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.

YAP prevents senescence of dermal fibroblast and inhibits melanogenesis via paracrine effect of DKK1.

Senile skin hyperpigmentation displays remarkable histopathological features of dermal aging. The crosstalk between melanocytes and dermal fibroblasts plays crucial roles in aging-related pigmentation. While senescent fibroblasts can upregulate pro-melanogenic factors, the role of anti-melanogenic factors, such as dickkopf1 (DKK1), and the upstream regulatory mechanism during aging remain obscure. This study investigated the roles of yes-associated protein (YAP) and DKK1 in the regulation of dermal fibroblast senescence and melanogenesis. Our findings demonstrated decreased YAP activity and DKK1 levels in intrinsic and extrinsic senescent fibroblasts. YAP depletion induced fibroblast senescence and downregulated the expression and secretion of DKK1, whereas YAP overexpression partially reversed the effect. The transcriptional regulation of DKK1 by YAP was supported by dual-luciferase reporter and chromatin immunoprecipitation assays. Moreover, YAP depletion in fibroblasts upregulated Wnt/ß-catenin in melanocytes and stimulated melanogenesis, which was partially rescued by the re-supplementation of DKK1. Conversely, overexpression of YAP in senescent fibroblasts decreased Wnt/ß-catenin levels in melanocytes and inhibited melanogenesis. Additionally, reduced levels of YAP and DKK1 were verified in the dermis of solar lentigines. These findings suggest that, during skin aging, epidermal pigmentation may be influenced by YAP in the dermal microenvironment via the paracrine effect of DKK1.

Photodynamic Skincare: A Prospective Single-Center Study.

BACKGROUND: Peer-reviewed, clinical studies measuring the efficacy and usability of skin care products enhance their integrity and may guide experts in the field in providing recommendations. A single-blind, prospective clinical study was designed to assess the subject satisfaction, clinical benefit, and safety of three photodynamic topical formulations referred to as MMSRepose (MMSRep), MMSRevive (MMSRev), and MMSBalance (MMSB).  Methods: Thirteen male and female patients (mean age 49 +/- 17.8 years) applied one of the three topical serums twice daily over a period of 12 weeks. Subjects returned for photography, and blinded investigator evaluation of rhytides (fine lines) and dyspigmentation were measured on a 6- and 4-point scale, respectively. Patient-perceived efficacy of multiple clinical outcomes was measured on a 5-point scale.  Results: 100% of subjects reported at least a 1-grade improvement in global aesthetic at the conclusion of the study. Investigator assessment revealed an overall 53.3% decrease in rhytides, correlating to a mean point reduction from 1.65 +/- 0.77 to 0.77 +/- 0.53 (P<0.001) from baseline to week 12. Investigator assessment of dyspigmentation revealed a 62.7% decrease, correlating to a mean point reduction of 1.85 +/- 0.68 from week 1 to 0.69 +/- 0.48 at week 12 (P<0.001). CONCLUSION: Photodynamic serums demonstrate clinical efficacy in skin rejuvenation and high user satisfaction. There were no serious adverse events. This study is limited by the inability to randomize to placebo due to the small sample size, as subject retention was heavily impacted by the SARS-CoV-2 pandemic. Future studies may be indicated to undergo comparison with a larger cohort.  J Drugs Dermatol. 2024;23(5):332-337. doi:10.36849/JDD.7167.

Causal relationship between dyslipidemia and risk of facial aging: Insights from Mendelian randomization in East Asian populations.

BACKGROUND: Emerging observational studies showed an association between dyslipidemia and aging. However, it remains unclear whether this association is causal, particularly in the case of Asians, which are aging more rapidly than other continents. Given the visible manifestations of aging often include changes in facial appearance, the objective of this study is to assess the causal relationship between dyslipidemia and facial aging in East Asian populations. METHODS: SNPs related to dyslipidemia in East Asian people such as Total cholesterol (TC), High-density-lipoprotein cholesterol (HDL), Low-density-lipoprotein cholesterol (LDL), and Triglyceride (TG) along with outcomes data on facial aging, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse variance weighted (IVW) method. RESULTS: Totally, 88 SNPs related to HDL among 70657 East Asian participants in GWAS. Based on the primary causal effects model using MR analyses with the IVW method, high HDL level was demonstrated as significantly related to the risk of facial aging (OR, 1.060; 95% CI, 1.005-1.119, p = 0.034), while high TC level (OR, 0.995; 95% CI, 0.920-1.076, p = 0.903), high LDL level (OR, 0.980, 95% CI, 0.924-1.041, p = 0.515), as well as high TG level (OR, 0.999, 95% CI, 0.932-1.071, p = 0.974), showed no significant correlation with facial aging. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between high HDL levels and facial aging. In contrast, facial aging demonstrated no significant correlation with high levels of TC, LDL, or TG. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding nutrition management to delay the aging process among old patients in East Asia.

