Evaluation of the anti-aging effects of Zinc-α2-glycoprotein peptide in clinical and in vitro study.

BACKGROUND: Skin aging, characterized by the deterioration of skin density and elasticity, is a common concern among individuals seeking to maintain a youthful appearance. Zinc-α2-glycoprotein (ZAG) is secreted by various body fluids, and is associated with lipolysis and identified as an atopic dermatitis biomarker. This study evaluated the potential of ZAG peptides, which exert multiple benefits such as anti-aging. MATERIALS AND METHODS: We conducted a 4-week clinical trial on patients with noticeable periorbital wrinkles (n = 22) using a ZAG peptide-containing product. The effects of the products on skin density, elasticity, and the depth of periorbital wrinkles were evaluated using Cutometer Dual MPA580, Ultrascan, and Antera 3D CS, respectively. The effect of ZAG peptides on UVB-treated keratinocyte cells was evaluated in vitro to understand the mechanisms underlying its effects against impaired skin barrier function, collagen degradation, and senescence. In addition, the effects of ZAG peptides on cell viability and expression of aging and skin barrier-related genes were assessed using cell counting kit assay and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: The patients demonstrated improved skin density, elasticity, and reduced periorbital wrinkles. Further, more than 85% patients scored the product as satisfactory regarding anti-aging effects. Furthermore, ZAG peptides reduced SA-ß-gal staining, downregulated the senescence-related genes, and upregulated the skin barrier function-related genes in UVB-irradiated keratinocyte cells. CONCLUSIONS: Our clinical and in vitro findings showed that ZAG peptides exert anti-aging effects and improve skin barrier functions, suggesting their promising potential as therapeutic agents to combat skin aging and improve skin health.

Oral consumption of Bonito fish-derived elastin peptide (VGPG Elastin® ) improves biophysical properties in aging skin: A randomized, double-blinded, placebo-controlled study.

BACKGROUND: Recent in vitro and in vivo studies have suggested that the elastin peptide improves the skin's biophysical properties, enhancing the proliferation of fibroblasts and elastin synthesis, resulting in anti-aging properties. Therefore, we conducted a randomized, double-blinded, placebo-controlled study to clinically evaluate the effect of elastin peptide intake on human skin. MATERIALS AND METHODS: Healthy adult participants (N = 100) were randomly assigned to receive a test product containing 100 mg of Bonito elastin peptide (VGPG Elastin® ) or placebo. In this study, all participants were Asian from Korea. The parameters of skin wrinkles, hydration, and brightening (melanin index) were measured at baseline and 4, 8, and 12 weeks after intervention. RESULTS: The average skin roughness, maximum peak-to-valley values, maximum peak height of the wrinkle, maximum valley depth of the wrinkle, average maximum height of the wrinkle, and eye wrinkle volume improved considerably in the test group compared with the placebo after 12 weeks of intervention. Skin hydration was enhanced, and the melanin index was significantly lower in the test group than in the placebo group. No participant experienced adverse events related to the test product. CONCLUSION: Oral consumption of Bonito elastin peptide (VGPG Elastin®) reduced fine wrinkles, enhanced skin moisture, and decreased melanin index without significant adverse effects and may be a promising anti-wrinkle, anti-dryness, and anti-pigmentation treatment.

Efficacy and safety of a home-use handheld multi-energy-based device for skin rejuvenation: clinical, ex vivo, and histological studies.

