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Reactive Metabolites and AGE/RAGE-Mediated Cellular Dysfunction Affect the Aging Process – A Mini-ReviewFleming T.H. · Humpert P.M. · Nawroth P.P. · Bierhaus A.
Department of Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany Corresponding Author
Angelika Bierhaus, PhD
Department of Medicine I and Clinical Chemistry
Im Neuenheimer Feld 410, DE–69120 Heidelberg (Germany)
Tel. +49 6221 564 752, Fax +49 6221 564 754
Aging is a dynamic process in which its rate and subsequent longevity of an organism are dependent upon the balance between the reactive intermediates of normal cellular metabolism and the ability of the body to reduce these by-products through a multifaceted antioxidant defence system. Every disturbance of this balance constitutes a clear and present danger to the macromolecular integrity of the body. When defence mechanisms become diminished or impaired, the resulting imbalance results in accumulation of endogenous agents, such as reactive oxygen and carbonyl species, and a state of increased cellular stress, which can accelerate the rate of aging. Glycation is the non-enzymatic glycosylation of proteins, nucleotides and lipids by saccharide derivatives. Glucose and other reducing sugars are important glycating agents, but the most reactive physiological relevant glycating agents, are the dicarbonyls, in particular methylglyoxal. Endogenously formed dicarbonyl compounds can react with proteins to form advanced glycation endproducts (AGEs). Experimental models have recently provided evidence that reduced detoxification of AGE precursors by the glyoxalase system, engagement of the cellular receptor RAGE and RAGE-dependent sustained activation of the pro-inflammatory transcription factor nuclear factor ĸB might significantly contribute to the rate of aging and the onset of age-related neurodegenerative, musculoskeletal and vascular diseases.
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