Modest inhibition of the growth hormone axis does not affect mitochondrial reactive oxygen species generation or redox state, unlike calorie restriction

Aim: Modest inhibition of the growth hormone (GH) axis by overexpression of the antisense GH gene in male Wistar rats reduced food intake and body weight, and lengthened the lifespan, even if fed ad libitum (AL). These findings were comparable with those induced by 30% calorie restriction (CR) in wild-type (WT) rats, suggesting importance of the GH signal pathway in the effect of CR. The present study evaluated the effects of GH inhibition and CR on mitochondrial oxidative stress and redox state in the liver. Methods: Transgenic and WT rats were fed AL or 30% CR diets from 6weeks of age. Liver tissues were collected at 6 and 24months of age. The mitochondria fraction was prepared from liver tissue homogenates. The total reactive oxygen species (ROS) generation, the protein levels of glutathione (GSH) and oxidized GSH (GSSG), and the superoxide dismutase 2 activity were measured. Results: The results revealed that CR, but not modest inhibition of GH, decreased mitochondrial ROS generation and increased the mitochondrial GSH redox potential. Conclusion: The present study suggests that CR affects mitochondrial function and redox state through a pathway distinct from GH signaling.