[3] Aging leads to progressive loss of elasticity and stiffening of tissues rich in the ECM such as joints, cartilage, arteries, lungs and skin.

This leads to increased cross-link accumulation and is thought to be linked to the thickening of basement membranes in capillaries, glomeruli, lens, and lungs.

[8] Atomic-force microscopy experiments identified nanoscale morphologic differences in collagen fibril structures as a function of ageing in skin.

[9] Computational studies using all-atom simulations revealed that glucosepane results in less tightly held helical structure in the collagen molecule and increase porosity to water.

[16] The particular reaction path proceeding from the Amadori product to the α-dicarbonyl intermediate that will yield glucosepane was difficult to determine.

[17] The best mechanism proposed is that the α-dicarbonyl N 6-(2,3-dihydroxy-5,6-dioxohexyl)-L-lysinate,[18] a key intermediate in the glucosepane reaction, forms from the Amadori product through a carbonyl shift all the way down the 6 carbon sugar backbone by keto-enol tautomerism and the elimination of the C-4 hydroxyl.

[23] 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.

[27] 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.

[30] 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.

[32] Two thiazolium molecules, PTB (N-phenacylthiazolium bromide)[33] and ALT-711,[34] have demonstrated success at reducing glucosepane levels in rats.