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Bioenergetics of aging skeletal muscle
Phosphorous magnetic resonance spectroscopy was used to study the bioenergetics of skeletal muscle, with specific focus on the effects of senescence. In study 1 I found that the capacity for oxidative phosphorylation was unimpaired with old age. Furthermore, glycolytic flux was higher in young men, while older men relied more on oxidative phosphorylation. In addition to demonstrating unimpaired mitochondrial function with age, the results from this study raised the question of whether older adults exhibit impaired glycolytic capacity or an ability to adequately meet the energetic demands without using anaerobic glycolysis to its full potential. In studies 2 and 3, I investigated these possibilities by studying bioenergetics during free-flow (FF) and ischemic (ISC) contractions in young and older subjects. In study 2 12 younger subjects performed FF and ISC ankle dorsiflexion with measures of muscle energetics using 31P-MRS. The overall aim of this study was to investigate the effects of ischemia on fatigue and ATP synthesis. Although fatigue was more pronounced ISC than FF, ATP supply and demand were matched under both conditions. The balance between ATP supply and demand was maintained, not through increased reliance on anaerobic glycolysis, but through increased metabolic economy and decreased rates of ATP hydrolysis. Secondary to the main findings of this study, I also provide evidence in support of a glycolytic contribution to phosphocreatine recovery in the absence of muscle contraction: a finding that conflicts with the common dogma that phosphocreatine recovery is an entirely oxidative process. The aim of study 3 was to apply the same protocol used in study 2 to investigate the metabolic adaptability of young and older skeletal muscle under conditions where oxidative phosphorylation is negligible. As expected, glycolytic flux was lower in old compared to young during FF, however, glycolytic flux in older adults increased to a level similar to the young during ISC, suggesting that the capacity for anaerobic glycolysis in vivo remains intact in aged muscle. Furthermore, the results point to an age-related increase in metabolic economy as a mechanism that may allow older muscle to engage in maximal work with lower glycolytic flux compared to young.
Lanza, Ian R, "Bioenergetics of aging skeletal muscle" (2007). Doctoral Dissertations Available from Proquest. AAI3254929.