Epidemiology

Impaired mitochondrial function may lead to age-related insulin resistance

Last Updated: 2003-05-15 14:00:16 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The high prevalence of diabetes in the elderly may be related to age-associated reductions in mitochondrial function, researchers at Yale University School of Medicine suggest.

Intracellular fat content in muscle and liver is strongly related to insulin resistance in these two tissues, Dr. Gerald I. Shulman and associates in New Haven, Connecticut, explain in the May 16th issue of Science. To see how insulin resistance arises, Dr. Shulman's group studied 15 healthy, lean elderly subjects (ages 61 to 84) and 13 young control subjects (ages 18 to 39) matched for lean body mass and fat mass.

According to hyperinsulinemic-euglycemic clamp studies, the rate of glucose infusion required to maintain euglycemia, as well as insulin-stimulated rates of peripheral glucose uptake, were about 40% lower in the elderly group.

Nuclear magnetic resonance (NMR) spectroscopy then showed intramyocellular lipid content was approximately 45% higher in the older group. Although intrahepatic triglyceride content was more than twice as high among the older subjects compared with controls, hepatic insulin resistance was not observed.

Dr. Shulman's group suggest that "insulin resistance was confined mostly to skeletal muscle and that increased basal rates of peripheral lipolysis, and/or defects in insulin suppression of lipolysis, do not play a major role in causing the increased intramyocellular and intrahepatic triglyceride content in the elderly."

NMR also showed that rates of mitochondrial oxidative and phosphorylation activity were both reduced by about 40% in the older age group.

Therefore, the authors posit that insulin resistance in the elderly is associated with an age-associated reduction in mitochondrial number or function or both. They reason that mitochondrial energy metabolism also plays a role in pancreatic beta cell mitochondrial function, and that these data together "might help explain the high prevalence of diabetes in the elderly."

Science 2003;300:1140-1142.