The heatmap listing the top altered biological terms between club cells from lungs of the elderly and young individuals revealed a distinct subset of aged club cells characterized by hallmarks of aging, such as a loss of proteostasis (regulation of IRE1 mediated unfolded protein response) and cellular senescence (negative regulation of mitotic cell cycle), which were mainly derived from COPD lungs (Fig. 5A). Here, ERN1 is linked to chronic obstructive pulmonary disease.