Piezo1 Activation Drives Enhanced Collagen Synthesis in Aged Animal Skin Induced by Poly L-Lactic Acid Fillers.

Poly L-lactic acid (PLLA) fillers stimulate collagen synthesis by activating various immune cells and fibroblasts. Piezo1, an ion channel, responds to mechanical stimuli, including changes in extracellular matrix stiffness, by mediating Ca2+ influx. Given that elevated intracellular Ca2+ levels trigger signaling pathways associated with fibroblast proliferation, Piezo1 is a pivotal regulator of collagen synthesis and tissue fibrosis. The aim of the present study was to investigate the impact of PLLA on dermal collagen synthesis by activating Piezo1 in both an H2O2-induced cellular senescence model in vitro and aged animal skin in vivo. PLLA elevated intracellular Ca2+ levels in senescent fibroblasts, which was attenuated by the Piezo1 inhibitor GsMTx4. Furthermore, PLLA treatment increased the expression of phosphorylated ERK1/2 to total ERK1/2 (pERK1/2/ERK1/2) and phosphorylated AKT to total AKT (pAKT/AKT), indicating enhanced pathway activation. This was accompanied by upregulation of cell cycle-regulating proteins (CDK4 and cyclin D1), promoting the proliferation of senescent fibroblasts. Additionally, PLLA promoted the expression of phosphorylated mTOR/S6K1/4EBP1, TGF-ß, and Collagen I/III in senescent fibroblasts, with GsMTx4 treatment mitigating these effects. In aged skin, PLLA treatment similarly upregulated the expression of pERK1/2/ERK1/2, pAKT/AKT, CDK4, cyclin D1, mTOR/S6K1/4EBP1, TGF-ß, and Collagen I/III. In summary, our findings suggest Piezo1's involvement in PLLA-induced collagen synthesis, mediated by heightened activation of cell proliferation signaling pathways such as pERK1/2/ERK1/2, pAKT/AKT, and phosphorylated mTOR/S6K1/4EBP1, underscoring the therapeutic potential of PLLA in tissue regeneration.

Photothermal Biostimulation of Platelet-Rich Plasma Improves Hand Rejuvenation Clinical Outcome: A Pilot Study.

Objective: This study aimed to evaluate physical skin changes and patients' subjective perception of treatment with photothermal bioactivated platelet-rich plasma (MCT Plasma) for hand rejuvenation. Background: Age-related changes in the dorsum of the hand include volume loss, dyschromia, and soft-tissue atrophy, which result in wrinkles and prominent deep structures. Methods: We conducted a prospective, single-center, randomized pilot study on 10 healthy female volunteers from 30 to 65 years with hand aging signs. Patients received two sessions of MCT Plasma on the treated hand and two sessions of standard platelet-rich plasma (PRP) on the control hand. Results were assessed through high-frequency ultrasonography, photographs, a patient satisfaction survey, patient perception of skin aspect, and patient perception of amelioration survey. Results: Ten women with a mean age of 57.5 years (standard deviation 10.5, range 31 - 67) were included, and seven (70%) completed the study. The treated hands' skin subepidermal low-echogenic band (SLEB) decreased from 20% to 60%, and 57.1% (n = 4) had better results than control. Twenty percent of patients were very satisfied with the results, 40% were satisfied, 40% were neutral, and none were unsatisfied or very unsatisfied. Patients perceived the skin of the treated hand (MCT Plasma) as "much better" (20%), "better" (60%), and "no changes" (20%) compared with the skin of the control hand (standard PRP). No treatment-related adverse events were reported during the study. Conclusions: Hands treated with MCT Plasma tended to have better outcomes in reducing SLEB compared with those treated with standard PRP. Patients were satisfied and the treatment was safe with no technical complications. However, further randomized controlled trials with larger sample sizes are mandatory to validate the extent of improvement provided by this device based on photothermal biomodulation.

Cellular senescence and wound healing in aged and diabetic skin.

Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it is often accompanied by the secretion of various factors, such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes tissue repair, regeneration, and development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, tissue dysfunction, and intractable wounds. The effects of cellular senescence on skin wound healing can be both beneficial and detrimental, depending on the condition. Here, we reviewed the functional differences in cellular senescence that emerge during wound healing, chronic inflammation, and skin aging. We also review the latest mechanisms of wound healing in the epidermis, dermis, and subcutaneous fat, with a focus on cellular senescence, chronic inflammation, and tissue regeneration. Finally, we discuss the potential clinical applications of promoting and inhibiting cellular senescence to maximize benefits and minimize detrimental effects.

[Practical problems with the use of topicals in geriatric dermatology]. / Praktische Aspekte bei der Anwendung von Topika in der geriatrischen Dermatologie.

Changes related to aging affect all layers of the skin and are influenced by both intrinsic conditions and extrinsic factors. The extent of the senescent changes can vary enormeously in seniors, so that an individual assessment is useful and often necessary. Of particular clinical importance are changes in the epidermis, which entail a complex reduction of the barrier function and a reduction in the compensatory capacity with regard to exogenous noxae. This results in increased susceptibility, especially toward infection and cancer. Against this background, a prophylactic strategy for the substitution of the physicochemical and thus also the microbiological barrier in the context of basic care is very important. In order to be able to implement these consistently, recommendations for preparations explicitly designed for aging skin as well as practical instructions for use are highly meaningful. The latter should take into account limitations regarding mobility as well as possible cognitive deficits of seniors. For this purpose, creams and suitable preparations in terms of viscosity and composition should be recommended. In order to facilitate implementation, written or pictorial recommendations for application as well as digital assistance systems can be used. Due to demographic developments in Germany and Europe, the clinical relevance of geriatric dermatology will significantly increase in the future.

Poly-D,L-Lactic Acid Filler Increases Extracellular Matrix by Modulating Macrophages and Adipose-Derived Stem Cells in Aged Animal Skin.

Poly-D,L-lactic acid (PDLLA) filler corrects soft tissue volume loss by increasing collagen synthesis in the dermis; however, the mechanism is not fully understood. Adipose-derived stem cells (ASCs) are known to attenuate the decrease in fibroblast collagen synthesis that occurs during aging, and nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) increases ASCs survival by inducing M2 macrophage polarization and IL-10 expression. We evaluated the ability of PDLLA to induce collagen synthesis in fibroblasts by modulating macrophages and ASCs in a H2O2-induced cellular senescence model and aged animal skin. PDLLA increased M2 polarization and NRF2 and IL-10 expression in senescence-induced macrophages. Conditioned media from senescent macrophages treated with PDLLA (PDLLA-CMMΦ) reduced senescence and increased proliferation and expression of transforming growth factor-ß (TGF-ß) and fibroblast growth factor (FGF) 2 in senescence-induced ASCs. Conditioned media from senescent ASCs treated with PDLLA-CMMΦ (PDLLA-CMASCs) increased the expression of collagen 1a1 and collagen 3a1 and reduced the expression of NF-κB and MMP2/3/9 in senescence-induced fibroblasts. Injection of PDLLA in aged animal skin resulted in increased expression of NRF2, IL-10, collagen 1a1, and collagen 3a1 and increased ASCs proliferation in aged animal skin. These results suggest that PDLLA increases collagen synthesis by modulating macrophages to increase NRF2 expression, which stimulates ASCs proliferation and secretion of TGF-ß and FGF2. This leads to increased collagen synthesis, which can attenuate aging-induced soft tissue volume loss.

Oleuropein-Rich Gellan Gum/Alginate Films as Innovative Treatments against Photo-Induced Skin Aging.

