Aging is a multifactorial process that leads to molecular and cellular changes, contributing to the susceptibility of most lung diseases. However, the molecular and genetic mechanism of lung aging remains poorly understood. Here, we performed RNA-seq transcriptome analysis of the lung tissues of 68 subjects and analyzed their gene expression profile to evaluate candidate genes related to lung aging. The subjects were classified into two groups (Younger group and Older group) based on their age. Lung tissues were obtained from surgically resected specimens, processed, and analyzed with RNA-seq. The median age of the subjects was 45 years in the Younger group and 74 years in the Older group. Around 71% and 53% of the subjects were female in the Younger and Older groups, respectively. After gene quality control and filtering, differentially expressed gene analysis showed that MAP3K15, CHRM2, and GALNT13 were upregulated in the Younger group, whereas COL17A1 and EDA2R were upregulated in the Older group. Multivariate analysis with adjustment for covariates showed that EDA2R was a risk factor for lung aging. Our study identified differences in the gene expression of the lungs of older subjects compared with younger subjects. These findings may have implications in lung aging.