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中国健康老年人的个人空气传播化学物质暴露与表观遗传衰老生物标志物:来自混合方法的证据。

Personal airborne chemical exposure and epigenetic ageing biomarkers in healthy Chinese elderly individuals: Evidence from mixture approaches.

作者信息

Shi Wanying, Gao Xu, Cao Yaqiang, Chen Yuanyuan, Cui Qian, Deng Fuchang, Yang Bo, Lin Elizabeth Z, Fang Jianlong, Li Tiantian, Tang Song, Godri Pollitt Krystal J, Shi Xiaoming

机构信息

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China; Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China.

出版信息

Environ Int. 2022 Dec;170:107614. doi: 10.1016/j.envint.2022.107614. Epub 2022 Nov 3.

Abstract

BACKGROUND

Air pollution is associated with accelerated biological ages determined by DNA methylation (DNAm) patterns, imposing further risks of age-related adverse effects. However, little is known about the independent and joint effects of exposure to gaseous organic chemicals that may share a common source.

METHODS

We conducted a panel study with the 3-day exposure assessment monthly among 73 Chinese healthy elderly people aged 60 to 69 years in Jinan, Shandong province during September 2018 to January 2019.Exposure to 26 ambient organic chemical contaminants were measured by wearable passive samplers, including volatile organic compounds, polycyclic aromatic hydrocarbons (PAHs), phthalates (PAEs), nitroaromatics (NIs), polybrominated diphenyl ethers, chlorinated hydrocarbons, and organophosphate esters. The Illumina MethylationEPIC BeadChip was used to measure DNA methylation levels in blood samples, and based on which, epigenetic ageing biomarkers, including Hannum clock, Horvath clock, DNAm PhenoAge, DNAm GrimAge, and DNAm estimator of telomere length (DNAmTL) were calculated. Linear mixed effect models were used to estimate the linear associations between 3-day personal chemical exposure and the epigenetic biomarkers, Weighted quantile sum (WQS) regression and the Bayesian kernel machine regression (BKMR) model were further used to evaluate the effect of chemical mixtures.

RESULTS

Multiple linear mixed effects regression models showed that DNAmPhenoAge acceleration was significantly and positively associated with exposure to PAEs, NIs, and PAHs in healthy elderly individuals. Both WQS regression and BKMR models showed a significant positive association with DNAmPhenoAge acceleration with chemical exposures, in which the effect of di-n-butyl phthalate exposure showed the greatest importance.

CONCLUSION

These findings suggest that exposure to a mixture of airborne chemicals significantly increase the acceleration of the epigenetic biomarker of phenotypic age. These findings serve to identify toxic chemicals in the air and facilitate the evaluation of their potentially severe health effects.

摘要

背景

空气污染与由DNA甲基化(DNAm)模式决定的生物年龄加速有关,会带来更多与年龄相关的不良影响风险。然而,对于可能具有共同来源的气态有机化学物质暴露的独立和联合影响,人们了解甚少。

方法

2018年9月至2019年1月期间,我们在山东省济南市对73名年龄在60至69岁的中国健康老年人进行了一项每月为期3天的暴露评估的队列研究。通过可穿戴式被动采样器测量了26种环境有机化学污染物的暴露情况,包括挥发性有机化合物、多环芳烃(PAHs)、邻苯二甲酸酯(PAEs)、硝基芳烃(NIs)、多溴二苯醚、氯代烃和有机磷酸酯。使用Illumina甲基化EPIC芯片测量血样中的DNA甲基化水平,并据此计算表观遗传衰老生物标志物,包括汉努姆时钟、霍瓦斯时钟、DNAm表型年龄、DNAm GrimAge和端粒长度的DNAm估计值(DNAmTL)。使用线性混合效应模型估计3天个人化学暴露与表观遗传生物标志物之间的线性关联,进一步使用加权分位数和(WQS)回归和贝叶斯核机器回归(BKMR)模型评估化学混合物的影响。

结果

多个线性混合效应回归模型显示,在健康老年人中,DNAm表型年龄加速与PAEs、NIs和PAHs的暴露显著正相关。WQS回归和BKMR模型均显示化学暴露与DNAm表型年龄加速显著正相关,其中邻苯二甲酸二正丁酯暴露的影响最为重要。

结论

这些发现表明,暴露于空气中的化学物质混合物会显著增加表型年龄的表观遗传生物标志物的加速。这些发现有助于识别空气中的有毒化学物质,并促进对其潜在严重健康影响的评估。

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