A Practical Algorithm for Integrating Skincare to Improve Patient Outcomes and Satisfaction With Energy-Based Dermatologic Procedures.

BACKGROUND: Medical aesthetic procedures for facial antiaging with laser and energy-based devices (EBDs) are rapidly increasing, but standards integrating skincare before, during, and after these treatments are lacking. The algorithm for integrated skin care for facial antiaging treatment with EBDs aims to stimulate healing, reduce downtime, and improve comfort and treatment outcomes. METHODS: A panel of 8 global physicians employed a modified Delphi method and reached a consensus on the algorithm integrating skincare based on the best available evidence, the panel's clinical experience, and opinions. RESULTS: The algorithm has a pretreatment (starts 2 - 4 weeks before the procedure) and treatment (day of treatment) section, followed by care after the procedure (0 - 7 days) and follow-up care (1 - 4 weeks after the procedure or ongoing). Applying a broad-spectrum sunscreen with an SPF 50 or higher, combined with protective measures such as wearing a wide-brimmed hat and sunglasses, is recommended to protect the face from sun exposure. Dyschromia is a significant concern for those with skin of color (SOC). Clinicians may recommend skincare using a gentle cleanser and moisturizer containing vitamins C and E, retinoid, or other ingredients such as niacinamide, kojic acid, licorice root extract, azelaic acid, and tranexamic acid, depending on the patient's facial skin condition. CONCLUSION: Medical aesthetic procedures for facial antiaging with EBDs integrating skincare or topical treatments may improve outcomes and patient satisfaction. Topical antioxidants and free radical quenchers can combat photodamage and may offer a safe alternative to topical hydroquinone.  J Drugs Dermatol. 2024;23(5):353-359.     doi:10.36849/JDD.8092.

What you need to know about common skin problems in older adults.

Skin ageing is a multifaceted process impacted by both intrinsic and extrinsic factors. Drier and less elastic skin with declining sebum levels in older age makes ageing skin more vulnerable to various skin conditions, including infections, inflammatory dermatoses, and cancers. Skin problems are common among older adults due to the effects of ageing, polypharmacy and multimorbidity impacting not only physical health but wellbeing and quality of life. In the UK, older adults in geriatric medicine wards may present with various skin conditions. Hospitalised older individuals may have undiagnosed skin problems unrelated to their admission, making hospitalisation an opportunity to manage unmet needs. Asteatotic eczema, incontinence associated dermatitis, seborrhoeic dermatitis, chronic venous insufficiency, and cellulitis are common disorders clinicians encounter in the geriatric medicine wards. This article outlines the importance of performing comprehensive skin assessments to help diagnose and commence management for these common conditions.

Intra-Individual Paired Mass Spectrometry Dataset for Decoding Solar-Induced Proteomic Changes in Facial Skin.

Photoaging is the premature aging of the skin caused by prolonged exposure to solar radiation. The visual alterations manifest as wrinkles, reduced skin elasticity, uneven skin tone, as well as other signs that surpass the expected outcomes of natural aging. Beyond these surface changes, there is a complex interplay of molecular alterations, encompassing shifts in cellular function, DNA damage, and protein composition disruptions. This data descriptor introduces a unique dataset derived from ten individuals, each with a minimum of 18 years of professional experience as a driver, who are asymmetrically and chronically exposed to solar radiation due to their driving orientation. Skin samples were independently collected from each side of the face using a microdermabrasion-like procedure and analyzed on an Exploris 240 mass spectrometer. Our adapted proteomic statistical framework leverages the sample pairing to provide robust insights. This dataset delves into the molecular differences in exposed skin and serves as a foundational resource for interdisciplinary research in photodermatology, targeted skincare treatments, and computational modelling of skin health.

The Effect of α-Arbutin on UVB-Induced Damage and Its Underlying Mechanism.

Ultraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1ß, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound.