Alongside increases in the average lifespan and a growing interest in anti-aging remedies, the demand for at-home skincare devices is rapidly expanding in the cosmetic market. This study aimed to assess the safety and efficacy of a novel home-use handheld multi-energy-based device for skin rejuvenation that simultaneously emits low level light, low-dose radiofrequency, low-energy microcurrent, and low-intensity ultrasonic wave. This prospective, randomized, split-face clinical trial enrolled 36 healthy Korean women. After 8 weeks of device use, parameters associated with skin aging were assessed. Additionally, a preliminary ex vivo study and skin biopsy following device use were performed to confirm safety and efficiency of the device. Parameters associated with skin aging including skin hydration, elasticity, roughness, skin pore size, and eye wrinkle volume showed significant improvements after 8 weeks of the device use, relative to baseline measurements and the control side. No adverse effects were observed during the follow-up period. Results of ex vivo and in vivo skin tissue studies correlated with clinical findings, which showed an increase in the expression of type 1 collagen and a decrease in the expression of matrix metalloproteinase-1, which is related to the skin aging phenotype. The expression of loricrin and involucrin, major components of the epidermal skin barrier, also increased after the use of the device. Multi-energy-based device is effective for skin rejuvenation and tolerable, without any considerable adverse effects.

Quantitative Analysis of Hair Luster in a Novel Ultraviolet-Irradiated Mouse Model.

Hair luster is a key attribute of healthy hair and a crucial aspect of cosmetic appeal, reflecting the overall health and vitality of hair. Despite its significance, the advancement of therapeutic strategies for hair luster enhancement have been limited due to the absence of an effective experimental model. This study aimed to establish a novel animal model to assess hair gloss, employing ultraviolet (UV) irradiation on C57BL/6 mice. Specifically, UVB irradiation was meticulously applied to the shaved skin of these mice, simulating conditions that typically lead to hair luster loss in humans. The regrowth and characteristics of the hair were evaluated using a dual approach: an Investigator's Global Assessment (IGA) scale for subjective assessment and an image-based pixel-count method for objective quantification. These methods provided a comprehensive understanding of the changes in hair quality post-irradiation. To explore the potential reversibility of hair luster changes, oral minoxidil was administered, a treatment known for its effects on hair growth and texture. Further, to gain insights into the underlying biological mechanisms, bulk RNA transcriptomic analysis of skin tissue was conducted. This analysis revealed significant alterations in the expression of keratin-associated protein (KRTAP) genes, suggesting modifications in hair keratin crosslinking due to UV exposure. These changes are crucial in understanding the molecular dynamics affecting hair luster. The development of this new mouse model is a significant advancement in hair care research. It not only facilitates the evaluation of hair luster in a controlled setting but also opens avenues for the research and development of innovative therapeutic strategies. This model holds promise for the formulation of more effective hair care products and treatments, potentially revolutionizing the approach towards managing and enhancing hair luster.

Efficacy and safety of persimmon leaf formulated with green tea and sophora fruit extracts (BLH308) on hair growth: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Recent research suggests that persimmon leaf extract (PLE) has an effect on inflammatory skin diseases. Previously, PLE is revealed to inhibit not only nitric oxide production but also inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels in mouse macrophages in vitro. Moreover, it significantly reduced IL-6 production and 5α-reductase expression in human follicle dermal papilla cells (HFDPCs). This study aimed to determine whether the PLE-containing BLH308 complex improves hair growth in clinical trials. MATERIALS AND METHODS: A total of 88 participants were recruited, and were instructed to orally take BLH308 or the placebo twice a day for 24 weeks. The mean age of the test group was 38.52 ± 7.98 years and that of placebo group was 38.98 ± 8.80 years. The study was conducted for 24 weeks, and hair density, thickness, and gloss were evaluated. All participants completed a satisfaction survey questionnaire. RESULTS: The test group showed significantly increased hair density and hair diameter at week 24 compared with the placebo group (p = 0.0015 and p = 0.0001, respectively). Although not statistically significant, the degree of gloss also showed higher improvement in the test group compared to the placebo group. CONCLUSIONS: Our data demonstrated that oral consumption of the BLH308 complex containing PLE significantly increased hair density and thickness compared to the placebo group, showing its possible role in promoting hair growth.

Age-related changes in scalp biophysical parameters: A comparative analysis of the 20s and 50s age groups.

BACKGROUND: Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations. MATERIALS AND METHODS: Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women. RESULTS: Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness. CONCLUSION: Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies.

