Mitochondriomic Biomarkers of Air Pollution Exposure and Respiratory Function Dec

描述(由申请人提供)：线粒体组学是一个新兴领域，可以为开发暴露和暴露相关疾病的新生物标志物提供独特的机会。重要的是，核编码的线粒体基因，大约900个基因，经历了与空气污染有关的DNA甲基化变化，这是一种表观遗传机制，对空气污染中发现的化学成分极其敏感。因此，线粒体基因中的表观基因组生物标记物作为过去毒性暴露的指标和未来疾病风险的预测因子具有相当大的前景。到目前为止，还没有研究调查这些基因的表观遗传调控。 与肺功能和疾病有关的基因，特别是作为促氧化剂潜在生物标志物的基因 回应。因此，我们建议发现并验证暴露于空气污染和肺功能的新的线粒体生物标记物，将这两条研究路线联系起来，以揭示空气污染物导致肺功能下降的潜在生物途径。当前 对这些机制的了解还很初级，而且往往是基于动物的高剂量。我们的甲基组研究是一种很有希望的新方法，可以在感兴趣的环境暴露范围内识别人类的重要途径。特别是在美国人口老龄化的情况下，迫切需要肺功能下降及其风险因素的生物标记物，如空气污染和黑碳。这些生物标志物可以帮助早期诊断和预防许多与空气污染相关的疾病。我们经验丰富的研究团队在流行病学、暴露生物学、表观遗传学、生物信息学、分子和细胞生物学、肺部病理生理学和统计学方面拥有关键专业知识。鉴于我们的资源，我们处于独特的地位，可以使用甲基组平台来表征在一项关于呼吸结果的环境原因的创新纵向研究中暴露的生物标记物。我们的方法利用了标准化老龄化研究(NAS)纵向队列，跟踪超过48年，包含丰富的DNA档案、数据库和广泛的肺功能数据，以及暴露于空气污染物的地理编码测量。

DESCRIPTION (provided by applicant): Mitochondriomics is an emerging field that can provide unique opportunities to develop novel biomarkers of exposures and exposure-related diseases. Importantly, nuclear-encoded mitochondrial genes, approximately 900+ genes, undergo air pollution-related changes in DNA methylation, an epigenetic mechanism incredibly sensitive to chemical components found in air pollution. Epigenomic biomarkers in mitochondrial genes, therefore, hold considerable promise as indicators of past toxic exposures and predictors of future disease risk. Until now, no study has yet investigated the epigenetic regulation of these genes in relation to lung function and disease, particularly as potential biomarkers of pro-oxidant responses. We propose, therefore, to discover and validate novel mitochondriomic biomarkers of exposure to air pollution and lung function, linking these two lines of investigation to inform potential biological pathways via which air pollutants contribute to lung function decline. Current understanding of these mechanisms in rudimentary, and it is often based on high doses in animals. Our methylomic study is a promising new approach for the identification of important pathways in humans at ambient exposure ranges of interest. Biomarkers of lung function decline and its risk factors, such as air pollution and black carbon, are badly needed, especially given the aging of the US population. These biomarkers can aid in the early diagnosis and prevention of many air pollution-associated diseases. Our experienced team of researchers has key expertise in epidemiology, exposure biology, epigenetics, bioinformatics, molecular and cellular biology, lung pathophysiology, and statistics. Given our resources, we are uniquely positioned to use methylomic platforms to characterize biomarkers of exposure in an innovative longitudinal study of environmental causes of respiratory outcomes. Our approach utilizes the Normative Aging Study (NAS) longitudinal cohort, followed for over 48 years, containing a rich DNA archive, database with extensive lung function data, and geocoded measures of exposure to air pollutants.