Intrinsic Aging Research Articles

Aromatic plants as cosmeceuticals: benefits and applications for skin health.

This review highlights the potential of aromatic plants as natural antioxidants in cosmeceuticals to combat skin aging and promote health and rejuvenation. Aromatic plant extracts, essential oils, or their phytoconstituents have a long history of use in skincare, dating back centuries. Currently, these plant-based sources are extensively researched and utilized in the cosmeceutical industry to formulate products that enhance skin health and promote a youthful appearance. These plants' diverse bioactivities and sensory properties make them ideal ingredients for developing anti-aging agents recommended for maintaining healthy skin through self-care routines, offering a natural alternative to synthetic products. Reactive oxygen species (ROS) accumulation in the dermis, attributed to intrinsic and extrinsic aging factors, particularly prolonged sun exposure, is identified as the primary cause of skin aging. Plant extracts enriched with antioxidant compounds including flavonoids, phenolics, tannins, stilbenes, terpenes, and steroids, are fundamental to counteract ROS-induced oxidative stress. Noteworthy effects observed from the use of these natural sources include photoprotective, senolytic, anti-inflammatory, anti-wrinkle, anti-acne, and anti-tyrosinase activities, encompassing benefits like photoprotection, wound healing, skin whitening, anti-pigmentation, tissue regeneration, among others. This review highlights several globally distributed aromatic plant species renowned for their benefits for skin, including Foeniculum vulgare Mill. (Apiaceae), Calendula officinalis L. and Matricaria chamomilla L. (Asteraceae), Thymus vulgaris L. (Lamiaceae), Litsea cubeba (Lour.) Pers. (Lauraceae), Althaea officinalis L. (Malvaceae), Malaleuca alternifolia (Maiden y Betche) Cheel (Myrtaceae), Cymbopogon citratus (DC.) Stapf (Poaceae), Rubus idaeus L. (Rosaceae), and Citrus sinensis L. Osbeck (Rutaceae), emphasizing their potential in skincare formulations and their role in promoting health and rejuvenation.

Novel Approach to Skin Anti-Aging: Boosting Pharmacological Effects of Exogenous Nicotinamide Adenine Dinucleotide (NAD+) by Synergistic Inhibition of CD38 Expression

Nicotinamide adenine dinucleotide (NAD+) is indispensable for the regulation of biological metabolism. Previous studies have revealed its role in aging and degenerative diseases, while crucially showing that supplementation with NAD+ or its precursors could ameliorate or reverse the progression of aging. Despite extensive evidence for the role and action of NAD+ in aging, its pharmacological activity on the skin, or even its mechanism, has not been elucidated. In this study, we established a novel approach to effectively utilize NAD+ for skin anti-aging by enhancing the pharmacological efficacy of exogenous NAD+ using a phytochemical complex consisting of quercetin, and enoxolone through inhibition of CD38. Through the comprehensive in vitro experiments based on human fibroblasts, we observed that exogenous NAD+ could exert protective effects against both extrinsic aging induced by ultraviolet light exposure and intrinsic aging. Additionally, we found that its effects were significantly boosted by quercetin and enoxolone. In this in-depth study, we demonstrated that these beneficial effects are mediated by improved sirtuin activation, autophagy, and mitochondrial functionality. Our approach is expected to verify the applicability of the topical application of NAD+ and offer more effective solutions for the unmet needs of patients and consumers who demand more effective anti-aging effects.

Antiaging in a Bottle: Bioactive Competency of Plasma-Generated Nitric Oxide Water for Modulation of Aging-Related Signature in Human Dermal Cells.

Nitric oxide (NO), a potential therapeutic antiaging molecule, modulates various physiological and cellular processes. However, alterations in endogenous NO levels brought on by aging impact multiple organ systems and heighten susceptibility to age-related skin diseases. This correlation underscores the importance of investigating NO-based antiaging interventions. Nonthermal plasma-generated NO is a promising avenue for cosmetic and regenerative medicine due to its capacity to stimulate cellular growth. Herein, we examine the potential of plasma-generated nitric oxide water (NOW) as a bioactive agent in human dermal fibroblasts, emphasizing gene expression patterns linked to extracellular matrix (ECM) breakdown and cellular senescence. The findings of our study indicate that administering NOW at lower dosages enhances cell migration and proliferation. Moreover, the genetic signatures associated with ECM synthesis, antioxidant defense, and antisenescence pathways have been analyzed in NOW-exposed cells. Notably, the downregulation of ECM-degrading enzyme transcripts─collagenase, elastase, and hyaluronidase─suggests NOW's potential in mitigating the intrinsic skin aging phenomena, emphasizing the promise of NO-based interventions in advancing antiaging strategies within regenerative medicine.

