intramolecular aldimine 6-(3,4-dihydroxy-6-oxo-3,4,5,6-tetrahydro-2H-azepinium-1-yl) norleucine. The ring is hypothesized to form by a nucleophilic attack of N on C-6 carbonyl, followed by elimination of a water (2). This then condenses with the arginine side chain to yield glucosepane in nucleophilic addition-elimination reactions of the nitrogens of arginine and the electrophilic carbonyls on the ring, eliminating two waters. Accumulation Glycation processes that lead to AGEs particularly affect long-lived proteins in the human body, such as collagen in the skin and crystallin in the eyes. Skin collagen, for instance, has a half-life of fifteen years. Because these proteins do not degrade as quickly as other proteins in the body, the Amadori product, which is stable and thus transforms very slowly, has time enough to convert into glucosepane. It has been estimated that 50-60% of the steady state levels of Amadori product is converted into glucosepane in old age. A suspected reason for the prevalence of the glucosepane cross-link product as opposed to others is that the α−dicarbonyl from which it forms, N 6-(2,3-dihydroxy-5,6-dioxohexyl)-L-lysinate, is a persisting glycating agent because it is irreversibly bound through lysine to a protein. Therefore, it is not easily degraded and thus is more commonly available to form a cross-link with arginine, unlike other cross-link α-dicarbonyl intermediates, which are found bound and free and thus more susceptible to being degraded by enzymes in the ECM. Prospects for inhibition or removal Because of the important role glucosepane has been found to play in many pathologies of aging, many researchers have been investigating ways in which the levels of glucosepane could be reduced in tissues. Various methods of doing so have been examined. α-Dicarbonyl trap One method attempted to inhibit glucosepane formation is to use an α-dicarbonyl trap molecule, aminoguanidine (AG). AG reacts with the α-dicarbonyl intermediate with a higher affinity than arginine, thus blocking the cross-link. While this method has been seen to have some success, it did not greatly interfere with the normal aging of rats. Thiazolium salts Another method that has been investigated is the use of thiazolium salts to break the α-dicarbonyl intermediate, therefore cutting off the reaction pathway that leads to glucosepane. These compounds are thought to act as bidentate nucleophiles that attack the adjacent carbonyls in the alpha-dicarbonyl intermediate, which then leads to the cleaving of the C-C bond between the carbonyls. However, an alternate hypothesis as to how they work is that they act