EFFECT OF AGE AND CALORIC-INTAKE ON PROTEIN OXIDATION IN DIFFERENT BRAIN-REGIONS AND ON BEHAVIORAL FUNCTIONS OF THE MOUSE

The objective of this study was to determine if oxidative stress/damag e is a possible causal factor in the senescence-related loss of brain functions in the mouse, If such a relationship indeed existed, it was expected that oxidative protein damage would increase with age within regions of the brain associated with senescence-related functional los s, and that calorie restriction, an intervention which retards certain aspects of age-associated functional loss, would reverse such increas es, Dietary restriction was found to retard age-associated decline of sensorimotor coordination and improve performance of aged mice on an a voidance learning problem. Protein carbonyl concentration, one measure of protein oxidation, increased from 8 to 27 months of age in most re gions of the mouse brain, with the most notable increases occurring in the striatum and hippocampus, regions of the brain strongly implicate d in age-associated functional loss. Age-associated loss of protein su lfhydryls was more uniform across brain regions and did not involve th e hippocampus. Dietary restriction resulted in reversal of the age-ass ociated regional trends in carbonyl and sulfhydryl concentration, with the largest changes occurring within the striatum. Cross over studies in aged calorie restricted and ad libitum fed mice indicated that low ering of carbonyl content by calorie restriction could be induced or r eversed within a time frame of 3 to 6 weeks. These findings suggest th at the beneficial effects of dietary restriction upon brain function a nd life span may depend upon its ability to acutely reduce steady-stat e levels of oxidative stress. (C) 1996 Academic Press, Inc.