Establishment and application of perceived age prediction model for the periocular aging research of Chinese Han women.

BACKGROUND: The assessment of skin aging through skin measurements faces limitations, making perceived age evaluation a more valuable and direct tool for assessing skin aging. Given that the aging process markedly affects the appearance of the eye contour, characterizing the eye region could be beneficial for perceived age assessment. This study aimed to analyze age-correlated changes in the eye contour within the Chinese Han female population and to develop, validate, and apply a multiple linear regression model for predicting perceived age. MATERIALS AND METHODS: A naïve panel of 107 Chinese women assessed the perceived ages of 212 Chinese Han women. Instrumental analysis evaluated periorbital parameters, including palpebral fissure width (PFW), palpebral fissure height (PFH), acclivity of palpebral fissure (AX), angle of inner canthal (AEN), and angle of outer canthal (AEX). These parameters were used to construct a multiple linear regression model for predicting the perceived ages of Chinese Han women. A combined treatment using Fotona 4D and an anti-aging eye cream, formulated with plant extracts, peptides, and antioxidants, was conducted to verify the cream's anti-aging efficacy and safety. This eye cream was then tested in a large-scale clinical trial involving 101 participants. The prediction model was employed in this trial to assess the perceived ages of the women after an 8-week application of the eye cream. RESULTS: All parameters were observed to decrease with age. An intergroup comparison indicated that eyelid aging in Chinese Han women accelerates beyond the age of 50. Consequently, a linear regression model was constructed and validated, with the perceived age being calculated as 183.159 - 1.078 * AEN - 4.487 * PFW + 6.061 * PFH - 1.003 * AX - 0.328 * AEX. The anti-aging efficacy and safety of the eye cream were confirmed through combined treatment with Fotona 4D, showing improvements in wrinkles, elasticity, and dark circles under the eyes. In a large-scale clinical evaluation using this eye cream, a perceived age prediction model was applied, suggesting that 8 weeks of use made participants appear 2.25 years younger. CONCLUSION: Our study developed and validated a multiple linear regression model to predict the perceived age of Chinese Han women. This model was successfully utilized in a large-scale clinical evaluation of anti-aging eye cream, revealing that 8 weeks of usage made participants appear 2.25 years younger. This method effectively bridges the gap between clinical research and consumer perceptions, explores the complex factors influencing perceived age, and aims to improve anti-aging formulations.

Use of platelet rich plasma for skin rejuvenation.

OBJECTIVE: Platelet-rich plasma (PRP) is recognized as a safe and effective therapy for regenerative skin healing and rejuvenation, utilizing autologous blood enriched with various growth factors. This review aims to assess the efficacy of PRP treatments for skin rejuvenation. METHODS: Keywords such as "platelet-rich plasma," "rejuvenation," "skin aging," and "wrinkles" were queried on Ovid, PubMed, and MEDLINE to identify pertinent studies on PRP treatment for skin rejuvenation. RESULTS: Analysis revealed that PRP treatment led to significant enhancements in multiple facial parameters after one to three sessions. Improvements were noted in skin pore size, texture, wrinkle reduction, pigmented spots, collagen density, hyaluronic acid levels, and protection against ultraviolet damage. Combining PRP with hyaluronic acid demonstrated a synergistic effect, particularly enhancing skin elasticity in patients with lower body mass index and firmness in individuals aged 50s and 60s. Incorporating both physical and biometric data for assessment proved superior to relying solely on physical observations for evaluating subtle skin quality and structural changes. CONCLUSION: This study underscores the efficacy of PRP monotherapy for skin rejuvenation and emphasizes the necessity of standardizing PRP preparation protocols in future investigations. Heightened awareness and advancements in technology have contributed to the emergence of higher-quality, less biased studies supporting PRP as a reliable and safe therapeutic option for skin rejuvenation.

A novel approach to the detection of facial wrinkles: Database, detection algorithm, and evaluation metrics.