Olea europaea L. leaf extracts (OLEs) represent highly value-added agro-industrial byproducts, being promising sources of significant antioxidant compounds, such as their main component, oleuropein. In this work, hydrogel films based on low-acyl gellan gum (GG) blended with sodium alginate (NaALG) were loaded with OLE and crosslinked with tartaric acid (TA). The films' ability to act as an antioxidant and photoprotectant against UVA-induced photoaging, thanks to their capability to convey oleuropein to the skin, were examined with the aim of a potential application as facial masks. Biological in vitro performances of the proposed materials were tested on normal human dermal fibroblasts (NhDFs), both under normal conditions and after aging-induced UVA treatment. Overall, our results clearly show the intriguing properties of the proposed hydrogels as effective and fully naturally formulated anti-photoaging smart materials for potential use as facial masks.

Poly-D,L-Lactic Acid Stimulates Angiogenesis and Collagen Synthesis in Aged Animal Skin.

Angiogenesis promotes rejuvenation in multiple organs, including the skin. Heat shock protein 90 (HSP90), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) are proangiogenic factors that stimulate the activities of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase 1/2 (ERK1/2). Poly-D,L-lactic acid (PDLLA), polynucleotide (PN), and calcium hydroxyapatite (CaHA) are dermal fillers that stimulate the synthesis of dermal collagen. However, it is not yet known whether these compounds promote angiogenesis, which leads to skin rejuvenation. Here, we evaluated whether PDLLA, PN, and CaHA stimulate angiogenesis and skin rejuvenation using H2O2-treated senescent macrophages and endothelial cells as an in vitro model for skin aging, and we used young and aged C57BL/6 mice as an in vivo model. Angiogenesis was evaluated via endothelial cell migration length, proliferation, and tube formation after conditioned media (CM) from senescent macrophages was treated with PDLLA, PN, or CaHA. Western blot showed decreased expression levels of HSP90, HIF-1α, and VEGF in senescent macrophages, but higher expression levels of these factors were found after treatment with PDLLA, PN, or CaHA. In addition, after exposure to CM from senescent macrophages treated with PDLLA, PN, or CaHA, senescent endothelial cells expressed higher levels of VEGF receptor 2 (VEGFR2), PI3K, phosphorylated AKT (pAKT), and phosphorylated ERK1/2 (pERK1/2) and demonstrated greater capacities for cell migration, cell proliferation, and tube formation. Based on the levels of 4-hydroxy-2-nonenal, the oxidative stress level was lower in the skin of aged mice injected with PDLLA, PN, or CaHA, while the tumor growth factor (TGF)-ß1, TGF-ß2, and TGF-ß3 expression levels; the density of collagen fibers; and the skin elasticity were higher in the skin of aged mice injected with PDLLA, PN, or CaHA. These effects were greater in PDLLA than in PN or CaHA. In conclusion, our results are consistent with the hypothesis that PDLLA stimulates angiogenesis, leading to the rejuvenation of aged skin. Our study is the first to show that PDLLA, PN, or CaHA can result in angiogenesis in the aged skin, possibly by increasing the levels of HSP90, HIF-1α, and VEGF and increasing collagen synthesis.

Aging and Wound Healing of the Skin: A Review of Clinical and Pathophysiological Hallmarks.

Aging is a universal process that can cause diminished function of organs and various diseases. The most striking consequences of aging can be seen visibly on the skin, which acts as a barrier against various external insults. Aging of the skin consists of intrinsic and extrinsic processes that work in concert and influence each other. Intrinsic aging involves biochemical degenerative processes that gradually takes place with age. Extrinsic aging are biochemical processes driven by external influences that lead to aging. There are significant morphological changes at all levels in aged skin that have a profound effect on the characteristics of the skin. Even though skin is subjected to damage by external insults, it is equipped with a healing capability in order to restore its normal structure and function. However, aging has a significant impact on the skin's healing function by prolonging the inflammatory phase and increasing the production of reactive oxygen species (ROS). This shifts the healing process towards having more protein degradation, which can lead to chronic wound healing with an abundance of complications.

Combined Treatment of Monopolar and Bipolar Radiofrequency Increases Skin Elasticity by Decreasing the Accumulation of Advanced Glycated End Products in Aged Animal Skin.

