, Volume 5, Issue 6, pp 365–373 | Cite as

Glucose, glycation and aging

  • George Suji
  • S. SivakamiEmail author
Review paper


Glycation, a deleterious form of post-translational modification of macromolecules has been linked to diseases such as diabetes, cataract, Alzheimer’s, dialysis related amyloidosis (DRA), atherosclerosis and Parkinson’s as well as physiological aging. This review attempts to summarize the data on glycation in relation to its chemistry, role in macromolecular damage and disease, dietary sources and its intervention. Macromolecular damage and biochemical changes that occur in aging and age-related disorders point to the process of glycation as the common event in all of them. This is supported by the fact that several age-related diseases show symptoms manifested by hyperglycemia. Free radical mediated oxidative stress is also known to arise from hyperglycemia. There is evidence to indicate that controlling hyperglycemia by antidiabetic biguanides prolongs life span in experimental animals. Caloric restriction, which appears to prolong life span by bringing about mild hypoglycemia and increased insulin sensitivity further strengthens the idea that glucose via glycation is the primary damaging molecule.


AGEs aging caloric restriction diet glycation hyperglycemia 



advanced glycation end products


caloric restriction






insulin receptor substrate


maillard reaction products


methyl glyoxal


nonenzymatic glycation


receptor for advanced glycation end products


reactive oxygen species


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahmed, MU, Thorpe, SR, Baynes, JW 1986Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated proteinJ Biol Chem26148894894Google Scholar
  2. Anisimov, VN, Semenchenko, AV, Yashin, AI 2003Insulin and longevity: antidiabetic biguanides as geroprotectorsBiogerontology4297307Google Scholar
  3. Bakala, H, Delaval, E, Hamelin, M, Bismuth, J, Borot-Laloi, C, Corman, B, Friguet, B 2003Changes in rat liver mitochondria with aging: Lon protease-like activity and N-carboxymethyllysine accumulation in the matrixEur J Biochem27022952302Google Scholar
  4. Baynes, JW 2000From life to death–the struggle between chemistry and biology during aging: the Maillard reaction as an amplifier of genomic damageBiogerontology1235246Google Scholar
  5. Beckman, KB, Ames, BN 1998The free radical theory of aging maturesPhysiol Rev78547581Google Scholar
  6. Bence, NF, Sampat, RM, Kopito, RR 2001Impairment of the ubiquitin–proteasome system by protein aggregationScience29215521555Google Scholar
  7. Boratynski, J, Gorski, A 2002BSE: a consequence of cattle feeding with glycated molecules host-unknown?Med Hypotheses58276278Google Scholar
  8. Bucala, R 2002New horizons in AGE researchTaniguchi, NHoriuchi, SHayase, FKurata, TOsawa, T eds. Proceedings of the Seventh International Symposium on the Maillard Reaction, 29 October–1 November 2001Elsevier ScienceKumamoto, Japan113117Google Scholar
  9. Bulteau, A-L, Verbeke, P, Petropoulos, I, Chaffotte, A-F, Friguet, B 2001Proteasome inhibition in glyoxal-treated fibroblasts and resistance of glycated glucose-6-phosphate dehydrogenase to 20S proteasome degradation in vitroJ Biol Chem2764566245668Google Scholar
  10. Bunn, Hf, Higgins, PJ 1981Reaction of monosaccharides with proteins: possible evolutionary significanceScience213222224Google Scholar
  11. Campisi, J 2000Aging, chromatin, and food restriction–connecting the dotsScience28920622063Google Scholar
  12. Cefalu, WT, Bell-Farrow, AD, Wang, ZQ, Sonntag, WE, Fu, MX, Baynes, JW, Thorpe, SR 1995Caloric restriction decreases age dependent accumulation of the glycoxidation products Nɛ-(carboxymethyl) lysine and pentosidineJ Gerontol50337341Google Scholar
  13. Cerami, C, Founds, H, Nicholl, I, Mitsuhashi, T, Giordano, D, Vanpatten, S, Lee, A, Al-Abed, Y, Vlassara, H, Bucala, R, Cerami, A 1997Tobacco smoke is a source of toxic reactive glycation productsProc Natl Acad Sci USA941391513920Google Scholar
  14. Chen, BH, Jiang, DY, Tang, LS 2003Advanced glycation end products induce apoptosis and expression of apoptotic genes in cultured bovine retinal capillary pericytesZhonghua Yan Ke Za Zhi39224227Google Scholar
  15. Conconi, M, Szweda, LI, Levine, RL, Stadtman, ER, Friguet, B 1996Age-related decline of rat liver multicatalytic proteinase activity and protection from oxidative inactivation by heat-shock protein 90Arch Biochem Biophys331232240Google Scholar