Enhanced SIRT1 Activity by Galangin Mitigates UVB-Induced Senescence in Dermal Fibroblasts via p53 Acetylation Regulation and Activation.

Human skin aging, a complex process influenced by intrinsic aging and extrinsic photoaging, is marked by the accumulation of reactive oxygen species (ROS) that cause DNA damage, impaired dermal fibroblast function, and wrinkle formation. External stressors, such as ultraviolet (UV) radiation, can trigger cellular senescence. Sirtuin-1 (SIRT1), an NAD+-dependent enzyme in the sirtuin family, plays a crucial role in deacetylating p53, thereby inhibiting its nuclear translocation and reducing skin senescence. Galangin, a flavonoid found in honey and Alpinia officinarum root, has antioxidant and anti-inflammatory properties. This study investigates the protective mechanism of galangin against UVB-induced senescence in human dermal fibroblasts (HDFs) by examining its effects on SIRT1 and its target, acetylated-p53. An in vitro model of UVB-induced senescence using HDFs and an in vivo model using nude mice were employed to assess the dermal protective effects of galangin. The results demonstrate that while UVB exposure does not decrease SIRT1 protein levels, it impairs its enzymatic function. However, galangin treatment counteracts these adverse effects. Additionally, UVB exposure significantly reduces cell viability and upregulates senescence markers like p16, p21, and p53 nuclear transactivation. An increase in senescence-associated β-galactosidase (SA-β-gal) positive cells was observed in UVB-exposed dermal fibroblasts. Galangin treatment mitigates UVB-induced cellular senescence by enhancing SIRT1-mediated p53 deacetylation, thereby inhibiting nuclear translocation and reducing dermal senescence. These findings suggest that galangin is a promising agent for alleviating UVB-induced skin aging and could be a potential component in antiaging cosmetic formulations.

Concordance between Clinical and Histopathological Diagnosis among Various Dermatoses in the Elderly: A 5-year Retrospective Cross-sectional Assessment from a Tertiary Care Center in Southern India

Background: Dermatoses in the elderly differ from those in the younger age group due to additional effects of intrinsic and extrinsic aging, increased prevalence of comorbidities, effects of polypharmacy, socioeconomic factors, and geographical factors. Various prevalence studies on the dermatoses in geriatric age group are available from the Indian subcontinent. Studies focusing on the agreement between their clinical and histopathological diagnosis, however, are scarce. Aims and Objectives: The study aimed at categorizing and describing the various dermatoses in the geriatric population subjected to biopsy and to determine the level of agreement between the clinical diagnosis made and the histopathological diagnosis offered in them. Materials and Methodology: Histopathological records of skin biopsies performed in patients belonging to the age group of ≥60 years in the past 5 years were analyzed. Demographic characteristics, clinical diagnosis made or the differential diagnoses considered, and histopathological diagnosis offered in each case were noted. The various dermatoses among the patients in whom a histopathological diagnosis was offered were categorized into inflammatory (infections and noninfectious dermatoses), neoplastic, and other dermatoses groups. The level of agreement between clinical and histopathological diagnosis was described as complete agreement, partial agreement, and disagreement. Statistical significance was assessed using the Chi-square test, and the strength of association was assessed using kappa statistics. Results: A total of 109 biopsies meeting the inclusion criteria were analyzed. The mean age of the study population was 67.02 ± 6.624 years, with a male-to-female ratio of 1.6:1. Majority of the dermatoses belonged to the noninfectious inflammatory group (52 [47.70%]) followed by neoplasms (28 [25.68%]). Overall, complete agreement between the clinical diagnosis made or one of the differential diagnoses considered and the histopathological diagnosis offered was seen in 91 of 109 cases (83.5%), which was statistically significant (P = 0.0001). A higher level of complete agreement was noted among the inflammatory dermatoses (67 of 79 cases [84.81%]) when compared to neoplastic dermatoses (22 of 28 cases [78.57%]). Among the inflammatory dermatoses, complete agreement was more for the noninfectious (46 [88.46%]) than the infectious (21 [77.78%]) dermatoses. All the cases (2) belonging to the other group of dermatoses showed complete agreement. Disagreement was highest among the neoplasms (6 [21.43%]), followed by the noninfectious inflammatory dermatoses (5 [9.62%]). Partial agreement with the clinical diagnosis was maximum for the infectious diseases (5 [18.51%]). Conclusion: This study noted a statistically significant high rate of concordance (Chi-square test –P = 0.0001) between the clinical and histopathological diagnosis among the dermatoses in the geriatric population when taken together as well as among individual categories. Noninfectious inflammatory dermatoses constituted the major group with the highest and statistically significant concordance between the clinical and histopathological diagnosis. Furthermore, there was almost perfect strength of association (kappa statistics –P = 0.000) noted among the individual categories of dermatoses.

