Nonenzymatic glycosylation: A biochemical link between chronic hyperglycemia and pathophysiologic processes associated with diabetic complications and aging related debilities

Diabetes and aging, both are characterized by the formation of advanced glycosylation endproducts (AGEs). A complex cascade of nonenzymatic reactions of reducing sugars and biological amines forms AGEs. It is now clear that excessive formation of AGEs may act as a mediator, not only of diabetic complications but also of widespread aging related dysfunctions such as neurodegenerative disease, atherosclerosis, cataracts, nephropathy, pulmonary fibrosis, male erectile dysfunction and arthritis. A number of AGE-specific receptors have been identified that may catalyze the generation of reactive oxygen species and mediates the release of pro-inflammatory molecules, that contributes towards the cellular dysfunctions and cell death. AGE formation is enhanced by hyperglycemia and leading to acceleration of many aging related debilities. This article also considers pharmacological strategies to prevent or inhibit the effects of AGEs. The increasingly complex and diverse AGE biochemistry continues to create new challenges for AGE inhibition.