Effects of glucose/insulin perturbations on aging and chronic disorders of aging: the evidence.

Among changes associated with aging is a decline in glucose tolerance. The reported causes are increased insulin resistance from receptor and/or post receptor disturbances and diminished pancreatic islet B-cell sensitivity to glucose. Many recent reports indicate that insulin resistance with hyperinsulinemia and/or hyperglycemia contribute to or even causes many chronic disorders associated with aging, i.e., chronic metabolic perturbations including noninsulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerosis. How could such disturbances in glucose/insulin metabolism lead to many chronic disorders associated with aging? In aging, similar to diabetes, the elevation in circulating glucose and other reducing sugars secondary to age-induced insulin resistance can react nonenzymatically with proteins and nucleic acids to form products that affect function and diminish tissue elasticity. Also, perturbations in glucose/insulin metabolism are associated with enhanced lipid peroxidation secondary to greater free radical formation. Free radicals of oxygen are important known causes of tissue damage and have been associated with many aspects of aging including inflammatory diseases, cataracts, diabetes, and cardiovascular diseases. Augmented free radical formation and lipid peroxidation are not uncommon in diabetes mellitus, commonly associated with "premature aging". Ingestion of sugars, fats, and sodium have been linked to decreased insulin sensitivity, while caloric restriction, exercise, ingestion of chromium, vanadium, soluble fibers, magnesium, and certain antioxidants are associated with greater insulin sensitivity. Thus, manipulation of diet by influencing the glucose/insulin system may favorably affect lifespan and reduce the incidence of chronic disorders associated with aging.