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Aging and disease    2018, Vol. 9 Issue (5) : 880-900     DOI: 10.14336/AD.2017.1121
Review |
Glycation Damage: A Possible Hub for Major Pathophysiological Disorders and Aging
Maxime Fournet1, Frédéric Bonté2, Alexis Desmoulière3,*
1University of Limoges, Faculty of Pharmacy, Department of Physiology, EA 6309, F-87025 Limoges, France
2LVMH Recherche, F-45800 St-Jean-de-Braye, France
3University of Limoges, Faculty of Pharmacy, Department of Physiology, EA 6309, F-87025 Limoges, France
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Glycation is both a physiological and pathological process which mainly affects proteins, nucleic acids and lipids. Exogenous and endogenous glycation produces deleterious reactions that take place principally in the extracellular matrix environment or within the cell cytosol and organelles. Advanced glycation end product (AGE) formation begins by the non-enzymatic glycation of free amino groups by sugars and aldehydes which leads to a succession of rearrangements of intermediate compounds and ultimately to irreversibly bound products known as AGEs. Epigenetic factors, oxidative stress, UV and nutrition are important causes of the accumulation of chemically and structurally different AGEs with various biological reactivities. Cross-linked proteins, deriving from the glycation process, present both an altered structure and function. Nucleotides and lipids are particularly vulnerable targets which can in turn favor DNA mutation or a decrease in cell membrane integrity and associated biological pathways respectively. In mitochondria, the consequences of glycation can alter bioenergy production. Under physiological conditions, anti-glycation defenses are sufficient, with proteasomes preventing accumulation of glycated proteins, while lipid turnover clears glycated products and nucleotide excision repair removes glycated nucleotides. If this does not occur, glycation damage accumulates, and pathologies may develop. Glycation-induced biological products are known to be mainly associated with aging, neurodegenerative disorders, diabetes and its complications, atherosclerosis, renal failure, immunological changes, retinopathy, skin photoaging, osteoporosis, and progression of some tumors.

Keywords exogenous glycation      endogenous glycation      advanced glycation end product      aging      neurodegenerative disorders      diabetes     
Corresponding Authors: Alexis Desmouliere   
About author: These authors contributed equally to this work.
Issue Date: 22 September 2017
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Fournet Maxime
Bonté Frédéric
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Fournet Maxime,Bonté Frédéric,Desmoulière Alexis. Glycation Damage: A Possible Hub for Major Pathophysiological Disorders and Aging[J]. Aging and disease, 2018, 9(5): 880-900.
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Figure 1.  In vivo glycation processes.
Figure 2.  All AGEs formed in the body due to glycation and four other metabolic pathways.
Glycation within the dermal and epidermal extracellular matrix
➢ Increased rigidity of the skin and decreased elasticity
➢ Activation of RAGE: secretion of cytokines and growth factors
➢ Induction of senescence and apoptosis in fibroblasts and disruption of keratinocytes
➢ Changes in the synthesis of components of the extracellular matrix and of metalloproteinases
Intracellular glycation
➢ Decreased effectiveness of the proteasome when its enzymes are affected by glycation
➢ Accumulation of glycated vimentin within fibroblasts and decreased contractile activity of these cells in collagen gels
Effects of UV rays
➢ Effect of UVA rays on certain AGEs in the skin: stimulation of the products of reactive oxygen species, which are not eliminated as effectively following the glycation of catalase and superoxide dismutase
➢ Stimulation of the production of AGEs and of the expression of RAGEs in the skin due to exposure to sunlight
Table 1  Summary of effects (suggested by various studies) of glycation on skin aging.
Figure 3.  Diagram of the effects (suggested by various studies) of glycation on skin aging.
Figure 4.  Carboxymethyl-lysine immunostaining (red) on normal human skin: glycated (A) and non-glycated (B) areas

Nuclei are stained using DAPI (blue). E: epidermis; D: dermis. Magnification x200.

Figure 5.  The role played by stimulated RAGEs in Alzheimer’s disease as suggested by various studies.
[1] Jang H, Serra C (2014). Nutrition, epigenetics, and diseases. Clin Nutr Res, 3:1-8.
[2] Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, et al (2010). Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc, 110: 911-6.
[3] Birlouez-Aragon I, Saavedra G, Tessier FJ, Galinier A, Ait-Ameur L, Lacoste F, et al (2010). A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. Am J Clin Nutr, 91:1220-6.
[4] Kanauchi M, Tsujimoto N, Hashimoto T (2001). Advanced glycation end products in nondiabetic patients with coronary artery disease. Diabetes Care, 24:1620-3.
[5] Gul A, Rahman MA, Salim A, Simjee SU (2009). Advanced glycation end products in senile diabetic and nondiabetic patients with cataract. J Diabetes Complicat, 23:343-8.
[6] Salahuddin P, Rabbani G, Khan RH (2014). The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach. Cell Mol Biol Lett, 19:407-37.
[7] Bargnoux AS, Morena M, Badiou S, Dupuy AM, Canaud B, Cristol JP, et al (2009). Carbonyl stress and oxidatively modified proteins in chronic renal failure. Ann Biol Clin (Paris), 67:153-8.
[8] Bonnefont-Rousselot D (2004). Advanced glycation endproducts and hyperglycemia. Métabolismes Hormones Diabètes et Nutrition (VIII), 3: 118-23.