Skin wrinkles result from intrinsic aging processes and extrinsic influences, including prolonged exposure to ultraviolet radiation and tobacco smoking. Hence, the identification of wrinkles holds significant importance in skin aging and medical aesthetic investigation. Nevertheless, current methods lack the comprehensiveness to identify facial wrinkles, particularly those that may appear insignificant. Furthermore, the current assessment techniques neglect to consider the blurred boundary of wrinkles and cannot differentiate images with varying resolutions. This research introduces a novel wrinkle detection algorithm and a distance-based loss function to identify full-face wrinkles. Furthermore, we develop a wrinkle detection evaluation metric that assesses outcomes based on curve, location, and gradient similarity. We collected and annotated a dataset for wrinkle detection consisting of 1021 images of Chinese faces. The dataset will be made publicly available to further promote wrinkle detection research. The research demonstrates a substantial enhancement in detecting subtle wrinkles through implementing the proposed method. Furthermore, the suggested evaluation procedure effectively considers the indistinct boundaries of wrinkles and is applicable to images with various resolutions.

Exosomes and Signaling Nanovesicles from the Nanofiltration of Preconditioned Adipose Tissue with Skin-B® in Tissue Regeneration and Antiaging: A Clinical Study and Case Report.

Background and Objectives: This three-year clinical trial aimed to demonstrate that only the signaling vesicles produced by ADSCa, containing mRNA, microRNA, growth factors (GFs), and bioactive peptides, provide an advantage over classical therapy with adipose disaggregate to make the tissue regeneration technique safer due to the absence of interfering materials and cells, while being extremely minimally invasive. The infiltration of disaggregated adipose nanofat, defined by the Tonnard method, for the regeneration of the dermis and epidermis during physiological or pathological aging continues to be successfully used for the presence of numerous adult stem cells in suspension (ADSCa). An improvement in this method is the exclusion of fibrous shots and cellular debris from the nanofat to avoid inflammatory phenomena by microfiltration. Materials and Methods: A small amount of adipose tissue was extracted after surface anesthesia and disaggregated according to the Tonnard method. An initial microfiltration at 20/40 microns was performed to remove fibrous shots and cellular debris. The microfiltration was stabilized with a sterile solution containing hyaluronic acid and immediately ultrafiltered to a final size of 0.20 microns to exclude the cellular component and hyaluronic acid chains of different molecular weights. The suspension was then injected into the dermis using a mesotherapy technique with microinjections. Results: This study found that it is possible to extract signaling microvesicles using a simple ultrafiltration system. The Berardesca Scale, Numeric Rating Scale (NRS), and Modified Vancouver Scale (MVS) showed that it is possible to obtain excellent results with this technique. The ultrafiltrate can validly be used in a therapy involving injection into target tissues affected by chronic and photoaging with excellent results. Conclusions: This retrospective clinical evaluation study allowed us to consider the results obtained with this method for the treatment of dermal wrinkles and facial tissue furrows as excellent. The method is safe and an innovative regenerative therapy as a powerful and viable alternative to skin regeneration therapies, antiaging therapies, and chronic inflammatory diseases because it lacks the inflammatory component produced by cellular debris and fibrous sprouts and because it can exclude the mesenchymal cellular component by reducing multiple inflammatory cytokine levels.

Skin homeostasis: Mechanism and influencing factors.

BACKGROUND: The skin is the largest organ in the human body, not only resisting the invasion of harmful substances, but also preventing the loss of moisture and nutrients. Maintaining skin homeostasis is a prerequisite for the proper functioning of the body. Any damage to the skin can lead to a decrease in local homeostasis, such as ultraviolet radiation, seasonal changes, and air pollution, which can damage the skin tissue and affect the function of the skin barrier. OBJECTIVE: This article reviews the maintenance mechanism and influencing factors of skin homeostasis and the symptoms of homeostasis imbalance. METHODS: We searched for articles published between 1990 and 2022 in English and Chinese using PubMed, Web of Science, CNKI, and other databases in the subject area of dermatology, using the following search terms in various combinations: "skin homeostasis," "skin barrier," and "unstable skin." Based on our results, we further refined our search criteria to include a series of common skin problems caused by the destruction of skin homeostasis and its treatments. Limitations include the lack of research on dermatological and cosmetic problems triggered by the disruption of skin homeostasis. RESULTS: This study describes the neuroendocrine-immune system, skin barrier structure, and skin metabolic system that maintain skin homeostasis. In addition, we discuss several common symptoms that occur when skin homeostasis is out of balance, such as dryness, redness, acne, sensitivity, and aging, and explain the mechanism of these symptoms. CONCLUSION: This article provides an update and review for students and practitioners, and provides a theoretical basis for the development of skin care products for the maintenance and repair of skin homeostasis.

