and PBM promote a photoprotective effect in hairless mice skin against epidermal thickening and low collagen density. Both strategies, singly and combined, can be used to reduce the UVR-induced cutaneous photoaging.

The Secretome of Aged Fibroblasts Promotes EMT-Like Phenotype in Primary Keratinocytes from Elderly Donors through BDNF-TrkB Axis.

Age-related changes in the dermis can play a primary role in tumor initiation promoting the unrestrained proliferation of precancerous keratinocytes (KCs) through cytokines and GF secretion. We found a high percentage of epithelial-to-mesenchymal transition-like colonies raising in primary human KC cultures from old subjects after treatment with aged fibroblast supernatants (SPNs). Continuous extracellular signals were required for maintaining these changes. Conversely, the secretome did not induce epithelial-to-mesenchymal transition-like colonies in KCs from young subjects. SPN-treated aged KCs displayed the activation of pathways involved in the disjunction of cell‒cell adhesion, extracellular matrix remodeling, manifestation of a mesenchymal phenotype, and dedifferentiation programs. Moreover, they recovered proliferation and clonogenic ability and showed enhanced migration. We identified an age-related increase of the BDNF secretion from fibroblasts as well as of the expression of its receptor TrkB in KCs. BDNF treatment of aged KCs induced TrkB phosphorylation and recapitulated the modifications promoted by aged fibroblast SPN. Furthermore, the treatment with a specific antibody against BDNF or a TrkB antagonist inhibited the paracrine signaling preventing SPN-mediated morphological and molecular changes. Finally, BDNF induced signs of matrix invasion in a three-dimensional organotypic model. Therefore, we demonstrate that aged fibroblast SPN promotes phenotypic plasticity in KCs from the elderly through BDNF-TrkB axis.

The bright and dark side of skin senescence. Could skin rejuvenation anti-senescence interventions become a "bright" new strategy for the prevention of age-related skin pathologies?

The number of senescent cells in the skin is increasing with age. Numerous studies have attempted to elucidate the role of these cells in normal aging of the skin as well as in age-related skin conditions. In recent years, attempts have also been made to find treatments that aim either to cleanse the skin tissues of senescent cells or to neutralize their effects (referred to as senolytics and senomorphics respectively) and thus prevent the consequences, particularly on the skin's appearance in advanced age. Through this review, we have tried to gather data on the role of senescent cells in the skin, in treatments aimed at removing them, and we are asking a reasonable question as to whether anti-senescence treatments may contribute to the protection against age-related skin pathologies, including skin cancer, such as non-melanoma skin cancer, in addition to their involvement in skin rejuvenation.

Cellular Senescence and the Senescence-Associated Secretory Phenotype as Drivers of Skin Photoaging.

Chronic exposure to UVR is known to disrupt tissue homeostasis, accelerate the onset of age-related phenotypes, and increase the risk for skin cancer-a phenomenon defined as photoaging. In this paper, we review the current knowledge on how UV exposure causes cells to prematurely enter cellular senescence. We describe the mechanisms contributing to the accumulation of senescent cells in the skin and how the persistence of cellular senescence can promote impaired regenerative capacity, chronic inflammation, and tumorigenesis associated with photoaging. We conclude by highlighting the potential of senolytic drugs in delaying the onset and progression of age-associated phenotypes in the skin.

[Skin aging: Pathophysiology and innovative therapies]. / Vieillissement cutané - Physiopathologie et thérapies innovantes.

One of the major challenges of the 21st century is the fight against aging, defined as a set of physiological mechanisms altering the physical and intellectual capacities of human beings. Aging of the skin is only one visible part of this process. It is associated with major healing defects linked in part to the alteration of the biomechanical properties of skin cells, mainly dermal fibroblasts. The immune system, another key component in maintaining skin homeostasis and the efficient healing of wounds, also suffers the effects of time: the consequent skin immunosenescence would limit the anti-infectious and vaccine response, while promoting a pro-tumor environment. The main skin damages due to aging, whether intrinsic or extrinsic, will be detailed before listing the effective anti-aging strategies to combat age-related dermal and epidermal stigmas.