[9] Boulanger E, Dequiedt P, Wautier JL (2002). Advanced glycosylation end products (AGE): new toxins? Nephrologie, 23: 351-9.
[10] Piroddi M, Depunzio I, Calabrese V, Mancuso C, Aisa CM, Binaglia L, et al (2007). Oxidatively-modified and glycated proteins as candidate pro-inflammatory toxins in uremia and dialysis patients. Amino Acid, 32:573-92.
[11] Annibal A, Riemer T, Jovanovic O, Westphal D, Griesser E, Pohl EE, et al (2016). Structural, biological and biophysical properties of glycated and glycoxidized phosphatidylethanolamines. Free Radic Biol Med, 95:293-307.
[12] Hsu P, Shi Y (2017). Regulation of autophagy by mitochondrial phospholipids in health and diseases. Biochim Biophys Act, 1862:114-29.
[13] Simões C, Silva AC, Domingues P, Laranjeira P, Paiva A, Domingues MRM (2013). Modified phosphatidylethanolamines induce different levels of cytokine expression in monocytes and dendritic cells. Chem Phys Lipids, 175-176:57-64.
[14] Rabbani N, Thornalley PJ (2008). Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stress. Biochem Soc Trans 36:1045-50.
[15] Pun PB, Murphy MP (2012). Pathological significance of mitochondrial glycation. Int J Cell Biol, 2012:843505.
[16] Takeuchi M, Kikuchi S, Sasaki N, Suzuki T, Watai T, Iwaki M, et al (2004). Involvement of advanced glycation end-products (AGEs) in Alzheimer’s disease. Curr Alzheimer Res, 1:39-46.
[17] Wrolstad RE, editor. Food carbohydrate chemistry. Somerset (NJ): John Wiley & Sons; 2012.
[18] Ajandouz EH, Puigserver A (1999). Nonenzymatic browning reaction of essential amino acids: effect of pH on caramelization and Maillard reaction kinetics. J Agric Food Chem, 47:1786-93.
[19] Yen GC, Lai YH (1987). Influence of antioxidants on Maillard browning reaction in a casein-glucose model system. J Food Sci, 52:1115-16.
[20] Chesne S, Rondeau P, Armenta S, Bourdon E (2006). Effects of oxidative modifications induced by the glycation of bovine serum albumin on its structure and on cultured adipose cells. Biochimie, 88:1467-77.
[21] DeGroot J, Verzijl N, Wenting-van Wijk MJG, Jacobs KMG, Van El B, Van Roermund PM, et al (2004). Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis. Arthritis Rheum, 50: 1207-15.
[22] Gillery P (2006). Stress oxydant et glycation des protéines au cours du diabète sucré. Ann Biol Clin, 64:309-14.
[23] Bunn HF, Higgins PJ (1981). Reaction of monosaccharides with proteins: possible evolutionary significance. Science, 213:222-4.
[24] Chen J, Jing J, Yu S, Song M, Tan H, Cui B, et al (2016). Advanced glycation endproducts induce apoptosis of endothelial progenitor cells by activating receptor RAGE and NADPH oxidase/JNK signaling axis. Am J Transl Res, 8:2169-78.
[25] Bonnefont-Rousselot D, Beaudeux JL, Thérond P, Peynet J, Legrand A, Delattre J (2004). Diabetes mellitus, oxidative stress and advanced glycation endproducts. Ann Pharm Fr, 62:147-57.
[26] Goldin A, Beckman JA, Schmidt AM, Creager MA (2006). Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation, 114:597-605.
[27] Alavi P, Yousefi R, Amirghofran S, Karbalaei-Heidari HR, Moosavi-Movahedi AA (2013). Structural analysis and aggregation propensity of reduced and nonreduced glycated insulin adducts. Appl Biochem Biotechnol, 170:623-38.
[28] Song F, Schmidt AM (2012). Glycation and insulin resistance: novel mechanisms and unique targets? Arterioscler Thromb Vasc Biol, 32:1760-5.
[29] Guo Q, Mori T, Jiang Y, Hu C, Osaki Y, Yoneki Y, et al (2009). Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats. J Hypertens, 27:1664-71.
[30] Miele C, Riboulet A, Maitan MA, Oriente F, Romano C, Formisano P, et al (2003). Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate (IRS) signaling through a protein kinase C alpha-mediated mechanism. J Biol Chem, 278:47376-87.
[31] Lee BW, Chae HY, Kwon SJ, Park SY, Ihm J, Ihm SH (2010). RAGE ligands induce apoptotic cell death of pancreatic β-cells via oxidative stress. Int J Mol Med, 26:813-8.
[32] Lin N, Zhang H, Su Q (2012). Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress. Diabetes Metab, 38:250-7.
[33] Mastorikou M, Mackness B, Liu Y, Mackness M (2008). Glycation of paraoxonase-1 inhibits its activity and impairs the ability of high-density lipoprotein to metabolize membrane lipid hydroperoxides. Diabet Med, 25:1049-55.
[34] Josse D, Masson P (2001). Human plasma paraoxonase (HuPON1): an anti-atherogenic enzyme with organophosphate hydrolase activity. Ann Pharm, Fr 59:108-18.
[35] Pageon H (2010). Reaction of glycation and human skin: the effects on the skin and its components, reconstructed skin as a model. Pathol Biol, 58:226-31.
