Fig. 8. Working model illustrating the role of autophagy in oxidative stress-induced senescence and cell death.

A Oxidative stress triggers durable autophagy in human LECs which leads to excessive degradation of p62 protein, and subsequently results in premature senescence. Low level of p62 scaffold protein can not sustain the pro-survival PKCι-IKK-NF-κB signaling, and hence facilitates apoptosis induced by oxidative stress. B Autophagy is inhibited by genetic deletion of the Atg gene or a chemical inhibitor. The elevated level of p62 delays the senescence process, and antagonizes pro-apoptotic signaling via boosting the sufficient pro-survival signaling PKCι-IKK-NF-κB cascades.