Image-based investigation of lip aging features in a large number of Korean women.

BACKGROUND: The lips play a significant role in shaping facial aesthetics. Due to the distinct attributes of lips in contrast to other facial skin, a unique approach is imperative for managing lip aging. We analyzed lip characteristics (morphology, wrinkles, and color) to investigate visual changes and distinctive attributes of aging lips. METHODS: By utilizing image data processing methods, including facial landmark detection, pattern recognition, and color quantification, we extracted 11 lip characteristic indices (four morphological indices, four wrinkle indices, and three color indices) from high-resolution images of 1000 Korean women aged 20-69. Correlation tests were conducted to assess the relationship between lip characteristic indices and age, and also between lip morphological and wrinkle indices. RESULTS: Lip height significantly decreased, while lip width and lip ratio (lip width divided by the sum of the upper and lower lip height) significantly increased with aging. Lip wrinkles significantly increased with aging, whereas lip colors (redness and yellowness) decreased. The lip wrinkle indices, which are segmented for the first time in this study, exhibited significant correlations with lip width, and three of them additionally were correlated with lip ratio (p < 0.05). The results imply such morphological changes can be associated with wrinkle formation of human lips. CONCLUSION: The indices suggested in this study can be used for assessing lip aging characteristics, and the study results can contribute to deeper understanding of lip aging.

Comparative analysis of skin characteristics evaluation by a dermatologist and the Janus-III measurement system.

BACKGROUND: The Janus-III measurement system evaluates the overall skin characteristics such as skin pore, wrinkle, sebum, porphyrin, skin pigmentation, and skin color using high-resolution facial images. The values are measured from five different facial areas, namely, the forehead, nose, corner of/skin below the eyes, and cheeks. Owing to its convenience and diverse measuring characteristics, Janus-III has been widely used in skin research and the cosmetic industry in Korea. In our previous study, we revealed the consistency and reliability of the system with repeatedly measured values. Its measuring performance was investigated statistically, but to make it more reliable for academic skin research, additional verification by a professional dermatologist is needed. MATERIALS AND METHODS: In this study, we conducted comparative analysis of three skin characteristics (pigmented spot, skin color, and eye wrinkle) by a dermatologist and the Janus-III measurement system. We utilized 330 image data that were cropped from the whole facial images of 330 different participants to avoid correlation among the three measuring items. Pearson's correlation coefficient exhibited similar patterns between the system and the dermatologist's findings. RESULTS: The main finding of our study was that the measured value of skin characteristics by the Janus-III system showed clear correlation with the values evaluated by a dermatologist, especially in a pigmented spot. CONCLUSION: Therefore, it would be a plausible idea to consider the Janus-III system for specialized research of skin characteristics even with a small sample size.

Repeated measurements of facial skin characteristics using the Janus-â ¢ measurement system.

BACKGROUND: For personalized skin care, noninvasive quantitative methods to evaluate facial skin characteristics are important. Janus-III is one of the most widely used imaging analysis devices in the skin care industry in Korea. Janus-III generates values for a range of skin characteristics. Due to the convenience of obtaining results for a variety of skin characteristics in a single measurement, the use of Janus-III in cosmetic stores and research institutes has been recently increasing. However, the consistency of skin measurements of Janus-III has not been elucidated yet. MATERIALS AND METHODS: In this study, we repeated skin measurements three times for 70 different subjects and compared each numerical value in order to assess the consistency of the Janus-III. For this purpose, we compared between-sample distances and within-sample distances. RESULTS: We found important patterns for future analyses in terms of consistency. First, the average values of skin measurement categories were more reliable than individual part values of facial segments. Second, center part values such as forehead and nose were more reliable than side part values such as left and right part segments. CONCLUSION: If researchers who use Janus-III for studies of facial characteristics analyze average and center part values first, they can obtain relatively reliable patterns of facial skin characteristics.

Skin aging-related microbial types separated by Cutibacterium and α-diversity.

