The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging.

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVR-induced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention.

Skin Rejuvenation by Modulation of DNA Methylation.

Skin aging is driven by a complex set of cellular pathways. Among these, epigenetic mechanisms have garnered particular attention, because of their sensitivity to environmental and lifestyle factors. DNA methylation represents the longest known and best understood epigenetic mechanism. We explain how DNA methylation might function as an interface between the environment and the genome of human skin. Exposures to different environmental factors and lifestyles are known to modulate age-related methylation patterns, as illustrated by their effect on DNA methylation clocks. Human skin provides a particularly well-suited tissue for understanding age-related methylation changes and it has been shown recently that modulation of DNA methylation can induce skin rejuvenation. We explain how the use of mildly demethylating agents can be safeguarded to ensure the specific removal of age-related DNA methylation changes. We also identify important areas of future research, leading to a deeper understanding of the mechanisms that drive epigenetic aging and to the development of further refined intervention strategies.

Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes.

Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.

The m6A writer KIAA1429 regulates photoaging progression via MFAP4-dependent collagen synthesis.

BACKGROUND: N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. OBJECTIVES: This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. METHODS: m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. RESULTS: m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. CONCLUSIONS: The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

Identification of a new human senescent skin cell marker ribonucleoside-diphosphate reductase subunit M2 B.

In skin aging, it has been hypothesized that aging fibroblasts accumulate within the epidermal basal layer, dermis, and subcutaneous fat, causing abnormal tissue remodeling and extracellular matrix dysfunction, thereby inducing an aging-related secretory phenotype (SASP). A new treatment for skin aging involves the specific elimination of senescent skin cells, especially fibroblasts within the dermis and keratinocytes in the basal layer. This requires the identification of specific protein markers of senescent cells, such as ribonucleoside-diphosphate reductase subunit M2 B (RRM2B), which is upregulated in various malignancies in response to DNA stress damage. However, the behavior and role of RRM2B in skin aging remain unclear. Therefore, we examined whether RRM2B functions as a senescence marker using a human dermal fibroblast model of aging. In a model of cellular senescence induced by replicative aging and exposure to ionizing radiation or UVB, RRM2B was upregulated at the gene and protein levels. This was correlated with decreased uptake of the senescence-associated ß-galactosidase activity and proliferation marker bromodeoxyuridine. RRM2B upregulation was concurrent with the increased expression of SASP factor genes. Furthermore, using fluorescence flow cytometry, RRM2B-positive cells were recovered more frequently in the aging cell population. In aging human skin, RRM2B was also found to be more abundant in the dermis and epidermal basal layer than other proteins. Therefore, RRM2B may serve as a clinical marker to identify senescent skin cells.

Facial pore refining by targeting dermal and epidermal functions: Assessment across age and gender.

BACKGROUND: Conspicuous facial pores are benign but represent a cosmetic concern for men and women. Recent works described dermal and epidermal impairments as clinical causes of enlarged pores. Morphological modifications of skin at the site of pores were associated with collagen density loss, possible alteration of extracellular matrix and abnormal differentiation of keratinocytes. AIMS: A composition containing mannose-6-phosphate (Active Complex) was designed to address these different aspects of pore enlargement. In vitro and ex vivo evaluations were conducted in different models mimicking disturbance of dermal and epidermal functions. The pore refining activity of Active Complex was assessed in two clinical trials studying a Caucasian women cohort and an Asian men cohort. RESULTS: At the dermal level, Active Complex upregulated collagen I and decorin synthesis, and genes encoding collagens I, III, V, VII, XVII; suggesting its ability to favor collagen fiber organization and anchorage. The downregulation of matrix metalloprotease, involved in extracellular matrix degradation, reinforced the protective effect of Active Complex in the dermis. Active Complex down modulated differentiation markers in keratinocytes as well as genes involved in cell renewal. Study of reconstructed human epidermis modeling keratinocyte hyperproliferation revealed that Active Complex mitigated two markers of this state: number of nuclei in the stratum corneum and involucrin expression. Clinical trials confirmed the pore refining activity of Active Complex on men and women of different ages and ethnicities; -24% total skin pore area after 56 days of application on women, and -30.2% on men after 7 days. CONCLUSIONS: This work demonstrates the interest to target dermal and epidermal modifications described in conspicuous pore area, especially dermis fiber organization, to address this cosmetic concern.

Genome-wide identification of copy number variations in wrinkled skin cases of Xiang pigs.