Rejuvenation in Men Facial Aging: A Combined Approach.

Facelift surgery, also known as rhytidectomy, is a popular cosmetic procedure aimed at reversing the signs of facial aging. While facelift surgery is more commonly performed in women, an increasing number of men are seeking this procedure to maintain a youthful appearance. The long recovery period conflicts the overall primary outcome anticipated by men undergoing rhytidectomy, i.e., appear younger, youthful, and ready to reaffirm their value in the working environment. Anterior direct neck lift, blepharoplasty (upper and lower eyelid blepharoplasty), and lipofilling are three techniques that have been shown to be effective in improving facial rejuvenation outcomes in elderly male patients. However, there is little to no evidence of the safety and efficacy of these techniques when used in combination. By combining these techniques, we hypothesized that we could achieve outcomes comparable to traditional facelift surgery, but with a lower risk of complications and a shorter recovery time. We conducted a retrospective case series study of 18 male patients who underwent facial rejuvenation surgery using the combination of anterior direct neck lift, blepharoplasty (upper and lower eyelid blepharoplasty), and lipofilling at our institution between 2018 and 2021. All 18 patients completed the study, with an average follow-up of 12 months. No major complications were observed, and all patients reported a high level of satisfaction with their outcomes.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Novel Hyaluronic Acid Matrix Ingredient with Regenerative, Anti-Aging and Antioxidant Capacity.

Hyaluronic acid (HA) and proteoglycans (such as dermatan sulphate (DS) and chondroitin sulphate (CS)) are the main components of the extracellular matrix of the skin, along with collagen and elastin. These components decrease with age, which implies a loss of skin moisture causing wrinkles, sagging and aging. Currently, the external and internal administration of effective ingredients that can reach the epidermis and dermis is the main alternative for combating skin aging. The objective of this work was to extract, characterise and evaluate the potential of an HA matrix ingredient to support anti-aging. The HA matrix was isolated and purified from rooster comb and characterised physicochemically and molecularly. In addition, its regenerative, anti-aging and antioxidant potential and intestinal absorption were evaluated. The results show that the HA matrix is composed of 67% HA, with an average molecular weight of 1.3 MDa; 12% sulphated glycosaminoglycans, including DS and CS; 17% protein, including collagen (10.4%); and water. The in vitro evaluation of the HA matrix's biological activity showed regenerative properties in both fibroblasts and keratinocytes, as well as moisturising, anti-aging and antioxidant effects. Furthermore, the results suggest that the HA matrix could be absorbed in the intestine, implying a potential oral as well as topical use for skin care, either as an ingredient in a nutraceutical or a cosmetic product.

Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Introducing aesthetic regenerative scaffolds: An immunological perspective.

