Figure 1.

Main pathways associated with response to CR. Metabolic fluctuations signal through a nutrient and energy level. A decrease in the nutrient levels down-regulates the IIS pathway and the nutrient-dependent kinases TOR, PKA, and AKT, which in turn up-regulate stress response organizers such as the transcription factors NF-κB and FOXOs. In parallel, the cell's energetic imbalance produced by CR up-regulates the NAD⁺-dependent family of Sirtuins and the nutrient-dependent kinase AMPK, which in turn activate and modulate the stress response. Sirtuins are also involved in the activation of the LKB1 kinase. Overall, as is shown in the bottom part of the figure, survival and life span increase is activated through the activation of several processes (in blue) and inhibition of others (in green).