Aging, Body Fat, and Carbohydrate Metabolism

This chapter reviews the effect of old age on body fat distribution and on carbohydrate metabolism, especially insulin secretion and insulin action. Aging is associated with increased insulin resistance and risk for diabetes. One of the most important factors leading to insulin resistance in aging is the increase in fat mass (FM), especially visceral fat (VF). The elderly are likely to have normal body weight but increase in waist circumference, indicating abdominal obesity. Physiologically, insulin regulates glycogenolysis and gluconeogenesis in the liver to control hepatic glucose production. It promotes peripheral glucose uptake and glycogen synthesis in the muscle and triglyceride synthesis in the adipose tissues. Genetic models with tissue-specific knockout of insulin receptor have helped understand the critical role of various tissues, and especially the role of FM in life span. The brain-specific insulin receptor (IR) knockout mice provide the evidence that insulin may play a role in regulation of body weight at a central level. Old-age-related increase in FM and VF is associated with hepatic and peripheral insulin resistance. Age-related increase in FM determines the age-related decline in peripheral insulin sensitivity, and the occurrence of type 2 diabetes mellitus, coronary artery disease, stroke, and death.