BACKGROUND: Skin aging arises from immunological responses to tissue deterioration and damage. Tissue repair processes encompass the regeneration of original tissue and 'scarless' wound healing seen in foetuses, and the extreme fibrotic responses and scarring seen in adults. Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function. At filler injection sites, an inflammatory response occurs that causes a spectrum of outcomes, ranging from tissue regeneration to fibrosis and filler encapsulation. Importantly, the resulting inflammatory pathway can be predetermined by the biomaterial injected. AIMS: By understanding this immunological process, we can develop Aesthetic Regenerative Scaffolds (ARS) - aesthetic injectable biomaterials - to direct inflammatory wound healing away from chronic, fibrotic responses, and towards physiological tissue regeneration. MATERIALS AND METHODS: We identified and reviewed literature on the immunological and cellular responses to injected dermal fillers, whereby the wound healing response to the injection was moderated under the influence of an injected biomaterial. RESULTS: We described the mechanisms of dermal wound healing and the use of ARS to direct healing towards tissue regeneration instead of scarring. We also summarised studies on extracellular matrix remodeling by calcium hydroxylapatite. We found that Calcium hydroxylapatite fillers produce collagen as they gradually degrade and their spherical structures serve as a scaffold for tissue regeneration. Furthermore, CaHA improved fibroblast contractility, collagen type III and elastin production, proliferation and angiogenesis with less inflammation than hyaluronic acid fillers. DISCUSSION: Regneration pathways can be influenced at specific points between a facial filler biomaterial and the wound healingmechanisms at its site of implantaion. CONCLUSION: Physicians can select scaffolds that direct the immune response away from a fibrotic chronic inflammatory pathway and towards regeneration to enable true repair of the aging skin.

Unparallel improvement patterns of dynamic wrinkles and skin quality after botulinum toxin type A treatment on the upper face.

BACKGROUND: Botulinum toxin type A (BoNT-A) can not only reduce the dynamic wrinkles but also improve the skin quality. This study aims to quantitaively and comprehensively assess the improvement of dynamic wrinkles and skin quality following BoNT-A treatment on the upper face. METHODS: Patients were recruited to receive BoNT-A treatment of the glabellar, frontal, and lateral periorbital wrinkles. Antera 3D camera was used to evaluate the skin quality and dynamic wrinkle severity. Follow-up visits were at 1 week, 1 month, 3 months, and 6 months after treatment. Different filters were utilized to quantitatively detect the severity of fine wrinkles (FWS), the volume of pores (PV), the roughness of skin texture (STR), and the severity of dynamic wrinkles (DWS). RESULTS: Twenty-four participants (average 30.5 ± 7.2 years) were recruited. The significant improvement of PV, FWS, and STR in different areas usually maintained from 1 to 6 months after injections but of DWS only existed within 3 months. For each area, the improvement rates of FWS, PV, and STR peaked at 3 months or 6 months after treatment while the maximal improvement of DWS was observed at 1 month posttreatment. CONCLUSION: After BoNT-A treatment for dynamic wrinkles on the upper face, the skin quality of target regions can also be ameliorated. The improvement of skin quality and dynamic wrinkles presented unparallel patterns. The former is with a slower onset but longer duration while the latter exhibits a more rapid onset but shorter duration.

Activation of OR10A3 by Suberic Acid Promotes Collagen Synthesis in UVB-Irradiated Dermal Fibroblasts via the cAMP-Akt Pathway.

In recent years, there has been a great deal of interest in the ectopic roles of olfactory receptors (ORs) throughout the human body. Especially, the ectopic function of OR in the skin is one of the most actively researched areas. Suberic acid, a scent compound, was hypothesized to increase collagen synthesis in the ultraviolet B (UVB)-irradiated human dermal fibroblasts (Hs68) through a specific olfactory receptor. Suberic acid ameliorated UVB-induced decreases in collagen production in Hs68 cells. Using in silico docking to predict the binding conformation and affinity of suberic acid to 15 ectopic ORs detectable in Hs68, several ORs were identified as promising candidates. The effect of suberic acid on collagen synthesis in UVB-exposed dermal fibroblasts was nullified only by a reduction in OR10A3 expression via specific siRNA. In addition, using the cells transiently expressing OR10A3, we demonstrated that suberic acid can activate OR10A3 by assessing the downstream effector cAMP response element (CRE) luciferase activity. We examined that the activation of OR10A3 by suberic acid subsequently stimulates collagen synthesis via the downstream cAMP-Akt pathway. The findings support OR10A3 as a promising target for anti-aging treatments of the skin.

Premna microphylla Turcz pectin protected UVB-induced skin aging in BALB/c-nu mice via Nrf2 pathway.

