Advanced glycation end-product protein-protein cross-links (AGE cross-links) (AGE cross-links)

Advanced glycation end-products (AGEs) are a heterogeneous group of molecules formed through the non-enzymatic reaction between reducing sugars and the amino groups of proteins, lipids, or nucleic acids [PMID: 24354186]. Protein-protein cross-links represent a specific subset of AGEs that covalently bond adjacent protein fibers, leading to increased tissue stiffness and loss of elasticity in the extracellular matrix [PMID: 11733224]. These cross-links are particularly prevalent in long-lived proteins like collagen and elastin, contributing significantly to the pathology of aging, diabetic complications, and cardiovascular stiffening [PMID: 15356013]. In disease states, the accumulation of AGE cross-links impairs organ function and triggers inflammatory signaling through the Receptor for Advanced Glycation End-products (RAGE) [PMID: 12488523]. Therapeutic strategies involve "AGE-breakers" designed to cleave these covalent bonds or inhibitors that prevent their formation by scavenging reactive intermediates [PMID: 11113300]. Despite promising preclinical data showing reversal of arterial stiffness, clinical translation has faced challenges regarding efficacy and safety in human trials [PMID: 18445619].

Other names

AGEsAdvanced glycation end-productsMaillard reaction productsProtein-protein cross-linking

Cleavage of alpha-diketone bonds in protein-protein cross-links (AGE-breaking) [PMID: 9535621]; Inhibition of AGE formation by scavenging reactive dicarbonyl precursors [PMID: 15155812].