Role of the Maillard reaction in diabetes mellitus and diseases of aging.
Advanced glycation end-products (AGEs) are formed by spontaneous chemical reactions between carbohydrates and tissue proteins. The accumulation of AGEs in long-lived proteins contributes to the age-related increase in brown colour, fluorescence and insolubilisation of lens crystallins and to the gradual crosslinking and decrease in elasticity of connective tissue collagens with age. These nonenzymatic reactions, known collectively as Maillard or browning reactions, are also implicated in the development of pathophysiology in age-related diseases such as diabetes mellitus, atherosclerosis, Alzheimer's disease, and in dialysis-related amyloidosis. Oxygen and oxidation reactions accelerates Maillard reactions in vitro, and the structurally characterised AGEs that accumulate in long-lived tissue proteins are in fact glycoxidation products, formed by sequential glycation and oxidation reactions. In addition to their immediate effects on protein structure and function, AGEs also induce oxidative stress, leading to inflammation and propagation of tissue damage. Thus, glycation of protein, formation of AGEs and resultant oxidative stress, which accelerate Maillard reactions, can initiate an autocatalytic cycle of deleterious reactions in tissues. Pharmacological inhibition of the Maillard reaction should improve the prognosis for a broad range of age-related diseases. The role of oxidative stress as a catalyst and the consequences of Maillard reaction damage in tissues suggests that antioxidant therapy may also retard the progression of age-related pathology.
Thorpe
S R
SR
Department of Chemistry and Biochemistry, University of South Carolina, Columbia 29208, USA.
Baynes
J W
JW
D000375:Aging / Q000378:metabolism*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D015416:Maillard Reaction