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Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart
Abstract
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 (mtDNA) damage. It has been postulated that these alterations may result in a decline in the content and rate of production of ATP, 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. Lifelong 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 H 2 O 2 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 H 2 O 2 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 is tissue specific, in that it occurs in skeletal muscle but not heart, and that mitochondrial ATP production was unaltered by caloric restriction in both tissues.
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“In addition, CR enhances the expression of genes involved in ROS scavenging and alters the fatty acid composition of mitochondrial membranes, thereby reducing lipid oxidation and proton leakage (Drew et al., 2003; Short et al., 2005).”
Background
Metadata
- Authors
- Drew, B., Phaneuf, S., Dirks, A., Selman, C., Gredilla, R., Lezza, A., Barja, G., & Leeuwenburgh, C.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2003-02-01
- Volume
- 284
- Issue
- 2
- Pages
- R474-R480
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2047945064
- Cited by
- 287
- References
- 4
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- closed
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