TITLE: Vieillissement cutané - Physiopathologie et thérapies innovantes. ABSTRACT: Un des enjeux majeurs de ce XXIe siècle est la lutte contre le vieillissement, défini comme un ensemble de mécanismes physiologiques altérant les capacités physiques et intellectuelles de l'organisme. Le vieillissement de la peau n'est qu'un trait visible de ce processus. Il est associé à des défauts de cicatrisation majeurs liés à l'altération des propriétés biomécaniques des cellules cutanées, essentiellement des fibroblastes dermiques. Le système immunitaire, autre composante clé du maintien de l'homéostasie cutanée et du bon déroulement de la cicatrisation des plaies, subit aussi les effets du temps : l'immunosénescence cutanée consécutive limiterait la réponse anti-infectieuse et vaccinale, tout en favorisant un environnement pro-tumoral. Les principales atteintes cutanées dues au vieillissement, que celui-ci soit intrinsèque ou extrinsèque, seront détaillées avant d'énumérer les stratégies anti-âges efficaces pour lutter contre les stigmates dermiques et épidermiques liées à l'âge.

The role of Hrd1 in ultraviolet (UV) radiation induced photoaging.

The purpose of the present study was to evaluate the role of Hrd1 in the ultraviolet (UV) radiation induced photoaging and explore its potential mechanism. The nude mice were exposed to the UVA/UVB irradiation for 10 weeks. The animals were subcutaneously injected with AAV5-NC, Hrd1-shRNA-AAV5, or Hrd1-overexpression-AAV5. The HSF cells were also transfected with Ad-NC, Ad-shRNA-Hrd1, or Ad-Hrd1, and irradiated by UVA/UVB stimulation. The clinical skin samples were harvested for detecting Hrd1 and IGF-1R expressions. As a result, the knockdown of Hrd1 attenuated the histopathological alteration and collagen degradation in UV-induced nude mice. The inhibition of Hrd1 by Hrd1-shRNA-AAV5 and Ad-shRNA-Hrd1 inhibited the Hrd1 expression and promoted IGF-1R, Type I collagen and type III collagen in mice and HSF cells. The overexpression of Hrd1 exerted the reverse effect. The Co-IP assay also indicated the interaction between Hrd1 and IGF-1R. Hrd1-mediated IGF-1R downregulation and collagen degradation were also observed in clinical skin samples. In conclusion, the present results demonstrated that Hrd1 degraded IGF-1R and collagen formation in UV-induced photoaging.

The Role of microRNAs in Organismal and Skin Aging.

The aging process starts directly after birth and lasts for the entire lifespan; it manifests itself with a decline in an organism's ability to adapt and is linked to the development of age-related diseases that eventually lead to premature death. This review aims to explore how microRNAs (miRNAs) are involved in skin functioning and aging. Recent evidence has suggested that miRNAs regulate all aspects of cutaneous biogenesis, functionality, and aging. It has been noted that some miRNAs were down-regulated in long-lived individuals, such as let-7, miR-17, and miR-34 (known as longevity-related miRNAs). They are conserved in humans and presumably promote lifespan prolongation; conversely, they are up-regulated in age-related diseases, like cancers. The analysis of the age-associated cutaneous miRNAs revealed the increased expression of miR-130, miR-138, and miR-181a/b in keratinocytes during replicative senescence. These miRNAs affected cell proliferation pathways via targeting the p63 and Sirtuin 1 mRNAs. Notably, miR-181a was also implicated in skin immunosenescence, represented by the Langerhans cells. Dermal fibroblasts also expressed increased the levels of the biomarkers of aging that affect telomere maintenance and all phases of the cellular life cycle, such as let-7, miR-23a-3p, 34a-5p, miR-125a, miR-181a-5p, and miR-221/222-3p. Among them, the miR-34 family, stimulated by ultraviolet B irradiation, deteriorates collagen in the extracellular matrix due to the activation of the matrix metalloproteinases and thereby potentiates wrinkle formation. In addition to the pro-aging effects of miRNAs, the plausible antiaging activity of miR-146a that antagonized the UVA-induced inhibition of proliferation and suppressed aging-related genes (e.g., p21WAF-1, p16, and p53) through targeting Smad4 has also been noticed. Nevertheless, the role of miRNAs in skin aging is still not fully elucidated and needs to be further discovered and explained.

tBHP treatment as a model for cellular senescence and pollution-induced skin aging.