Copy number variation (CNV) tends to occur in genetically enriched regions and is likely associated with a number of complex diseases such as skin aging. In this study, we investigated the genome-wide CNVs in 20 wrinkled skin cases (WSC) of Xiang pigs and 63 controls, and identified 7893 copy number variable regions (CNVRs). We estimated the F-statistic (Fst) at each locus and identified that 93 case-controls stratified CNVRs (Fst > = 0.15) overlapped with 87 known genes. Functional enrichment analysis showed that most of these genes were predominantly enriched in pathways and terms related to the extracellular matrix. Finally, we found that some CNVs were predicted to have high effects on genes such as VCAN, TIMP1 and FOXO1 through transcriptional amplification, transcript ablation and so on. Most of the genes overlapped with those CNVRs have been reported to be related to aging in human or animals. The copy numbers presented the positive correlations with the transcript level of the genes in skins between the cases and controls. Our results suggested that those 22 CNVRs, including 19 CNV losses and 3 CNV gains, were putatively associated with the skin wrinkle of Xiang pigs.

Development of a biomarker-based platform for comprehensive skin characterization using minimally invasive skin sampling and quantitative real-time PCR.

BACKGROUND: Classifying diverse skin types is crucial for promoting skin health. However, efficiently identifying and analyzing relevant biomarkers from a vast array of available genetic data is challenging. Therefore, this study aimed to develop a precise and efficient platform for analyzing specific skin biomarkers using quantitative real-time PCR (qRT-PCR) with the minimal invasive skin sampling method (MISSM). MATERIALS AND METHODS: MISSM was used for RNA extraction from skin samples, followed by qRT-PCR analysis to quantify the expression of 20 biomarkers associated with skin characteristics (four biomarkers each for five skin characteristics). Noninvasive measurements from 299 Korean participants were utilized to correlate biomarker expression with skin parameters. Statistical analyses were conducted between biomarker expression levels and noninvasive skin measurements to select the relatively best-performing biomarker for each skin characteristic. RESULTS: Collagen type 1 alpha 1 (COL1A1) and moesin (MSN) were identified as skin aging biomarkers. Krüppel-like factor 4 (KLF4) and serine peptidase inhibitor Kazal type 5 (SPINK5) were identified as skin dryness biomarkers, whereas melan-A (MLANA) was selected as a biomarker for understanding pigmentation dynamics. Myelin protein zero like 3 (MPZL3) and high mobility group box 2 (HMGB2) were identified as markers of oily skin and skin sensitivity, respectively. Statistically significant correlations were found between the biomarker expression levels and noninvasive skin characteristic measurements. CONCLUSION: This study successfully developed a platform for the precise evaluation of individual skin characteristics using MISSM and qRT-PCR biomarker analysis. By selecting biomarkers that correlate with noninvasive measurements of skin characteristics, we demonstrated the platform's efficacy in assessing diverse skin conditions.

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.

Unveiling the causal relationship between circulating levels of micronutrients and risk of facial aging: A Mendelian randomization study.

Facial aging involves a continuous sequence of complex, interrelated events that impact numerous facial tissues. The aim of the study was to elucidate the casual relationship between circulating micronutrients and risk of facial aging. A two-sample Mendelian randomization analysis was performed using genetic data from genome-wide association studies. The inverse-variance weighted method is used for causal effect estimation, and additional tools such as Mendelian randomization-Egger, weighted median, simple mode, and weighted mode were used to refine the analysis. We conducted an in-depth examination of the correlation between several micronutrient blood levels and the risk of facial aging, and identified 3 key micronutrients (selenium, carotene, and iron) that may have a significant impact on skin health. Inverse-variance weighted results indicate that selenium levels were positively correlated with the risk of facial aging (odds ratio [OR] 1.005, P = .027), while a negative causal effect of carotene (OR 0.979, P = .024) and iron (OR 0.976, P = .009) on age-related facial alterations was observed. This study offers a new and insightful perspective on the current understanding of antiaging strategies, particularly the importance of appropriate consumption of essential micronutrients to maintain healthy skin condition.

Alterations of Matrisome Gene Expression in Naturally Aged and Photoaged Human Skin In Vivo.