Ferulic acid in synergy with retinol alleviates oxidative injury of HaCaT cells during UVB-induced photoaging.

Application of retinol (Vitamin A, VA) in skincare is limited for instability, poor water solubility, and skin intolerance that combats skin aging. We employed computer-aided virtual screening and cell experiments with transcriptomics, thereby unveiling the comprehensive gene expression and regulation pathway of photoaging HaCaT cell treated with ferulic acid (FA) in synergizing with VA. Through network pharmacology analysis, the combined use of VA and FA exhibited highly correlated cross-targets with skin aging acting on EGFR, PTPN1, ESR2, GSK3B, BACE1, PYGL, PTGS2 and APP. The indicators of oxidative stress, such as SOD, GSH, MDA, CAT and ROS in HaCaT cells after co-administration, were significantly improved from those in photoaging group (p<0.0001). 155 differential expressed genes (DEGs) were specific between groups, while reducing the expression of PTGS2 was identified as an important regulatory factor in photoaging HaCaT cells by VA and FA. Those DEGs of co-administration group focused on oxidative-reduction enzyme activity, skin growth, keratinization, and steroid biosynthesis. Apparently, the co-administration of VA and FA effectively mitigated the process of UVB-induced photoaging by reducing oxidative stress injury, inflammation responses, and regulating cell growth. This synergistic approach significantly slowed down the photoaging progression and improved the applied performance of VA in HaCaT cells.

Research Progress on Bioactive Factors against Skin Aging.

The relentless pursuit of effective strategies against skin aging has led to significant interest in the role of bioactive factors, particularly secondary metabolites from natural sources. The purpose of this study is to meticulously explore and summarize the recent advancements in understanding and utilization of bioactive factors against skin aging, with a focus on their sources, mechanisms of action, and therapeutic potential. Skin, the largest organ of the body, directly interacts with the external environment, making it susceptible to aging influenced by factors such as UV radiation, pollution, and oxidative stress. Among various interventions, bioactive factors, including peptides, amino acids, and secondary metabolites, have shown promising anti-aging effects by modulating the biological pathways associated with skin integrity and youthfulness. This article provides a comprehensive overview of these bioactive compounds, emphasizing collagen peptides, antioxidants, and herbal extracts, and discusses their effectiveness in promoting collagen synthesis, enhancing skin barrier function, and mitigating the visible signs of aging. By presenting a synthesis of the current research, this study aims to highlight the therapeutic potential of these bioactive factors in developing innovative anti-aging skin care solutions, thereby contributing to the broader field of dermatological research and offering new perspectives for future studies. Our findings underscore the importance of the continued exploration of bioactive compounds for their potential to revolutionize anti-aging skin care and improve skin health and aesthetics.

Human Dermal Decellularized ECM Hydrogels as Scaffolds for 3D In Vitro Skin Aging Models.

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modeling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues is becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit a behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging-on-a-chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.

Research Progress in Skin Aging and Immunity.

Skin aging is a complex process involving structural and functional changes and is characterized by a decrease in collagen content, reduced skin thickness, dryness, and the formation of wrinkles. This process is underpinned by multiple mechanisms including the free radical theory, inflammation theory, photoaging theory, and metabolic theory. The skin immune system, an indispensable part of the body's defense mechanism, comprises macrophages, lymphocytes, dendritic cells, and mast cells. These cells play a pivotal role in maintaining skin homeostasis and responding to injury or infection. As age advances, along with various internal and external environmental stimuli, skin immune cells may undergo senescence or accelerated aging, characterized by reduced cell division capability, increased mortality, changes in gene expression patterns and signaling pathways, and altered immune cell functions. These changes collectively impact the overall function of the immune system. This review summarizes the relationship between skin aging and immunity and explores the characteristics of skin aging, the composition and function of the skin immune system, the aging of immune cells, and the effects of these cells on immune function and skin aging. Immune dysfunction plays a significant role in skin aging, suggesting that immunoregulation may become one of the important strategies for the prevention and treatment of skin aging.

Treatment of horizontal neck wrinkles by Endolift laser: Biometric measurement.