The effect of aging on mast cell density in human skin: a comparative analysis of photoexposed and photoprotected regions.

Mast cells are mononuclear cells originating from bone marrow. They produce various biologically active substances, which allow them to actively participate in immune and inflammatory processes associated with intrinsic and extrinsic skin aging. This research focused on distribution and density of mast cells in healthy skin in different stages of skin aging. This project included samples of photoexposed and photoprotected skin, obtained from 90 cadavers aged 0-82 years. The samples were classified into five age groups: newborns, young age, middle age, senior age and the oldest age. In order to visualize the mast cells, we have employed several histochemical staining protocols. The number of mast cells of the photoexposed skin significantly correlated to the individual's age. The number of mast cells of the photoprotected skin was in general statistically significantly lower in younger compared to older groups; however, the correlation of the mast cell density in photoprotected skin and the age did not reach statistical significance. In middle age, senior age and the oldest age groups, a significantly higher number of mast cells was recorded in the skin of the photoexposed compared to photoprotected region. The increase in mast cell density correlated with age only in photoexposed skin. Age-related higher accumulation of dermal mast cells in photoexposed skin can be an important factor in the photoaging process, as well as the contributing factor in the occurrence of skin cancer.

Sex-dependent effects in the aged melanoma tumor microenvironment influence invasion and resistance to targeted therapy

There is documented sex disparity in cutaneous melanoma incidence and mortality, increasing disproportionately with age and in the male sex. However, the underlying mechanisms remain unclear. While biological sex differences and inherent immune response variability have been assessed in tumor cells, the role of the tumor-surrounding microenvironment, contextually in aging, has been overlooked. Here, we show that skin fibroblasts undergo age-mediated, sex-dependent changes in their proliferation, senescence, ROS levels, and stress response. We find that aged male fibroblasts selectively drive an invasive, therapy-resistant phenotype in melanoma cells and promote metastasis in aged male mice by increasing AXL expression. Intrinsic aging in male fibroblasts mediated by EZH2 decline increases BMP2 secretion, which in turn drives the slower-cycling, highly invasive, and therapy-resistant melanoma cell phenotype, characteristic of the aged male TME. Inhibition of BMP2 activity blocks the emergence of invasive phenotypes and sensitizes melanoma cells to BRAF/MEK inhibition.

Effect of Helix aspersa Mucus on the Regeneration of Skin with Photoaging Features in Different Methods of Application

Skin aging is associated with both intrinsic and extrinsic aging, with extrinsic aging caused by environmental factors and overlaying the effects of chronological aging. The main aim of this study was to evaluate the effect of preparations containing Helix aspersa snail mucus on skin regeneration with photoaging features. Before and 3 months after the series of treatments, skin biopsy specimens from the right preauricular region of the face were taken from six women. Histological, morphometric, and immunohistochemical analyses were performed. Positive changes, indicating a reduction in photoaging related to the reduction in epidermis thickness 3 months after the end of the treatments, were noted in each group. A statistically significant increase in the thickness of the collagen fiber bundles was also observed in the patients 3 months after a series of micro-needle mesotherapy treatments with snail mucus and 0.9% NaCl. There was a significant increase in the immuno-expression of Ki-67 and PCNA in the dermis. The aforementioned significance applies to patients in whom snail mucus was introduced with the use of micro-needle mesotherapy and needle-free mesotherapy. Moreover, a statistically significant increased area with the immunoexpression of MMP-2 in the dermis was observed in the above-mentioned groups of patients, who were treated with the preparation containing snail filtrate. The results of the study suggest that the use of snail mucus preparations for skincare, as well as its introduction by micro-needle and needleless mesotherapy, had a beneficial effect on the condition of the skin.

