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From life to death – the struggle between chemistryand biology during aging: the Maillard reaction as an amplifier of genomic damage

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Abstract

Biogerontology is the study of the agingof biological systems. This review addresses therelationship between chemistry and biology duringaging, proposing that chemistry is responsible for theaging of biological systems. In the continuingstruggle between chemistry and biology, chemistry isalways the short-term, tactical winner – death of theindividual is inevitable. However, barring theextinction of species, biology is the long-term,strategic victor – life survives, and the strugglecontinues. The rate of random chemical damage to thegenome is considered the major factor determininglifespan of species. Oxidative stress and reactiveoxygen species are recognized as a primary source ofdamage in aging and chronic disease. The Maillardreaction, involving nonenzymatic, oxidative reactionsof carbohydrate and lipid substrates, is seen as anamplifier of reactive oxygen damage. Maillardreaction products in protein are viewed as integratorsof cumulative damage by reactive oxygen, and possiblyas initiators of protective responses, but the primaryfactor affecting lifespan is identified as silentcumulative damage to the genome, resulting fromimperfect repair. Maillard reaction inhibitors showpromise for treatment of chronic diseases, such asdiabetes and atherosclerosis, and also have a positiveeffect on health in normal animals. Future studiesshould focus on evaluation of the effects of theseinhibitors on genomic damage and lifespan extension.

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References

  • Ahmed MU, Brinkmann-Frye E, Degenhardt TP et al. (1997) N_-(carboxyethyl)lysine, a product of chemical modification of protein by methylglyoxal, increases with age in human lens proteins. Biochem J 324: 565–570

    PubMed  Google Scholar 

  • Bailey AJ, Paul RG and Knott L (1998) Mechanisms of maturation and ageing of collagen. Mech Ageing Dev 106: 1–56

    PubMed  Google Scholar 

  • Baynes JW (1991) The role of oxidative stress in the development of complications in diabetes. Diabetes 40: 405–412

    PubMed  Google Scholar 

  • Baynes JW and Thorpe SR (1999a)The role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48: 1–9

    PubMed  Google Scholar 

  • Baynes JW and Thorpe SR (1999b) Glycation and advanced glycation reactions. In: Turtle JR, Kaneko T and Osato S (eds) Diabetes in the New Millennium, pp 337–350. Endocrinology and Diabetes Research Foundation, University of Sydney

  • Bjorksten J (1968) The crosslinkage theory of aging. J Am Geriatr Soc 16: 408–427

    PubMed  Google Scholar 

  • Brinkmann Frye E, Degenhardt TP, Thorpe SR et al. (1998) Role of the Maillard reaction in aging of tissue proteins: age-dependent increase in imidazolium crosslinks in human lens protein. J Biol Chem 273: 18714–18719

    PubMed  Google Scholar 

  • Brownlee M, Vlassara H, Kooney A et al. (1986) Aminoguanidine prevents diabetes-induced arterial wall protein crosslinking. Science 232: 1629–1632

    Google Scholar 

  • Cefalu WT, Bell-Farrow AD, Wang ZQ et al. (1995) Caloric restriction decreases the rate of age-dependent accumulation of the glycoxidation products, N_-(carboxymethyl)lysine and pentosidine, in rat skin collagen. J Gerontol 50A: B337-B441

    Google Scholar 

  • Chellan P and Nagaraj RH (1999) Protein crosslinking by the Maillard reaction; dicarbonyl-derived imidazolium crosslinks in aging and diabetes. Arch Biochem Biophys 368: 98–104

    PubMed  Google Scholar 

  • Corman B, Duriez M, Poitevin P et al. (1998) Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy. Proc Natl Acad Sci USA 95: 1301–1306

    PubMed  Google Scholar 

  • Degenhardt TP, Alderson NL, Thorpe SR et al. (1998) Pyridoxamine, a post-Amadori inhibitor of advanced glycation reactions, preserves renal function in diabetic rats. J Am Soc Nephrol 9 (Suppl 1): 628a

  • Dyer DG, Blackledge JA, Thorpe SR et al. (1991) Formation of pentosidine during nonenzymatic browning of proteins by glucose: identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. J Biol Chem266: 11654–11660

    PubMed  Google Scholar 

  • Dyer DG, Dunn JA, Thorpe SR et al. (1993) Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest 91: 2463–2469

    PubMed  Google Scholar 

  • Fu MX, Wells-Knecht KJ, B lackledge JA et al. (1994) Glycation, glycoxidation and crosslinking of collagen by glucose: kinetics, mechanisms and inhibition of late stages of theMaillard reaction. Diabetes 43: 676–683

