Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance

TLDR

Insulin resistance is a major contributor to type 2 diabetes in the elderly. The study investigates how insulin resistance develops by comparing healthy, lean elderly and young participants matched for lean body mass and fat mass. Researchers assessed insulin‑stimulated muscle glucose metabolism, intramuscular and hepatic fat by 1H NMR spectroscopy, and mitochondrial oxidative phosphorylation by in vivo 13C/31P NMR spectroscopy. Elderly participants exhibited marked insulin resistance due to reduced muscle glucose uptake, accompanied by increased muscle and liver fat and a ~40 % reduction in mitochondrial oxidative phosphorylation, supporting the hypothesis that age‑related mitochondrial decline drives insulin resistance.

Abstract

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 1H nuclear magnetic resonance (NMR) spectroscopy, and with a approximately 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.