  16. Derham, BK, Harding, JJ 1997Effect of aging on the chaperone-like function of human alpha-crystallin assessed by three methodsBiochem J328763768Google Scholar
  17. Derham, BK, Harding, JJ 1999Alpha-crystallin as a molecular chaperoneProg Retin Eye Res18463509Google Scholar
  18. Dyer, DG, Blackledge, JA, Thorpe, SR, Baynes, JW 1991Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo.J Biol Chem2661165411660Google Scholar
  19. Dyer, DG, Dunn, JA, Thorpe, SR, Bailie, KE, Lyons, TJ, McCance, DR, Baynes, JW 1993Accumulation of Maillard reaction products in skin collagen in diabetes and agingJ Clin Invest9124632469Google Scholar
  20. Edwards, IJ, Rudel, LL, Terry, JG, Kemnitz, JW, Weindruch, R, Cefalu, WT 1998Caloric restriction in rhesus monkeys reduces low density lipoprotein interaction with arterial proteoglycansJ Gerontol A Biol Sci Med Sci53443448Google Scholar
  21. Friguet, B, Stadtman, ER, Szweda, LI 1994Modification of glucose-6-phosphate dehydrogenase by 4-hydroxy-2- nonenal. Formation of cross-linked protein that inhibits the multicatalytic protease.J Biol Chem2692163921643Google Scholar
  22. Fulop, T, Larbi, A, Douziech, N 2003Insulin receptor and ageingPathol Biol (Paris)51574580Google Scholar
  23. Giacomoni, PU, Rein, G 2001Factors of skin ageing share common mechanismsBiogerontology2219229Google Scholar
  24. Gredilla, R, Sanz, A, Lopez-Torres, M, Barja, G 2001Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heartFASEB J1515891591Google Scholar
  25. Halliwell, B 1997Antioxidants and human disease: a general introductionNutr Rev55S44S52Google Scholar
  26. Halliwell, B 1999Free Radicals in Biology and Medicine3Oxford University PressOxford, EnglandGoogle Scholar
  27. Halliwell, B 2000The antioxidant paradoxLancet35511791180Google Scholar
  28. Hamada, Y, Araki, N, Koh, N, Nakamura, J, Horiuchi, S, Hotta, N 1996Rapid formation of advanced glycation end products by intermediate metabolites of glycolytic pathway and polyol pathwayBiochem Biophys Res Commun228539543Google Scholar
  29. Harding, JJ, Beswick, HT, Ajiboye, R, Huby, R, Blackytny, R, Rixon, KC 1989Non-enzymatic post transalational modification of proteins in aging: a reviewMech Ageing Dev50716Google Scholar
  30. Harman, D 1965The free radical theory of aging: effect of age on serum copper levelsJ Gerontol20151153Google Scholar
  31. Harman, D 1981The aging processProc Natl Acad Sci USA7871247128Google Scholar
  32. Heath, MM, Rixon, KC, Harding, JJ 1996Glycation-induced inactivation of malate dehydrogenase protection by aspirin and a lens molecular chaperone, alpha-crystallinBiochim Biophys Acta1315176184Google Scholar
  33. Higami, Y, Shimokawa, I 2000Apoptosis in the aging processCell Tissue Res301125132Google Scholar
  34. Kemnitz, JW, Roecker, EB, Weindruch, R, Elson, DF, Baum, ST, Bergman, RN 1994Dietary restriction increases insulin sensitivity and lowers blood glucose in rhesus monkeysAm J Physiol Endocrinol Metab266540547Google Scholar
  35. Kent, MJ, Light, ND, Bailey, AJ 1985Evidence for glucose-mediated covalent cross-linking of collagen after glycosylation in vitroBiochem J225745752Google Scholar
  36. Kikuchi, S, Shinpo, K, Takeuchi, M, Yamagishi, S, Makita, Z, Sasaki, N, Tashiro, K 2003Glycation – a sweet tempter for neuronal deathBrain Res Rev41306323Google Scholar
  37. Kimura, T, Takamatsu, J, Miyata, T, Miyakawa, T, Horiuchi, S 1998Localization of identified advanced glycation end-product structures, N epsilon(carboxymethyl)lysine and pentosidine, in age-related inclusions in human brainsPathol Int48575579Google Scholar
  38. Koschinsky, T, Ci-Jiang, HE, Mitsuhashi, T, Bucala, R, Liu, C, Buenting, C, Heitmann, K, Vlassara, H 1997Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor indiabetic nephropathyProc Natl Acad Sci USA9464746479Google Scholar
  39. Koutsilieri, E, Scheller, C, Grunblatt, E, Nara, K, Li, J, Riederer, P 2002Free radicals in Parkinson’s diseaseJ Neurol24915Google Scholar
  40. Krajcovicova-Kudlackova, M, Sebekova, K, Schinzel, R, Klvanova, J 2002Advanced glycation end products and nutritionPhysiol Res51313316Google Scholar
  41. Lee, AT, Cerami, A 1987Elevated glucose 6-phosphate levels are associated with plasmid mutations in vivoProc Natl Acad Sci USA8483118314Google Scholar
