DNA methylation of skeletal muscle function-related secretary factors identifies FGF2 as a potential biomarker for sarcopenia.

BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001). CONCLUSIONS: Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.

Association of volatile organic compound exposure with metabolic syndrome and its components: a nationwide cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a health issue consisting of multiple metabolic abnormalities. The impact of exposure to volatile organic compounds (VOCs) on MetS and its components remains uncertain. This study aimed to assess the associations of individual urinary metabolites of VOC (mVOCs) and mVOC mixtures with MetS and its components among the general adult population in the United States. METHODS: A total of 5345 participants with eligible data were filtered from the 2011-2020 cycles of the National Health and Nutrition Examination Survey. Multivariate logistic regression models were applied to assess the associations of individual mVOCs with MetS and its components. The least absolute shrinkage and selection operator (LASSO) regression models were constructed to identify more relevant mVOCs. The weight quantile sum regression model was applied to further explore the links between mVOC co-exposure and MetS and its components. RESULTS: The results indicated positive associations between multiple mVOCs and MetS, including CEMA, DHBMA, and HMPMA. CEMA was found to be positively correlated with all components of MetS. HMPMA was associated with elevated triglyceride (TG), reduced high-density lipoprotein, and fasting blood glucose (FBG) impairment; 3HPMA was associated with an elevated risk of high TG and FBG impairment; and DHBMA had positive associations with elevated TG and high blood pressure. The co-exposure of LASSO-selected mVOCs was associated with an increased risk of elevated TG, high blood pressure, and FBG impairment. CONCLUSION: Positive associations of certain individual urinary mVOCs and mVOC mixtures with MetS and its components were observed by utilizing multiple statistical models and large-scale national data. These findings may serve as the theoretical basis for future experimental and mechanistic studies and have important implications for public health.

Urinary caffeine and its metabolites in association with advanced liver fibrosis and liver steatosis: a nationwide cross-sectional study.

Aim: This study used urinary caffeine and its metabolites to evaluate their relationships with liver steatosis and advanced liver fibrosis. Methods: A total of 2068 adult participants with required data were filtered from the 2009-2014 National Health and Nutrition Examination Survey (NHANES) cycles. Non-invasive scores were applied to define liver steatosis and advanced liver fibrosis. Logistic regression models, weighted quantile sum (WQS) regression models, quantile-based g-computation (QG-Comp) models, and restricted cubic spline (RCS) regression models were used to assess the associations of urinary caffeine and its metabolites with liver steatosis and advanced liver fibrosis. A series of additional analyses were conducted to examine the subgroup-specific differences and test the robustness of the observed results. Results: The major caffeine metabolite mixture and most individual caffeine metabolites were found to be negatively associated with the risk of advanced liver fibrosis with subgroup-specific variations. Only 7-MX consistently showed a negative association with liver steatosis in all analyses, while no association was observed between the major caffeine metabolite mixture and liver steatosis. Conclusion: The major caffeine metabolite mixture and most individual urinary caffeine metabolites exhibited inverse associations with advanced liver fibrosis with subgroup differences. Further prospective and experimental studies are urgently needed to verify our results and further identify the possible mechanisms.

Association of AST/ALT (De Ritis) ratio with sarcopenia in a Chinese population of community-dwelling elderly.

Background: The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, also known as De Ritis ratio, has been reportedly associated with malnutrition which plays a crucial role in sarcopenia. The aim of this study was to examine the relationship between AST/ALT ratio and sarcopenia in the Chinese community-dwelling elderly. Methods: A cross-sectional study with 2751 participants (1343 men and 1408 women) aged ≥60 years was performed. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were measured to diagnose sarcopenia according to the latest Asian Working Group for Sarcopenia (AWGS) consensus. The association of AST/ALT ratio with sarcopenia was examined using logistic regression analysis. Results: The prevalence of sarcopenia in the present study was 4.4%. AST/ALT ratio was higher in the sarcopenia group than in the non-sarcopenia group (1.30 ± 0.33 vs. 1.16 ± 0.62, P = 0.010). AST/ALT ratio was negatively correlated with the components of sarcopenia, including ASMI, grip strength, and gait speed. Logistic regression analysis indicated that high AST/ALT ratio (>1.20) was associated with increased risk of sarcopenia even after adjustment for potential confounders (adjusted OR = 2.33, 95%CI = 1.48-3.68, P < 0.001). Stratification analyses indicated that the association of high AST/ALT ratio with high risk of sarcopenia was more significant in males and the elderly with ≥70 years. Conclusions: Our findings demonstrate that high AST/ALT ratio is associated with increased risk of sarcopenia in a Chinese population of community-dwelling elderly.