[36] Blakytny R, Harding JJ (1992). Glycation (non-enzymic glycosylation) inactivates glutathione reductase. Biochem J, 288:303-7.
[37] Ketterer B, Coles B, Meyer DJ (1983). The role of glutathione in detoxication. Environ Health Perspect, 49:59-69.
[38] Mir AR, uddin M, Alam K, Ali A (2014). Methylglyoxal mediated conformational changes in histone H2A-generation of carboxyethylated advanced glycation end products. Int J Biol Macromol, 69:260-6.
[39] Ahmad S, Moinuddin null, Dixit K, Shahab U, Alam K, Ali A (2011). Genotoxicity and immunogenicity of DNA-advanced glycation end products formed by methylglyoxal and lysine in presence of Cu2+. Biochem Biophys Res Commun, 407:568-74.
[40] Roberts MJ, Wondrak GT, Laurean DC, Jacobson MK, Jacobson EL (2003). DNA damage by carbonyl stress in human skin cells. Mutat Res, 522:45-56.
[41] Vlassara H, Palace MR (2002). Diabetes and advanced glycation endproducts. J Intern Med 251:87-101.
[42] Dolhofer-Bliesener R, Gerbitz KD (1990). Impairment by glycation of immunoglobulin G Fc fragment function. Scand J Clin Lab Invest, 50:739-46.
[43] Berrou J, Fougeray S, Venot M, Chardiny V, Gautier J-F, Dulphy N, et al (2013). Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes. PLoS ONE, 8:e62418.
[44] Needell JC, Zipris D (2016). The role of the intestinal microbiome in type 1 diabetes pathogenesis. Curr Diab Rep, 16:89.
[45] Paun A, Danska JS (2016). Modulation of type 1 and type 2 diabetes risk by the intestinal microbiome. Pediatr Diabetes, 17:469-77.
[46] Turk Z, Ljubic S, Turk N, Benko B (2001). Detection of autoantibodies against advanced glycation endproducts and AGE-immune complexes in serum of patients with diabetes mellitus. Clin Chim Acta, 303:105-15.
[47] Ligier S, Fortin PR, Newkirk MM (1998). A new antibody in rheumatoid arthritis targeting glycated IgG: IgM anti-IgG-AGE. Br J Rheumatol, 37:1307-14.
[48] Lucey MD, Newkirk MM, Neville C, Lepage K, Fortin PR (2000). Association between IgM response to IgG damaged by glyoxidation and disease activity in rheumatoid arthritis. J Rheumatol, 27:319-23.
[49] Witztum JL, Steinbrecher UP, Kesaniemi YA, Fisher M (1984). Autoantibodies to glucosylated proteins in the plasma of patients with diabetes mellitus. Proc Natl Acad Sci USA, 81:3204-8.
[50] Kiener PA, Rankin BM, Davis PM, Yocum SA, Warr GA, Grove RI (1995). Immune complexes of LDL induce atherogenic responses in human monocytic cells. Arterioscler Thromb Vasc Bio, 15:990-9.
[51] Daffu G, Shen X, Senatus L, Thiagarajan D, Abedini A, Hurtado Del Pozo C, et al (2015). RAGE suppresses ABCG1-mediated macrophage cholesterol efflux in diabetes. Diabetes, 64:4046-60.
[52] Calvo C (1997). Non-enzymatic glycosylation of lipoproteins in the pathogenesis of atherosclerosis in diabetics. Rev Med Chil, 125:460-5.
[53] Bacchetti T, Masciangelo S, Armeni T, Bicchiega V, Ferretti G (2014). Glycation of human high-density lipoprotein by methylglyoxal: effect on HDL-paraoxonase activity. Metab Clin Exp, 63:307-11.
[54] Moheimani F, Morgan PE, van Reyk DM, Davies MJ (2010). Deleterious effects of reactive aldehydes and glycated proteins on macrophage proteasomal function: possible links between diabetes and atherosclerosis. Biochim Biophys Acta, 1802:561-71.
[55] Brownlee M, Vlassara H, Cerami A (1984). Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med, 101:527-37.
[56] Gugliucci A (2000). Glycation as the glucose link to diabetic complications. J Am Osteopath Assoc, 100:621-34.
[57] Thornalley PJ (2006). Advanced glycation end products in renal failure. J Ren Nutr, 16:178-84.
[58] Gerrits EG, Smit AJ, Bilo HJG (2009). AGEs, autofluorescence and renal function. Nephrol Dial Transplant, 24:710-3.
[59] Araki N, Higashi T, Mori T, Shibayama R, Kawabe Y, Kodama T, et al (1995). Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction. Eur J Biochem, 230:408-15.
[60] Svistounov D, Oteiza A, Zykova SN, Sørensen KK, McCourt P, McLachlan AJ, et al (2013). Hepatic disposal of advanced glycation end products during maturation and aging. Exp Gerontol, 48:549-56.
[61] Schmidt AM, Yan SD, Yan SF, Stern DM (2001). The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest, 108:949-55.
[62] Oliveira MIA, Souza EM de, Pedrosa F de O, Réa RR, Alves A da SC, Picheth G, et al (2013). RAGE receptor and its soluble isoforms in diabetes mellitus complications. Jornal Brasileiro de Patologia e Medicina Laboratorial, 49:97-108.
[63] Ding Q, Keller JN (2005). Evaluation of rage isoforms, ligands, and signaling in the brain. Biochim Biophys Acta, 1746:18-27.
