Aging is a universal biological process characterized by a progressive deterioration in functional capacity and an increased risk of morbidity and mortality over time. In the lungs, there are considerable changes in lung structure and function with advancing age; however, research on the transcriptomic profile implicated in this process is scanty. In this study, we addressed the lung transcriptome changes during aging, through a global gene expression analysis of normal lungs of mice aged 4- and 18-months old. Functional pathway enrichment analysis by Ingenuity Pathway Analysis (IPA) revealed that the most enriched signaling pathways in aged mice lungs are involved in the regulation of cell apoptosis, senescence, development, oxidative stress, and inflammation. We also found 25 miRNAs significantly different in the lungs of old mice compared with their younger littermates, eight of them upregulated and 17 downregulated. Using the miRNet database we identified TNFα, mTOR, TGFβ, WNT, FoxO, Apoptosis, Cell cycle, and p53 signaling pathways as the potential targets of several of the dysregulated miRNAs supporting that old lungs have increased susceptibility for apoptosis, inflammation, and fibrosis. These findings reveal differential expression profiles of genes and miRNAs affecting cell survival and the inflammatory response during lung aging.