    PubMed  Google Scholar 

  • Fu M-X, Requena JR, Jenkins AJ et al. (1996) The advanced glycation end-product, N_-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem 271: 9982–9986

    PubMed  Google Scholar 

  • Fujii N, Momose Y, Ishii N et al. (1999) The mechanisms of simultaneous stereoinversion, racemization, and isomerization at specific aspartyl residues of aged lens proteins. Mech Ageing Dev 107: 347–358

    PubMed  Google Scholar 

  • Fujisawa H, Nishikawa T, Zhu B-H et al. (1999) Aminoguanidine supplementation delays the onset of senescence in vitro in dermal fibroblast-like cells from senescence-accelerated mice. J Gerontol 54A: B276-B282

    Google Scholar 

  • Golubev AG (1996) The other side of metabolism. Biokhimiia 61: 2018–2039

    PubMed  Google Scholar 

  • Harding JJ, Beswick HT, Ajiboye R et al. (1989) Non-enzymic posttranslational modification of proteins in aging: a review. Mech Ageing Dev 50: 7–16

    PubMed  Google Scholar 

  • Harman D (1992) Free radical theory of aging: history. EXS 62: 1–10

    PubMed  Google Scholar 

  • Hayase F, Nagaraj RH, Miyata S et al. (1989) Aging of proteins: immunological detection of a glucose-derived pyrrole formed during Maillard reaction in vivo. J Biol Chem 264: 3758–3764

    PubMed  Google Scholar 

  • Heinecke JW (1999) Mass spectrometric quantification of amino acid oxidation product in proteins: insights into pathways that promote LDL oxidation in the human artery wall. FASEB J 13: 1113–1120

    PubMed  Google Scholar 

  • Hoenders HJ and Bloemendal H (1983) Lens proteins and aging. J Gerontol 38: 278–286

    PubMed  Google Scholar 

  • Hood BD, Garner B and Truscott RJW (1999) Human lens coloration and aging: evidence for crystallin modification by the major ultraviolet filter, 3-hydroxy-kynurenine-O-_-D-glucoside. J Biol Chem 274: 32547–32550

    PubMed  Google Scholar 

  • Kato Y, Mori Y, Makino Y et al. (1999) Formation of N_-(hexanoyl)lysine in protein exposed to lipid hydroperoxide. A plausible marker for lipid hydroperoxide-derived protein modi-fication. J Biol Chem 274: 20406–20410

    PubMed  Google Scholar 

  • Lee C, Yim MB, Chock PB et al. (1998) Oxidation-reduction properties of methylglyoxal-modified protein in relation to free radical generation. J Biol Chem 273: 25272–25278

    PubMed  Google Scholar 

  • Lee AT, Reis D and Eriksson UJ (1999) Hyperglycemia-induced embryonic dysmorphogenesis correlates with genomic DNA mutation frequency in vitro and in vivo. Diabetes 48: 371–376

    PubMed  Google Scholar 

  • Leeuwenburgh C, Rasmussen JE, Hsu FF et al. (1997) Mass spectrometric quantification of markers for protein oxidation by tyrosyl radical, copper, and hydroxyl radical in low density lipoprotein isolated from human atherosclerotic plaques. J Biol Chem 272: 3520–3526

    PubMed  Google Scholar 

  • Leinonen J, Lehtimaki T, Toyokuni S et al. (1997) New biomarker evidence of oxidative DNA damage in patients with non-insulindependent diabetes mellitus. FEBS Lett 417: 150–152

    PubMed  Google Scholar 

  • Li ML, Steffes M, Donnelley T et al. (1996) Prevention of cardiovascular and renal pathology of aging by the advanced glycation inhibitor aminoguanidine. Proc Natl Acad Sci USA 93: 3902–3907

    PubMed  Google Scholar 

  • Lo TW, Westwood ME, McLellan AC et al. (1994) Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N_-acetylarginine, N_-aceylcysteine, and N_-acetyl-lysine, and bovine serum albumin. J Biol Chem 269: 32299–32305

    PubMed  Google Scholar 

  • Lovaas E and Carlin G (1991) Spermine: an anti-oxidant and antiinflammatory agent. Free Radic Biol Med 11: 455–461

    PubMed  Google Scholar 

  • Miyata T, Inagi R, Asahi K et al. (1998) Generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid an polyunsaturated fatty acids. FEBS Lett 437: 24–28

    PubMed  Google Scholar 

  • Nakamura K, Nakazawa Y and Ienaga K (1997) Acid-stable fluorescent advanced glycation end products: vesperlysines A, B, and C are formed as crosslinked products in the Maillard reaction between lysine or proteins with glucose. Biochem Biophys Res Commun 232: 227–230