The main component of human skin is a collagen-rich extracellular matrix (ECM), known as the matrisome. The matrisome is essential for maintaining the structural integrity and mechanical properties of the skin. Recently, we reported notable decreases in matrisome proteins in natural aging and photoaging human skin. This study aims to investigate the mRNA expression of the core matrisome proteins in human skin, comparing young versus aged and sun-protected versus sun-exposed skin by quantitative real-time PCR and immunostaining. Our findings reveal a notable decrease in core matrisome transcription in aged skin. The mRNA expression of the core matrisome, such as collagen 1A1 (COL1A1), decorin, and dermatopontin, is significantly reduced in aged skin compared to its young skin. Yet, the majority of collagen mRNA expression levels of aged sun-exposed skin are similar to those found in young sun-exposed skin. This discrepancy is primarily attributable to a substantial decrease in collagen transcription in young sun-exposed skin, suggesting early molecular changes in matrisome transcription due to sun exposure, which preceded the emergence of clinical signs of photoaging. These findings shed light on the mRNA transcript profile of major matrisome proteins and their alterations in naturally aged and photoaged human skin, offering valuable insights into skin matrisome biology.

LincRNA-EPS Promotes Proliferation of Aged Dermal Fibroblast by Inducing CCND1.

The aging process is linked to numerous cellular changes, among which are modifications in the functionality of dermal fibroblasts. These fibroblasts play a crucial role in sustaining the healing of skin wounds. Reduced cell proliferation is a hallmark feature of aged dermal fibroblasts. Long intergenic non-coding RNA (lincRNAs), such as LincRNA-EPS (Erythroid ProSurvival), has been implicated in various cellular processes. However, its role in aged dermal fibroblasts and its impact on the cell cycle and its regulator, Cyclin D1 (CCND1), remains unclear. Primary dermal fibroblasts were isolated from the skin of 17-week-old (young) and 88-week-old (aged) mice. Overexpression of LincRNA-EPS was achieved through plasmid transfection. Cell proliferation was detected using the MTT assay. Real-time PCR was used to quantify relative gene expressions. Our findings indicate a noteworthy decline in the expression of LincRNA-EPS in aged dermal fibroblasts, accompanied by reduced levels of CCND1 and diminished cell proliferation in these aging cells. Significantly, the overexpression of LincRNA-EPS in aged dermal fibroblasts resulted in an upregulation of CCND1 expression and a substantial increase in cell proliferation. Mechanistically, LincRNA-EPS induces CCND1 expression by sequestering miR-34a, which was dysregulated in aged dermal fibroblasts, and directly targeting CCND1. These outcomes underscore the crucial role of LincRNA-EPS in regulating CCND1 and promoting cell proliferation in aged dermal fibroblasts. Our study provides novel insights into the molecular mechanisms underlying age-related changes in dermal fibroblasts and their implications for skin wound healing. The significant reduction in LincRNA-EPS expression in aged dermal fibroblasts and its ability to induce CCND1 expression and enhance cell proliferation highlight its potential as a therapeutic target for addressing age-related skin wound healing.

Is diet related to skin condition? A Mendelian randomization study.

Observational studies have revealed associations between various dietary factors and skin conditions. However, the causal relationship between diet and skin condition is still unknown. Data on 17 dietary factors were obtained from the UK Biobank. Data on four skin conditions were derived from the UK Biobank and another large-scale GWAS study. Genetic predictions suggested that the intake of oily fish was associated with a lower risk of skin aging (OR: 0.962, P = 0.036) and skin pigmentation (OR: 0.973, P = 0.033); Tea intake was associated with a lower risk of skin pigmentation (OR: 0.972, P = 0.024); Salad/raw vegetables intake was associated with a lower risk of keratinocyte skin cancer (OR: 0.952, P = 0.007). Coffee intake was associated with increased risk of skin aging (OR: 1.040, P = 0.028); Pork intake was associated with increased risk of skin aging (OR: 1.134, P = 0.020); Beef intake was associated with increased risk of cutaneous melanoma (OR: 1.013, P = 0.016); Champagne plus white wine intake was associated with increased risk of cutaneous melanoma (OR: 1.033, P = 0.004); Bread intake was associated with increased risk of keratinocyte skin cancer (OR: 1.026, P = 0.013). Our study results indicate causal relationships between genetically predicted intake of oily fish, tea, salad/raw vegetables, coffee, pork, beef, champagne plus white wine, and bread and skin conditions.

Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and therapeutic target for skin aging.

Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.

A miRNA-based epigenetic molecular clock for biological skin-age prediction.