[64] Zhang Q, O’Hearn S, Kavalukas SL, Barbul A (2012). Role of high mobility group box 1 (HMGB1) in wound healing. J Surg Res, 176:343-7.
[65] Raucci A, Cugusi S, Antonelli A, Barabino SM, Monti L, Bierhaus A, et al (2008). A soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB J, 22:3716-27.
[66] Vlassara H (2001). The AGE-receptor in the pathogenesis of diabetic complications. Diabetes Metab Res Rev, 17:436-43.
[67] Lu C, He JC, Cai W, Liu H, Zhu L, Vlassara H (2004). Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. Proc Natl Acad Sci USA, 101:11767-72.
[68] Ott C, Jacobs K, Haucke E, Navarrete Santos A, Grune T, Simm A (2014). Role of advanced glycation end products in cellular signaling. Redox Biology, 2:411-29.
[69] Xue J, Rai V, Frolov S, Singer D, Chabierski S, Xie J, et al (2011). Advanced glycation end product (AGE) recognition by the receptor for AGEs (RAGE). Structure, 19: 722-732.
[70] Renard C, Fredenrich A, Van Obberghen E (2004). L’athérosclérose accélérée chez les patients diabétiques. Métabolismes Hormones Diabètes et Nutrition (VIII), 3: 131-6.
[71] Stary HC (1989). Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis, 9(1 Suppl): I19-32.
[72] Yoshida N, Okumura K, Aso Y (2005). High serum pentosidine concentrations are associated with increased arterial stiffness and thickness in patients with type 2 diabetes. Metab Clin Exp, 54:345-50.
[73] King P, Peacock I, Donnelly R (1999). The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol, 48:643-8.
[74] Grimaldi A, Heurtier A (1999). Epidemiology of cardio-vascular complications of diabetes. Diabetes Metab, 25(Suppl 3):12-20.
[75] Paul RG, Bailey AJ (1999). The effect of advanced glycation end-product formation upon cell-matrix interactions. Int J Biochem Cell Biol, 31:653-60.
[76] Charonis AS, Reger LA, Dege JE, Kouzi-Koliakos K, Furcht LT, Wohlhueter RM, et al (1990). Laminin alterations after in vitro nonenzymatic glycosylation. Diabetes, 39:807-14.
[77] Forbes JM, Yee LTL, Thallas V, Lassila M, Candido R, Jandeleit-Dahm KA, et al (2004). Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes, 53:1813-23.
[78] Brownlee M, Cerami A, Vlassara H (1988). Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med, 318:1315-21.
[79] Xu B, Chibber R, Ruggiero D, Kohner E, Ritter J, Ferro A, et al (2003). Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J, 17:1289-91.
[80] Hogan M, Cerami A, Bucala R (1992). Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus. J Clin Invest, 90:1110-5.
[81] Yamagishi S, Fujimori H, Yonekura H, Yamamoto Y, Yamamoto H (1998). Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells. Diabetologia, 41:1435-41.
[82] Quehenberger P, Bierhaus A, Fasching P, Muellner C, Klevesath M, Hong M, et al (2000). Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells. Diabetes, 49:1561-70.
[83] Bikfalvi A, editor. Encyclopedic reference of vascular biology & pathology. Springer; 2013.
[84] Esposito C, Gerlach H, Brett J, Stern D, Vlassara H (1989). Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J Exp Med, 170:1387-407.
[85] Ren X, Shao H, Wei Q, Sun Z, Liu N (2009). Advanced glycation end-products enhance calcification in vascular smooth muscle cells. J Int Med Res, 37:847-54.
[86] Alkhawam H, Sogomonian R, El-Hunjul M, Kabach M, Syed U, Vyas N, et al (2016). Risk factors for coronary artery disease and acute coronary syndrome in patients ≤40 years old. Future Cardiol, 12:545-52.
[87] Vinokur V, Weksler-Zangen S, Berenshtein E, Eliashar R, Chevion M (2016). The loss of myocardial benefit following ischemic preconditioning is associated with dysregulation of iron homeostasis in diet-induced diabetes. PLoS ONE, 11: e0159908.
[88] Sabanayagam C, Yip W, Ting DSW, Tan G, Wong TY (2016). Ten emerging trends in the epidemiology of diabetic retinopathy. Ophthalmic Epidemiol, 23:209-22.
[89] Tan GS, Cheung N, Simó R, Cheung GC, Wong TY (2017). Diabetic macular oedema. Lancet Diabetes Endocrinol, 5:143-155.
[90] Curtis TM, Hamilton R, Yong PH, McVicar CM, Berner A, Pringle R, et al (2011). Müller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products. Diabetologia, 54: 690-8.
[91] Hammes HP, Alt A, Niwa T, Clausen JT, Bretzel RG, Brownlee M, et al (1999). Differential accumulation of advanced glycation end products in the course of diabetic retinopathy. Diabetologia, 42:728-36.
[92] Choudhuri S, Dutta D, Sen A, Chowdhury IH, Mitra B, Mondal LK, et al (2013). Role of N-ε-carboxy methyl lysine, advanced glycation end products and reactive oxygen species for the development of nonproliferative and proliferative retinopathy in type 2 diabetes mellitus. Mol Vis, 19:100-13.
[93] Barile GR, Schmidt AM (2007). RAGE and its ligands in retinal disease. Curr Mol Med, 7: 758-65.
