Integrative, age-related changes in genome and epigenome in human lung in relation to smoking

PROJECT NARRATIVE Aging is the main risk factor for many age-related lung diseases, including COPD and pulmonary fibrosis. It has been speculated that this aging-disease relationship is due to the complex interaction of multiple genetic, epigenetic and transcriptomic alterations that occur in normal human lung over time. In turn, these age-related changes are impacted by environmental factors, such as cigarette smoking. This project will integrate comprehensive interrogations of DNA mutations, reversible DNA alterations called cytosine methylation, and gene expression in normal human lung bronchial lining cells in relation to age and tobacco smoke exposure. This will provide reference data for future comparisons to lung disease states, enhance our understanding of age-and smoking-related mechanisms of lung disease, and thereby facilitate the development of early detection, prevention and therapeutic strategies.