Advanced glycation and oxidation products

Advanced glycation end products (AGEs) are formed during nonenzymatic reactions of reducing sugars and other reactive carbonyls with proteins.

Together with glycation, proteins in vivo are also modified by reactive oxygen species (ROS). These reactions are also accelerated in diabetes and end stage renal disease.

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Vitamin C mediates chemical aging of lens crystallins

Senile cataracts are associated with progressive oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. We hypothesized that the Maillard reaction, which leads browning and aroma development during the baking of foods, would occur between the lens proteins and the highly reactive oxidation products of vitamin C. To test this hypothesis, we engineered a mouse that selectively overexpresses the human vitamin C transporter SVCT2 in the lens. Consequently, lenticular levels of vitamin C and its oxidation products were 5- to 15-fold elevated, resulting in a highly compressed aging process and accelerated formation of several protein-bound advanced Maillard reaction products identical with those of aging human lens proteins. These data strongly implicate vitamin C in lens crystallin aging and may serve as a model for protein aging in other tissues particularly rich in vitamin C, such as the hippocampal neurons and the adrenal gland. The hSVCT2 mouse is expected to facilitate the search for drugs that inhibit damage by vitamin C oxidation products.

Read more in:
Fan X, Reneker LW, Obrenovich ME, Strauch C, Cheng R, Jarvis SM, Ortwerth BJ, Monnier VM.: Vitamin C mediates chemical aging of lens crystallins by the Maillard reaction in a humanized mouse model. Proc Natl Acad Sci U S A. 2006 10316912-7.
Fan X, Monnier VM.: Nucleophilic compounds decrease crystallin ascorbylation in the hSVCT2 mouse model of lenticular aging. Invest Ophthalmol Vis Sci. 2008