It is well known that skin aging is related to the destruction of collagen and elastin fibers by metalloproteinases (MMPs). Aged fibroblasts have a decreased ability to synthesize collagen and elastin. Nuclear factor erythroid 2-related factor 2 (NRF2) involves glyoxalase (GLO) activation, which inhibits the production of advanced glycated end products (AGE) and the expression of its receptor (RAGE). RAGE increases nuclear transcription factor-kappa B (NF-κB), which upregulates MMPs and decreases skin elasticity. NRF2 also decreases M1 macrophages, which secrete tumor necrosis factor-alpha (TNF-α), thereby decreasing AGE production. It is well known that radiofrequency (RF) decreases skin elasticity by increasing collagen synthesis. We evaluated whether RF increases skin elasticity via NRF2/GLO and whether they decrease AGE and RAGE expression in aged animal skin. We also compared the effects of RF based on the modes (monopolar or bipolar) or the combination used. In aged skin, NRF2, GLO-1, and M2 macrophage expression was decreased, and their expression increased when RF was applied. M1 and TNF-α demonstrated increased expression in the aged skin and decreased expression after RF application. AGE accumulation and RAGE, NF-κB, and MMP2/3/9 expression were increased in the aged skin, and they were decreased by RF. The papillary and reticular fibroblast markers showed decreased expression in young skin and increased expression in aged skin. The densities of collagen and elastin fiber in the aged skin were low, and they were increased by RF. In conclusion, RF leads to increased collagen and elastin fibers by increasing NRF2/GLO-1 and modulating M1/M2 polarization, which leads to decreased AGE and RAGE and, consequently, decreased NF-κB, which eventually slows collagen and elastin destruction. RF also leads to increased collagen and elastin fiber synthesis by increasing papillary and reticular fibroblast expression.

2,4-Dihydroxyphenyl-benzo[d]thiazole (MHY553), a synthetic PPARα agonist, decreases age-associated inflammatory responses through PPARα activation and RS scavenging in the skin.

We previously reported that 2,4-dihydroxyphenyl-benzo[d]thiazole (MHY553) is a PPARα agonist, which has been shown to inhibit tyrosinase activity in murine melanocyte and alleviate hepatic steatosis in aged rats. This study investigated the effects of MHY553 on the age-related occurrence of inflammatory responses via the molecular modulation of the nuclear factor-κB (NF-κB) signaling pathway in the skin of aged rats and skin fibroblast cells. Moreover, we investigated the antioxidant effect of MHY553 via in vitro assays of reactive oxygen species (ROS) and peroxynitrite (ONOO-) scavenging activities. We also scrutinized the ability of MHY553 as a PPARα activator in aged rat skin and H2O2-induced Hs27 fibroblast cells. In vivo experiments were performed in young, aged, and MHY553-fed aged rats (3 mg or 5 mg∙kg -1∙day -1 for 4 weeks). MHY553 dose-dependently scavenged ROS and ONOO-. Furthermore, we found that MHY553 suppressed the NF-κB transcription factor and downregulated mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling. MHY553 also inhibited the expression of pro-inflammatory cytokines including COX-2, iNOS, IL-1ß, and IL-6. Our findings indicate the MHY553 scavenges ROS/reactive nitrogen species and inhibits inflammatory cytokines through PPARα activation in the skin. Thus, these results suggest that MHY553 may be of therapeutic interest for protecting skin from oxidative stress-induced damage and intrinsic aging.

Potential anti-ageing effect of chondroitin sulphate through skin regeneration.

