Brain Region-specific Effects of Long-term Caloric Restriction on Redox Balance of the Aging Rat

Caloric restriction (CR) is the most effective intervention to improve health span and extend lifespan in preclinical models. This anti-aging effect of CR is related to attenuation of oxidative damage in various tissues, with divergent results in the brain. We addressed how brain oxidoreductive balance would be modulated in male Sprague-Dawley (SD) rats submitted to a 40% CR from 8 to 19 months of age, by reference to ad libitum-fed (AL) rats at 2 and 19 months of age. Four brain structures were compared: hippocampus, striatum, parietal cortex, cerebellum. Our CR diet elicits significant prevention of oxidative damages with the upregulation of antioxidant defenses (levels of glutathione [GSH], mRNAs of clusterin and of three key antioxidant enzymes) as compared to age-matched AL controls, in a strikingly region-specific pattern. CR also prevented a drastic rise of the glial fibrillary acidic protein in the hippocampus of old AL rats. Besides, the CR effects at age 19 months mainly consist in improving endogenous defenses before the onset of age-related redox alterations. These effects are more prominent in the hippocampus.