Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

Bisphenol A (BPA) is a widespread environmental pollutant whose exact effects on prostate cancer (PCa) progression remain understudied. This study aims to investigate the effect and underlying molecular mechanisms between BPA exposure and PCa in a comprehensive approach. The multicenter cohort study found that BPA exposure plays an important role in promoting biochemical recurrence and death of PCa. BPA exposure significantly promoted PCa progression in both the animal model and in vitro experiments. RNA sequencing revealed a disruption of mitochondrial energy homeostasis in BPA-treated cells. In multiple datasets, 17 prognostic genes such as PFKFB4 were obtained to construct and verify a mitochondrial energy metabolism Score system. Based on network toxicology methods and transcriptome sequencing data, ESR1 was identified as a potential transcription factor targeting glycolytic enzyme PFKFB4 under BPA exposure. With the support of lncRNA and circRNA sequencing data, a molecular regulatory network of BPA promoting prostate cancer through mitochondrial energy metabolism reprogramming was constructed. Further molecular docking revealed that BPA has higher binding free energy to ERα than its natural ligand estradiol. Given the widespread presence of BPA in the environment, minimizing exposure to this chemical could represent a feasible approach in improving clinical outcomes.

Introduction: After adulthood, as a person grows older, the secretion of sex hormones in the body gradually decreases, and the risk of periodontitis increases. But the relationship between sex hormones and periodontitis is still controversial.Methods: We investigated the association between sex hormones and periodontitis among Americans over 30 years old. 4,877 participants containing 3,222 males and 1,655 postmenopausal females who had had periodontal examination and detailed available sex hormone levels, were included in our analysis from the 2009-2014 National Health and Nutrition Examination Surveys cycles. We applied multivariate linear regression models to estimate the connection between sex hormones and periodontitis after converting sex hormones into categorical variables through tertile. Additionally, to ensure the stability of the analysis results, we carried out a trend test, subgroup analysis, and interaction test. Results: After fully adjusting the covariates, estradiol levels were not associated with periodontitis in both males and females with a P for trend = 0.064 and 0.064, respectively. For males, we found that sex hormone-binding globulin was positively associated with periodontitis (tertile3 vs tertile1: OR=1.63, 95% CI=1.17-2.28, p = 0.004, P for trend = 0.005). Congruously, free testosterone (tertile3 vs tertile1: OR=0.60, 95% CI=0.43-0.84, p = 0.003), bioavailable testosterone (tertile3 vs tertile1: OR=0.51, 95% CI=0.36-0.71, p < 0.001), and free androgen index (tertile3 vs tertile1: OR=0.53, 95% CI=0.37-0.75, p < 0.001) was found to be negatively associated with periodontitis. Moreover, subgroup analysis of age found a closer relationship between sex hormones and periodontitis in those younger than 50 years.Conclusion: Our research suggested that males with lower bioavailable testosterone levels affected by sex hormone-binding globulin were at a higher risk of periodontitis. Meanwhile, estradiol levels were not associated with periodontitis in postmenopausal women.

Importance: Exposure to high altitudes elicits multiple adaptive mechanisms that intricately impact the entire body, causing deleterious health outcomes. However, high-altitude exposure effects on accelerated aging and aging-related changes remain uncertain.Objective: To comprehensively assess the associations of high-altitude exposure with overall aging and related changes and to provide insights into the treatment and prevention of aging-associated deficits in populations living in high-altitude areas.Design, Setting, and Participants: This population-based cross-sectional study used data from 2 prospective studies in Western China: West China Natural Population Cohort (WCNPCS) and West China Health and Aging Trend (WCHAT). The WCNPCS cohort was constructed from May 2019 to June 2021. Data were collected from participants aged 18 years and older in 4 populous regions (Mianzhu, Longquan, Pidu, and Ganzi) in Sichuan Province. The WCHAT was initiated in 2018 and recruited participants aged 50 years and older from various regions (Sichuan, Yunnan, Guizhou, and Xinjiang). Participants were selected via sequential cluster sampling from the permanent residents of the participating community. Data for the present study were analyzed between March and October 2024.Exposure: The participants’ altitudes were determined using the global Shuttle Radar Topography Mission 4 data based on residential addresses. High-altitude areas refer to regions with altitudes of greater than or equal to 1500 m (4921 feet) above the mean sea level.Main Outcomes and Measures: Biological aging (BA) and aging acceleration (AA) were measured through the Klemera–Doubal Biological Age (KDM-BA) and PhenoAge methods. Multidimensional aging-related metrics were based on questionnaire, measurement, and self-report.Results: A total of 9846 participants from the WCNPCS cohort (mean [SD] age, 55.73 [11.06] years; 6730 women [68.35%]) and 3593 participants from the WCHAT cohort (mean [SD] age, 62.27 [8.40] years; 2253 women [62.71%]) were included. The participants living at high altitudes presented increased KDM-BA acceleration by 0.85 years for the WCNPCS cohort and 0.71 years for the WCHAT cohort. The PhenoAge results were similar, with even larger effect sizes (WCNPCS, β, 2.08 years; 95% CI, 1.77-2.39 years; WCHAT, β, 2.23 years; 95% CI, 1.91-2.54 years). The association between high-altitude exposure and biologically accelerated aging was particularly pronounced among smokers. Associations between high-altitude exposure and various multidimensional aging-related metrics were also observed.Conclusions and Relevance: These findings suggest that extended periods at high altitudes may hasten BA and contribute to the onset of aging-related illnesses. Implementing public health interventions for individuals residing in high-altitude regions may aid in alleviating the disease burden within these communities.