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

Achim Lass, Barbara H. Sohal, Richard Weindruch, Michael J. Forster, Rajindar S. Sohal

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

Abstract

The purpose of this study was to understand the nature of the causes underlying the senescence-related decline in skeletal muscle mass and performance. Protein and lipid oxidative damage to upper hindlimb skeletal muscle mitochondria was compared between mice fed ad libitum and those restricted to 40% fewer calories - a regimen that increases life span by ~30-40% and attenuates the senescence-associated decrement in skeletal muscle mass and function. Oxidative damage to mitochondrial proteins, measured as amounts of protein carbonyls and loss of protein sulfhydryl content, and to mitochondrial lipids, determined as concentration of thiobarbituric acid reactive substances, significantly increased with age in the ad libitum-fed (AL) C57BL/6 mice. The rate of superoxide anion radical generation by submitochondrial particles increased whereas the activities of antioxidative enzymes superoxide dismutase, catalase, and glutathione peroxidase in muscle homogenates 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. Crossover studies, involving the transfer of 18- to 22- month-old mice fed on the AL regimen to the CR regimen, and vice versa, indicated that the mitochondrial oxidative damage could not be reversed by CR or induced by AL feeding within a time frame of 6 weeks. Results of this study indicate that mitochondria in skeletal muscles accumulate significant amounts of oxidative damage during aging. Although such damage is largely irreversible, it can be prevented by restriction of caloric intake.

Original languageEnglish
Pages (from-to)1089-1097
Number of pages9
JournalFree Radical Biology and Medicine
Volume25
Issue number9
DOIs
StatePublished - Dec 1998

Keywords

  • Aging
  • Caloric restriction
  • Free radicals
  • Mitochondia
  • Oxidative stress
  • Protein oxidation
  • Skeletal muscle

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