Idiopathic Fatigue of Aging
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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 PowerPoint PPT Presentation


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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

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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

Idiopathic Fatigue of Aging

Oxidative Stress and Fatigue

Francisco H. Andrade

Department of Physiology

University of Kentucky, Lexington KY 40536 USA


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

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


Reactive oxygen species muscle function and dysfunction

Reactive oxygen species:Muscle function and dysfunction

Andrade, et al. FASEB J 15:309, 2001


Skeletal muscle not just for walking

Skeletal muscle: Not just for walking


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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