Figure 1. Calorie restriction triggers an active defense program to reduce oxidative stress and prevent aging and aging-associated diseases.

SIRT1 and SIRT3 reduce oxidative stress by regulating the transcriptional expression or posttranslational modification of antioxidants. AMPK reduces fatty acid synthesis and increases NADPH level to combat against oxidative stress. Inhibition of mTOR kinase suppresses mitochondrial biogenesis. Both inhibition of mTOR and activation of GCN2 facilitate the clearance of oxidized proteins and damaged mitochondria through autophagy.