[94] Yu Y, Yang L, Lv J, Huang X, Yi J, Pei C, et al (2015). The role of high mobility group box 1 (HMGB-1) in the diabetic retinopathy inflammation and apoptosis. Int J Clin Exp Pathol, 8: 6807-13.
[95] Moore TCB, Moore JE, Kaji Y, Frizzell N, Usui T, Poulaki V, et al (2003). The role of advanced glycation end products in retinal microvascular leukostasis. Invest Ophthalmol Vis Sci, 44: 4457-64.
[96] Lecleire-Collet A, Tessier LH, Massin P, Forster V, Brasseur G, Sahel JA, et al (2005). Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants. Br J Ophthalmol, 89:1631-3.
[97] Treins C, Giorgetti-Peraldi S, Murdaca J, Van Obberghen E (2001). Regulation of vascular endothelial growth factor expression by advanced glycation end products. J Biol Chem, 276:43836-41.
[98] Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AEB, Al-Shabrawey M, Platt DH, et al (2003). Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev, 19:442-55.
[99] Chiarelli F, Santilli F, Mohn A (2000). Role of growth factors in the development of diabetic complications. Horm Res, 53:53-67.
[100] Vlassara H, Striker LJ, Teichberg S, Fuh H, Li YM, Steffes M (1994). Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats. Proc Natl Acad Sci USA, 91:11704-8.
[101] Beisswenger PJ, Makita Z, Curphey TJ, Moore LL, Jean S, Brinck-Johnsen T, et al (1995). Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes. Diabetes, 44: 824-9.
[102] Tanji N, Markowitz GS, Fu C, Kislinger T, Taguchi A, Pischetsrieder M, et al (2000). Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease. J Am Soc Nephro, 11:1656-66.
[103] Mott JD, Khalifah RG, Nagase H, Shield CF, Hudson JK, Hudson BG (1997). Nonenzymatic glycation of type IV collagen and matrix metalloproteinase susceptibility. Kidney Int, 52:1302-12.
[104] Abrass CK (1995). Diabetic nephropathy. Mechanisms of mesangial matrix expansion. West J Med, 162:318-21.
[105] Forbes JM, Cooper ME, Oldfield MD, Thomas MC (2003). Role of advanced glycation end products in diabetic nephropathy. J Am Soc Nephrol, 14: S254-8.
[106] Pastino AK, Greco TM, Mathias RA, Cristea IM, Schwarzbauer JE (2017). Stimulatory effects of advanced glycation endproducts (AGEs) on fibronectin matrix assembly. Matrix Biol, 59:39-53
[107] Chung ACK, Zhang H, Kong YZ, Tan JJ, Huang XR, Kopp JB, et al (2010). Advanced glycation end-products induce tubular CTGF via TGF-beta-independent Smad3 signaling. J Am Soc Nephrol, 21:249-60.
[108] Holderied A, Romoli S, Eberhard J, Konrad LA, Devarapu SK, Marschner JA, et al (2015). Glomerular parietal epithelial cell activation induces collagen secretion and thickening of Bowman’s capsule in diabetes. Lab Invest, 95:273-82.
[109] Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, et al (2001). Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest, 108: 261-8.
[110] Gariani K, de Seigneux S, Pechère-Bertschi A, Philippe J, Martin PY (2012). Néphropathie diabétique. Rev Med Suisse, 8: 473-9.
[111] Müller-Krebs S, Kihm LP, Madhusudhan T, Isermann B, Reiser J, Zeier M, et al (2012). Human RAGE antibody protects against AGE-mediated podocyte dysfunction. Nephrol Dial Transplant, 27:3129-6.
[112] Makita Z, Radoff S, Rayfield EJ, Yang Z, Skolnik E, Delaney V, et al (1991). Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med, 325:836-42.
[113] Said G (2013). Diabetic neuropathy. Handb Clin Neurol, 115:579-89.
[114] Kuntzer T, Ruiz J (2014). Diabetic neuropathies: clinical sub-types, early detection and asking help from the specialist. Rev Med Suisse, 10: 950-3.
[115] Gautier JF, Cahagne B, Edan G, Balarac N, Halimi S, Allannic H (1997). Peripheral diabetic neuropathy. Recommendations of ALFEDIAM (French Language Association for the Study of Diabetes and Metabolic Diseases). Diabetes Metab, 23:335-42.
[116] Sugimoto K, Nishizawa Y, Horiuchi S, Yagihashi S (1997). Localization in human diabetic peripheral nerve of N(epsilon)-carboxymethyllysine-protein adducts, an advanced glycation endproduct. Diabetologia, 40: 1380-7.
[117] Sugimoto K, Yasujima M, Yagihashi S (2008). Role of advanced glycation end products in diabetic neuropathy. Curr Pharm Des, 14: 953-61.
[118] Sekido H, Suzuki T, Jomori T, Takeuchi M, Yabe-Nishimura C, Yagihashi S (2004). Reduced cell replication and induction of apoptosis by advanced glycation end products in rat Schwann cells. Biochem Biophys Res Commun, 320: 241-8.
[119] Duran-Jimenez B, Dobler D, Moffatt S, Rabbani N, Streuli CH, Thornalley PJ, et al (2009). Advanced glycation end products in extracellular matrix proteins contribute to the failure of sensory nerve regeneration in diabetes. Diabetes, 58:2893-903.