BACKGROUND: Studies on the skin microbiome have been conducted to uncover the relationship between skin microbes and the host. However, most of these studies have primarily focused on analyzing individual microbial compositions, which has resulted in a limited understanding of the overall relationship. METHODS: We analyzed the facial skin characteristics and microbial profiles of 100 healthy Korean female volunteers using the V1-V2 region of the 16S ribosomal RNA gene. RESULTS: The two most prominent features of the facial skin microbiome, the proportion of Cutibacterium and α-diversity, were associated with most of the skin characteristics. Based on clustering results, we proposed four types of facial skin microbiome: type C for Cutibacterium, type B for balanced, type CB for those between types C and B, and type O for others. Type C, which has a high proportion of Cutibacterium, showed high levels of pigmentation, wrinkles, pores, and sagging pores, indicating a tendency for severe skin aging. Type B, which has no dominant species and high microbial diversity, had lower values for pigmentation and wrinkles indicating less severe skin aging. Type CB was an intermediate type between type C and type B in terms of microbial composition and the level of skin aging. Type O dominated by microorganisms other than Cutibacterium, had high levels of sebum and pores but low levels of wrinkles. CONCLUSION: We proposed a criterion for classifying facial skin microbial types, each of which showed distinct facial skin aging features. Our simplified microbial types will contribute to a better understanding of facial skin microbial studies.

Mapping and annotating genomic loci to prioritize genes and implicate distinct polygenic adaptations for skin color.

Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color evolution and genetics in East Asians are understudied. We quantified skin color in 48,433 East Asians using image analysis and identified associated genetic variants and potential causal genes for skin color as well as their polygenic interplay with sun exposure. This genome-wide association study (GWAS) identified 12 known and 11 previously unreported loci and SNP-based heritability was 23-24%. Potential causal genes were determined through the identification of nonsynonymous variants, colocalization with gene expression in skin tissues, and expression levels in melanocytes. Genomic loci associated with pigmentation in East Asians substantially diverged from European populations, and we detected signatures of polygenic adaptation. This large GWAS for objectively quantified skin color in an East Asian population improves understanding of the genetic architecture and polygenic adaptation of skin color and prioritizes potential causal genes.

Longitudinal study of the interplay between the skin barrier and facial microbiome over 1 year.

Skin is a diverse ecosystem that provides a habitat for microorganisms. The skin condition and the skin microbiome interact each other under diverse environmental conditions. This study was conducted on 10 study participants for a one-year, from September 2020 to August 2021, to investigate the variability of skin microbiome and skin biophysical parameters [TEWL, hydration, and elasticity (R5)] according to season, and to understand the interplay between skin microbiome and skin characteristics. We identified that Cutibacterium, Corynebacterium, Staphyloccocus, unclassified genus within Neisseriaceae, and Streptococcus were major skin microbial taxa at the genus level, and fluctuated with the seasons. Cutibacterium was more abundant in winter, while Corynebacterium, Staphylococcus, and Streptococcus were more abundant in summer. Notably, Cutibacterium and skin barrier parameter, TEWL, exhibited a co-decreasing pattern from winter to summer and showed a significant association between Cutibacterium and TEWL. Furthermore, functional profiling using KEGG provided clues on the impact of Cutibacterium on the host skin barrier. This study enhances our understanding of the skin microbiome and its interplay with skin characteristics and highlights the importance of seasonal dynamics in shaping skin microbial composition.

Genome-scale metabolic modeling and in silico analysis of opportunistic skin pathogen Cutibacterium acnes.

Cutibacterium acnes, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting C. acnes, which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent C. acnes, iCA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of C. acnes in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in C. acnes compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti-C. acnes targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa.

Two newly developed indices evaluating facial skin aging.