Skin aging is one of the visible characteristics of the aging process in humans. In recent years, different biological clocks have been generated based on protein or epigenetic markers, but few have focused on biological age in the skin. Arrest the aging process or even being able to restore an organism from an older to a younger stage is one of the main challenges in the last 20 years in biomedical research. We have implemented several machine learning models, including regression and classification algorithms, in order to create an epigenetic molecular clock based on miRNA expression profiles of healthy subjects to predict biological age-related to skin. Our best models are capable of classifying skin samples according to age groups (18-28; 29-39; 40-50; 51-60 or 61-83 years old) with an accuracy of 80% or predict age with a mean absolute error of 10.89 years using the expression levels of 1856 unique miRNAs. Our results suggest that this kind of epigenetic clocks arises as a promising tool with several applications in the pharmaco-cosmetic industry.

FTO-mediated regulation of m6A methylation is closely related to apoptosis induced by repeated UV irradiation.

BACKGROUND: Ultraviolet (UV) damage is closely related to skin photoaging and many skin diseases, including dermatic tumors. N6-methyladenosine (m6A) modification is an important epigenetic regulatory mechanism. However, the role of m6A methylation in apoptosis induced by repeated UV irradiation has not been characterized. OBJECTIVE: To explore m6A methylation changes and regulatory mechanisms in the repeated UV-induced skin damage process, especially apoptosis. METHODS: HaCaT cells and BALB/c-Nu nude mice were exposed to repeated UVB/UVA+UVB irradiation. Colorimetry and flow cytometry were used to measure cellular viability and apoptosis. m6A-modified genes were detected via colorimetry and methylated RNA immunoprecipitation (MeRIP) sequencing. Methyltransferases and demethylases were detected via RT-PCR, western blotting and immunohistochemistry. Transfection of siRNA and plasmid was performed to knock down or overexpress the selected genes. RESULTS: After UVB irradiation, 861 m6A peaks were increased and 425 m6A peaks were decreased in HaCaT cells. The differentially modified genes were enriched in apoptosis-related pathways. The m6A demethylase FTO was decreased in both HaCaT cells and mouse skin after UV damage. Overexpressing FTO could improve cell viability, inhibit apoptosis and decrease RNA-m6A methylation, including LPCAT3-m6A, which increase LPCAT3 expression, cell viability promotion and apoptosis inhibition. CONCLUSION: Our study identified the cell m6A methylation change lists after repeated UVB irradiation, and revealed that FTO and LPCAT3 play key roles in the m6A methylation pathogenesis of UV-induced skin cell apoptosis. FTO-m6A-LPCAT3 might serve as a novel upstream target for preventing and treating photoaging and UV-induced skin diseases.

Comparisons between wrinkles and photo-ageing detected and self-reported by the participant or identified by trained assessors reveal insights from Chinese individuals in the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort.

BACKGROUND: Changes develop on the facial skin as a person ages. Other than chronological time, it has been discovered that gender, ethnicity, air pollution, smoking, nutrition, and sun exposure are notable risk factors that influence the development of skin ageing phenotypes such as wrinkles and photo-ageing. These risk factors can be quantified through epidemiological collection methods. We previously studied wrinkles and photo-ageing in detail using photo-numeric scales. The analysis was performed on the ethnic Chinese skin by three trained assessors. Recent studies have shown that it is possible to use self-reported data to identify skin-related changes including skin colour and skin cancer. In order to investigate the association between risk factors and skin ageing phenotypic outcomes in large-scale epidemiological studies, it would be useful to evaluate whether it is also possible for participants to self-report signs of ageing on their skin. AIM: We have previously identified several validated photo-numeric scales for wrinkling and photo-ageing to use on ethnic Chinese skin. Using these scales, our trained assessors grade wrinkling and photo-ageing with moderately high inter-assessor concordance and agreement. The main objective of this study involves letting participants grade self-reported wrinkling and photo-ageing using these same scales. We aim to compare the concordance and agreement between signs of skin ageing by the participant and signs of ageing identified by our assessors. METHOD: Three trained assessors studied facial photo-ageing on 1081 ethnic Chinese young adults from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort. Self-reported facial photo-ageing data by the same 1081 participants were also collated and the two sets of data are compared. RESULTS: Here, we found that self-reported signs of photo-ageing are concordant with photo-ageing detected by our assessors. This finding is consistent whether photo-ageing is evaluated through studying wrinkle variations (Spearman's rank correlation (ρ) value: 0.246-0.329) or through studying dyspigmentation patterns (Spearman's rank correlation (ρ) value 0.203-0.278). When studying individual wrinkles, both participants and assessors often detect the presence of the same wrinkle (Spearman's rank correlation (ρ) value 0.249-0.366). A weak-to-fair level of agreement between both participants and assessors (Cohen's kappa (κ) values: 0.041-0.233) persists and is statistically significant after accounting for agreements due to chance. Both the participant and the assessor are largely consistent in evaluating the extent of photo-ageing (area under curve (AUC) values 0.689-0.769) and in discerning between the presence or absence of a given facial wrinkle (area under curve (AUC) values 0.601-0.856). CONCLUSION: When we analyse the overall appearance of the face, our results show that signs of photo-ageing identified by the participant are concordant with signs of photo-ageing identified by our assessors. When we focused our analysis on specific areas of the face, we found that participants were more likely to identify and self-report the same wrinkles that our assessors have also detected. Here, we found that self-reported signs of skin ageing provide a satisfactory approximation to the signs of skin ageing identified by our assessors. The ability to use self-reported signs of skin ageing should also be evaluated on scales beyond the ones discussed in this study. Currently, there are not as many photo-numeric scales for quantifying dyspigmentation patterns as there are for quantifying wrinkle variations. As Chinese skin is known to become dyspigmented more easily with age, more photo-numeric scales need to be developed and properly validated.