[120] Mustapa A, Justine M, Mohd Mustafah N, Jamil N, Manaf H (2016). Postural control and gait performance in the diabetic peripheral neuropathy: a systematic review. Biomed Res Int, 2016:9305025.
[121] Toosizadeh N, Mohler J, Armstrong DG, Talal TK, Najafi B (2015). The influence of diabetic peripheral neuropathy on local postural muscle and central sensory feedback balance control. PLoS ONE, 10:e0135255.
[122] Barwick AL, Tessier JW, Janse de Jonge X, Ivers JR, Chuter VH (2016). Peripheral sensory neuropathy is associated with altered postocclusive reactive hyperemia in the diabetic foot. BMJ Open Diabetes Res Care, 4:e000235.
[123] Makrantonaki E, Jiang D, Hossini AM, Nikolakis G, Wlaschek M, Scharffetter-Kochanek K, et al (2016). Diabetes mellitus and the skin. Rev Endocr Metab Disord, 17:269-82.
[124] Van Puyvelde K, Mets T, Njemini R, Beyer I, Bautmans I (2014). Effect of advanced glycation end product intake on inflammation and aging: a systematic review. Nutr Rev, 72:638-50.
[125] Uribarri J, Cai W, Peppa M, Goodman S, Ferrucci L, Striker G, et al (2007). Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging. J Gerontol A Biol Sci Med Sci, 62:427-33.
[126] Sen P, Shah PP, Nativio R, Berger SL (2016). Epigenetic mechanisms of longevity and aging. Cell, 166:822-39.
[127] Carmona JJ, Michan S (2016). Biology of healthy aging and longevity. Rev Invest Clin, 68:7-16.
[128] van Heijst JWJ, Niessen HWM, Hoekman K, Schalkwijk CG (2005). Advanced glycation end products in human cancer tissues: detection of Nepsilon-(carboxymethyl)lysine and argpyrimidine. Ann NY Acad Sci, 1043:725-33.
[129] Wang D, Li T, Ye G, Shen Z, Hu Y, Mou T, et al (2015). Overexpression of the receptor for advanced glycation endproducts (RAGE) is associated with poor prognosis in gastric cancer. PLoS ONE, 10:e0122697.
[130] Danby FW (2010). Nutrition and aging skin: sugar and glycation. Clin Dermatol, 28:409-11.
[131] Miksik I, Struzinsky R, Deyl Z (1991). Change with age of UV absorbance and fluorescence of collagen and accumulation of epsilon-hexosyllysine in collagen from Wistar rats living on different food restriction regimes. Mech Ageing Dev, 57:163-74.
[132] Sanguineti R, Puddu A, Mach F, Montecucco F, Viviani GL (2014). Advanced glycation end products play adverse proinflammatory activities in osteoporosis. Mediators Inflamm 2014:975872.
[133] Galliera E, Marazzi MG, Gazzaruso C, Gallotti P, Coppola A, Montalcini T, et al (2017). Evaluation of circulating sRAGE in osteoporosis according to BMI, adipokines and fracture risk: a pilot observational study. Immun Ageing, 14:13.
[134] Handa JT, Cano M, Wang L, Datta S, Liu T (2016). Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related Macular Degeneration. Biochim Biophys Acta, 1862:430-40.
[135] Roehlecke C, Valtink M, Frenzel A, Goetze D, Knels L, Morawietz H, et al (2016). Stress responses of human retinal pigment epithelial cells to glyoxal. Graefes Arch Clin Exp Ophthalmol, 254:2361-72.
[136] Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH (2002). The Alzheimer’s A beta-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA, 99:11830-5.
[137] Ma W, Lee SE, Guo J, Qu W, Hudson BI, Schmidt AM, et al (2007). RAGE ligand upregulation of VEGF secretion in ARPE-19 cells. Invest Ophthalmol Vis Sci, 48:1355-61.
[138] Nagaraj RH, Linetsky M, Stitt AW (2012). The pathogenic role of Maillard reaction in the aging eye. Amino Acids, 42:1205-20.
[139] Rabbani N, Thornalley PJ (2015). Dicarbonyl stress in cell and tissue dysfunction contributing to ageing and disease. Biochem Biophys Res Commun, 458:221-6.
[140] Semba RD, Nicklett EJ, Ferrucci L (2010). Does accumulation of advanced glycation end products contribute to the aging phenotype? J Gerontol A Biol Sci Med Sci, 65:963-75.
[141] Lohwasser C, Neureiter D, Weigle B, Kirchner T, Schuppan D (2006). The receptor for advanced glycation end products is highly expressed in the skin and upregulated by advanced glycation end products and tumor necrosis factor-alpha. J Invest Dermatol, 126:291-9.
[142] Gkogkolou P, Böhm M (2012). Advanced glycation end products: Key players in skin aging? Dermatoendocrinol, 4:259-70.
[143] Zhu P, Yang C, Chen LH, Ren M, Lao GJ, Yan L (2011). Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA. Arch Dermatol Res, 303:339-50.
[144] Lee EJ, Kim JY, Oh SH (2016). Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs. Sci Rep, 6:27848.
[145] Gorisse L, Pietrement C, Vuiblet V, Schmelzer CEH, Köhler M, Duca L, et al (2016). Protein carbamylation is a hallmark of aging. Proc Natl Acad Sci USA, 113:1191-6.
