Figure 2.

Skin oxidative stress-related signaling pathways. Exogenous stimuli (e.g., UV, chemicals, and PM2.5) and/or endogenous factors (e.g., mitochondrial oxidase and metabolism) induce ROS overproduction. ROS activate the antioxidant defense system and promote the expression of antioxidant enzymes through Nrf2 and SIRT1/FOXO pathways, which in turn reduce ROS production. When the antioxidant defense system fails to completely scavenge ROS, oxidative stress is induced. Excessive ROS activate MAPK, JAK/STAT, PI3K/AKT/mTOR, and NF-κB signaling pathways, thereby resulting in the expression of cytokines associated with skin cellular senescence, inflammation, and cancer. The transforming growth factor-β signaling pathway, related to collagen synthesis, is inhibited by ROS and the transcription factor AP-1 to accelerate skin cellular senescence.