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Idiopathic Fatigue of Aging Oxidative Stress and Fatigue Francisco H. Andrade Department of Physiology University of Ken

Idiopathic Fatigue of Aging Oxidative Stress and Fatigue Francisco H. Andrade Department of Physiology University of Kentucky, Lexington KY 40536 USA. CNN: “How Olympic Athletes Get Their Fuel”

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Idiopathic Fatigue of Aging Oxidative Stress and Fatigue Francisco H. Andrade Department of Physiology University of Ken

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  1. Idiopathic Fatigue of Aging Oxidative Stress and Fatigue Francisco H. Andrade Department of Physiology University of Kentucky, Lexington KY 40536 USA

  2. CNN: “How Olympic Athletes Get Their Fuel” “Dinner for the long-distance runner would be carbs -- potatoes, rice, bread -- with some protein -- salmon, chicken, lean beef -- and vegetables mixed in, she said. Antioxidants are key because athletes produce a lot of free radicals, which can result in cell damage.” (Quote attributed to Tara Gidus, dietician for the Orlando Magic) http://www.cnn.com/2008/HEALTH/diet.fitness/08/14/olympic.diet/index.html

  3. Oxidative stress and fatigue • Free radicals and skeletal muscle, a historical link (of sorts) • Gerschmann, et al. Science 119:623, 1954 • Fenn, et al. PNAS 43:1027, 1957 • Oxidative stress after exhaustive exercise • Dillard, et al. J. Appl. Physiol. 45:927, 1978 • Free radicals and muscle damage after exercise • Davies, et al. Biochem. Biophys. Res. Commun. 107:1198, 1982 • Antioxidant depletion accelerates fatigue • Morales, et al. Am. J. Respir. Crit. Care Med. 149:915, 1994 • Exogenous antioxidants delay fatigue • Shindoh, et al. J. Appl. Physiol. 68:2107, 1990

  4. Reactive oxygen species:Cellular sources • Mitochondrial respiration • Duchen. J. Physiol. 516:1, 1999 • Non-mitochondrial oxidoreductases • Kobzik, et al. Nature 372:546, 1994 • Xanthine dehydrogenase/oxidase • Apple, et al. Am. J. Anat. 192:319, 1991 • Eicosanoid metabolism • Morrow and Roberts. Prog. Lipid Res. 36:1, 1997

  5. Reactive oxygen species:Cellular sources Cellular heterogeneity Rat Diaphragm: DCF fluorescence

  6. Reactive oxygen species:Cellular targets • Sarcoplasmic reticulum • Aghdasi, et al. J. Biol. Chem. 272:3739, 1997 • Myofilaments • Crowder and Cooke. J. Muscle Res. Cell. Motil. 5:131, 1984 • Metabolic enzymes • Ziegler. Annu. Rev. Biochem. 54:305, 1985 • Signal transduction • Li, et al. Am. J. Physiol. Cell Physiol. 285:C806, 2003

  7. Reactive oxygen species: Effects on the sarcoplasmic reticulum Andrade, et al., FASEB J10.1096/fj.00-0507fje

  8. Reactive oxygen species:Effects on myofilament function Andrade, et al. J Physiol 509:565, 1998

  9. Reactive oxygen species:Muscle function and dysfunction Andrade, et al. FASEB J 15:309, 2001

  10. Skeletal muscle: Not just for walking

  11. Outstanding issues: • Sources of reactive oxygen species • During activity vs. disease • Effects of age • Species and cellular targets • Cellular and tissue heterogeneity • Production and sensitivity • Fiber type differences • Motor group differences • Interventions • Exogenous vs. endogenous antioxidants • Functional vs. biochemical endpoints • Worry about “tonic” levels of reactive oxygen species?

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