title: DNA-aptamers raised against AGEs as a blocker of various aging-related disorders.
abstract: A non-enzymatic reaction between sugars or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, which could impair their structural integrity and function. This process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions, such as rearrangements and dehydration to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress in a physiological aging process and at an accelerated rate under hyperglycemic, inflammatory and oxidative stress conditions. There is a growing body of evidence that AGEs and their receptor RAGE interaction play a role in the pathogenesis of various devastating disorders, including cardiovascular disease, Alzheimer's disease, insulin resistance, osteoporosis and cancer growth and metastasis. Furthermore, diet has been recently recognized as a major environmental source of AGEs that could also elicit pro-inflammatory reactions, thereby being involved in organ damage in vivo. Therefore, inhibition of AGE formation and/or blockade of the interaction of AGEs with RAGE may be a novel therapeutic target for aging-related disorders. This article discusses a potential utility of DNA-aptamers raised against AGEs for preventing aging and/or diabetes-associated organ damage, especially focusing on diabetic microvascular complications, vascular remodeling, metabolic derangements, and melanoma growth and expansion in animal models.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. shoichi@med.kurume-u.ac.jp.
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
authors.affiliation: Department of Medicine, Division of Nephrology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Medicine, Division of Nephrology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fukami
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: C000593871:AGER protein, human; D052157:Aptamers, Nucleotide; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products
keywords: AGE-aptamer; AGEs; Aging; Oxidative stress; RAGE