Idiopathic Fatigue of Aging Oxidative Stress and Fatigue
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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” “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
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
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
Reactive oxygen species: Cellular sources Cellular heterogeneity Rat Diaphragm: DCF fluorescence
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: C 806, 2003
Reactive oxygen species: Effects on the sarcoplasmic reticulum Andrade, et al. , FASEB J 10. 1096/fj. 00 -0507 fje
Reactive oxygen species: Effects on myofilament function Andrade, et al. J Physiol 509: 565, 1998
Reactive oxygen species: Muscle function and dysfunction Andrade, et al. FASEB J 15: 309, 2001
Skeletal muscle: Not just for walking
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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