Excessive exposure to ultraviolet B (UVB) irradiation is one of the major risk factors for skin photoaging. The aim of this study was to investigate the protective effect of Premna microphylla Turcz pectin (PMTP) against UVB-induced skin aging in BALB/c-nu mice. PMTP was characteristic of a low methoxyl RG-I pectin with Mw was 26.60 kDa, mainly composed of galacturonic acid. PMTP-containing cream efficiently inhibited the water loss, epidermal hyperplasia, matrix metalloproteinases-1 (MMP-1), and collagen destruction in UVB-induced skin injury mice. Additionally, topical administration of PMTP-containing cream significantly increased protein levels of the nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), macrophage-activating factor (Maf), and heme oxygenase 1 (HO-1), and the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). In contrast, application of PMTP-containing cream on mice skin decreased the protein levels of nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase ß (IKKß), and cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines. Taken togethmier, these findings suggest that PMTP might protect UVB-induced skin aging via activating Nrf2 pathway and suppressing NF-κB pathway.

Anti-Photoaging Effect of Hydrolysates from Pacific Whiting Skin via MAPK/AP-1, NF-κB, TGF-ß/Smad, and Nrf-2/HO-1 Signaling Pathway in UVB-Induced Human Dermal Fibroblasts.

Chronic exposure to ultraviolet (UV) light promotes the breakdown of collagen in the skin and disrupts the extracellular matrix (ECM) structure, leading to skin wrinkling. Pacific whiting (Merluccius productus) is a fish abundant on the Pacific coast. In the current study, we investigated the anti-wrinkle effect of hydrolysate from Pacific whiting skin gelatin (PWG) in UVB-irradiated human dermal fibroblasts and the molecular mechanisms involved. PWG effectively restored type 1 procollagen synthesis reduced by UVB-irradiation. Also, we found that PWG inhibited collagen degradation by inhibiting MMP1 expression. Furthermore, PWG decreased cytokines TNF-α, IL-6, and IL-1ß associated with inflammatory responses and increased antioxidant enzymes, HO-1, SOD, GPx, CAT, and GSH content, a defense system against oxidative stress. In terms of molecular mechanisms, PWG increased collagen synthesis through activating the transforming growth factor ß (TGF-ß)/Smad pathway and decreased collagen degradation through inhibiting the mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1) pathway. It also suppressed the inflammatory response through suppressing the nuclear factor-κB (NF-κB) pathway and increased antioxidant enzyme activity through activating the nuclear factor erythroid 2/heme oxygenase 1 (Nrf-2/HO-1) pathway. These multi-target mechanisms suggest that PWG may serve as an effective anti-photoaging material.

Anti-ageing and Anti-lung Carcinoma Effects of Vulpinic Acid and Usnic Acid Compounds and Biological Investigations with Molecular Modeling Study.

Disorganization and breakdown of extracellular matrix proteins like fibronectin, collagen, and elastin are key characteristics of skin aging due to the increased activation of important proteolytic enzymes like elastases and collagenase enzymes. Also, inhibition of their enzymatic activities by natural molecules might be a promising factor to prevent extrinsic skin aging. All chemicals were obtained from Sigma-Aldrich unless otherwise stated. The assay employed was based on spectrophotometric methods reported in the literature. The collagenase and elastase inhibition assays of some phenolic compounds were performed according to the previous studies. These compounds showed excellent to good inhibitory activities of vulpinic acid against studied these enzymes with IC50 values of 195.36 µM for collagenase and 25.24 µM for elastase. The molecular docking calculations were conducted to investigate the chemical and biological activity of vulpinic acid and usnic acid against collagenase and elastase. The results indicated that these two compounds can interact with the essential residues of the enzymes and affect their activities. The calculations of binding free energies were also performed to obtain more details about the characteristics and free energies of the ligand-enzyme complexes. Additionally, both compounds exhibited the most potent inhibition in the three lung cancer cells, with an IC50 value of 21-68 µM, indicating that vulpinic acid is more potent than Doxorubicin, which exhibited an IC50 value of 21-29 µM.

