[Aging: role and control of glycation].
OBJECTIVE
Advanced glycation end-products (AGEs) accumulate in aging tissues and organs during rheumatoid arthritis and Alzheimer disease. These aging toxins are especially involved in cell alteration during diabetes mellitus (glycotoxin) and renal failure (uremic toxin). AGEs participate to the endothelial dysfunction leading to diabetic macro but also micro-angiopathy. AGEs binding to cell receptors are critical steps in the deleterious consequences of AGE excess. AGE-receptor activation altered cell and organ functions by a pro-inflammatory, pro-coagulant and pro-fibrosis factors cell response.


BACKGROUND
Non-enzymatic glycation and glycoxidation with glucose auto-oxidation represent the two main pathways resulting in AGE formation. No exclusive AGE classification is actually available. Pathophysiological mechanisms are described to explain AGE toxicity. AGEs bind to cell receptors inducing deleterious consequences such as endothelial dysfunction after endothelial RAGE activation. AGEs can also have deleterious effects through glycated protein accumulation or in situ protein glycation.


CONCLUSIONS
Many in vitro or animal studies demonstrated that AGE deleterious effects can be prevented by glycation inhibitors, AGE cross-link breakers or AGE-RAGE interaction inhibition. New molecules are actually studied as new strategy to prevent or treat the deleterious effects of these aging toxins.
Boulanger
E
E
Biologie du vieillissement vasculaire, pôle de recherche, faculté de médecine, CHRU de Lille-II, 1, place de Verdun, 59045 Lille, France. eboulanger@chru-lille.fr
Puisieux
F
F
Gaxatte
C
C
Wautier
J-L
JL
D000375:Aging / Q000502:physiology*; D002241:Carbohydrates / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002463:Cell Membrane Permeability; D017127:Glycation End Products, Advanced / Q000502:physiology* / Q000633:toxicity*; D006801:Humans; D011506:Proteins / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology
D002241:Carbohydrates; D017127:Glycation End Products, Advanced; D011506:Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic