ROLE OF THE MAILLARD REACTION IN DIABETES-MELLITUS AND DISEASES OF AGING

Advanced glycation end-products (AGEs) are formed by spontaneous chemi cal reactions between carbohydrates and tissue proteins. The accumulat ion of AGEs in long-lived proteins contributes to the age-related incr ease in brown colour, fluorescence and insolubilisation of lens crysta llins and to the gradual crosslinking and decrease in elasticity of co nnective tissue collagens with age. These nonenzymatic reactions, know n 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 dialys is-related amyloidosis. Oxygen and oxidation reactions accelerates Mai llard reactions in vitro, and the structurally characterised AGEs that accumulate in long-lived tissue proteins are in fact glycoxidation pr oducts, formed by sequential glycation and oxidation reactions. In add ition to their immediate effects on protein structure and function, AG Es also induce oxidative stress, leading to inflammation and propagati on 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. P harmacological inhibition of the Maillard reaction should improve the prognosis for a broad range of age-related diseases. The role of oxida tive stress as a catalyst and the consequences of Maillard reaction da mage in tissues suggests that antioxidant therapy may also retard the progression of age-related pathology.