PDF(Pubmed)
Abstract：
Native American communities suffer disproportionately from elevated metal exposures and increased risk for cardiovascular diseases and diabetes. DNA methylation is a sensitive biomarker of aging-related processes and novel epigenetic-based \"clocks\" can be used to estimate accelerated biological aging that may underlie increased risk. Metals alter DNA methylation, yet little is known about their individual and combined impact on epigenetic age acceleration. Our objective was to investigate the associations of metals on several DNA methylation-based aging measures in the Strong Heart Study (SHS) cohort.
Blood DNA methylation data from 2,301 SHS participants was used to calculate age acceleration of epigenetic clocks (PhenoAge, GrimAge, DunedinPACE, Hannum, Horvath). Urinary metals [arsenic (As), cadmium (Cd), tungsten (W), zinc (Zn), selenium (Se), molybdenum (Mo)] were creatinine-adjusted and categorized into quartiles. We examined associations of individual metals through linear regression models and used Bayesian Kernel Machine Regression (BKMR) for the impact of the total metal mixture on epigenetic age acceleration.
The mixture of nonessential metals (W, As, Cd) was associated with greater GrimAge acceleration and DunedinPACE, while the essential metal mixture (Se, Zn, Mo) was associated with lower epigenetic age acceleration. Cd was associated with increased epigenetic age acceleration across all clocks and BKMR analysis suggested nonlinear associations between Se and DunedinPACE, GrimAge, and PhenoAge acceleration. No interactions between individual metals were observed. The associations between Cd, Zn, and epigenetic age acceleration were greater in never smokers in comparison to current/former smokers.
Nonessential metals were positively associated with greater epigenetic age acceleration, with strongest associations observed between Cd and DunedinPACE and GrimAge acceleration. In contrast, essential metals were associated with lower epigenetic aging. Examining the influence of metal mixtures on epigenetic age acceleration can provide insight into metals and aging-related diseases.
Blood DNA methylation data from 2,301 SHS participants was used to calculate age acceleration of epigenetic clocks (PhenoAge, GrimAge, DunedinPACE, Hannum, Horvath). Urinary metals [arsenic (As), cadmium (Cd), tungsten (W), zinc (Zn), selenium (Se), molybdenum (Mo)] were creatinine-adjusted and categorized into quartiles. We examined associations of individual metals through linear regression models and used Bayesian Kernel Machine Regression (BKMR) for the impact of the total metal mixture on epigenetic age acceleration.
The mixture of nonessential metals (W, As, Cd) was associated with greater GrimAge acceleration and DunedinPACE, while the essential metal mixture (Se, Zn, Mo) was associated with lower epigenetic age acceleration. Cd was associated with increased epigenetic age acceleration across all clocks and BKMR analysis suggested nonlinear associations between Se and DunedinPACE, GrimAge, and PhenoAge acceleration. No interactions between individual metals were observed. The associations between Cd, Zn, and epigenetic age acceleration were greater in never smokers in comparison to current/former smokers.
Nonessential metals were positively associated with greater epigenetic age acceleration, with strongest associations observed between Cd and DunedinPACE and GrimAge acceleration. In contrast, essential metals were associated with lower epigenetic aging. Examining the influence of metal mixtures on epigenetic age acceleration can provide insight into metals and aging-related diseases.
摘要：
背景：美国原住民社区不成比例地遭受金属暴露的增加以及心血管疾病和糖尿病的风险增加。DNA甲基化是衰老相关过程的敏感生物标志物，基于表观遗传的新型“时钟”可用于估计可能导致风险增加的加速生物衰老。金属改变DNA甲基化,然而，对他们的个体和对表观遗传年龄加速的综合影响知之甚少。我们的目的是研究金属与强心研究（SHS）队列中几种基于DNA甲基化的衰老指标的关联。
方法：使用来自2,301名SHS参与者的血液DNA甲基化数据来计算表观遗传时钟的年龄加速（PhenoAge，GrimAge,DunedinPACE,汉纳姆,Horvath）。尿中金属[砷（As），镉(Cd),钨(W),锌(Zn),硒(Se),钼（Mo）]进行肌酐调整并分类为四分位数。我们通过线性回归模型检查了单个金属的关联，并使用贝叶斯内核机器回归（BKMR）来研究总金属混合物对表观遗传年龄加速的影响。
结果：非必要金属的混合物（W，As,Cd)与更大的GrimAge加速度和DunedinPACE相关，而必需的金属混合物(Se，Zn,Mo)与较低的表观遗传年龄加速有关。Cd与所有时钟的表观遗传年龄加速度增加有关，BKMR分析表明Se和DunedinPACE之间存在非线性关联，GrimAge,和PhenoAge加速度。没有观察到单个金属之间的相互作用。Cd之间的关联，Zn,与目前/以前吸烟者相比,不吸烟者的表观遗传年龄加速度更大.
结论：非必要金属与更大的表观遗传年龄加速呈正相关，在Cd和DunedinPACE与GrimAge加速度之间观察到最强的关联。相比之下,必需金属与较低的表观遗传老化有关。检查金属混合物对表观遗传年龄加速的影响可以提供对金属和衰老相关疾病的了解。
方法：使用来自2,301名SHS参与者的血液DNA甲基化数据来计算表观遗传时钟的年龄加速（PhenoAge，GrimAge,DunedinPACE,汉纳姆,Horvath）。尿中金属[砷（As），镉(Cd),钨(W),锌(Zn),硒(Se),钼（Mo）]进行肌酐调整并分类为四分位数。我们通过线性回归模型检查了单个金属的关联，并使用贝叶斯内核机器回归（BKMR）来研究总金属混合物对表观遗传年龄加速的影响。
结果：非必要金属的混合物（W，As,Cd)与更大的GrimAge加速度和DunedinPACE相关，而必需的金属混合物(Se，Zn,Mo)与较低的表观遗传年龄加速有关。Cd与所有时钟的表观遗传年龄加速度增加有关，BKMR分析表明Se和DunedinPACE之间存在非线性关联，GrimAge,和PhenoAge加速度。没有观察到单个金属之间的相互作用。Cd之间的关联，Zn,与目前/以前吸烟者相比,不吸烟者的表观遗传年龄加速度更大.
结论：非必要金属与更大的表观遗传年龄加速呈正相关，在Cd和DunedinPACE与GrimAge加速度之间观察到最强的关联。相比之下,必需金属与较低的表观遗传老化有关。检查金属混合物对表观遗传年龄加速的影响可以提供对金属和衰老相关疾病的了解。