Beyond the genome: protecting the proteome may be the key to preventing skin aging.

Skin aging is associated with a progressive decline in physiological functions, skin cancers and, ultimately, death. It may be categorized as intrinsic or extrinsic, whereby intrinsic aging is attributed to chronological and genetic factors. At the molecular level, skin aging involves changes in protein conformation and function. The skin proteome changes constantly, mainly through carbonylation; an irreversible phenomenon leading to protein accumulation as toxic aggregates that impair cellular physiology and accelerate skin aging. This review details the central role of proteostasis during skin aging and why proteome protection may be a promising approach in mitigating skin aging. A comprehensive literature review of 87 articles focusing on the proteome, proteostasis, proteotoxicity, protein carbonylation, and the impact of the damaged proteome on aging, and in particular skin aging, was conducted. Skin aging is associated with deficiencies in the repair mechanisms of DNA, transcriptional control, mitochondrial function, cell cycle control, apoptosis, cellular metabolism, changes in hormonal levels secondary to toxicity of damaged proteins, and cell-to-cell communication for tissue homeostasis, which are largely controlled by proteins. In this context, a damaged proteome that leads to the loss of proteostasis may be considered as the first step in tissue aging. There is growing evidence that a healthy proteome plays a central role in skin and in maintaining healthy tissues, thus slowing down the process of skin aging. Hence, protecting the proteome against oxidative or other damage may be an appropriate strategy to prevent and delay skin aging.

Skin Aging and the Upcoming Role of Ferroptosis in Geroscience.

The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin of a young adult from that of an older adult. These changes are caused by a combination of intrinsic and extrinsic aging. We report the interactions between skin aging and its metabolism, showing that the network is due to several factors. For example, iron is an important nutrient for humans, but its level increases with aging, inducing deleterious effects on cellular functions. Recently, it was discovered that ferroptosis, or iron-dependent cell death, is linked to aging and skin diseases. The pursuit of new molecular targets for ferroptosis has recently attracted attention. Prevention of ferroptosis is an effective therapeutic strategy for the treatment of diseases, especially in old age. However, the pathological and biological mechanisms underlying ferroptosis are still not fully understood, especially in skin diseases such as melanoma and autoimmune diseases. Only a few basic studies on regulated cell death exist, and the challenge is to turn the studies into clinical applications.

Mentha piperita leaf extract suppresses the release of ATP from epidermal keratinocytes and reduces dermal thinning as well as wrinkle formation.

To achieve a more beautiful and younger appearance, reducing wrinkles is a key concern. The process of wrinkle formation is complex and the development of truly effective cosmetic ingredients to reduce wrinkles remains a challenge. Recent studies have revealed a close relationship between wrinkles and skin thinning, suggesting that preventing skin thinning could also prevent wrinkle formation. In this study, we examined the role of extracellular adenosine triphosphate (eATP) in the progression of thinning, as eATP reportedly increases skin ageing factors, such as senescence-associated secreted phenotype (SASP) factors in epidermal cells. We determined the effects of Mentha piperita leaf extract on suppressing eATP to reduce thinning and wrinkles. Adenosine triphosphate (ATP) levels were measured in normal human epidermal keratinocytes (NHEK) in the presence of M. piperita leaf extract. Dryness, high pH, and UVB radiation were used as extrinsic ageing factors. Intrinsic skin ageing was evaluated by comparing cells from adults (AD-NHEK) and newborns (NB-NHEK). A placebo-controlled invivo study was carried out with a formulation containing 1% M. piperita leaf extract. The eATP levels were significantly higher in AD-NHEK compared with that in NB-NHEK cells. M. piperita leaf extract significantly decreased eATP levels in adult cells. Extrinsic ageing factors increased eATP levels in NHEK, whereas M. piperita leaf extract significantly suppressed eATP under all conditions. The active components of M. piperita leaf extract, luteolin glucuronide and rosmarinic acid, also decreased eATP. Moreover, compared with placebo lotion, M. piperita leaf extract-formulated lotion markedly increased dermal thickness and reduced wrinkles associated with crow's feet and the neck area. We demonstrated for the first time that M. piperita leaf extract containing rosmarinic acid and luteolin-7-O-glucuronide has the potential to reduce eATP release from epidermal keratinocytes. An increase in eATP was observed not only during inflammation but also during natural ageing. Furthermore, the invivo experiment revealing that 1% M. piperita leaf extract-containing lotion improved dermal thinning and wrinkles across multiple areas is attributed to the amelioration of dermal thinning. Thus, our data suggest the possibility of a novel cosmetic approach for reducing skin ageing by reducing eATP-mediated dermal thinning.