OBJECTIVE: Skin ageing is inevitably exposed through its typical features such as wrinkles and sagging. Therefore, skin anti-ageing is a major issue in cosmetic research to prevent and improve ageing symptoms using effective ingredients. Chondroitin sulphate (CS), a type of glycosaminoglycan, is an important structural component of the extracellular matrix (ECM) and is involved in various biological processes, such as cell proliferation, differentiation and migration. Here, we aimed to investigate the effects of CS on skin regeneration and examine its efficacy as a potential safe and effective skin anti-ageing ingredient. METHODS: We investigated the effects of CS on cell proliferation in normal human keratinocytes and fibroblasts. Then, cell migration, ECM synthesis and related signalling pathways were examined in fibroblasts through gene and protein expression analysis. Finally, the effect on skin wound healing and regeneration was validated using a full-thickness skin wound model and an aged skin model. RESULTS: Chondroitin sulphate treatment increased the proliferation of keratinocytes and fibroblasts. It also stimulated the migration and synthesis of ECM components of fibroblasts. Further analysis revealed that CS induced the expression of type I procollagen by activating the extracellular signal-regulated kinase pathway. Using a full-thickness skin wound model and an aged skin model, we confirmed that CS treatment promoted skin wound healing and regeneration. CONCLUSION: Together, our results indicated that CS has the potential to facilitate skin regeneration, implying that CS could be clinically applied to improve skin ageing.

OBJECTIF: Le vieillissement cutané est inévitable, dans ses caractéristiques intrinsèques nous trouvons l'apparition des rides et l'affaissement de la peau. Sachant cela, l'anti-âge cutané est un enjeu majeur de la recherche cosmétique où sa prévention ou son amélioration sont faites à l'aide d'ingrédients efficaces. Le sulfate de chondroïtine (CS), un type de glycosaminoglycane, est un composant structurel important de la matrice extracellulaire (ECM) et il est aussi impliqué dans les divers processus biologiques, tels que la prolifération, la différenciation et la migration cellulaire. Dans le travail présenté ici, nous avons étudié les effets du CS sur la régénération de la peau et son efficacité en tant qu'ingrédient anti-âge cutané sûr. MÉTHODES: Nous avons étudié les effets du CS sur la prolifération cellulaire des kératinocytes et fibroblastes humains normaux. Ensuite, la migration cellulaire, la synthèse de la ECM et les voies de signalisation associées ont été examinées dans les fibroblastes par l'analyse de l'expression des gènes et des protéines. Finalement, l'effet sur la cicatrisation et la régénération cutanées a été validé à l'aide d'un modèle de plaie cutanée « full thickness ¼ et d'un modèle de peau âgée. RÉSULTATS: Le traitement au sulfate de chondroïtine a augmenté la prolifération des kératinocytes et des fibroblastes. Il a également stimulé la migration et la synthèse des composants de la MEC des fibroblastes. Une analyse plus approfondie a démontré que CS induisait l'expression du procollagène du type I en activant la voie de la kinase régulée par le signal extracellulaire. En utilisant un modèle de plaie cutanée « full thickness ¼ et un modèle de peau âgée, nous avons confirmé que le traitement CS favorisait la cicatrisation et la régénération des blessures cutanées. CONCLUSION: Dans l'ensemble, nos résultats ont indiqué que le CS a le potentiel de faciliter la régénération de la peau, ce qui implique que le CS pourrait être appliqué cliniquement pour améliorer le vieillissement cutané.

Low molecular weight heparan sulfate containing facial skin care for reducing inflammation and restoring aged-skin homeostasis.

BACKGROUND: Chronic exposure of the skin to environmental factors, including solar radiation and air pollution, promotes skin aging by inducing inflammation which damages the skin. Heparan sulfate (HS) is one of the glycosaminoglycans, which has a central role in modulating skin repair. In its appearance in the skin, HS is large and highly polar and therefore unable to penetrate the skin. As a component in a topical formulation, the modified to a low molecular weight heparan sulfate analog (LMW-HS) showed biological modulation activity. AIMS: This review discusses the potential role of topical formulations containing LMW-HS in restoring aged-skin homeostasis and skin health. METHODS: An expert panel of dermatologists who regularly treat clinical signs of facial photoaging explored the role of LMW-HS containing formulations for reducing inflammation and facial-aging signs. For this purpose, evidence from the conducted literature searches was used together with expert opinion and experience of the panel. RESULTS: Extrinsic factors contribute to skin aging through oxidative stress, stimulating inflammation involved in extracellular matrix degradation. Evidence showed that chemokines require heparan sulfate for their full range of functional activities during innate immunity. Studies showed the LMW-HS containing topical formulation to penetrate the skin within 48 hours of once-daily application. LMW-HS used in the periorbital area improved discoloration and wrinkles at Week 2 with continuous improvement up to Week 12. CONCLUSION: The LMW-HS containing formulation showed improvements in skin condition when applied on photo-damaged skin, indicating its therapeutic potential.

