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.
This project is relevant to environmental health research because it will identify changes in gene-specific methylation that can be used as novel epigenetic biomarkers of air pollution exposure, using blood as an easily accessible tissue. Concurrently, it will identify gene-specific methylation signatures, particularly in nuclear- encoded mitochondrial genes, that precede changes in key indicators of pulmonary function-vital capacity, inflammation, etc.-and the incidence of respiratory pathologies.