Short-term CR decreases cardiac mitochondrial oxidant production but increases carbonyl content.

Abstract

Lifelong caloric restriction (CR) reduces the rate of mitochondrial oxidant production and the accumulation of oxidized proteins and prevents some of the age-associated decline in 20S proteasome activity. However, few studies have investigated how rapidly the beneficial effects of CR take place. We investigated whether 2 mo of CR in 6-mo-old rats would be of sufficient duration to elicit these beneficial changes. Mitochondrial oxidant production was significantly diminished in the CR rats compared with the ad libitum-fed animals. Short-term CR also caused a significant decrease in mitochondrial superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, but there were no differences in cytosolic SOD and GPX activities, whereas mitochondrial and cytosolic catalase (CAT) activity was increased with CR. However, protein carbonyl content was significantly elevated in both the mitochondrial and cytosolic fractions from CR rats. Of the three major 20S proteasome activities (chymotrypsin-like, trypsin-like, and peptidylglutamyl-peptide hydrolase), the peptidylglutamyl-peptide hydrolase activity was significantly elevated in the CR animals, possibly because of the fact that there were more oxidized proteins to be degraded. Although fewer oxidants were produced in the CR animals, it is possible that the ability to scavenge oxidants was transiently suppressed because of the reduction in mitochondrial antioxidant enzyme activities, which may explain the observed increases in carbonyl content.