Skin tears: prevention and management.

Skin tears commonly occur at the extremes of age and are associated with skin changes in ageing skin. They are considered to be acute wounds caused by mechanical forces, such as blunt trauma. While the true prevalence and incidence of skin tears is unknown, the available evidence suggests that these wounds occur in all healthcare settings. Importantly, skin tears are preventable with the implementation of a risk-reduction programme, which includes twice-daily skin moisturisation. Where these injuries do occur, it is important to categorise the extent of damage as well as to choose the most appropriate dressing to avoid adding any risks for further trauma.

Neuroendocrine Aspects of Skin Aging.

Skin aging is accompanied by a gradual loss of function, physiological integrity and the ability to cope with internal and external stressors. This is secondary to a combination of complex biological processes influenced by constitutive and environmental factors or by local and systemic pathologies. Skin aging and its phenotypic presentation are dependent on constitutive (genetic) and systemic factors. It can be accelerated by environmental stressors, such as ultraviolet radiation, pollutants and microbial insults. The skin's functions and its abilities to cope with external stressors are regulated by the cutaneous neuroendocrine systems encompassing the regulated and coordinated production of neuropeptides, neurohormones, neurotransmitters and hormones, including steroids and secosteroids. These will induce/stimulate downstream signaling through activation of corresponding receptors. These pathways and corresponding coordinated responses to the stressors decay with age or undergo pathological malfunctions. This affects the overall skin phenotype and epidermal, dermal, hypodermal and adnexal functions. We propose that skin aging can be attenuated or its phenotypic presentation reversed by the topical use of selected factors with local neurohormonal activities targeting specific receptors or enzymes. Some of our favorite factors include melatonin and its metabolites, noncalcemic secosteroids and lumisterol derivatives, because of their low toxicity and their desirable local phenotypic effects.

Skin acidification with a water-in-oil emulsion (pH 4) restores disrupted epidermal barrier and improves structure of lipid lamellae in the elderly.

The pH of the skin surface increases with age and thus reduces epidermal barrier function. Aged skin needs appropriate skin care to counterbalance age-related pH increase and improve barrier function. This confirmatory randomized study investigated the efficacy of water-in-oil (w/o) emulsions with either pH 4 or pH 5.8 in 20 elderly subjects after 4 weeks of treatment. After the treatment, the skin was challenged with a sodium dodecyl sulphate (SDS) solution in order to analyze barrier protection properties of both formulations. The pH 4 w/o emulsion resulted in a significantly lower skin pH compared with the pH 5.8 w/o emulsion and an improved skin hydration after 4-week treatment. Further, the pH 4 emulsion led to more pronounced improvements in length of intercellular lipid lamellae, lamellar organization as well as lipid levels than the pH 5.8 emulsion. Following SDS-induced barrier damage to the skin, the pH of all test areas increased, but the area treated with the pH 4 emulsion showed the lowest increase compared with baseline. In addition, even after the SDS challenge the skin area treated with the pH 4 emulsion still maintained a significantly increased length of intercellular lipid lamellae compared with the beginning of the study. This study provides evidence that topical application of a w/o emulsion with pH 4 reacidifies the skin in elderly and has beneficial effects on skin moisturization, regeneration of lipid lamellae and lipid content. Application of a pH 4 emulsion can improve the epidermal barrier as well as the stratum corneum organization in aged skin.

Rejuvenation of aged rat skin with pulsed electric fields.