A mechanistic view on the aging human skin through ex vivo layer-by-layer analysis of mechanics and microstructure of facial and mammary dermis.

Age-related changes in skin mechanics have a major impact on the aesthetic perception of skin. The link between skin microstructure and mechanics is crucial for therapeutic and cosmetic applications as it bridges the micro- and the macro-scale. While our perception is governed by visual and tactile changes at the macroscopic scale, it is the microscopic scale (molecular assemblies, cells) that is targeted by topical treatments including active compounds and energies. We report here a large dataset on freshly excised human skin, and in particular facial skin highly relevant for cosmetics and aesthetic procedures. Detailed layer-by-layer mechanical analysis revealed significant age-dependent decrease in stiffness and elastic recoil of full-thickness skin from two different anatomical areas. In mammary skin, we found that the onset of mechanical degradation was earlier in the superficial papillary layer than in the deeper, reticular dermis. These mechanical data are linked with microstructural alterations observed in the collagen and elastic networks using staining and advanced imaging approaches. Our data suggest that with ageing, the earliest microstructural and mechanical changes occur in the top-most layers of dermis/skin and then propagate deeper, providing an opportunity for preventive topical treatments acting at the level of papillary dermis.

Regeneration of collagen fibrils at the papillary dermis by reconstructing basement membrane at the dermal-epidermal junction.

The epidermal basement membrane deteriorates with aging. We previously reported that basement membrane reconstruction not only serves to maintain epidermal stem/progenitor cells in the epidermis, but also increases collagen fibrils in the papillary dermis. Here, we investigated the mechanism of the latter action. Collagen fibrils in the papillary dermis were increased in organotypic human skin culture treated with matrix metalloproteinase and heparinase inhibitors. The expression levels of COL5A1 and COL1A1 genes (encoding collagen type V α 1 chain and collagen type I α 1 chain, respectively) were increased in fibroblasts cultured with conditioned medium from a skin equivalent model cultured with the inhibitors and in keratinocytes cultured on laminin-511 E8 fragment-coated plates. We then examined cytokine expression, and found that the inhibitors increased the expression of PDGF-BB (platelet-derived growth factor consisting of two B subunits) in epidermis. Expression of COL5A1 and COL1A1 genes was increased in cultured fibroblasts stimulated with PDGF-BB. Further, the bifunctional inhibitor hydroxyethyl imidazolidinone (HEI) increased skin elasticity and the thickness of the papillary dermis in the skin equivalent. Taken together, our data suggests that reconstructing the basement membrane promotes secretion of PDGF-BB by epidermal keratinocytes, leading to increased collagen expression at the papillary dermis.

Polymethoxyflavones from Kaempferia parviflora ameliorate skin aging in primary human dermal fibroblasts and ex vivo human skin.

Skin aging is accompanied by an increase in the number of senescent cells, resulting in various pathological outcomes. These include inflammation, impaired barrier function, and susceptibility to skin disorders such as cancer. Kaempferia parviflora (Thai black ginger), a medicinal plant native to Thailand, has been shown to counteract inflammation, cancer, and senescence. This study demonstrates that polymethoxyflavones (5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, and 3,5,7,3',4'-pentamethoxyflavone) purified from K. parviflora rhizomes suppressed cellular senescence, reactive oxygen species, and the senescence-associated secretory phenotype in primary human dermal fibroblasts. In addition, they increased tropocollagen synthesis and alleviated free radical-induced cellular and mitochondrial damage. Moreover, the compounds mitigated chronological aging in a human ex vivo skin model by attenuating senescence and restoring expression of essential components of the extracellular matrix, including collagen type I, fibrillin-1, and hyaluronic acid. Finally, we report that polymethoxyflavones enhanced epidermal thickness and epidermal-dermal stability, while blocking age-related inflammation in skin explants. Our findings support the use of polymethoxyflavones from K. parviflora as natural anti-aging agents, highlighting their potential as active ingredients in cosmeceutical and nutraceutical products.