Figure 2.

Schematic illustration of putative aging signaling in COPD under oxidative stress.

Notes: Accumulation of endogenous reactive oxygen species (ROS) activates PI3K signaling, leading dysfunction of FOXO and Nrf2 via defect of HDAC2 and sirtuins. PTEN reduction amplifies PI3K signaling, and AMPK inactivation also contributes to reduction of sirtuin activity. At the same time, mTOR is activated as downstream molecule of PI3K. Consequently, the level of stress resistance and DNA repair ability are reduced, inflammaging is amplified and abnormal proteins are accumulated, causing accelerating aging and progress of COPD.