  42. Levi, B, Werman, MJ 2001Fructose triggers DNA modification and damage in an Escherichia coli plasmidJ Nutr Biochem12235241Google Scholar
  43. Monnier, VM 1989Toward a Maillard reaction theory of agingProg Clin Biol Res304122Google Scholar
  44. Monnier, VM, Sell, DR, Wu, X, Rutter, K 2002The prospects of health and longevity from the inhibition of the Maillard reaction in vivo.Horiuchi, STaniguchi, NHayase, FKurata, TOsawa, T eds. Proceedings of the Seventh International Symposium on the Maillard Reaction, 29 October – 1 November 2001Elsevier ScienceKumamoto, Japan919Google Scholar
  45. Nicholl, ID, Stitt, AW, Moore, JE, Ritchie, AJ, Archer, DB, Bucala, R 1998Increased levels of advanced glycation endproducts in the lenses and blood vessels of cigarette smokersMol Med4594601Google Scholar
  46. Niwa, T, Katsuzaki, T, Ishizaki, Y, Hayase, F, Miyazaki, T, Uematsu, T, Tatemichi, N, Takei, Y 1997Imidazolone, a novel advanced glycation end product, is present at high levels in kidneys of rats with streptozotocin-induced diabetesFEBS Lett407297302Google Scholar
  47. Njoroge, FG, Sayre, LM, Monnier, VM 1987Detection of d -glucose-derived pyrrole compounds during Maillard reaction under physiological conditionsCarbohydr Res167211220Google Scholar
  48. Obayashi, H, Nakano, K, Shigeta, H, Yamaguchi, M, Yoshimori, K, Fukui, M, Fujii, M, Kitagawa, Y, Nakamura, N, Nakamura, K, Nakazawa, Y, Ienaga, K, Ohta, M, Nishimura, M, Fukui, I, Kondo, M 1996Formation of crossline as a fluorescent advanced glycation end product in vitro and in vivoBiochem Biophys Res Commun2263741Google Scholar
  49. Odetti, PR, Borgoglio, A, Rolandi, R 1992Age-related increase of collagen fluorescence in human subcutaneous tissueMetabolism41655658Google Scholar
  50. Rochette, A de La, Birlouez-Aragon, I, Silva, E, Morliere, P 2003Advanced glycation endproducts as UVA photosensitizers of tryptophan and ascorbic acid: consequences for the lensBiochim Biophys Acta1621235241Google Scholar
  51. Rodríguez-García, J, Requena, JR, Rodríguez-Segade, S 1998Increased concentrations of serum pentosidine in rheumatoid arthritisClin Chem44250255Google Scholar
  52. Sell, DR, Kleinman, NR, Monnier, VM 2000Longitudinal determination of skin collagen glycation and glycoxidation rates predicts early death in C57BL/6NNIA miceFASEB14145156Google Scholar
  53. Shamsi, FA, Sharkey, E, Creighton, D, Nagaraj, RH 2000Maillard reactions in lens proteins: methylglyoxal-mediated modifications in the rat lensExp Eye Res70369380Google Scholar
  54. Sharma, SD, Pandey, BN, Mishra, KP, Sivakami, S 2002Amadori product and age formation during nonenzymatic glycosylation of bovine serum albumin in vitroJ Biochem Mol Biol Biophys6233242Google Scholar
  55. Stitt, AW 2001Advanced glycation: an important pathological event in diabetic and age related ocular diseaseBr J Ophthalmol85746753Google Scholar
  56. Szweda, PA, Camouse, M, Lundberg, KC, Oberley, TD, Szweda, LI 2003Aging, lipofuscin formation, and free radical-mediated inhibition of cellular proteolytic systemsAgeing Res Rev2383405Google Scholar
  57. Tanaka, M, Gong, J, Zhang, J, Yamada, Y, Borgeld, HJ, Yagi, K 2000Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesisMech Ageing Dev1166576Google Scholar
  58. Thornalley, PJ, Wolff, SP, Crabbe, MJ, Stern, A 1984The oxidation of oxyhaemoglobin by glyceraldehyde and other simple monosaccharidesBiochem J217615622Google Scholar
  59. Thornalley, PJ, Langborg, A, Minhas, HS 1999Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucoseBiochem J344109116Google Scholar
  60. Thorpe, SR, Baynes, JW 1996Role of the Maillard reaction in diabetes mellitus and diseases of agingDrugs Aging96977Google Scholar
  61. Vlassara, H 1996Protein glycation in the kidney: role in diabetes and agingKidney Int4917951804Google Scholar
  62. Weindruch, R, Keenan, KP, Carney, JM, Fernandes, G, Feuerse, RJ, Floydf, RA, Halterg, JB, Ramseyh, JJ, Richardsoni, A, Rothj, GS, Spindlerk, SR 2001Caloric restriction mimetics: metabolic interventionsJ Gerontol A Biol Sci Med Sci562033Google Scholar
  63. Yim, MB, Yim, H-S, Lee, C, Kang, S-O, Chock, PB 2001Protein glycation creation of catalytic sites for free radical generationAnn N Y Acad Sci9284853Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  1. 1.Department of Life SciencesUniversity of MumbaiMumbaiIndia

Personalised recommendations