Advanced glycation end products

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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AGE; AGEs; Glycation product

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Advanced Glycation Endproducts (AGEs)" are long-lived glycated reaction products that are formed by non-enzymatic glycation (glycation) in the Maillard reaction. They are formed endogenously or are also supplied exogenously via food. Biochemically, glycation is a multi-stage, non-enzymatic process (Maillard reaction) in which proteins, lipids and nucleic acid react with carbohydrates. This is the difference between this non-enzymatic reaction form and enzymatic glycosylation.

Exogenous AGEs are mainly formed when food is heated above 120°C. AGEs are responsible, for example, for giving bread a brown crust, fried meat a brown crust and beer its yellow-brown colour.

Endogenous glycation products are mainly caused by an increased supply of sugars. Thus, foods that increase blood sugar the most also induce the strongest AGE formation (transient hyperglycaemia). Fructose is the stronger AGE-producer than glucose. Cereals, especially wheat, are also strong AGE producers (the amylopectin A of wheat is split fastest by amylase. This results in a rapid increase in blood glucose). Furthermore, the content of AGEs is particularly high in grilled food (Ramsauer B et al.2019). Regardless of the supply of glycating sugar molecules, endogenous AGE production is increased by oxidative stress and chronic inflammatory reactions.

HbA1c, a glycated hemoglobin, is a diagnostically important endogenous AGE that reflects the quality of blood glucose control as "blood sugar memory". The higher the HbA1c value, the more haemoglobin molecules have reacted with sugar molecules, the poorer the patient's blood glucose control.

AGEs accumulate in the organs as well as in the skin. The accumulation of AGEs in the skin can be measured by skin autofluorescence (SAF). The SAF increases with age. SAF is one of the strongest prognostic mortality markers.

General information
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AGEs are involved in the pathogenesis of various chronic inflammatory reactions, such as diabetes mellitus type II, vascular and cardiovascular diseases (Koschinsky T et al. 1997), osteoporosis and arthritis (Vlassara H et al. 1996). It is assumed that AGEs are responsible for the increased cardiovascular risk of haemodialysis patients. Glycation is believed to interfere with the functionality of important regulatory enzymes and membrane systems. In monocytes and macrophages, expression of interleukin-1, interleukin-6, TNF-α and insulin-like growth factor-1(IGF-1) is stimulated (Chuah et al. 2013). Endothelial cells express the adhesion molecules VCAM-1 and ICAM under the influence of AGEs. This induces endothelial inflammation (Uribarri J et al.2007). AGEs can also activate the inducible NO synthase (iNOS) (Wewer RM 1998). Glycation of myelin of neurons promotes neuropathies, e.g. in diabetes mellitus, but also in Alzheimer's disease (Angeloni C 2014).

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Autofluorescence: AGEs are long-lived reaction products. They accumulate in different organs and also in the skin. Due to the autofluorescence property of some AGEs, their concentration in the skin can be measured non-invasively with a fluorescence scanner. In patients with diabetes the autofluorescence of the skin (AFH) correlates well with the mean values of HbA1c.

The receptor for AGEs, RAGE, a "pattern recognition receptor", is also involved in the organism's response to injury, infection and inflammation (Egron C et al. 2018). RAGE is a membrane receptor, but also generates a soluble form (sRAGE). The soluble AGE receptor binds AGEs- and thus prevents their binding to the actual membrane receptor (Lyu Y et al. 2018). Among other things, the sRAGE level correlates with the severity of neutrophilic asthma. A deficiency in sRAGE is associated with an increased inflammatory response in various chronic diseases (Sukkar MB et al. 2012).

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Last updated on: 29.10.2020