[146] Alikhani M, Maclellan CM, Raptis M, Vora S, Trackman PC, Graves DT (2007). Advanced glycation end products induce apoptosis in fibroblasts through activation of ROS, MAP kinases, and the FOXO1 transcription factor. Am J Physiol Cell Physiol, 292:C850-6.
[147] Childs BG, Durik M, Baker DJ, van Deursen JM (2015). Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med, 21:1424-35.
[148] Ravelojaona V, Robert AM, Robert L (2009). Expression of senescence-associated beta-galactosidase (SA-beta-Gal) by human skin fibroblasts, effect of advanced glycation end-products and fucose or rhamnose-rich polysaccharides. Arch Gerontol Geriatr, 48:151-4.
[149] Zhu P, Ren M, Yang C, Hu YX, Ran JM, Yan L (2012). Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes. Exp Dermatol, 21:123-9.
[150] Pageon H, Técher MP, Asselineau D (2008). Reconstructed skin modified by glycation of the dermal equivalent as a model for skin aging and its potential use to evaluate anti-glycation molecules. Exp Gerontol, 43:584-8.
[151] Kueper T, Grune T, Prahl S, Lenz H, Welge V, Biernoth T, et al (2007). Vimentin is the specific target in skin glycation. Structural prerequisites, functional consequences, and role in skin aging. J Biol Chem, 282:23427-36.
[152] Masaki H, Okano Y, Sakurai H (1999). Generation of active oxygen species from advanced glycation end-products (AGEs) during ultraviolet light A (UVA) irradiation and a possible mechanism for cell damaging. Biochim Biophys Acta, 1428:45-56.
[153] Okano Y, Masaki H, Sakurai H (2001). Pentosidine in advanced glycation end products (AGEs) during UVA irradiation generates active oxygen species and impairs human dermal fibroblasts. J Dermatol Sci, 27(Suppl 1):S11-8.
[154] Yan H, Harding JJ (1997). Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase. Biochem J, 328:599-605.
[155] Mizutari K, Ono T, Ikeda K, Kayashima K, Horiuchi S (1997). Photo-enhanced modification of human skin elastin in actinic elastosis by N(epsilon)-(carboxymethyl)lysine, one of the glycoxidation products of the Maillard reaction. J Invest Dermatol 108:797-802.
[156] Yoshinaga E, Kawada A, Ono K, Fujimoto E, Wachi H, Harumiya S, et al (2012). N(ε)-(carboxymethyl)lysine modification of elastin alters its biological properties: implications for the accumulation of abnormal elastic fibers in actinic elastosis. J Invest Dermatol, 132:315-23.
[157] Frey J (2001). Is there sugar in the Alzheimer’s disease? Ann Biol Clin (Paris), 59:253-7.
[158] Tiwari SS, Mizuno K, Ghosh A, Aziz W, Troakes C, Daoud J, et al (2016). Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss. Brain, 139:2751-65.
[159] Clark TA, Lee HP, Rolston RK, Zhu X, Marlatt MW, Castellani RJ, et al (2010). Oxidative stress and its implications for future treatments and management of Alzheimer disease. Int J Biomed Sci, 6:225-7.
[160] Arbor SC, LaFontaine M, Cumbay M (2016). Amyloid-beta Alzheimer targets - protein processing, lipid rafts, and amyloid-beta pores. Yale J Biol Med, 89:5-21.
[161] Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM (1999). Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology, 53:1937-42.
[162] Redondo MT, Beltrán-Brotóns JL, Reales JM, Ballesteros S (2016). Executive functions in patients with Alzheimer’s disease, type 2 diabetes mellitus patients and cognitively healthy older adults. Exp Gerontol, 83:47-55.
[163] Peila R, Rodriguez BL, Launer LJ (2002). Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes, 51:1256-62.
[164] Tariot PN, Ogden MA, Cox C, Williams TF (1999). Diabetes and dementia in long-term care. J Am Geriatr Soc, 47:423-9.
[165] MacKnight C, Rockwood K, Awalt E, McDowell I (2002). Diabetes mellitus and the risk of dementia, Alzheimer’s disease and vascular cognitive impairment in the Canadian Study of Health and Aging. Dement Geriatr Cogn Disord, 14:77-83.
[166] Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L (2004). Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology, 63:1181-6.
[167] Heitner J, Dickson D (1997). Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective postmortem immunocytochemical and histofluorescent study. Neurology, 49:1306-11.
[168] Monacelli F, Borghi R, Pacini D, Serrati C, Traverso N, Odetti P (2014). Pentosidine determination in CSF: a potential biomarker of Alzheimer’s disease? Clin Chem Lab Med 52:117-20.
[169] Smith MA, Taneda S, Richey PL, Miyata S, Yan SD, Stern D, et al (1994). Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci USA, 91:5710-4.
[170] Sasaki N, Fukatsu R, Tsuzuki K, Hayashi Y, Yoshida T, Fujii N, et al (1998). Advanced glycation end products in Alzheimer’s disease and other neurodegenerative diseases. Am J Pathol, 153:1149-55.
[171] Takeuchi M, Kikuchi S, Sasaki N, Suzuki T, Watai T, Iwaki M, et al (2004). Involvement of advanced glycation end-products (AGEs) in Alzheimer’s disease. Curr Alzheimer Res, 1:39-46.
[172] Münch G, Cunningham AM, Riederer P, Braak E (1998). Advanced glycation endproducts are associated with Hirano bodies in Alzheimer’s disease. Brain Res, 796:307-10.
