Sexual dimorphism in liver mitochondrial oxidative capacity is conserved under caloric restriction conditions

Caloric restriction (CR) without malnutrition has been shown to increase maximal life span and delay the rate of aging in a wide range of species. It has been proposed that reduction in energy expenditure and oxidative damage may explain the life-extending effect of CR. Sex-related differences also have been shown to influence longevity and energy expenditure in many mammalian species. The aim of the present study was to determine the sex-related differences in rat liver mitochondrial machinery, bioenergetics, and oxidative balance in response to short-term CR. Mitochondria were isolated from 6-mo-old male and female Wistar rats fed ad libitum or subjected to 40% CR for 3 mo. Mitochondrial O2 consumption, activities of the oxidative phosphorylation system (complexes I, III, IV, and V), antioxidative activities [MnSOD, glutathione peroxidase (GPx)], mitochondrial DNA and protein content, mitochondrial H2O2 production, and markers of oxidative damage, as well as cytochrome C oxidase and mitochondrial transcription factor A levels, were measured. Female rats showed a higher oxidative capacity and GPx activity than males. This sexual dimorphism was not modified by CR. Restricted rats showed slightly increased oxygen consumption, complex III activity, and GPx antioxidant activity together with lower levels of oxidative damage. In conclusion, the sexual dimorphism in liver mitochondrial oxidative capacity was unaffected by CR, with females showing higher mitochondrial functionality and ROS protection than males.