FIG. 3.

FoxO role in the regulation of oxidative stress is evolutionarily conserved. FoxO are the mammalian homologues of DAF-16 in Caenorhabditis elegans. These transcription factors are regulated by the highly conserved IGF-1 (Insulin)/PI3-kinase/AKT signaling pathway that suppress the activity of FoxO. Activation of DAF-16 enhances the worm's life span in part through resistance to oxidative stress. In mammals, active FoxO plays key roles in the regulation of transcription of several antioxidant enzymes, as well as the cell cycle, DNA repair, apoptosis, and cell-differentiation proteins.