Caloric restriction prevents age-associated accrual of oxidative damage tomouse skeletal muscle mitochondria

The purpose of this study was to understand the nature of the causes underl ying the senescence-related decline in skeletal muscle mass and performance . Protein and lipid oxidative damage to upper hindlimb skeletal muscle mito chondria was compared between mice fed ad libitum and those restricted to 4 0% fewer calories-a regimen that increases life span by similar to 30-40% a nd attenuates the senescence-associated decrement in skeletal muscle mass a nd function. Oxidative damage to mitochondrial proteins, measured as amount s of protein carbonyls and loss of protein sulfhydryl content, and to mitoc hondrial lipids, determined as concentration of thiobarbituric acid reactiv e substances, significantly increased with age in the ad libitum-fed (AL) C 57BL/6 mice. The rate of superoxide anion radical generation by submitochon drial particles increased whereas the activities of antioxidative enzymes s uperoxide dismutase, catalase, and glutathione peroxidase in muscle homogen ates remained unaltered with age in the AL group. In calorically-restricted (CR) mice there was no age-associated increase in mitochondrial protein or lipid oxidative damage, or in superoxide anion radical generation. Crossov er studies, involving the transfer of 18- to 22-month-old mice fed on the A L regimen to the CR regimen, and vice versa, indicated that the mitochondri al oxidative damage could not be reversed by CR or induced by AZ,feeding wi thin a time frame of 6 weeks. Results of this study indicate that mitochond ria in skeletal muscles accumulate significant amounts of oxidative damage during aging. Although such damage is largely irreversible, it can be preve nted by restriction of caloric intake. (C) 1998 Elsevier Science Inc.