Cutaneous neurogenic inflammation mediated by TRPV1-NGF-TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites.

BACKGROUND: Rosacea is a common chronic inflammatory skin condition that is often refractory to treatment, with frequent relapses. Alterations in the skin immunological response and Demodex mite infestation are the primary aetiologic factors targeted for treatment. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a nociceptive cation channel that plays a role in cutaneous neurogenic pain and can be activated by various rosacea triggers. OBJECTIVES: We investigated the effects of TRPV1 modulation in rosacea, focussing on Demodex mite colonization and cutaneous neurogenic inflammation. METHODS: We examined mRNA expression levels according to Demodex population counts. An in vitro study using capsazepine as a TRPV1 antagonist was performed to assess the influence of TRPV1 in keratinocytes. A rosacea-like mouse model was generated by the injection of the 37-amino acid C-terminal cathelicidin peptide (LL37), and changes in the skin, dorsal root ganglion (DRG) and ears were examined. RESULTS: Increased Demodex mite population counts were associated with increased expression levels of TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), and these levels could be reduced by capsazepine treatment in keratinocytes. In an in vivo study, the downstream effects of TRPV1 activation were investigated in the skin, DRG and ears of the rosacea-like mouse model. CONCLUSIONS: The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments targeting the NGF-TrkA-TRPV1 pathway. The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research, potentially resulting in more effective and targeted rosacea treatments. This study contributes to an improved understanding of rosacea pathophysiology, which may lead to the development of more effective treatments in the future.

Silibinin Downregulates Types I and III Collagen Expression via Suppression of the mTOR Signaling Pathway.

Keloid scars are fibro-proliferative conditions characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition. The mammalian target of the rapamycin (mTOR) pathway has emerged as a potential therapeutic target in keloid disease. Silibinin, a natural flavonoid isolated from the seeds and fruits of the milk thistle, is known to inhibit the mTOR signaling pathway in human cervical and hepatoma cancer cells. However, the mechanisms underlying this inhibitory effect are not fully understood. This in vitro study investigated the effects of silibinin on collagen expression in normal human dermal and keloid-derived fibroblasts. We evaluated the effects of silibinin on the expressions of collagen types I and III and assessed its effects on the suppression of the mTOR signaling pathway. Our findings confirmed elevated mTOR phosphorylation levels in keloid scars compared to normal tissue specimens. Silibinin treatment significantly reduced collagen I and III expressions in normal human dermal and keloid-derived fibroblasts. These effects were accompanied by the suppression of the mTOR signaling pathway. Our findings suggest the potential of silibinin as a promising therapeutic agent for preventing and treating keloid scars. Further studies are warranted to explore the clinical application of silibinin in scar management.

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study.

The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required.

Idiopathic bone cavity mimicking a botryoid odontogenic cyst: A rare radiographic presentation in an older adult.

OBJECTIVES: This report describes an unusual case of a multilocular idiopathic bone cavity (IBC) that presented as a botryoid odontogenic cyst situated between the mandibular lateral incisor and canine in an older adult. BACKGROUND: The IBC represents an intraosseous concavity that appears radiographically as a unilocular or multilocular radiolucent lesion found in various skeletal sites, including the jaw. Atypical cases of gnathic IBC have not been appreciated in the gerodontologic literature. MATERIALS AND METHODS: The teeth adjacent to the bony lesion had normal pulpal responses to cold. A full-thickness flap was elevated and provided a direct entry into a bony concavity, which was devoid of an epithelial lining and fluid. RESULTS: The lack of a cystic lining within the empty osseous lesion following surgical entry, concomitant with the vital pulpal status of the proximal teeth, led to a diagnosis of an IBC. The bony walls underwent curettage and copious irrigation prior to primary closure. A 10-month follow-up revealed partial evidence of osseous repair. The patient will continue to be monitored. CONCLUSION: Timely surgical intervention of central lesions of the jaws may improve clinical outcomes. Variants of the IBC should be included in the differential diagnosis of multilocular lesions, particularly in the geriatric population.

