Molecular effects of advanced glycation end products on cell signalling pathways, ageing and pathophysiology

Abstract

that result in the formation of irreversibly bound moieties known as AGEs that (among others) include N ε -(carboxymethyl)lysine (CML), pentosidine (a fl uorescent crosslinker AGE), other fl uorescent AGEs, and protein crosslinks [3].Apart from the endogenous biological processes, AGEs are also derived from exogenous sources that mostly relate to heat-processed AGE-rich diet [4]. A major marker for AGEs in food analyses is CML that is generated by the oxidative cleavage of Amadori products and is an important biological marker of oxidative stress in vivo [5]. The CML content in the same food can vary signifi cantly as a result of diff erent conditions and temperature of processing. Food that is eaten raw or processed at lower temperatures has low CML content, whereas foods with high lipid and protein content prepared at high temperatures are characterised by increased CML content [6] AbstractAdvanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the Maillard chemical process of nonenzymatic glycation of free amino groups of proteins, lipids and nucleic acids. This chemical modifi cation of biomolecules is triggered by endogeneous hyperglycaemic or oxidative stress-related processes. Additionally, AGEs can derive from exogenous, mostly diet-related, sources. Considering that AGE accumulation in tissues correlates with ageing and is a hallmark in several age-related diseases it is not surprising that the role of AGEs in ageing and pathology has become increasingly evident. The receptor for AGEs (RAGE) is a single transmembrane protein being expressed in a wide variety of human cells. RAGE binds a broad repertoire of extracellular ligands and mediates responses to stress conditions by activating multiple signal transduction pathways being mostly responsible for acute and/or chronic infl ammation. RAGE activation has been implicated in ageing as well as in a number of age-related diseases, including atherosclerosis, neurodegeneration, arthritis, stoke, diabetes and cancer. Here we present a synopsis of fi ndings that relate to AGEs-reported implication in cell signalling pathways and ageing, as well as in pathology. Potential implications and opportunities for translational research and the development of new therapies are also discussed.

Advanced Glycation End Products (Ages) in Food: Focusing on Mediterranean Pasta

“…RAGE, a single trans-membrane multi-ligand receptor, belongs to the immunoglobulin superfamily, whose members include AGE-R, SR-A (macrophage scavenger receptor types I and II), and SR-B (SR-B type I and CD36) [3,37].…”

“…Differently to RAGE, two receptors AGE-R1 and R3, belonged to immunoglobulin superfamily, once bound to AGEs activate protective pathways, involved in preventing ROS formation and activating AGE degradation and urinary excretion [3,39].…”

“…Then Amadori products can undergo further chemical reactions that result in the AGE formation [2]. AGEs are formed continuously in the body, as a part of normal metabolism, but if excessively high, they reach tissue and circulation and can become pathological [3].…”

“…Recently, different studies on mice and human have demonstrated that dAGEs can be absorbed at intestinal level, and be potentially toxic [1,3,4].…”

“…Their toxic effects are essentially related to their ability to promote oxidative stress and inflammation by binding to cell surface receptors or cross-linking with body proteins, altering their structure and function [3,4].…”