Additional mechanistic evidence comes from a study that showed bleomycin directly binds to annexin A2 (ANXA2) in lung epithelial cells, thereby preventing the nuclear translocation of TFEB; thus, there is an inhibition of the autophagy flux resulting in fibrotic lung disease pathogenesis [159]. Moreover, torin1-mediated TFEB activation restores autophagy flux and ameliorates bleomycin-induced pulmonary fibrosis [159]. Autophagy dysfunction is also reported in human lung fibroblasts from IPF patients, and it is believed that defective autophagy is required to maintain a cell death-resistant phenotype in IPF fibroblasts, suggesting that autophagy dysfunction is a profibrotic mechanism and promotes IPF pathogenesis [64]. Hence, in age-related IPF pathogenesis, autophagy declines with age and the resulting imbalance of inflammatory-oxidative responses is anticipated to mediate the initiation of fibrotic pathophysiology. However, further clinical evaluation is needed to evaluate the therapeutic potential of autophagy augmentation in IPF patients.