AGE-RAGE AXIS: IMPLICATION IN FIBROSIS AND AGING

Abstract

Glycation is a major mechanism of aging. AGEs (Advanced Glycation End-products) are formed and accumulate during diabetes, renal failure, inflammation and aging (endogenous AGEs). AGEs are also formed during high temperature sterilization and cooking (exogenous AGEs). The human health effects of dietary AGEs are underestimated. AGEs are irreversibly formed through the Maillard reaction, resulting from the binding of a sugar to a protein. AGEs exert their toxicity through 3 main mechanisms: in situ glycation, AGE deposits and interaction with the receptor for AGE (RAGE). In our group, we demonstrate that dietary CML (CarboxyMethylLysin), AGE with the highest affinity for RAGE, accelerates vascular and renal aging in a RAGE-dependent manner. 1/ CML-enriched diet is followed by increased arterial stiffness and wall thickness, elastin fiber disruption and decreased expression of SIRT1, a marker of aging. 2/ Dietary CML predominantly accumulates in kidney. CML-enriched diet was followed by a significant accelerated glomerulosclerosis. RAGEnull animals were protected from vascular and renal alterations induced by a CML-enriched diet.