Intrinsic doping and ageing of indium oxide thin films

Indium oxide (In2O3) is one of the most used materials for the synthesis of transparent electronics devices and currently tin-doped indium oxide (ITO) dominates the field of Transparent Conductive Oxides for most applications, from ICT to photovoltaics. In this work we present a study on the responses of indium oxide upon the formation, and stabilization, of point defects induced with different methods. After the deposition of In2O3 thin films via RF magnetron sputtering, treatments such as Ion Implantation (I.I.), Ultraviolet (UV) irradiation and Sun exposure were employed to generate oxygen vacancies as intrinsic dopants. Both I.I. and UV irradiations significantly improved the electrical conductivity of films, increasing the carrier density by up to 3 orders of magnitude. Moreover, after I.I. also the crystalline quality of the films was enhanced.To monitor the stability of oxygen vacancies upon exposure to ambient atmosphere, the ageing of samples was followed and recorded for a couple of weeks, reporting a fast and strong degradation of electrical properties. As a facile strategy to counteract the sheet resistance increase, samples were encapsulated in an ultra-thin (≈10 nm) SiO2 layer deposited via sputtering. Irradiated and encapsulated films retained a much lower sheet resistance throughout the observation time, preserving the samples conductivity.

Changes in human skin composition due to intrinsic aging: a histologic and morphometric study

Skin represents the main barrier against the external environment, but also plays a role in human relations, as one of the prime determinants of beauty, resulting in a high consumer demand for skincare-related pharmaceutical products. Given the importance of skin aging in both medical and social spheres, the present research aims to characterize microscopic changes in human skin composition due to intrinsic aging (as opposed to aging influenced by external factors) via histological analysis of a photoprotected body region. Samples from 25 autopsies were taken from the periumbilical area and classified into four age groups: group 1 (0–12 years), group 2 (13–25 years), group 3 (26–54 years), and group 4 (≥ 55 years). Different traditional histological (hematoxylin–eosin, Masson’s trichrome, orcein, toluidine, Alcian blue, and Feulgen reaction) and immunohistochemical (CK20, CD1a, Ki67, and CD31) stains were performed. A total of 1879 images photographed with a Leica DM3000 optical microscope were morphometrically analyzed using Image ProPlus 7.0 for further statistical analysis with GraphPad 9.0. Our results showed a reduction in epidermis thickness, interdigitation and mitotic indexes, while melanocyte count was raised. Papillary but not reticular dermis showed increased thickness with aging. Specifically, in the papillary layer mast cells and glycosaminoglycans were expanded, whereas the reticular dermis displayed a diminution in glycosaminoglycans and elastic fibers. Moreover, total cellularity and vascularization of both dermises were diminished with aging. This morphometric analysis of photoprotected areas reveals that intrinsic aging significantly influences human skin composition. This study paves the way for further research into the molecular basis underpinning these alterations, and into potential antiaging strategies.

Cutis Rhomboidalis Nuchae and Solar Lentigo with Squamous and Basal Cell Carcinoma – A Quartet of Chronic Sun Exposure

Abstract Aging is of two types, namely extrinsic and intrinsic aging. Extrinsic aging or photoaging is caused mainly due to damage caused by solar radiation. We report the case of a elderly male who presented with large growth on the scalp and ulcer on the face. However, on clinical examination, almost all the changes of photoaging, namely solar lentigo, cutis rhomboidalis nuchae squamous, and basal cell carcinoma were present. This case highlights the importance of thorough clinical examination needed in the geriatric population for the early diagnosis and timely management of their ailments. This will not only prolong but also improve their quality of life.

