Mitochondrial function and insulin resistance during aging: a mini-review.

BACKGROUND Insulin resistance, i.e. impaired insulin sensitivity, and type 2 diabetes are more prevalent in elderly humans. Both conditions relate to lower aerobic performance and increased body fatness, which have been linked to reduced mitochondrial oxidative capacity. Thus, lower insulin sensitivity in the elderly could result from age-related diminished energy metabolism or from lifestyle-related abnormalities. OBJECTIVE This review addresses the question whether insulin sensitivity and mitochondrial oxidative capacity are independently affected during aging and type 2 diabetes. METHODS Only studies were analyzed which included elderly persons and employed state-of-the-art methodology to assess insulin sensitivity and oxidative capacity, e.g. electron microscopic imaging, in vivo magnetic resonance spectroscopy or ex vivo high-resolution respirometry. RESULTS Humans with or at risk of type 2 diabetes frequently exhibit insulin resistance along with structural and functional abnormalities of muscular mitochondria. Low mitochondrial oxidative capacity causes muscular fat accumulation, which impedes insulin signaling via lipid intermediates, in turn affecting oxidative capacity. However, insulin sensitivity is not generally reduced with age, when groups are carefully matched for physical activity and body fatness. Moreover, lifestyle intervention studies revealed discordant responses of mitochondrial oxidative capacity and insulin sensitivity. CONCLUSIONS In the elderly, low mitochondrial oxidative capacity likely results from age-related effects acquired during life span. Insulin resistance occurs independently of age mostly due to unhealthy lifestyle on top of genetic predisposition. Thus, insulin sensitivity and mitochondrial function may not be causally related, but mutually amplify each other during aging.