[Demonstration of the cytotoxic effect of Advanced Glycation Endproducts (AGE-s)]

Advanced Glycation End-products (AGE-s) were shown to exhibit a number of potentially harmful properties in contact with cells and tissues. As their concentrations increases with age, faster even in hyperglycemic individuals, they are considered important for aging- and age-associated pathologies, especially for athero-arteriosclerosis and type II diabetes. We describe here the methods used for the demonstration of a direct cytotoxicity of several AGE-products when added to human skin fibroblast cultures. This cytotoxicity was still demonstrable when cells, previously cultured with AGE-s, were transferred to new medium without AGE-s. This effect, the remanence of cytotoxicity in absence of AGE-s, suggests a certain degree of inheritance, possibly by epigenetic mechanisms, of the cytotoxic effect of AGE-s, mediated by the AGE-receptors (RAGE-s) and inhibited by free radical-scavengers, such as L-Carnosine, Catalase and Rhamnose-rich oligo- and polysaccharides. Such cytotoxicity can occur not only on the skin but also in other tissues. It appears thus that besides the crosslinking of collagen and other macromolecules, the products of the Maillard reaction can exert their harmful cytotoxic effects directly on the cells.