P01 Remodelling of the dermoepidermal junction occurs in intrinsically aged Far East Asian skin without significant epidermal atrophy

Abstract Introduction and aims Ageing is characterized by a gradual decline in physiological function and is influenced by both intrinsic genetic and extrinsic lifestyle and environmental factors. However, much of our knowledge of cutaneous ageing comes from the study of White populations. We have previously shown that the organization of young healthy skin is ethnicity-dependent and that altered epidermal morphology in White volunteers correlates with loss of biomechanical function in the skin. In this study, we used epidermal morphometry to determine whether parameters associated with intrinsic skin ageing in White skin are also observed in Far East Asian skin. Methods Archival skin samples were obtained from the Asian Skin Biobank [young (3–21 years), N = 38, 37 male samples (Chinese, n = 16; Malay, n = 16; other Far East, n = 6); aged (61–86 years), N = 7, one male sample (Chinese, n = 6; Malay, n = 1)] and stained with haematoxylin and eosin prior to image analysis for dermoepidermal junction (DEJ) convolution and measurement of epidermal thickness. Weigert’s resorcin-fuchsin stain was used to ensure samples were photoprotected. Results Weigert’s resorcin-fuchsin stain revealed that all samples were photoprotected, with no evidence of solar elastosis. We next compared whether geographic ancestry of our local Far East Asian population impacted epidermal morphology in young skin; neither DEJ convolution nor epidermal thickness were impacted by geographic ancestry. However, a significant flattening of the DEJ was observed between young and aged samples (P < 0.01). Interestingly, no significant difference in epidermal thickness was observed as a function of age. Conclusions While intrinsically aged Asian skin undergoes the same flattening of the DEJ that is seen in White populations, epidermal thickness does not significantly alter; this is in stark contrast to intrinsically aged White skin, where epidermal atrophy is observed. Hence, the trajectory of intrinsic cutaneous ageing may be ethnicity-dependent, providing further evidence that studies of skin from different ethnicities are necessary.

Elimination of damaged mitochondria during UVB-induced senescence is orchestrated by NIX-dependent mitophagy.

Skin aging is the result of two types of aging, "intrinsic aging" an inevitable consequence of physiologic and genetically determined changes and "extrinsic aging," which is dependent on external factors such as exposure to sunlight, smoking, and dietary habits. UVB causes skin injury through the generation of free radicals and other oxidative byproducts, also contributing to DNA damage. Appearance and accumulation of senescent cells in the skin are considered one of the hallmarks of aging in this tissue. Mitochondria play an important role for the development of cellular senescence, in particular stress-induced senescence of human cells. However, many aspects of mitochondrial physiology relevant to cellular senescence and extrinsic skin aging remain to be unraveled. Here, we demonstrate that mitochondria damaged by UVB irradiation of human dermal fibroblasts (HDF) are eliminated by NIX-dependent mitophagy and that this process is important for cell survival under these conditions. Additionally, UVB-irradiation of human dermal fibroblasts (HDF) induces the shedding of extracellular vesicles (EVs), and this process is significantly enhanced in UVB-irradiated NIX-depleted cells. Our findings establish NIX as the main mitophagy receptor in the process of UVB-induced senescence and suggest the release of EVs as an alternative mechanism of mitochondrial quality control in HDF.

Revisiting the Effect of Aging on the Transport of Molecules through the Skin.

Both intrinsic and extrinsic aging lead to a series of morphological changes in the skin including the flattening of the dermal-epidermal junction, increased stratum corneum dryness, reduction in sebaceous gland activity and enzyme activity as well as atrophy of blood vessels. In this study, the impact of these changes on the transport of molecules through the skin was revised. The increase in the number of transdermal formulations on the market in recent decades and life expectancy represent the main reasons for an in-depth discussion of this topic. Furthermore, elderly subjects have often been excluded from clinical trials due to polypharmacy, raising concerns in terms of efficacy and safety. In this way, ex vivo and in vivo studies comparing the transport of molecules through the mature and young skin were analyzed in detail. The reduced water content in mature skin had a significant impact on the transport rate of hydrophilic molecules. The lower enzymatic activity in aged skin, in turn, would explain changes in the activation of prodrugs. Interestingly, greater deposition of nanoparticles was also found in mature skin. In vivo models should be prioritized in future experimental studies as they allow to evaluate both absorption and metabolism simultaneously, providing more realistic information.