    PubMed  Google Scholar 

  • Nilsson BO (1999) Biological effects of aminoguanidine: an update. Inflamm Res 48: 509–515

    PubMed  Google Scholar 

  • Niwa T, Katsuzaki T, Miyazaki S et al. (1997) Immunohistochemical detection of imidazolone, a novel advanced glycation end product, in kidneys and aortas of diabetic patients. J Clin Invest 99: 1272–1280

    PubMed  Google Scholar 

  • Obayashi H, Nakano K, Shigeta H et al. (1996) Formation of crossline as a fluorescent advanced glycation end product in vitro and in vivo. Biochem Biophys Res Commun 226: 37–41

    PubMed  Google Scholar 

  • Owen WF Jr, Hou FF, Stuart RO et al. (1998) Beta 2-microglobulin modified with advanced glycation end products modulates collagen synthesis by human fibroblasts. Kidney Int 53: 1365–1373

    PubMed  Google Scholar 

  • Oya T, Hattori N, Mizuno Y et al. (1999) Methylglyoxal modi-fication of protein: chemical and immunochemical characterization of methylglyoxal-arginine adducts. J Biol Chem 274: 18492–18502

    PubMed  Google Scholar 

  • Qian M, Liu M and Eaton JW(1998) Transition metals bind to glycated proteins forming redox active 'glycochelates': implications for the pathogenesis of certain diabetic complications. Biochem Biophys Res Commun 250: 385–389

    PubMed  Google Scholar 

  • Rattan SI, Derventzi A and Clark BF (1992) Protein synthesis, posttranslational modifications, and aging. Ann NY Acad Sci 663: 48–62

    PubMed  Google Scholar 

  • Reckelhoff JF, Hennington BS, Kanji V et al. (1999) Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats. Am J Hypertens 12: 492–498

    PubMed  Google Scholar 

  • Reiser KM (1994) Influence of age and long-term dietary restriction on enzymatically mediated crosslinks and nonenzymatic glycation of collagen in mice. J Gerontol 49: B71-B79

    PubMed  Google Scholar 

  • Requena JR, Fu M-X, Ahmed MU et al. (1997) Quantitation of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein. Biochem J 322: 317–325

    PubMed  Google Scholar 

  • Rodriguez-Garcia J, Requena JR and Rodriguez-Segade S (1998) Increased concentrations of serum pentosidine in rheumatoid arthritis. Clin Chem 44: 250–255

    PubMed  Google Scholar 

  • Rosenfeld ME, Palinski W, Yla-Herttuala S et al. (1990) Distribution of oxidation specific lipid-protein adducts and apolipoprotein B in atherosclerotic lesions of varying severity from WHHL rabbits. Arteriosclerosis 10: 336–349

    PubMed  Google Scholar 

  • Salomon RG, Subbanagounder G, O'Neil J et al. (1997) Levuglandin E2-protein adducts in human plasma and vasculature. Chem Res Toxicol 10: 536–545

    PubMed  Google Scholar 

  • Sano H, Nagai R, Matsumoto K et al. (1999) Receptors for proteins modified by advanced glycation endproducts (AGE)-their functional role in atherosclerosis. Mech Ageing Dev 15: 333–346

    Google Scholar 

  • Saxena AK, Saxena P, Wu X et al. (1999) Protein aging by carboxymethylation of lysines generates sites for divalent metal and redox active copper binding: relevance to diseases of glycoxidative stress. Biochem Biophys Res Commun 260: 332–338

    PubMed  Google Scholar 

  • Sayre LM, Sha W, Xu G et al. (1996) Immunochemical evidence supporting 2-pentylpyrrole formation on proteins exposed to 4-hydroxy-2-nonenal. Chem Res Toxicol 9: 1194–1201

    PubMed  Google Scholar 

  • Schmidt AM, Hori O, Cao R et al. (1996) RAGE: a novel cellular receptor for advanced glycation end products. Diabetes 45 (Suppl 3): S77-S80

    PubMed  Google Scholar 

  • Sell DR and Monnier VM (1989) Structure elucidation of a senescence cross-link from human extracellular matrix: implication of pentoses in the aging process. J Biol Chem 264: 21597–21602

    PubMed  Google Scholar 

  • Sell DR and Monnier VM (1997) Age-related association of tail tendon break time with tissue pentosidine in DBA/2 vs. C57BL/6 mice: the effect of dietary restriction. J Gerontol 52: B277–284

    Google Scholar 

  • Sell DR, Lane MA, Johnson WA et al. (1996) Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence. Proc Natl Acad Sci USA 93: 485–490

