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Am J Physiol Regul Integr Comp Physiol (October 3, 2002). doi:10.1152/ajpregu.00455.2002
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Articles in PresS, published online ahead of print October 3, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00455.2002
Submitted on July 25, 2002
Accepted on September 30, 2002

Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart

Barry Drew1, Sharon Phaneuf1, Amie Dirks1, Colin Selman1, Ricardo Gredilla2, Angela Lezza3, Gustavo Barja2, and Christiaan Leeuwenburgh1*

1 Biochemistry of Aging Laboratory, University of Florida, Gainesville, FL, USA
2 Department of Animal Biology-II (Animal Physiology), Complutense University, Madrid, Spain
3 Department of Biochemistry and Molecular Biology, University of Bari, Bari, Italy

* To whom correspondence should be addressed. E-mail: cleeuwen{at}ufl.edu.

Mitochondria are chronically exposed to reactive oxygen intermediates. As a result, various tissues, including skeletal muscle and heart, are characterized by an age-associated increase in reactive oxidant-induced mitochondrial DNA damage. It has been postulated that these alterations may result in a decline in the content and rate of production of adenosine tri-phosphate, which may affect tissue function, contribute to the aging process, and lead to several disease states. We show that with age, ATP content and production decreased by ~50% in isolated rat mitochondria from the gastrocnemius muscle; however, no decline was observed in heart mitochondria. The decline observed in skeletal muscle may be a factor in the process of sarcopenia, which increases in incidence with advancing age. Life long caloric restriction, which prolongs maximum life span in animals, did not attenuate the age-related decline in ATP content or rate of production in skeletal muscle and had no effect on the heart. 8-Oxo-7,8-dihydro-2'-deoxyguanosine in skeletal muscle mtDNA was unaffected by aging but decreased 30% with caloric restriction, suggesting that the mechanisms that decrease oxidative stress in these tissues with caloric restriction are independent from ATP availability. The generation of reactive oxygen species, as indicated by H2O2 production in isolated mitochondria, did not change significantly with age in skeletal muscle or in the heart. Caloric restriction tended to reduce the levels of H2O2 production in the muscle, but not in the heart. These data are the first to show that an age-associated decline in ATP content and rate of ATP production are tissue-specific, in that they occur in skeletal muscle but not heart and that mitochondrial ATP production was unaltered by caloric restriction in both tissues.




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