Acute stress response modified by modest inhibition of growth hormone axis: a potential machinery of the anti-aging effect of calorie restriction

Abstract

Calorie restriction (CR) may exert antiaging effects by inhibiting the growth hormone (GH)/IGF-1 axis. The present study investigated the effect of modest inhibition of GH signaling on stress response and compared it with the effect of CR. Heterozygous (tg/-) rats of a transgenic strain of male rats, whose GH signaling was inhibited by overexpression of the anti-sense GH gene, and wild-type (WT) rats were used. Rats were fed ad libitum (AL) or 30% CR diets from 6 weeks of age. At 6 months of age, rats were killed between 0 and 8h after lipopolysaccharide (LPS) injection to evaluate the acute phase stress response. tg/- rats had less tissue injury, indicated by blood aspartate aminotransferase (AST) concentrations, than WT rats. Successive waves of incremental plasma TNF-α, IL-6, and interferon (IFN)-γ levels were also attenuated in tg/- rats. Activation of NF-κB, a redox-sensitive transcription factor, was slightly diminished in tg/- rats, whereas the AP-1 activity was increased. Similar trends were also observed in the CR groups as compared to the AL groups. The present results suggest an involvement of the GH/IGF-1 axis in the effect of CR for stress response, even if CR does not act solely through the GH axis.