Nwanaji-Enwerem Jamaji C, Dai Lingzhen, Colicino Elena, Oulhote Youssef, Di Qian, Kloog Itai, Just Allan C, Hou Lifang, Vokonas Pantel, Baccarelli Andrea A, Weisskopf Marc G, Schwartz Joel D
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Environ Int. 2017 May;102:57-65. doi: 10.1016/j.envint.2016.12.024. Epub 2017 Mar 9.
Long-term PM exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM on human health.
We assessed the relationship of major PM component species (ammonium, elemental carbon, organic carbon, nitrate, and sulfate) with Horvath and Hannum DNA methylation (DNAm) age, two DNA methylation-based predictors of chronological age.
This analysis included 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n=940 visits). We estimated 1-year PM species levels at participants' addresses using the GEOS-chem transport model. Blood DNAm-age was calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. We fit linear mixed-effects models, controlling for PM mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM species associated with DNAm-age.
Sulfate and ammonium were selected by the LASSO in the Horvath DNAm-age models. In a fully-adjusted multiple-species model, interquartile range increases in both 1-year sulfate (95%CI: 0.28, 0.74, P<0.0001) and ammonium (95%CI: 0.02, 0.70, P=0.04) levels were associated with at least a 0.36-year increase in Horvath DNAm-age. No PM species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM levels within US EPA national ambient air quality standards.
Our results demonstrate that sulfate and ammonium were most associated with Horvath DNAm-age and suggest that DNAm-age measures differ in their sensitivity to ambient particle exposures and potentially disease.
长期暴露于细颗粒物（PM）和衰老与多种共同疾病有关；研究它们之间的关系是进一步了解PM对人类健康不利影响的一种有前景的策略。
我们评估了主要PM成分种类（铵、元素碳、有机碳、硝酸盐和硫酸盐）与霍瓦斯（Horvath）和汉纳姆（Hannum）DNA甲基化（DNAm）年龄的关系，这是两种基于DNA甲基化的实际年龄预测指标。
该分析纳入了来自规范衰老研究的552名参与者，他们在2000年至2011年间多次接受随访（共940次随访）。我们使用GEOS-chem传输模型估算参与者住址处的1年PM种类水平。使用Illumina HumanMethylation450 BeadChip上的CpG位点计算血液DNAm年龄。我们拟合线性混合效应模型，将PM质量以及生活方式/环境因素作为固定效应进行控制，并采用自适应套索罚分法来识别与DNAm年龄相关的PM种类。
在霍瓦斯DNAm年龄模型中，套索法选择了硫酸盐和铵。在一个完全调整的多物种模型中，1年硫酸盐（95%CI：0.28，0.74，P<0.0001）和铵（95%CI：0.02，0.70，P=0.04）水平的四分位数间距增加与霍瓦斯DNAm年龄至少增加0.36岁相关。在汉纳姆DNAm年龄模型中，套索法未选择任何PM种类。我们的研究结果在敏感性分析中依然成立，该分析仅纳入了美国环境保护局国家环境空气质量标准范围内1年PM水平的随访数据。
我们的结果表明，硫酸盐和铵与霍瓦斯DNAm年龄的关联最为密切，并表明DNAm年龄测量方法对环境颗粒物暴露和潜在疾病的敏感性存在差异。