[173] Yan SD, Bierhaus A, Nawroth PP, Stern DM (2009). RAGE and Alzheimer’s disease: a progression factor for amyloid-beta-induced cellular perturbation? J Alzheimers Dis, 16:833-43.
[174] Chuah YK, Basir R, Talib H, Tie TH, Nordin N (2013). Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflam, 2013:403460.
[175] Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al (2000). Inflammation and Alzheimer’s disease. Neurobiol Aging, 21:383-421.
[176] Fuller S, Steele M, Münch G (2010). Activated astroglia during chronic inflammation in Alzheimer’s disease--do they neglect their neurosupportive roles? Mutat Res, 690:40-9.
[177] Guglielmotto M, Aragno M, Tamagno E, Vercellinatto I, Visentin S, Medana C, et al (2012). AGEs/RAGE complex upregulates BACE1 via NF-κB pathway activation. Neurobiol Aging, 196: e13-27.
[178] Fang F, Lue LF, Yan S, Xu H, Luddy JS, Chen D, et al (2010). RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning/memory in a mouse model of Alzheimer’s disease. FASEB J, 24:1043-55.
[179] Cai Z, Liu N, Wang C, Qin B, Zhou Y, Xiao M, et al (2016). Role of RAGE in Alzheimer’s disease. Cell Mol Neurobiol, 36:483-95.
[180] Durany N, Münch G, Michel T, Riederer P (1999). Investigations on oxidative stress and therapeutical implications in dementia. Eur Arch Psychiatry Clin Neurosc, 249(Suppl 3):68-73.
[181] Alavi Naini SM, Soussi-Yanicostas N (2015). Tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies? Oxid Med Cell Longev, 2015:151979.
[182] Taguchi A (2009). Vascular factors in diabetes and Alzheimer’s disease. J Alzheimers Dis, 16:859-64.
[183] Du H, Li P, Wang J, Qing X, Li W (2012). The interaction of amyloid β and the receptor for advanced glycation endproducts induces matrix metalloproteinase-2 expression in brain endothelial cells. Cell Mol Neurobiol, 32:141-7.
[184] Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, et al (2003). RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9:907-13.
[185] Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, et al (2000). Clearance of Alzheimer’s amyloid-ss (1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 106:1489-99.
[186] Sun MK, editor. Research progress in Alzheimer’s disease and dementia, volume 3. Hauppauge (NY): Nova Science Publishers;2008.
[187] Geroldi D, Falcone C, Emanuele E (2006). Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target. Curr Med Chem, 13:1971-8.
[188] Emanuele E, D’Angelo A, Tomaino C, Binetti G, Ghidoni R, Politi P, et al (2005). Circulating levels of soluble receptor for advanced glycation end products in Alzheimer disease and vascular dementia. Arch Neurol, 62:1734-6.
[189] de la Monte SM, Wands JR (2008). Alzheimer’s disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol, 2:1101-13.
[190] Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, et al (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease--is this type 3 diabetes? J Alzheimers Dis, 7:63-80.
[191] Ajith TA, Vinodkumar P (2016). Advanced glycation endproducts: association with the pathogenesis of diseases and the current therapeutic advances. Curr Clin Pharmacol, 11:118-27.
[192] Wetzels S, Wouters K, Schalkwijk CG, Vanmierlo T, Hendriks JJA (2017). Methylglyoxal-derived advanced glycation endproducts in multiple sclerosis. Int J Mol Sci, 18:421.
[193] Jaisson S, Desmons A, Gorisse L, Gillery P (2017). Protein molecular aging: which role in physiopathology? Med Sci (Paris), 33:176-82.
[194] Goh SY, Cooper ME (2008). The role of avanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab, 93:1143-52.
[195] Nishimoto S, Koike S, Inoue N, Suzuki T, Ogasawara Y (2017). Activation of Nrf2 attenuates carbonyl stress induced by methylglyoxal in human neuroblastoma cells: Increase in GSH levels is a critical event for the detoxification mechanism. Biochem Biophys Res Commun, 483:874-9.
[196] Maessen DE, Stehouwer CD, Schalkwijk CG (2015). The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases. Clin Sci (Lond), 128:839-61.
[197] Nigro C, Leone A, Raciti GA, Longo M, Mirra P, Formisano P, et al (2017). Methylglyoxal-glyoxalase 1 balance: the root of vascular damage. Int J Mol Sci, 18/188.
[198] Stinghen AEM, Massy ZA, Vlassara H, Striker GE, Boullier A (2016). Uremic toxicity of advanced glycation end products in CKD. J Am Soc Nephrol, 27:354-70.
[199] Chinchansure AA, Korwar AM, Kulkarni MJ, Joshi SP (2015). Recent development of plant products with anti-glycation activity: a review. RSC Adv, 5:31113-38.
[200] Takeuchi M, Takino J, Furuno S, Shirai H, Kawakami M, Muramatsu M, et al (2015). Assessment of the concentrations of various advanced glycation end-products in beverages and foods that are commonly consumed in Japan. PLoS One, 10: e0118652.
[201] Kellow NJ, Coughlan MT, Reid CM (2018). Association between habitual dietary and lifestyle behaviours and skin autofluorescence (SAF), a marker of tissue accumulation of advanced glycation end products (AGEs) in healthy adults. Eur J Nutr, 57(6):2209-2216.
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