Crosstalk between endothelial cells and dermal papilla entails hair regeneration and angiogenesis during aging

IntroductionTissues maintain their function through interaction with microenvironment. During aging, both hair follicles and blood vessels (BV) in skin undergo degenerative changes. However, it is elusive whether the changes are due to intrinsic aging changes in hair follicles or blood vessels respectively, or their interactions. ObjectiveTo explore how hair follicles and blood vessels interact to regulate angiogenesis and hair regeneration during aging. MethodsSingle-cell RNA-sequencing (scRNA-seq) analyses were used to identify the declined ability of dermal papilla (DP) and endothelial cells (ECs) during aging. CellChat and CellCall were performed to investigate interaction between DP and ECs. Single-cell metabolism (scMetabolism) analysis and iPATH were applied to analyze downstream metabolites in DP and ECs. Hair-plucking model and mouse cell organoid model were used for functional studies. ResultsDuring aging, distance and interaction between DP and ECs are decreased. DP interacts with ECs, with decreased EDN1-EDNRA signaling from ECs to DP and CTF1-IL6ST signaling from DP to ECs during aging. ECs-secreted EDN1 binds to DP-expressed EDNRA which enhances Taurine (TA) metabolism to promote hair regeneration. DP-emitted CTF1 binds to ECs-expressed IL6ST which activates alpha-linolenic acid (ALA) metabolism to promote angiogenesis. Activated EDN1-EDNRA-TA signaling promotes hair regeneration in aged mouse skin and in organoid cultures, and increased CTF1-IL6ST-ALA signaling also promotes angiogenesis in aged mouse skin and organoid cultures. ConclusionsOur finding reveals reciprocal interactions between ECs and DP. ECs releases EDN1 sensed by DP to activate TA metabolism which induces hair regeneration, while DP emits CTF1 signal received by ECs to enhance ALA metabolism which promotes angiogenesis. Our study provides new insights into mutualistic cellular crosstalk between hair follicles and blood vessels, and identifies novel signaling contributing to the interactions of hair follicles and blood vessels in normal and aged skin.

Skin Color Analysis of Various Body Parts (Forearm, Upper Arm, Elbow, Knee, and Shin) and Changes with Age in 53 Korean Women, Considering Intrinsic and Extrinsic Factors.

Background/Objectives: Skin color is innately determined by race and other genetic factors, and it also undergoes acquired changes due to various intrinsic and extrinsic factors. Previous studies on skin color have mainly focused on the face, and research has recently expanded to other body parts. However, there is limited information about the age-dependent changes in the skin color of these body parts. The purpose of this study is to analyze the differences in skin color between various body parts and the changes in skin color of each body part with age. Methods: This study examined the skin color of 53 Korean women subjects evenly distributed in age from the 20s to 60s on several body parts: forearm, upper arm, elbow (extended or folded), knee (extended or folded), thigh, and shin. The lightness (L*), redness (a*), and yellowness (b*) were measured using a spectrophotometer, and the individual typology angle (ITA°) was calculated from the L* and b* values. The melanin index and erythema index were measured using the mexameter. Results: The results showed that the elbow skin had the lowest L* and ITA° values and the highest a* and b* values among the examined body parts, followed by the knee. The melanin index and erythema index were also high in the skin of these body parts. In the analysis of age-dependent changes in the skin color of various body parts, the forearm skin exhibited the most notable decrease in the L* and ITA° values and increases in the a* and b* values, followed by upper-arm skin. The melanin and erythema indices in the forearm also increased as the subjects aged, whereas those in the elbow and knee rather decreased with age. Conclusions: This study suggests that differences in intrinsic and extrinsic skin aging in various body parts may be expressed as different changes in skin color and raises the need for cosmetic and dermatological research to identify the physiological significance of these changes.

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.