Life Extension - Pathology

Advanced Glycemic End PRoducts (AGEs) - updated: 03 February 2009

Advanced glycation end product

From Wikipedia, the free encyclopedia

Advanced Glycation End products (AGEs) are the result of a chain of chemical reactions after an initial glycation reaction. The intermediate products are known, variously, as Amadori, Schiff base and Maillard products, named after the researchers who first described them. (The literature is inconsistent in applying these terms. For example, Maillard reaction products are sometimes considered intermediates and sometimes end products.) Side products generated in intermediate steps may be oxidizing agents (such as hydrogen peroxide), or not (such as beta amyloid proteins). "Glycosylation" is sometimes used for "glycation" in the literature, usually as 'non-enzymatic glycosylation.'

Publication Types:

• Review

Aging and glycoxidant stress

Hormones (Athens). 2008 Apr-Jun;7(2):123-32

Peppa M, Uribarri J, Vlassara H.

Aging and related diseases are accompanied by increased Oxidative Stress (OS) and accumulation of Advanced Glycation End products (AGEs). One important component of AGEs accumulation with aging appears to be the sustained exposure to dietary AGE (dAGEs), which contributes to overloading of anti-AGE receptors and depletion of anti-oxidant reserves. In this review, we present experimental animal and human data which support this postulation. Lowering the content of AGEs in the normal diet significantly prevents AGEs accumulation and the increased OS caused by aging and also extends lifespan in mice. In humans, short-term trials indicate that a Low AGEs diet reduces oxidant burden and inflammatory markers. Long-term studies are in progress and will help establish definitive causality between age-related disease states and modern dietary practices in Western societies.

Publication Types:

• Review

The role of AGEs in aging: causation or correlation

Exp Gerontol. 2001 Sep;36(9):1527-37

Baynes JW.

Over a dozen advanced glycation end-products (AGEs) have been identified in tissue proteins by chemical or immunological methods. Of these, about half are known to accumulate with age in collagen at a rate that correlates with the half-life of the collagen. AGEs may be formed by oxidative and non-oxidative reactions and are in some cases identical to advanced lipoxidation end-products (ALEs) formed in protein during lipid peroxidation reactions. AGEs affect the biochemical and physical properties of proteins and the extracellular matrix (ECM), including the charge, hydrophobicity, turnover and elasticity of collagen, and the cell adhesion, permeability and pro-inflammatory properties of the ECM. A number of scavenger and AGE-specific receptors have been identified that may mediate the turnover of AGE-proteins, catalyze the local production of reactive oxygen species and attract and activate tissue macrophages. Although AGEs in proteins are probably correlative, rather than causative, with respect to aging, they accumulate to high levels in tissues in age-related chronic diseases, such as atherosclerosis, diabetes, arthritis and neurodegenerative disease. Inhibition of AGE formation in these diseases may limit oxidative and inflammatory damage in tissues, retarding the progression of pathophysiology and improve the quality of life during aging.

Publication Types:

• Review

Aging: role and control of glycation

Rev Med Interne. 2007 Dec;28(12):832-40

Boulanger E, Puisieux F, Gaxatte C, Wautier JL.

PURPOSE: 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. CURRENT KNOWLEDGE AND KEY POINTS: 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. FUTURE PROSPECTS AND PROJECTS: 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.

Publication Types:

• Review

Advanced glycosylation end products: a new disease marker for diabetes and aging

J Clin Lab Anal. 1993;7(5):252-5

Wu JT.

Advanced glycosylation end products (AGEs) are a potentially useful marker for monitoring glycemic control, predicting the risk of diabetes- and aging-associated clinical complications, and monitoring the treatment of patients with micro- and macrovascular diseases, including retinopathy, atherosclerosis, nephropathy, and neuropathy. AGEs or AGE-proteins are derived from nonenzymatically glycated proteins (Amadori products) after further cross-linking with other proteins and additional rearrangement. AGE-proteins can be assayed by either radioreceptor or immunoassays in blood and tissues. No commercial kit is available at this time

Publication Types:

• Study

Could glucose be a proaging factor?

J Cell Mol Med. 2008 Aug;12(4):1194-8

Kassi E, Papavassiliou AG.

There is an ever-increasing scientific interest for the interplay between cell's environment and the aging process. Although it is known that calorie restriction affects longevity, the exact molecular mechanisms through which nutrients influence various cell signalling/modulators of lifespan remain a largely unresolved issue. Among nutrients, glucose constitutes an evolutionarily stable, precious metabolic fuel, which is catabolized through glycolytic pathway providing energy in the form of ATP and consuming NAD. Accumulating evidence shows that among the important regulators of aging process are autophagy, sirtuin activity and oxidative stress. In light of recent work indicating that glucose availability decreases lifespan whilst impaired glucose metabolism extends life expectancy, the present article deals with the potential role of glucose in the aging process by regulating--directly through its metabolism or indirectly through insulin secretion--autophagy, sirtuins as well as other modulators of aging like oxidative stress and advanced glycation end-products (AGEs).

Publication Types:

• Review

Glycoxidation: the menace of diabetes and aging

Mt Sinai J Med. 2003 Sep;70(4):232-41

Vlassara H, Palace MR

Advanced glycation end products (AGE) form via the Maillard reaction in vivo and are also consumed from exogenous sources such as diet and smoking. They alter the structure and function of molecules and increase oxidative stress in biological systems. These consequences promote the pathogenesis of diabetic complications and changes associated with aging, including atherosclerosis, and renal, eye, and neurological disease. Both specific and nonspecific receptor mechanisms mediate these detrimental effects but also participate in the removal and degradation of AGE. AGE toxicity may be averted by promising dietary and pharmacological strategies which are currently being investigated

Publication Types:

• Review

Publication Types:

• Review

Publication Types:

• Review