An Exploratory In Vivo Study on the Effect of Annurca Apple Extract on Hair Growth in Mice.

Hair loss is an important problem affecting the quality of life in modern society. Recent studies show that Annurca apple extract (AAE), enriched in procyanidin B2 and nutraceuticals, promotes hair growth and induces keratin production. In this study, we investigated the effects of AAE by orally administering AAE in six-week-old C57BL/6 mice once a day for 21 d. We observed improvement in hair length, thickness, weight, and density. The gene expression of two growth factors related to hair growth, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 7 (FGF-7), were measured using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). The gene expression of both VEGFA and FGF-7 increased significantly in the AAE-treated group. Additionally, treatment with AAE suppressed the gene expression of type 1 5α-reductase. Histological analysis showed that protein levels of cytokeratin 5 and 10 were increased in the skin tissues of the AAE-treated group. These results suggest that AAE might be a potential therapeutic natural product that prevents hair loss by promoting the expression of hair growth-related factors.

Particulate matter-induced atmospheric skin aging is aggravated by UVA and inhibited by a topical l-ascorbic acid compound.

Ambient particulate matter (PM) is a major contributor to environmental air pollution-associated skin damage. However, most published studies are observational or epidemiologic and have not mechanistically investigated the effects of air pollutants on cellular senescence and aging, particularly in combination with ultraviolet (UV) radiation. Herein, we analyzed whether UVA aggravates the PM-induced inflammatory cascade, which contributes to the aging of skin-derived cells. We hypothesized that cellular senescence is involved in PM&UVA-induced aging and tested whether an l-ascorbic acid compound (LAC), containing vitamin E and ferulic acid, can inhibit PM&UVA-induced aging. PM&UVA-exposed HDFs showed further elevated reactive oxygen species (ROS) levels detected by flow cytometry. We then demonstrated that PM induces MAPK signaling activation and the expression of AhR and NF-κB, responses that are both exacerbated by UVA. The levels of inflammatory cytokines, IL-1ß and IL-6, were significantly higher in the PM&UVA-exposed group which resulted in increased transcription of MMPs, causing downregulation of type I collagen. Meanwhile, treatment with LAC reduced the levels of ROS and inflammatory cytokines. Additionally, PM&UVA-induced SA-ß-gal production (staining assay) was reduced by LAC. These findings suggest a role of atmospheric pollution and UVA radiation in cellular senescence induction. Our findings also suggest a possible role of AhR inhibition by topical antioxidants to prevent atmospheric pollution-induced skin aging.

Treatment of Human Immunodeficiency Virus-Associated Facial Lipoatrophy With Hyaluronic Acid Filler Mixed With Micronized Cross-Linked Acellular Dermal Matrix.

BACKGROUND: Human immunodeficiency virus (HIV)-associated facial lipoatrophy (FLA) is a stigmatizing side effect associated with the use of highly active antiretroviral therapy. We sought to evaluate the safety and efficacy of the hyaluronic acid filler mixed with micronized cross-linked acellular dermal matrix (HA/MADM) in HIV-associated FLA. METHODS: We conducted an open-label safety and efficacy study in patients with HIV-associated FLA. Fourteen patients received single injection of the HA/MADM, and 13 patients completed the 24-week follow-up evaluation. Treatment efficacy, safety, and patient and physician satisfaction were evaluated. Repeated measure analysis of variance with post-hoc analysis with the Wilcoxon signed rank test was performed to compare and incorporate parameters at each time point. RESULTS: All 13 patients maintained a significant improvement of the Carruthers Lipoatrophy Severity Scale grade throughout the study period, along with improvement of the depressed volume due to lipoatrophy measured using a three-dimensional camera system. More than 80% of patients and physicians were satisfied with the treatment, and no treatment-related adverse events were reported, except for one case of transient subcutaneous nodule formation. CONCLUSION: Our study findings suggest that injectable HA/MADM is a potentially effective and safe treatment option for treating HIV-positive patients with FLA.

