title: Cross-linking of the extracellular matrix by the maillard reaction in aging and diabetes: an update on "a puzzle nearing resolution".
abstract: The aging extracellular matrix is characterized by an age-related increase in insolubilization, yellowing, and stiffening, all of which can be mimicked by the Maillard reaction in vitro. These phenomena are accelerated in metabolic diseases such as diabetes and end-stage renal disease, which have in common with physiological aging the accumulation of various glycation products and cross-links. Eight years ago we concluded that the evidence favored oxidative cross-linking in experimental diabetes [Monnier, V.M. et al. 1996. The mechanism of collagen cross-linking in diabetes: a puzzle nearing completion. Diabetes 45(Suppl. 3): 67-72] and proposed a major role for a putative non-UV active cross-link derived from glucose. Below, we provide an update of the field that leads to the conclusion that, while oxidation might be important for Maillard reaction-mediated cross-linking via Strecker degradation and allysine formation, the single most important collagen cross-link known to date in diabetes and aging is glucosepane, a lysyl-arginine cross-link that forms under nonoxidative conditions.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. vmm3@cwru.edu
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Monnier
authors.forename: Georgian T
authors.initials: GT
authors.lastname: Mustata
authors.forename: Klaus L
authors.initials: KL
authors.lastname: Biemel
authors.forename: Oliver
authors.initials: O
authors.lastname: Reihl
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Lederer
authors.forename: Dai
authors.initials: D
authors.lastname: Zhenyu
authors.forename: David R
authors.initials: DR
authors.lastname: Sell
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003432:Cross-Linking Reagents; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D015416:Maillard Reaction
chemical_list: D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced