Advanced glycation end-products (AGEs) are proteins or lipids that become glycated after exposure to sugars. They are formed through a series of non-enzymatic reactions explained in further detail below, and their accumulation is associated with a variety of metabolic diseases such as diabetes, atherosclerosis, chronic kidney disease, age-related macular degeneration (even in non-diabetic animals), and Alzheimer's disease. Notably, AGEs are believed to play a causative role in the vascular complications of diabetes mellitus and age related macular degeneration (AMD).

Dietary sources of AGEs

Animal-derived foods that are high in fat and protein are generally rich in AGEs, and are especially prone to further AGE formation during cooking. This raises uncertainty about the role of dietary AGEs in disease and aging, whether they significantly contribute, or if only endogenously produced AGEs (those formed within the body) are relevant. Most endogenous AGEs are produced intracellularly, and their rates of production and accumulation increase in response to high glycemic index diets, extended exposure to glycating moieties in vitro, and aging in laboratory animals and humans- even in non-diabetics. AGEs also accumulate upon aging, which is explained in more detail below. cardiovascular disease, and stroke. Additionally, AGE accumulation has been observed in the eye lens and retina of animals fed high glycemic index diets, as well as in HEK-293 and HELA cells exposed to methyglyoxal.

In the context of cardiovascular disease, AGEs can induce crosslinking of collagen, which can cause vascular stiffening and entrapment of low-density lipoprotein particles (LDL) in the artery walls. Oxidized LDL is one of the major factors in the development of atherosclerosis. AGEs can bind to RAGE receptors and cause oxidative stress as well as activation of inflammatory pathways in vascular endothelial cells. This receptor, when binding AGEs, is under preliminary research to determine if it contributes to age- and diabetes-related chronic inflammatory diseases. AGEs can be detected and quantified using bioanalytical and immunological methods.

Effects

thumb|444px|Glycation often entails the modification of the guanidine group of arginine residues with [[glyoxal (R = H), methylglyoxal (R = Me), and 3-deoxyglucosone, which arise from the metabolism of high-carbohydrate diets. Thus modified, these proteins contribute to complications from diabetes.]]

AGEs can be produced in the body and in manufactured foods. and some age-related chronic diseases. They are also believed to play a causative role in the vascular complications of diabetes mellitus.

AGEs may arise under certain pathological conditions, such as oxidative stress due to hyperglycemia in patients with diabetes. AGEs may have a role as proinflammatory mediators in gestational diabetes.

In other diseases

AGEs have been implicated in Alzheimer's disease and cardiovascular diseases.

<!-- not disease specific Because AGEs are related to elevated blood sugar levels, a low calorie diet may reduce AGE body load. -->

Pathology

In laboratory studies, AGEs have a range of pathological effects, such as: Therefore, substances that inhibit AGE formation may limit the progression of disease and may offer new tools for therapeutic interventions in the therapy of AGE-mediated disease

  • AGEs have specific cellular receptors; the best-characterized are those called RAGE. Such increases in oxidative stress lead to the activation of the transcription factor NF-κB and promote the expression of NF-κB regulated genes that have been associated with atherosclerosis.

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Nevertheless, the resistance of extracellular matrix proteins to proteolysis renders their advanced glycation end products less conducive to being eliminated.

AGE free adducts are the major form through which AGEs are excreted in urine, with AGE-peptides occurring to a lesser extent

have been implicated in this process, although the real-life involvement of the liver has been disputed.

thumb|right|Endothelial cell

Large AGE proteins unable to enter the Bowman's capsule are capable of binding to receptors on endothelial and mesangial cells and to the mesangial matrix. and decreasing kidney function in patients with unusually high AGE levels.

Peptides and free adducts, the only breakdown products of AGE that are suitable for urinary excretion, are more aggressive than the AGE proteins from which they are derived, and they can perpetuate related pathology in people with diabetes, even after hyperglycemia has been brought under control.