BACKGROUND: Skin assessment methodologies have focused mainly on intuitive aging characteristics, including facial wrinkles and pigmented spots, and usually adopt pattern recognition algorithms. Recently, distinct methods of interpreting skin aging, such as the detection of facial landmarks and age prediction using machine learning techniques, have been conducted. MATERIALS AND METHODS: We defined two indices that represent the severity of facial aging. The first index was the ratio of the bizygomatic distance and bigonial distance. The second index was the ratio of the degrees of the near mandible. The indices extracted from two-dimensional frontal face images were intended to show the deformation of the facial skin downward with aging progress. To validate whether these proposed indicators can represent facial aging, we conducted correlation tests with age and facial skin characteristics and performed association tests between the indices and facial skin characteristics, adjusted for age. RESULTS: The indices showed strong correlations with age (r = 0.557 and 0.464, respectively) and facial skin characteristics. Although there were correlations between the indices and facial skin features, the associations between the indices and facial skin characteristics adjusted for age were weak or not significant. This suggests that the newly developed indices are appropriate for evaluating facial skin aging and distinct from typical measurements. CONCLUSION: We suggest two novel indices for evaluating facial aging based on frontal face images. The indices exhibited strong correlations with age and representative facial skin characteristics. The newly developed values can be differentiated indicators of facial aging compared with general skin features.

GWAS Identifies Multiple Genetic Loci for Skin Color in Korean Women.

Human skin color is largely determined by genetic factors. Recent GWASs have reported several genetic variants associated with skin color, mostly in European and African populations. In this study, we performed GWAS in 17,019 Korean women to identify genetic variants associated with facial skin color, quantitatively measured as CIELAB color index. We identified variants in three, one, and six genomic loci associated with facial skin color index L∗, a∗, and b∗ values, respectively, and replicated the associations (combined analysis P-value < 5.0 × 10-8). The significant loci included variants in known genes (OCA2 rs74653330, BNC2 rs16935073, rs72620727 near KITLG, and SLC6A17 rs6689641) and to our knowledge previously unreported genes (SCARB1 rs10846744, SYN2 rs12629034, and LINC00486 rs6543678). This is GWAS to elucidate genetic variants of facial skin color in a Korean female population. Further functional characterizations of the investigated genes are warranted to elucidate their contribution to skin pigmentation-related traits.

Anti-Irritant Strategy against Retinol Based on the Genetic Analysis of Korean Population: A Genetically Guided Top-Down Approach.

Retinol, one of the most powerful cosmetic materials for anti-aging supported by a solid scientific background, exhibits a wide range of type and severity of irritation while showing limited user compliance. The lack of understanding of the mechanism of retinol-induced irritation has been the main hurdle in the development of anti-irritation strategies. Here, we identified 30 genetic markers related to the susceptibility to retinol-induced irritation in the Korean population. Based on the genetic analysis, a novel formula against retinol-induced irritation was developed, which mitigated the molecular pathogenesis-as indicated by the genetic markers-of the retinol-induced irritation. In human tests, this formula effectively decreased retinol-induced irritation. Furthermore, a polygenic risk score model for irritation was constructed and validated. Our comprehensive approach for the analysis of retinol-induced irritation will not only aid the development of anti-irritation strategies to ensure higher user compliance but also contribute to improving the current knowledge about the biological effects of retinoids.

GWAS Analysis of 17,019 Korean Women Identifies the Variants Associated with Facial Pigmented Spots.

Variation in skin pigmentation can be affected by both environmental factors and intrinsic factors such as age, gender, and genetic variation. Recent GWASs revealed that genetic variants of genes functionally related to a pigmentation pathway were associated with skin pigmentary traits. However, these GWASs focused on populations with European ancestry, and only a few studies have been performed on Asian populations, limiting our understanding of the genetic basis of skin pigmentary traits in Asians. To evaluate the genetic variants associated with facial pigmented spots, we conducted a GWAS analysis of objectively measured facial pigmented spots in 17,019 Korean women. This large-scale GWAS identified several genomic loci that were significantly associated with facial pigmented spots (five previously reported loci and two previously unreported loci, to our knowledge), which were detected by UV light: BNC2 at 9p22 (rs16935073; P-value = 2.11 × 10-46), PPARGC1B at 5q32 (rs32579; P-value = 9.04 × 10-42), 10q26 (rs11198112; P-value = 9.66 × 10-38), MC1R at 16q24 (rs2228479; P-value = 6.62 × 10-21), lnc01877 at 2q33 (rs12693889; P-value = 1.59 × 10-11), CDKN2B-AS1 at 9p21 (rs643319; P-value = 7.76 × 10-9), and MFSD12 at 19p13 (rs2240751; P-value = 9.70 × 10-9). Further functional characterization of the candidate genes needs to be done to fully evaluate their contribution to facial pigmented spots.

