Journal of the American Aging Association

, Volume 26, Issue 1–2, pp 19–28 | Cite as

Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging

  • W. Thomas JohnsonEmail author
  • Samuel M. NewmanJr.


Heart mitochondria experience age-related declines in cytochrome c oxidase (CCO) activity and increases in the generation of reactive oxygen species (ROS) that may contribute to loss of cardiac function and the development of disease that occur with advancing age. In a manner similar to aging, copper deficiency also suppresses heart CCO activity and has cardiovascular consequences related to increased peroxidation. Food restriction is often used as a tool to study oxidative mechanisms of aging and the present study examines the potential of copper deficiency to model the role of mitochondria in cardiac aging by determining if the effect of food restriction on CCO activity and oxidative stress in heart mitochondria parallels its effect on cardiac mitochondria during aging. Overall, copper deficiency severely inhibited CCO activity and increased both Mn superoxide dismutase (MnSOD) and glutathione peroxidase (GPX) in isolated heart mitochondria. However, a 20% reduction in food intake by copper-deficient rats increased CCO activity by 65% and decreased MnSOD activity by 25% but had no effect in rats fed adequate copper. Copper deficiency also reduced the carbonyl content of 80–100 kDa mitochondrial proteins, but the reduction in carbonyl content was unaffected by food restriction. Food restriction did, however, completely prevent the enlargement of cardiac mitochondria in copper-deficient rats. Together, these findings indicate that copper deficiency induces mitochondrial antioxidant enzyme activity and hypertrophy in cardiac tissue in response to reduced CCO activity and that food restriction may counteract these changes by reducing oxidative stress. Because the action of food restriction on CCO activity and mitochondrially generated oxidative stress are similar in copper deficiency and aging, copper deficiency may serve as a short-term model for studying the potential roles of mitochondria in cardiac aging.


Reactive Oxygen Species Glutathione Peroxidase Food Restriction Antioxidant Enzyme Activity Copper Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© American Aging Association, Inc. 2003

Authors and Affiliations

  1. 1.United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand Forks
  2. 2.USDA, ARS, GFHNRCGrand Forks

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