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1 Department of Aging and Geriatric Research, University of Florida, College of Medicine, Gainesville, FL, USA
2 Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
3 Department of Medicine (Centre for Diabetes and Endocrinology), UCL Centre for Research on Aging, University College London, London, United Kingdom
4 Aberdeen Centre for Energy Regulation and Obesity, School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom
* To whom correspondence should be addressed. E-mail: cleeuwen{at}aging.ufl.edu.
Evidence suggests that mitochondrial dysfunction and oxidant production, in association with an accumulation of oxidative damage, contribute to the aging process. Regular physical activity can delay the onset of morbidity, increase mean lifespan, and reduce the risk of developing several pathological states. No studies have examined age-related changes in oxidant production and oxidative stress in both subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria in combination with lifelong exercise. Therefore, we investigated whether long-term voluntary wheel running in Fischer 344 rats altered hydrogen peroxide (H2O2) production, antioxidant defenses and oxidative damage in cardiac SSM and IFM. At 10-11 weeks of age, rats were randomly assigned to one of two groups: sedentary, 8% food restriction (sedentary; n = 20) or wheel running, and 8% food restriction (runners; n = 20) and rats were sacrificed at 24 months of age. After the age of 6-months, running activity was maintained at an average of 1145 ± 248 meters/day. Daily energy expenditure determined by doubly-labeled water technique showed that runners expended on average approximately 70% more energy per day than the sedentary rats. Long-term voluntary wheel running significantly reduced H2O2 production from both SSM (-10.0%) and IFM (-9.6%) and increased daily energy expenditure (kJ/day) significantly in runners compared to sedentary controls. Additionally, manganese superoxide dismutase (MnSOD) activity was significantly lowered in SSM and IFM from wheel runners, which may reflect a reduction in mitochondrial superoxide production. Activities of the other major antioxidant enzymes (glutathione peroxidase and catalase) and glutathione levels were not altered by wheel running. Despite the reduction in mitochondrial oxidant production, no significant differences in oxidative stress levels (4-hydroxy-2-nonenal-modified proteins, protein carbonyls, and malondialdehyde) were detected between the two groups. The health benefits of chronic exercise may be, at least partially, due to a reduction in mitochondrial oxidant production, however we could not detect a significant reduction in several selected parameters of oxidative stress.
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