BACKGROUND: One of the common esthetic complaints of patients is horizontal neck wrinkles that have limited treatment modality. AIM: In the present study, we evaluated the efficacy of the Endolift laser on the horizontal neck wrinkles. METHODS: Totally, 10 healthy female and male patients suffering horizontal neck wrinkles were joined in this study. All patients are treated with Endolift laser. The effect of the Endolift methods on the horizontal neck wrinkles was evaluated by biometric parameter changed results with Cutometer, Visioface, and the Skin Ultrasound Imaging system. Also, three blinded dermatologists and patients' satisfaction were evaluated. RESULTS: The Visoface results showed that the Endolift laser treatment significantly decline the depth and area of horizontal neck wrinkle. The skin ultrasonography results reported the epidermis and dermis density and thickness were significantly increased. Also, the cutometer outcomes displayed that the Endolift laser treatment can increase skin elasticity. Also, significantly a greater number of patients were well satisfied with the technique. CONCLUSION: In conclusion, Endolift laser is a safe and effective method for decreasing the horizontal neck wrinkles and improving the appearance of the neck. This procedure does not require general anesthesia and recovery time.

The therapeutic effects of ADSCs on photoaging of skin induced by UVB irradiation.

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.

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.

Why do marionette lines appear? Exploring the anatomical perspectives and role of thread-based interventions.

The pathogenesis of marionette lines involves a complex interplay of anatomical, physiological, and age-related factors leading to the development of wrinkles around the oral commissures. This exploration delves into the distinct anatomical predispositions observed among different ethnicities, emphasizing the role of compact modiolus structures and muscle compositions. Notably, individuals of East Asian descent exhibit inherent facial structures that predispose them to pronounced sagging around the oral commissures during aging. The emergence of distinct facial lines, such as the commissural line and the melolabial fold, contributes to the formation of marionette lines. This specific wrinkle pattern, resembling a marionette puppet's mouth contours, is influenced by various factors like bone resorption, gravitational forces, fat compartment variations, muscle compression, ligament tethering, and skin aging. Treatment strategies for marionette lines encompass diverse interventions, including filler injections, botulinum neurotoxin, surgeries targeting fat reduction, thread lifting, and volumizing fillers. These approaches aim to address the underlying causes and mitigate the appearance of marionette lines. Botulinum neurotoxin injections, for instance, weaken specific facial muscles, reducing downward strain and aiding in tissue retraction. Anatomical considerations during procedures are crucial to avoid nerve or vascular damage. Delicate manipulation and precise entry points are essential to prevent inadvertent injuries, particularly concerning blood vessels like the facial artery and nerves like the mental nerve. Technical guidelines for procedures targeting marionette lines involve specific techniques like cogged thread reverse methods and volumizing thread placements. Attention to entry points, tissue engagement, and the direction of threads is crucial for effective treatment outcomes, minimizing complications, and ensuring patient safety.

Efficacy and Tolerability of Topical 0.1% Stabilized Bioactive Retinol for Photoaging: A Vehicle-Controlled Integrated Analysis.

INTRODUCTION: Chronic exposure to ultraviolet light photoages skin. Retinol, a precursor molecule to retinoic acid that causes less irritation, is available as a nonprescription, cosmetic retinoid and improves collagen production, skin elasticity, and signs of photoaging. Advances in formulation science have allowed the production of stabilized bioactive retinol formulations. This integrated analysis aims to build on previous studies and further examine the comprehensive efficacy and tolerability of topical 0.1% stabilized bioactive retinol. METHODS: This analysis included 6 vehicle-controlled studies of 0.1% stabilized bioactive retinol in women with mild-to-moderate signs of photodamage. Across all studies, the same dermatologist investigator assessed overall photodamage; wrinkles on the forehead, cheeks, and undereye area; crow’s feet wrinkles and fine lines; lack of even skin tone; and brown spots at baseline and weeks 4, 8, and 12 on a numerical scale. Tolerability was also assessed. RESULTS: Participants (retinol, N=237; vehicle, N=234) had a mean (SD) age of 47.4 (6.6) years. Retinol induced greater improvements from baseline in all signs of photoaging vs vehicle as early as week 4 and through 12 weeks of application. Few participants experienced irritation; all events were mild to moderate and transient. The most common signs of irritation were erythema (n=2) and skin scaling/peeling (n=5). CONCLUSIONS: This pooled analysis of 6 vehicle-controlled clinical studies provides new evidence for the efficacy of 0.1% stabilized bioactive retinol in improving signs of photoaging without causing major irritation. Topical 0.1% stabilized bioactive retinol was well tolerated with only a few reported cases of skin irritation. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8124.