Accumulation of senescent cells promotes the development of age-related pathologies and deterioration. In human skin, senescent cells potentially impair structure and function by secreting a mixture of signaling molecules and proteases that influence neighboring cells and degrade extracellular matrix components, such as elastin and collagen. One of the key underlying mechanisms of senescence and extrinsic skin aging is the increase of intracellular reactive oxygen species and resulting oxidative stress. Tert-butyl hydroperoxide (tBHP) is a known inducer of oxidative stress and cellular damage, acting at least in part by depleting the antioxidant glutathione. Here, we provide a detailed characterization of tBHP-induced senescence in human dermal fibroblasts in monolayer culture. In addition, results obtained with more physiological experimental models revealed that tBHP treated 3D reconstructed skin and ex vivo skin developed signs of chronic tissue damage, displaying reduced epidermal thickness and collagen fiber thinning. We, therefore, propose that tBHP treatment can be used as a model to study the effects of extrinsic skin aging, focusing mainly on the influence of environmental pollution.

Mitochondria in skin health, aging, and disease.

The skin is a high turnover organ, and its constant renewal depends on the rapid proliferation of its progenitor cells. The energy requirement for these metabolically active cells is met by mitochondrial respiration, an ATP generating process driven by a series of protein complexes collectively known as the electron transport chain (ETC) that is located on the inner membrane of the mitochondria. However, reactive oxygen species (ROS) like superoxide, singlet oxygen, peroxides are inevitably produced during respiration and disrupt macromolecular and cellular structures if not quenched by the antioxidant system. The oxidative damage caused by mitochondrial ROS production has been established as the molecular basis of multiple pathophysiological conditions, including aging and cancer. Not surprisingly, the mitochondria are the primary organelle affected during chronological and UV-induced skin aging, the phenotypic manifestations of which are the direct consequence of mitochondrial dysfunction. Also, deletions and other aberrations in the mitochondrial DNA (mtDNA) are frequent in photo-aged skin and skin cancer lesions. Recent studies have revealed a more innate role of the mitochondria in maintaining skin homeostasis and pigmentation, which are affected when the essential mitochondrial functions are impaired. Some common and rare skin disorders have a mitochondrial involvement and include dermal manifestations of primary mitochondrial diseases as well as congenital skin diseases caused by damaged mitochondria. With studies increasingly supporting the close association between mitochondria and skin health, its therapeutic targeting in the skin-either via an ATP production boost or free radical scavenging-has gained attention from clinicians and aestheticians alike. Numerous bioactive compounds have been identified that improve mitochondrial functions and have proved effective against aged and diseased skin. In this review, we discuss the essential role of mitochondria in regulating normal and abnormal skin physiology and the possibility of targeting this organelle in various skin disorders.

Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes.

Particulate matter (PM), a major air pollutant, is a complex mixture of solid and liquid particles of various sizes. PM has been demonstrated to cause intracellular inflammation in human keratinocytes, and is associated with various skin disorders, including atopic dermatitis, eczema, and skin aging. Resveratrol is a natural polyphenol with strong antioxidant properties, and its beneficial effects against skin changes due to PM remain elusive. Therefore, in the present study, we investigated the effect of resveratrol on PM-induced skin inflammation and attempted to deduce the molecular mechanisms underlying resveratrol's effects. We found that resveratrol inhibited PM-induced aryl hydrocarbon receptor activation and reactive oxygen species formation in keratinocytes. It also suppressed the subsequent cellular inflammatory response by inhibiting mitogen-activated protein kinase activation. Consequentially, resveratrol reduced PM-induced cyclooxygenase-2/prostaglandin E2 and proinflammatory cytokine expression, including that of matrix metalloproteinase (MMP)-1, MMP-9, and interleukin-8, all of which are known to be central mediators of various inflammatory conditions and aging. In conclusion, resveratrol inhibits the PM-induced inflammatory response in human keratinocytes, and we suggest that resveratrol may have potential for preventing air pollution-related skin problems.

