Fig. 8.

Proposed mechanism of protection. In the presence of chronic CS, p16 levels increase and cells become senescent. CS induces pro-inflammatory cytokines throughout the lung, and in the senescent cells SASPs are secreted, which perpetuate senescence and alveolar destruction (right side). When the cell cycle inhibitor p16 is not present (left side), basal levels of IGF1 are upregulated, resulting in stimulated insulin receptors and activation of Akt. Activated Akt stimulates cell proliferation evidenced by increases in Cyclin D expression and the maintenance of healthy alveoli