Cell senescence and fibrotic lung diseases

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal lung disorder with an unknown etiology and very limited therapeutic options. The incidence and severity of IPF increase with advanced age, suggesting that aging is a major risk factor for IPF. The mechanism underlying the aging-related susceptibility to IPF, however, remains unclear. Cellular senescence, a permanent arrest of cell growth, has been increasingly recognized as an important contributor to aging and aging-related diseases, including IPF. Senescent cells have been identified in IPF lungs and in experimental lung fibrosis models. Removal of senescent cells pharmacologically or genetically improves lung function and reverses pulmonary fibrosis induced by different stimuli in experimental fibrosis models. Treatment with senolytic drugs also improves clinical symptoms in IPF patients. These intriguing findings suggest that cellular senescence contributes importantly to the pathogenesis of fibrotic lung diseases and targeting senescent cells may represent a novel approach for the treatment of fibrotic lung disorders. In this mini review, we summarize the recent advance in the field regarding the role of cellular senescence in fibrotic lung diseases, with a focus on IPF. •Cellular senescence is a pathological feature of IPF lung and is evident in experimental lung fibrosis models.•Various types of lung cells, including alveolar epithelial cells and fibroblasts, undergo senescence in fibrotic lungs•Different mechanisms are involved in lung cell senescence: genetic, epigenetic, oxidative stress, and inflammation•Targeting senescent cells may be effective for the treatment of fibrotic lung disease.