CS induces impaired pulmonary function, emphysema, and increased alveolar epithelial cell (AECII) senescence in wild-type mice, whereas CS-exposed p16−/− mice exhibit normal pulmonary function, reduced emphysema, diminished AECII senescence, and increased pro-growth IGF1 signaling, suggesting that improved lung function in p16−/− mice was due to increased alveolar progenitor cell proliferation. The gene discussed is CDKN2A; the disease is pulmonary emphysema.