Effect of a Topical Collagen Tripeptide on Antiaging and Inhibition of Glycation of the Skin: A Pilot Study.

The glycation process has been recognized as one of the critical parameters that accelerate signs of skin aging, especially in skin exposed to environment factors, such as ultraviolet radiation. Although previous studies showed the anti-inflammatory and antiaging properties of the hydrolyzed collagen tripeptide (CTP), its exact mechanism is not fully understood. Therefore, in this study, we sought to investigate the effect of a topical CTP on facial skin. Our group designed a 4 week prospective, single-arm study of 22 Asian women who applied topical CTP. We observed significant improvements in skin wrinkles, elasticity, and density with a reduction in skin accumulation of advanced glycated end products (AGEs) at week 4 without any adverse effects. The in vitro study revealed a preventive effect of the topical CTP on the accumulation of AGEs, denatured collagen production, and reactive oxygen species in dermal fibroblasts. Moreover, treatment with the CTP decreased induction of matrix metalloproteinases while increasing the collagen 1 level. These results suggest that the application of a topical CTP might improve clinical aging phenotypes via the inhibition of glycation and oxidative stress, leading to a delay in cellular aging.

Stress-associated ectopic differentiation of melanocyte stem cells and ORS amelanotic melanocytes in an ex vivo human hair follicle model.

Hair greying depends on the altered presence and functionality of hair follicle melanocytes. Melanocyte stem cells (MelSCs) reside in the bulge of hair follicles and give rise to migrating and differentiating progeny during the anagen phase. Ageing, genotoxic stress, redox stress and multiple behaviour-associated acute stressors have been seen to induce hair greying by depleting the MelSC pool, a phenomenon which is accompanied by ectopic pigmentation of these cells, followed by their depletion from the stem cell niche. This aberrant differentiation produces a state from which a return to stem cell-like quiescence appears to be lost. The cellular features of stress-induced hair greying have been extensively studied in murine models. Here, we describe a method to assess and quantify human hair follicle MelSC differentiation by measuring ectopically pigmented MelSCs in isolated human hair follicles exposed to specific stress signal mediators. Ionizing radiation, hydrogen peroxide and noradrenaline have been shown to cause hair greying in mice. We demonstrate here that isolated, ex vivo cultured human hair follicles exposed to these treatments display similar ectopic pigmentation within the bulge area which is accompanied by induction of differentiated melanocytic markers. This study suggests that as in murine models, stress signalling induces closely matching phenotypic changes in human hair follicles which can be monitored and studied as a surrogate model for early steps in human hair greying.

Clinical characteristics and histopathologic changes of morphea: A single-center, retrospective study of 137 patients.

BACKGROUND: The clinicopathologic correlations and prognostic risk factors for refractory disease in morphea (localized scleroderma) are poorly described. OBJECTIVE: To investigate the association between clinical characteristics and histopathologic features of morphea and identify risk factors for refractory disease. METHODS: We retrospectively reviewed the clinical and histopathologic features, treatment regimens, and clinical responses for 137 patients with biopsy-proven morphea from January 2008 to May 2019. Multivariate analysis was conducted to identify factors associated with poor treatment response. RESULTS: We detected associations between the pattern and degree of sclerosis and the anatomic site of the lesion, as well as between severe inflammation and concomitant autoimmune disease. Additionally, both bottom-heavy sclerosis and increased inflammation were associated with functional limitations/clinical symptoms. Based on our multivariate analysis, we found that increased risk of poor treatment response was correlated with tissue eosinophils and basal pigmentation. LIMITATIONS: This was a single-center retrospective study. CONCLUSION: Skin biopsy samples could show specific features of morphea, including eosinophil infiltration and basal pigmentation, which may indicate the need for aggressive treatment and frequent monitoring.

Identification of skin aging biomarkers correlated with the biomechanical properties.

