The study investigates the role of mitochondrial dysfunction in insulin resistance among the elderly. Healthy, lean elderly and young participants were matched for lean body mass and fat mass. Elderly participants showed significantly higher insulin resistance compared to young controls, characterized by reduced insulin-stimulated muscle glucose metabolism. This was associated with increased fat accumulation in muscle and liver tissue, as measured by 1H nuclear magnetic resonance (NMR) spectroscopy, and a 40% reduction in mitochondrial oxidative and phosphorylation activity, assessed by in vivo 13C/31P NMR spectroscopy. These findings support the hypothesis that age-related mitochondrial dysfunction contributes to insulin resistance in the elderly, potentially explaining the high prevalence of type 2 diabetes in this population.The study investigates the role of mitochondrial dysfunction in insulin resistance among the elderly. Healthy, lean elderly and young participants were matched for lean body mass and fat mass. Elderly participants showed significantly higher insulin resistance compared to young controls, characterized by reduced insulin-stimulated muscle glucose metabolism. This was associated with increased fat accumulation in muscle and liver tissue, as measured by 1H nuclear magnetic resonance (NMR) spectroscopy, and a 40% reduction in mitochondrial oxidative and phosphorylation activity, assessed by in vivo 13C/31P NMR spectroscopy. These findings support the hypothesis that age-related mitochondrial dysfunction contributes to insulin resistance in the elderly, potentially explaining the high prevalence of type 2 diabetes in this population.