Figure 1.

General scheme for the induction of Nrf2-signaling pathway. The antioxidant response element (ARE) in the promoter region of select genes allows the coordinated up-regulation of antioxidant and detoxifying enzymes in response to dietary phytochemicals. This up-regulation is mediated through nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that may be activated by endogenous and exogenous molecules or stressful conditions. These agents disrupt the association between Nrf2 and Keap1 with subsequent nuclear translocation of Nrf2. In the cell nucleus Nrf2 interacts with small MAF protein, forming a heterodimer that binds to the ARE sequence in the promoter region and up-regulates transcription of many genes encoding detoxifying enzymes. We speculate that this signaling pathway is constitutively upregulated in long-lived individuals providing extension of longevity and health span.