Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan.
Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan.
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DOI：
10.1093/eep/dvac018
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发表时间：
2022
影响因子：
3.8
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中科院分区：
文献类型：
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虽然铅、汞、锰和铜对个体疾病过程的影响已得到充分了解，但很难估计长期接触这些在一般人群中经常观察到的低浓度金属对健康的影响。此外，联合接触多种金属对健康的影响难以估计。生物老化是指多种生理和分子变化的综合进展，使个体更容易患病。生物老化的生物标志物可能有助于估计人口水平的影响，金属暴露之前，在人口中的疾病发展。我们使用来自底特律社区健康研究的290名参与者的数据来估计血清铅，汞，锰和铜对生物衰老的三种基于DNA甲基化的生物标志物（Horvath Age，PhenoAge和GrimAge）的影响。我们使用混合模型和贝叶斯核机器回归，并控制参与者的性别，种族，民族，吸烟，收入，教育程度和街区组贫困。我们观察到铅和GrimAge加速度和汞和PhenoAge加速度之间的影响一致的积极估计。相反，我们观察到锰和表观年龄加速和汞和Horvath年龄加速之间始终存在负相关。我们还观察到铜和PhenoAge和GrimAge加速度之间的曲线关系。观察到的金属混合物的总暴露量增加与PhenoAge和GrimAge加速度增加和Horvath Age加速度降低有关。这些研究结果表明，在密歇根州底特律市的成年人中，血清铅或汞从第25百分位数增加到第75百分位数与两个表观遗传标记的全因死亡率增加0.25年有关。虽然很少有调查结果具有统计学意义，但其一致性和新奇值得关注。
Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that an increase in serum lead or mercury from the 25th to 75th percentile is associated with a ∼0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.