title: Advanced nonenzymatic glycation endproducts (AGE): their relevance to aging and the pathogenesis of late diabetic complications.
abstract: Several studies in the last decade have highlighted the importance of the hexose sugars and especially glucose, as being responsible for alterations to living protein and other molecules. The phenomenon of nonenzymatic glycation--by which the carbonyl group of glucose can directly condense with a free amino group--may be relevant for the process of aging and for the pathogenesis of late diabetic complications. Thus life-long exposure to normoglycemia in non diabetic subjects or a shorter exposure but continued association with a hyperglycemic milieu, as in diabetes mellitus, have both been shown to lead to the formation and accumulation of irreversible and highly reactive advanced glycation endproducts (AGE) over long-lived, fundamental molecules such as the constituents of arterial wall collagen, basement membranes, nerve myelin, DNA and others. For example, the introduction of foreign AGE groups into proteins might alter their tertiary structure and therefore modify their function or activity. By increasing protein-to-protein cross-links AGE could reduce protein turnover, with consequential increases in levels of modified and thus less reactive molecules. Moreover, AGE could initiate an immune response with the production of specific antibodies. Reducing the extent of nonenzymatic glycation could effectively reduce the accumulation of AGE. Many authors are experimenting with methods to achieve this aim. Amongst the products tested are aspirin and aminoguanidine which compete with glucose for the same protein amino group. D-lysine is also being investigated on the principle that by reacting with glucose in circulation, it could effectively prevent it from reaching the amino group on the protein.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Endocrinology, University La Sapienza, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sensi
authors.forename: F
authors.initials: F
authors.lastname: Pricci
authors.forename: D
authors.initials: D
authors.lastname: Andreani
authors.forename: U
authors.initials: U
authors.lastname: Di Mario
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003094:Collagen / Q000031:analogs & derivatives / Q000378:metabolism; D003459:Crystallins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004912:Erythrocytes / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D006031:Glycosylation; D006801:Humans; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D008565:Membrane Proteins / Q000097:blood; D009419:Nerve Tissue Proteins / Q000378:metabolism
chemical_list: D003459:Crystallins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C022814:glycosylated collagen; D003094:Collagen; D004247:DNA