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

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 J /fj fje

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?