BACKGROUND: Skin aging can be described as a combination of intrinsic and extrinsic aging. Various parameters for evaluating skin characteristics have been proposed. However, an accurate biomarker for skin aging and the relationship between biomarkers and biomechanical parameters of the skin is yet to be explored. MATERIALS AND METHODS: This study included 20 subjects by age. Skin aging was measured using non-invasive devices. Skin tissues were acquired through punch biopsy for immunohistochemistry and qRT-PCR of skin aging biomarkers, and analyzed correlation both, validated their use. RESULTS: Biomechanical properties of skin aging decreased with age. Among the biomarkers previously reported, we found that the expression of Moesin, TXNDC5, RhoGDI, and RSU1 decreased, while that of Vimentin and FABP5 increased with age. Pearson correlation showed that the expression levels of TXNDC5, RhoGDI, RSU1, and Vimentin were significantly correlated with the results of non-invasive measurements. In addition, the expression of TXNDC5, RhoGDI, and RSU1 increased, while that of Vimentin decreased, in skin explants upon treatment with one of the anti-aging compounds, retinoic acid. CONCLUSION: From this study, we identified practical molecular biomarkers of skin aging, TXNDC5, RhoGDI, RSU1, and Vimentin, which correlated with the skin biomechanical properties of skin aging.

Proteoglycan Combined with Hyaluronic Acid and Hydrolyzed Collagen Restores the Skin Barrier in Mild Atopic Dermatitis and Dry, Eczema-Prone Skin: A Pilot Study.

Dry and eczema-prone skin conditions such as atopic dermatitis and xerotic eczema primarily indicate an impaired skin barrier function, which leads to chronic pruritus. Here, we investigated the effects of a novel emollient containing H.ECMTM liposome, which contains a soluble proteoglycan in combination with hydrolyzed collagen and hyaluronic acid. A prospective, single-arm study was conducted on 25 participants with mild atopic dermatitis or dry skin to assess the hydration and anti-inflammatory effect of the novel emollient applied daily over four weeks. All efficacy parameters, including itching severity, transepidermal water loss, and skin hydration, improved significantly after four weeks. The in vitro and ex vivo studies confirmed the restoration of the skin's barrier function. The study revealed the clinical and laboratory efficacy of H.ECMTM liposome in reducing itching and improving the skin's barrier integrity. Thus, the use of H.ECMTM liposome can be considered a therapeutic option for dry and eczema-prone skin.

Cellular Senescence and Inflammaging in the Skin Microenvironment.

Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging phenotype is called "inflammaging". Inflammaging is not only related with age-associated chronic systemic diseases such as cardiovascular disease and diabetes, but also skin aging. As the largest organ of the body, skin is continuously exposed to external stressors such as UV radiation, air particulate matter, and human microbiome. In this review article, we present mechanisms for accumulation of senescence cells in different compartments of the skin based on cell types, and their association with skin resident immune cells to describe changes in cutaneous immunity during the aging process.

Synergistic Effect of 300 µm Needle-Depth Fractional Microneedling Radiofrequency on the Treatment of Senescence-Induced Aging Hyperpigmentation of the Skin.

Aging-associated dermatological pigmentary diseases are associated with accumulation of senescence cells and the disruption of basement membrane due to chronic ultraviolet radiation (UVR) exposure. Our study is on the synergistic effect of the novel 300 µm needle-depth fractional microneedling radiofrequency (FMR) treatment and conventional Q-switched ND:YAG laser on aging-associated hyperpigmentation of the skin. The prospective controlled clinical trial of 25 Asian women revealed significantly higher improvements not only on wrinkles, but also on hyperpigmentation. Additional ex vivo study revealed significant reduction of pro-melanogenic markers as well as senescent keratinocytes, while increased expression of collagen type IV on the epidermal basement membrane, after additional FMR treatment on UV-irradiated human tissues. These results demonstrate that 300 µm needle-depth FMR might effectively remove senescent keratinocytes that secrete pro-melanogenic markers, and repair disrupted basement membrane, therefore preventing constant hyperpigmentation of the aged skin.