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.

Comparisons between Caucasian-validated photo-numeric scales and Korean-validated photo-numeric scales for photo-ageing. Insights from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort.

BACKGROUND: Photo-ageing is a form of skin ageing which affects the entire face. A photo-aged skin has a diverse variety of wrinkles and dyspigmentation all over the face. Here, we discuss photo-ageing on the Chinese skin evaluated using a photo-numeric scale developed and validated on Caucasian skin (i.e., Caucasian scale) and evaluated using a photo-numeric scale developed and validated on Korean skin (i.e., Korean scale). The Korean scale can be subdivided into two scales that separately address the wrinkling and dyspigmentation constituents of photo-ageing. AIM: As there are currently no photo-ageing scales for Chinese skin, the main objective of this study is to adapt existing photo-ageing photo-numeric scales for use on ethnic Chinese skin. METHOD: Three trained assessors studied facial photo-ageing on 1,081 ethnic Chinese young adults from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort. RESULTS: All assessors are highly internally consistent (Weighted Kappa (κw) values≥0.952). We found that the Caucasian scale and Korean scale give nearly synonymous results for the wrinkling constituent of photo-ageing (R2 = 0.9386). The two scales are strongly concordant (Spearman's Rank Correlation (ρ) value: 0.62 ± 0.06, p = 1.31×10-84). A weak-to-moderate inter-scalar level of agreement (Cohen's Kappa (κ) values: 0.38 ± 0.05, p = 8.87×10-53) persists and is statistically significant after accounting for agreements due to chance. When tested on ethnic Chinese skin, both scales detect photo-ageing consistently (Area under curve [AUC] values: 0.76-0.84). Additionally, the Korean scale for the dyspigmentation constituent of photo-ageing is concordant with both the Caucasian scale (R2 = 0.7888) and the Korean scale for the wrinkling constituent of photo-ageing (R2 = 0.7734). CONCLUSION: Our results show that the Caucasian scale is suitable for capturing photo-ageing on Chinese skin, especially wrinkle variations. The Korean dyspigmentation scale supplements the Caucasian scale to capture dyspigmentation patterns on Chinese skin that may be absent on Caucasian skin. Currently, photo-ageing scales for Chinese skin are absent. When developed, these photo-ageing scales must be properly validated for their ability to capture photo-ageing of the entire face.

Role of epigenetics in the regulation of skin aging and geroprotective intervention: A new sight.

Multiple epigenetic factors play a regulatory role in maintaining the homeostasis of cutaneous components and are implicated in the aging process of the skin. They have been associated with the activation of the senescence program, which is the primary contributor to age-related decline in the skin. Senescent species drive a series of interconnected processes that impact the immediate surroundings, leading to structural changes, diminished functionality, and heightened vulnerability to infections. Geroprotective medicines that may restore the epigenetic balance represent valid therapeutic alliances against skin aging. Most of them are well-known Western medications such as metformin, nicotinamide adenine dinucleotide (NAD+), rapamycin, and histone deacetylase inhibitors, while others belong to Traditional Chinese Medicine (TCM) remedies for which the scientific literature provides limited information. With the help of the Geroprotectors.org database and a comprehensive analysis of the referenced literature, we have compiled data on compounds and formulae that have shown potential in preventing skin aging and have been identified as epigenetic modulators.