Nwanaji-Enwerem Jamaji C, Colicino Elena, Dai Lingzhen, Cayir Akin, Sanchez-Guerra Marco, Laue Hannah E, Nguyen Vy T, Di Qian, Just Allan C, Hou Lifang, Vokonas Pantel, Coull Brent A, Weisskopf Marc G, Baccarelli Andrea A, Schwartz Joel D
Department of Environmental Health, Harvard T.H. Chan School of Public Health , Boston, Massachusetts, 02115, United States.
Department of Environmental Health Sciences, Columbia Mailman School of Public Health , New York, New York, 10032, United States.
Environ Sci Technol. 2017 Jul 18;51(14):8185-8195. doi: 10.1021/acs.est.7b02409. Epub 2017 Jul 7.
The mitochondrial genome has long been implicated in age-related disease, but no studies have examined its role in the relationship of long-term fine particle (PM) exposure and DNA methylation age (DNAm-age)-a novel measure of biological age. In this analysis based on 940 observations between 2000 and 2011 from 552 Normative Aging Study participants, we determined the roles of mitochondrial DNA haplogroup variation and mitochondrial genome abundance in the relationship of PM with DNAm-age. We used the GEOS-chem transport model to estimate address-specific, one-year PM levels for each participant. DNAm-age and mitochondrial DNA markers were measured from participant blood samples. Nine haplogroups (H, I, J, K, T, U, V, W, and X) were present in the population. In fully adjusted linear mixed-effects models, the association of PM with DNAm-age (in years) was significantly diminished in carriers of haplogroup V (P = 0.01; β = 0.18, 95%CI: -0.41, 0.78) compared to noncarriers (β = 1.25, 95%CI: 0.58, 1.93). Mediation analysis estimated that decreases in mitochondrial DNA copy number, a measure of mitochondrial genome abundance, mediated 12% of the association of PM with DNAm-age. Our data suggests that the mitochondrial genome plays a role in DNAm-age relationships particularly in the context of long-term PM exposure.
长期以来，线粒体基因组一直被认为与年龄相关疾病有关，但尚无研究探讨其在长期细颗粒物（PM）暴露与DNA甲基化年龄（DNAm-age，一种衡量生物年龄的新指标）之间关系中的作用。在这项基于552名规范衰老研究参与者在2000年至2011年间的940次观察结果的分析中，我们确定了线粒体DNA单倍群变异和线粒体基因组丰度在PM与DNAm-age关系中的作用。我们使用GEOS-chem传输模型来估计每位参与者特定地址的一年期PM水平。从参与者的血液样本中测量DNAm-age和线粒体DNA标记。人群中存在9种单倍群（H、I、J、K、T、U、V、W和X）。在完全调整的线性混合效应模型中，与非携带者（β = 1.25，95%CI：0.58，1.93）相比，单倍群V携带者中PM与DNAm-age（以年为单位）的关联显著减弱（P = 0.01；β = 0.18，95%CI：-0.41，0.78）。中介分析估计，线粒体DNA拷贝数（一种衡量线粒体基因组丰度的指标）的下降介导了PM与DNAm-age关联的12%。我们的数据表明，线粒体基因组在DNAm-age关系中发挥作用，尤其是在长期PM暴露的情况下。
