Arterial stiffening is a progressive, ubiquitous and irreversible aging process that is interwoven with and accelerated by various diseases such as diabetes, atherosclerosis and hypertension. In large arteries, aging is characterized by decreased turnover of collagen and elastin and increased advanced glycation end-products (AGEs) and cross-links. Elastic fibers undergo lysis and disorganization subsequent to their replacement by collagen and other matrix components. These events cause the loss of elasticity and induce stiffening. Conceptual approaches to minimize AGE accumulation in arteries include caloric restriction, exercise, low dietary intake of AGEs, deglycation enzymes, increased clearance of AGEs, antagonists of AGE receptors and pharmaceutical interventions. Much optimism exists in the ability of ‘AGE breakers’ such as alagebrium (ALT-711) to cleave AGE cross-links and reverse the age-related stiffening of arteries. However, there is little evidence that these agents actually break pre-existing AGE cross-links in vivo. In contrast, many of these anti-AGE agents share in common the ability to chelate metals, thus acting as inhibitors of metal-catalyzed AGE and protein carbonyl formation. Future work on interventions into the causes of arterial stiffness in aging needs to address more rigorously the relationship between stochastic forms of damage, such a glycation and oxidation, and the changes in elastic fiber structure thought to contribute to loss of arterial elasticity.

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