Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
John B. Pierce Laboratory, Yale University School of Medicine, New Haven, CT 06520, USA.
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Insulin resistance is a major factor in the pathogenesis of type 2 diabetes in the elderly. To investigate how insulin resistance arises, we studied healthy, lean, elderly and young participants matched for lean body mass and fat mass. Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism. These changes were associated with increased fat accumulation in muscle and liver tissue assessed by 1Hnuclear magnetic resonance (NMR) spectroscopy, and with a ~40% reduction in mitochondrial oxidative and phosphorylation activity, as assessed by in vivo 13C/31P NMR spectroscopy. These data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.