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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

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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”

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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

slide2

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
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
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 sources1
Reactive oxygen species:Cellular sources

Cellular heterogeneity

Rat Diaphragm: DCF fluorescence

reactive oxygen species cellular targets
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
reactive oxygen species effects on the sarcoplasmic reticulum
Reactive oxygen species: Effects on the sarcoplasmic reticulum

Andrade, et al., FASEB J10.1096/fj.00-0507fje

reactive oxygen species effects on myofilament function
Reactive oxygen species:Effects on myofilament function

Andrade, et al. J Physiol 509:565, 1998

outstanding issues
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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