In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS.

BACKGROUND: Perturbed functional coupling between the metabotropic glutamate receptor-5 (mGluR5) and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory glutamatergic neurotransmission may contribute to the pathophysiology of psychiatric disorders such as schizophrenia. We aimed to establish the functional interaction between mGluR5 and NMDA receptors in brain of mice with genetic ablation of the mGluR5. METHODS: We first measured the brain glutamate levels with magnetic resonance spectroscopy (MRS) in mGluR5 knockout (KO) and wild-type (WT) mice. Then, we assessed brain glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography before and after the acute administration of an NMDA antagonist, MK-801 (0.5 mg/kg), in the same mGluR5 KO and WT mice. RESULTS: Between-group comparisons showed no significant differences in [18F]FDG standardized uptake values (SUVs) in brain of mGluR5 KO and WT mice at baseline, but widespread reductions in mGluR5 KO mice compared to WT mice after MK-801 administration (p < 0.05). The baseline glutamate levels did not differ significantly between the two groups. However, there were significant negative correlations between baseline prefrontal glutamate levels and regional [18F]FDG SUVs in mGluR5 KO mice (p < 0.05), but no such correlations in WT mice. Fisher's Z-transformation analysis revealed significant between-group differences in these correlations (p < 0.05). CONCLUSIONS: This is the first multimodal neuroimaging study in mGluR5 KO mice and the first report on the association between cerebral glucose metabolism and glutamate levels in living rodents. The results indicate that mGluR5 KO mice respond to NMDA antagonism with reduced cerebral glucose metabolism, suggesting that mGluR5 transmission normally moderates the net effects of NMDA receptor antagonism on neuronal activity. The negative correlation between glutamate levels and glucose metabolism in mGluR5 KO mice at baseline may suggest an unmasking of an inhibitory component of the glutamatergic regulation of neuronal energy metabolism.

In vivo metabotropic glutamate receptor 5 availability-associated functional connectivity alterations in drug-naïve young adults with major depression.

There has been increasing interest in glutamatergic neurotransmission as a putative underlying mechanism of depressive disorders. We performed [11C]ABP688 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in drug-naïve young adult patients with major depression to examine alterations in metabotropic glutamate receptor-5 (mGluR5) availability, and to investigate their functional significance relating to neural systems-level changes in major depression. Sixteen psychotropic drug-naïve patients with major depression without comorbidity (median age: 22.8 years) and fifteen matched healthy controls underwent [11C]ABP688 PET imaging and 3-T MRI. For mGluR5 availability, we quantified [11C]ABP688 binding potential (BPND) using the simplified reference tissue model. Seed-based functional connectivity analysis was performed using rs-fMRI data with regions derived from quantitative [11C]ABP688 PET analysis as seeds. In region-of-interest (ROI)-based and voxel-based analyses, the [11C]ABP688 BPND was significantly lower in patients than in controls in the prefrontal cortex ROI and in voxel clusters within the prefrontal, temporal, and parietal cortices, and supramarginal gyrus. The [11C]ABP688 BPND seed-based functional connectivity analysis showed significantly less negative connectivity from the inferior parietal cortex seed to the fusiform gyrus and inferior occipital cortex in patients than in controls. The correlation patterns between [11C]ABP688 BPND and functional connectivity strength (ß) for the superior prefrontal cortex seed were opposite in the depression and control groups. In conclusion, using a novel approach combining [11C]ABP688 PET and rs-fMRI analyses, our study provides a first evidence of lower mGluR5 availability and related functional connectivity alterations in drug-naïve young adults with major depression without comorbidity.