Thorpe S R, Baynes J W
Department of Chemistry and Biochemistry, University of South Carolina, Columbia 29208, USA.
Drugs Aging. 1996 Aug;9(2):69-77. doi: 10.2165/00002512-199609020-00001.
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.
晚期糖基化终产物（AGEs）是由碳水化合物与组织蛋白之间的自发化学反应形成的。AGEs在长寿蛋白中的积累导致晶状体蛋白的褐色、荧光和不溶性随年龄增长而增加，以及结缔组织胶原蛋白随年龄增长逐渐交联和弹性降低。这些非酶促反应统称为美拉德反应或褐变反应，也与糖尿病、动脉粥样硬化、阿尔茨海默病等与年龄相关疾病的病理生理学发展以及透析相关淀粉样变性有关。氧气和氧化反应在体外加速美拉德反应，而在长寿组织蛋白中积累的具有结构特征的AGEs实际上是糖氧化产物，由糖基化和氧化反应依次形成。除了对蛋白质结构和功能的直接影响外，AGEs还会诱导氧化应激，导致炎症和组织损伤的扩散。因此，蛋白质糖基化、AGEs形成以及由此产生的加速美拉德反应的氧化应激可在组织中引发有害反应的自催化循环。对美拉德反应的药理抑制应能改善多种与年龄相关疾病的预后。氧化应激作为催化剂的作用以及美拉德反应在组织中造成的损伤后果表明，抗氧化治疗也可能延缓与年龄相关病理的进展。