The demand for skin rejuvenation procedures has progressively increased in the past decade. Additionally, clinical trials have shown that current therapies might cause downtime and side effects in patients including prolonged erythema, scarring, and dyspigmentation. The goal of this study was to explore the effect of partial irreversible electroporation (pIRE) with pulsed electric fields in aged skin rejuvenation as a novel, non-invasive skin resurfacing technique. In this study, we used an experimental model of aged rats. We showed that treatment with pIRE promoted keratinocyte proliferation and blood flow in aged rat skin. We also found significant evidence indicating that pIRE reformed the dermal extracellular matrix (ECM). Both the collagen protein and fibre density in aged skin increased after pIRE administration. Furthermore, using an image-processing algorithm, we found that the collagen fibre orientation in the histological sections did not change, indicating a lack of scar formation in the treated areas. The results showed that pIRE approach could effectively stimulate keratinocyte proliferation, ECM synthesis, and angiogenesis in an aged rat model.

Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.

Relationship between skin color and solar elastosis in aged Asian skin: A colorimetric-pathologic correlation.

Aged skin is reported to be associated with unattractive skin color changes and solar elastosis. However, comparative studies have not documented the possible correlation between the two factors. This study investigated the plausible relationship between the facial skin color of elderly Asians and solar elastosis. A total of 22 skin specimens were collected from 22 Korean patients who underwent cheek skin biopsies. Skin color was quantitatively measured using colorimetric photography techniques to produce CIE L*a*b* values; the degree of solar elastosis was quantifiably assessed using a histologic grading scale. These values were used to investigate a correlation between the CIE L*a*b* coordinates and solar elastosis grade. The solar elastosis grade increased according to patient age (r = 0.67, p = .0006). However, the extent of solar elastosis was not statistically correlated with the CIE L*a*b* values, including L*, a*, and b* (r = 0.02, p = .95; r = 0.15, p = 0.50; r = -0.07, p = 0.76, respectively). The results showed that the solar elastosis grade increased, according to patient age, because of cumulative actinic damage. However, colorimetric skin color data did not correlate with the degree of solar elastosis. Therefore, cutaneous color changes and solar elastosis are separate, age-related phenomena. Physicians should be aware of the possible histologic changes in actinically damaged facial skin, regardless of the skin color.

A new dermocosmetic containing retinaldehyde, delta-tocopherol glucoside and glycylglycine oleamide for managing naturally aged skin: results from in vitro to clinical studies.

INTRODUCTION: Natural aging of skin tissues, the addition of the cumulative action of the time and radiation exposure result in skin atrophy, wrinkles and degeneration of the extracellular matrix (ECM). The aim of the study was to investigate the beneficial effect of a combination containing retinaldehyde (RAL), delta-tocopherol glucoside (delta-TC) and glycylglycine ole-amide (GGO) and of a dermocosmetic containing the combination. MATERIALS AND METHODS: The protective effect of the combination was assessed through in vitro gene expression of ultraviolet (UV)-irradiated fibroblasts. A skin aging assay using UV light on ex vivo skin samples and a clinical study conducted in 36 women aged from 35 to 55 years with a minimum of level 4 to a maximum of level 6 on the crow's feet photoscale assessed the antiaging effect of the dermocosmetic. RESULTS: When added to UV-irradiated fibroblasts, the combination substantially improved the ECM in activating the elastin fiber production (fibrillin 2, fibulin 1 and 5 and lysyl oxidase-like 2) as well as that of proteins involved in the cellular ECM interactions (integrin b1, paxillin and actin a2). An ex vivo photodamaged human skin model showed that the dermocosmetic formulation containing the combination of the active ingredients protected the elastic network against UV-induced alterations including both elastin and fibrillin-rich fibers in the dermis. A daily application of the dermocosmetic for 2 months on naturally aged skin resulted in a statistically significant improvement (p<0.05) of visible signs of aging comprising crow's feet, wrinkles and periocular fine lines. Finally, the formulation was well tolerated. CONCLUSION: The dermocosmetic containing RAL, delta-TC and GGO provides a substantial benefit in the daily care of naturally aged skin in women aged 35-55 years.