    PubMed  Google Scholar 

  • Sharov VS, Ferrington DA, Squier TC et al. (1999) Diastereoselective reduction of protein-bound methionine sulfoxide by methionine sulfoxide reductase. FEBS Lett 455: 247–250

    PubMed  Google Scholar 

  • Shipanova IN, GlombMA and Nagaraj RH (1997) Protein modification bymethylglyoxal: chemical nature and synthetic mechanism of a major fluorescent adduct. Arch Biochem Biophys 344: 29–36

    PubMed  Google Scholar 

  • Smith MA, Harris PL, Sayre LM et al. (1997) Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci USA 94: 9866–9888

    PubMed  Google Scholar 

  • Song X, Bao M, Li D et al. (1999) Advanced glycation in Dgalactose induced mouse aging model. Mech Ageing Dev 108: 239–251

    PubMed  Google Scholar 

  • Stadtman ER and Berlett BS (1998) Reactive oxygen-mediated protein oxidation in aging and disease. Drug Metab Rev 30: 225–243

    PubMed  Google Scholar 

  • Stevens A (1998) The contribution of glycation to cataract formation in diabetes. J Am Optom Assoc 69: 519–530

    PubMed  Google Scholar 

  • Sugiyama S, Miyata T, Inagi R et al. (1998) Implication of the glycoxidation and lipoxidation reactions in the pathogenesis of dialysis-related amyloidosis. Int J Mol Med 2: 561–565

    PubMed  Google Scholar 

  • Suzuki S, Hinokio Y, Komatu K et al. (1999) Oxidative damage to mitochondrial DNA and its relationship to diabetic complications. Diabetes Res Clin Pract 45: 161–168

    PubMed  Google Scholar 

  • Terman A and Brunk U (1998) Lipofuscin: mechanisms of formation and increase with age. APMIS 106: 265–276

    PubMed  Google Scholar 

  • Tessier F, Obrenovich M and Monnier VM (1999) Structure and mechanism of formation of human lens fluorophore LM-1. Relationship to vesperlysine A and the advanced Maillard reaction in aging, diabetes, and cataractogenesis. J Biol Chem 274: 20796–20804

    PubMed  Google Scholar 

  • Thorpe SR and Baynes JW (1996) Role of the Maillard reaction in diabetes mellitus and diseases of aging. Drugs & Aging 9: 69–77

    Google Scholar 

  • Tsai L, Szweda PA, Vinogradova O et al. (1998) Structural characterization and immunochemical detection of a fluorophore derived from 4-hydroxy-2-nonenal and lysine. Proc Natl Acad Sci USA 95: 7975–7980

    PubMed  Google Scholar 

  • Uchida K, Sakai K, Itakura K et al. (1997) Protein modification by lipid peroxidation products: formation of malondialdehydederived N_-(2-propenal)lysine in proteins. Arch Biochem Biophys 346: 45–52

    PubMed  Google Scholar 

  • Uchida K, Kanematsu M, Sakai K et al. (1998) Protein-bound acrolein: potential markers for oxidative stress. Proc Natl Acad Sci USA 95: 4882–4887

    PubMed  Google Scholar 

  • Weindruch R and Walford RL (1988) The Retardation of Aging and Disease by Dietary Restriction. Charles C Thomas, Springfield, Illinois

    Google Scholar 

  • Wells-Knecht MC, Lyons TJ, McCance DR et al. (1997) Agedependent accumulation of ortho-tyrosine and methionine sulfoxide in human skin collagen is not increased in diabetes: evidence against a generalized increase in oxidative stress in diabetes. J Clin Invest 100: 839–846

    PubMed  Google Scholar 

  • Wright HT (1991) Nonenzymatic deamidation of asparaginyl and glutaminyl residues in proteins. Crit Rev Biochem Mol Biol 26: 1–52

    PubMed  Google Scholar 

  • Yan LJ and Sohal RS (1998) Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci USA 95: 12896–12901

    PubMed  Google Scholar 

  • Yan LJ, Levine RL and Sohal RS (1997) Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci USA 94: 11168–11172

    PubMed  Google Scholar 

  • Yim HS, Kang SO, Hah YC et al. (1995) Free radicals generated during the glycation reaction of amino acids by methylglyoxal. A model study of protein-cross-linked free radicals. J Biol Chem 270: 28228–28233

    PubMed  Google Scholar 

  • Yin D (1996) Biochemical basis of lipofuscin, ceroid and age pigment-like fluorophores. Free Radic Biol Med 21: 871–888

    PubMed  Google Scholar 

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Baynes, J.W. From life to death – the struggle between chemistryand biology during aging: the Maillard reaction as an amplifier of genomic damage. Biogerontology 1, 235–246 (2000). https://doi.org/10.1023/A:1010034213093

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