Clinical improvement of photoaging-associated facial hyperpigmentation in Korean skin with a picosecond 1064-nm neodymium-doped yttrium aluminum garnet laser.

Traditional attempts at alleviating photoaging-associated facial pigmentation conditions such as melasma, mottled hyperpigmentation, and post-inflammatory hyperpigmentation have yielded disfiguring cosmetic results. Laser toning using a low-fluence Q-switched 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser has been more commonly applied to date. However, the treatment efficacy and safety of this approach have not been widely reported. This study therefore evaluated the efficacy and safety of picosecond 1064-nm Nd:YAG laser application for photoaging-associated facial pigmentation treatment in Korean subjects. Forty-seven Korean subjects with photoaging-associated facial pigmentation underwent picosecond 1064-nm laser application. The clinical improvement of 17 patients was assessed by objective measurements such as melanin and erythema indices. All subjects received six biweekly treatments with the laser in a three-pass fashion delivering approximately 2000 to 2500 shots using a zoom handpiece with a spot size of 7 mm, fluence ranging from 0.4 to 0.7 J/cm2, and a repetition rate of 10 Hz. Clinicians evaluated the improvement of pigmentation using the pigmentation area and severity index (PSI), and subjects reported their satisfaction level on a four-point scale. Statistical analyses were performed using the SPSS version 19.0 for Windows software program (IBM Corp., Armonk, NY, USA). Forty-seven subjects (45 females and two males) completed this study with a 12-week follow-up period. The average decrease in PSI value at 12 weeks after treatment was 6.85 ± 6.35 points (p < 0.001). The average decreases in the values of the erythema and melanin indices were 19.41 ± 64.64 points (p = 0.234) and 28.88 ± 32.89 points (p = 0.002). An analysis of 32 subjects' reports (68.1%) suggested good or excellent improvement. No serious adverse effects were observed during treatment or the follow-up period. Picosecond 1064-nm Nd:YAG laser application appears to be safe and effective in improving various photoaging-associated facial pigmentation conditions in Korean skin.

Suppressor of Fused Inhibits Skin Wound Healing.

Objectives: To investigate the effect of suppressor of fused (Sufu) on epidermal and dermal cellular properties and in wound healing. Approach: Transgenic (TG) mice overexpressing human Sufu (hSufu) in the epidermis were applied to investigate the effects of Sufu on epidermal and dermal cellular properties and in wound healing. Results: Histological staining revealed a reduction of epidermal and dermal thickness and an increase of hypodermal adipose tissue in homozygous K14-hSufu TG mice when compared with wild-type (WT) controls. TG mice exhibited significantly delayed skin wound healing. Moreover, the migratory and proliferative capabilities of cultured keratinocytes were decreased in K14-hSufuTG mice. Transforming growth factor-ß treatment increased the expression of α-smooth muscle actin more in WT than in TG fibroblasts. Sufu overexpression significantly decreased the expression of ß-catenin, glioma transcription factor 1 (Gli1), and matrix metalloproteinase-3 in wounds of K14-hSufu TG mice when compared with controls, probably indicating a delaying effect of Sufu on wound healing via blocking the hedgehog (Hh)/Gli and Wnt/ß-catenin pathway. Innovation: Our results indicate a new property of Sufu in the process of skin wound healing. It provides an important basis for Sufu as a potential target for skin wound healing. Conclusion: Our findings suggest that Sufu overexpression in the epidermis impairs wound healing via dampening the Hh/Gli and Wnt/ß-catenin signaling pathway. These data provide an important basis for further analyses of Sufu in skin wound healing.