Mitochondrial dysfunction in the elderly may contribute to insulin resistance. A study compared healthy elderly and young individuals matched for lean body mass and fat mass. Elderly participants showed marked insulin resistance, primarily due to reduced insulin-stimulated muscle glucose metabolism. This was associated with increased fat accumulation in muscle and liver, as well as a 40% reduction in mitochondrial oxidative and phosphorylation activity. These findings support the hypothesis that age-related mitochondrial dysfunction contributes to insulin resistance in the elderly. Type 2 diabetes is common in the elderly, affecting 30 million people over 65 in developed countries. Insulin resistance is a key factor in its development. The study found that elderly participants had higher plasma glucose and insulin levels during an oral glucose tolerance test, indicating insulin resistance. Hyperinsulinemic-euglycemic clamp studies showed that elderly participants required higher glucose infusion rates to maintain euglycemia, suggesting reduced insulin-stimulated glucose uptake in skeletal muscle. The study also found increased intramyocellular and hepatic triglyceride content in elderly participants, possibly due to age-related mitochondrial dysfunction. In vivo measurements using 13C and 31P NMR spectroscopy showed reduced mitochondrial oxidative and phosphorylation activity in the elderly. These results suggest that age-related mitochondrial dysfunction may contribute to increased intramyocellular fatty acid metabolites, leading to insulin resistance. The study also examined lipolysis and found that basal rates of whole-body glycerol turnover were similar in elderly and control participants. However, the results suggest that increased peripheral lipolysis and/or defects in insulin suppression of lipolysis may not be major factors in the increased intramyocellular and intrahepatic triglyceride content in the elderly. The study concludes that mitochondrial dysfunction may play a significant role in the development of insulin resistance in the elderly, contributing to the high prevalence of type 2 diabetes in this population. The findings support the hypothesis that a decline in mitochondrial oxidative and phosphorylation energy production may also have an important role in aging.Mitochondrial dysfunction in the elderly may contribute to insulin resistance. A study compared healthy elderly and young individuals matched for lean body mass and fat mass. Elderly participants showed marked insulin resistance, primarily due to reduced insulin-stimulated muscle glucose metabolism. This was associated with increased fat accumulation in muscle and liver, as well as a 40% reduction in mitochondrial oxidative and phosphorylation activity. These findings support the hypothesis that age-related mitochondrial dysfunction contributes to insulin resistance in the elderly. Type 2 diabetes is common in the elderly, affecting 30 million people over 65 in developed countries. Insulin resistance is a key factor in its development. The study found that elderly participants had higher plasma glucose and insulin levels during an oral glucose tolerance test, indicating insulin resistance. Hyperinsulinemic-euglycemic clamp studies showed that elderly participants required higher glucose infusion rates to maintain euglycemia, suggesting reduced insulin-stimulated glucose uptake in skeletal muscle. The study also found increased intramyocellular and hepatic triglyceride content in elderly participants, possibly due to age-related mitochondrial dysfunction. In vivo measurements using 13C and 31P NMR spectroscopy showed reduced mitochondrial oxidative and phosphorylation activity in the elderly. These results suggest that age-related mitochondrial dysfunction may contribute to increased intramyocellular fatty acid metabolites, leading to insulin resistance. The study also examined lipolysis and found that basal rates of whole-body glycerol turnover were similar in elderly and control participants. However, the results suggest that increased peripheral lipolysis and/or defects in insulin suppression of lipolysis may not be major factors in the increased intramyocellular and intrahepatic triglyceride content in the elderly. The study concludes that mitochondrial dysfunction may play a significant role in the development of insulin resistance in the elderly, contributing to the high prevalence of type 2 diabetes in this population. The findings support the hypothesis that a decline in mitochondrial oxidative and phosphorylation energy production may also have an important role in aging.