The causes and consequences of ageing are likely to be complex and involve the interaction of many processes. It has been proposed that the decline in mitochondrial function caused by the accumulation of oxidatively damaged molecules plays a significant role in the ageing process. In agreement with previous reports we have shown that the activities of
NADH CoQ1 reductase and
cytochrome oxidase declined with increasing age in both rat liver and gastrocnemius muscle mitochondria. However, only in the liver were the changes in lipid peroxidation and membrane fluidity suggestive of an age-related increase in oxidative stress. After 12 weeks on a
vitamin E deficient diet,
vitamin E levels were undetectable in both gastrocnemius muscle and liver. In skeletal muscle, this was associated with a statistically significant increase in lipid peroxidation, a decrease in
cytochrome oxidase activity after 48 weeks, and an exacerbation in the age-related rate of decline of
NADH CoQ1 reductase activity. This was consistent with the suggestion that an imbalance between
free radical generation and
antioxidant defence may contribute to the
mitochondrial dysfunction with age. In contrast to this,
vitamin E deficiency in the liver caused a significant increase in mitochondrial respiratory chain activities with increasing age despite evidence of increased lipid peroxidation. Comparison of other features in these samples suggested
vitamin E deficiency; did not have a significant impact upon
mtDNA translation; induced a compensatory increase in
glutathione levels in muscle, which was less marked in the liver, but probably most interestingly caused a significant decrease in the mitochondrial membrane fluidity in muscle but not in liver mitochondria. These data suggest that while increased lipid peroxidation exacerbated the age-related decline in muscle respiratory chain function this relationship was not observed in liver. Consequently other factors are likely to be contributing to the age-related decline in mitochondrial function and specific stimuli may influence or even reverse these age-related effects as observed with
vitamin E deficiency in the liver.