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Profiling the Aging Cardiovascular System: Transcriptional, Proteomic, SNPs, Gene Mapping and Epigenetics Analysis

  • José Marín-García
  • Michael J. Goldenthal
  • Gordon W. Moe

Keywords

Fatty Acid Oxidation Replicative Senescence Microsomal Triglyceride Transfer Protein Physiol Heart Circ Aging Phenotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Lee CK, Allison DB, Brand J, Weindruch R, Prolla TA. Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci USA 2002;99:14988–14993PubMedGoogle Scholar
  2. 2.
    Bronikowski AM, Carter PA, Morgan TJ, Garland T Jr, Ung N, Pugh TD, Weindruch R, Prolla TA. Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart. Physiol Genomics 2003;12:129–138Google Scholar
  3. 3.
    Fu C, Hickey M, Morrison M, McCarter R, Han ES. Tissue specific and non-specific changes in gene expression by aging and by early stage CR. Mech Ageing Dev 2006;127:905–916PubMedGoogle Scholar
  4. 4.
    Iemitsu M, Miyauchi T, Maeda S, Tanabe T, Takanashi M, Irukayama-Tomobe Y, Sakai S, Ohmori H, Matsuda M, Yamaguchi I. Aging-induced decrease in the PPAR-alpha level in hearts is improved by exercise training. Am J Physiol Heart Circ Physiol 2002;283:H1750–H760PubMedGoogle Scholar
  5. 5.
    LeMoine CM, McClelland GB, Lyons CN, Mathieu-Costello O, Moyes CD. Control of mitochondrial gene expression in the aging rat myocardium. Biochem Cell Biol 2006;84:191–198PubMedGoogle Scholar
  6. 6.
    Bodyak N, Kang PM, Hiromura M, Sulijoadikusumo I, Horikoshi N, Khrapko K, Usheva A. Gene expression profiling of the aging mouse cardiac myocytes. Nucleic Acids Res 2002;30:3788–3794PubMedGoogle Scholar
  7. 7.
    Goyns MH, Charlton MA, Dunford JE, Lavery WL, Merry BJ, Salehi M, Simoes DC. Differential display analysis of gene expression indicates that age-related changes are restricted to a small cohort of genes. Mech Ageing Dev 1998;101:73–90PubMedGoogle Scholar
  8. 8.
    Shida M, Isoyama S. Effects of age on c-fos and c-myc gene expression in response to hemodynamic stress in isolated, perfused rat hearts. J Mol Cell Cardiol 1993;25:1025–1035PubMedGoogle Scholar
  9. 9.
    Gadaleta MN, Petruzzella V, Renis M, Fracasso F, Cantatore P. Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. Eur J Biochem 1990;187:501–506Google Scholar
  10. 10.
    Andreu AL, Arbos MA, Perez-Martos A, Lopez-Perez MJ, Asin J, Lopez N, Montoya J, Schwartz S. Reduced mitochondrial DNA transcription in senescent rat heart. Biochem Biophys Res Commun 1998;252:577–581PubMedGoogle Scholar
  11. 11.
    Hudson EK, Tsuchiya N, Hansford RG. Age-associated changes in mitochondrial mRNA expression and translation in the Wistar rat heart. Mech Ageing Dev 1998;103:179–193PubMedGoogle Scholar
  12. 12.
    Barazzoni R, Short KR, Nair KS. Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart. J Biol Chem 2000;275:3343–3347PubMedGoogle Scholar
  13. 13.
    Dinardo MM, Musicco C, Fracasso F, Milella F, Gadaleta MN, Gadaleta G, Cantatore P. Acetylation and level of mitochondrial transcription factor A in several organs of young and old rats. Biochem Biophys Res Commun 2003;301:187–191PubMedGoogle Scholar
  14. 14.
    Masuyama M, Iida R, Takatsuka H, Yasuda T, Matsuki T. Quantitative change in mitochondrial DNA content in various mouse tissues during aging. Biochim Biophys Acta 2005;1723:302–308PubMedGoogle Scholar
  15. 15.
    Lezza AM, Pesce V, Cormio A, Fracasso F, Vecchiet J, Felzani G, Cantatore P, Gadaleta MN. Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects. FEBS Lett 2001;501:74–78PubMedGoogle Scholar
  16. 16.
    Kumazaki T, Sakano T, Yoshida T, Hamada K, Sumida H, Teranishi Y, Nishiyama M, Mitsui Y. Enhanced expression of mitochondrial genes in senescent endothelial cells and fibroblasts. Mech Ageing Dev 1998;101:91–99PubMedGoogle Scholar
  17. 17.
    Volkova M, Garg R, Dick S, Boheler KR. Aging-associated changes in cardiac gene expression. Cardiovasc Res 2005;66:194–204PubMedGoogle Scholar
  18. 18.
    Young ME, Razeghi P, Cedars AM, Guthrie PH, Taegtmeyer H. Intrinsic diurnal variations in cardiac metabolism and contractile function. Circ Res 2001;89:1199–1208PubMedGoogle Scholar
  19. 19.
    Young ME. Circadian rhythms in cardiac gene expression. Curr Hypertens Rep 2003;5:445–453PubMedGoogle Scholar
  20. 20.
    Durgan DJ, Trexler NA, Egbejimi O, McElfresh TA, Suk HY, Petterson LE, Shaw CA, Hardin PE, Bray MS, Chandler MP, Chow CW, Young ME. The circadian clock within the cardiomyocyte is essential for responsiveness of the heart to fatty acids. J Biol Chem 2006;281:24254–24269PubMedGoogle Scholar
  21. 21.
    Young ME. The circadian clock within the heart: potential influence on myocardial gene expression, metabolism, and function. Am J Physiol Heart Circ Physiol 2006;290:H1–H16PubMedGoogle Scholar
  22. 22.
    Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ. Extensive and divergent circadian gene expression in liver and heart. Nature 2002;417:78–83PubMedGoogle Scholar
  23. 23.
    Duffy PH, Feuers RJ. Biomarkers of aging: changes in circadian rhythms related to the modulation of metabolic output. Biomed Environ Sci 1991;4:182–191PubMedGoogle Scholar
  24. 24.
    Claustrat F, Fournier I, Geelen G, Brun J, Corman B, Claustrat B. Aging and circadian clock gene expression in peripheral tissues in rats. Pathol Biol (Paris) 2005;53:257–260Google Scholar
  25. 25.
    Kunieda T, Minamino T, Katsuno T, Tateno K, Nishi J, Miyauchi H, Orimo M, Okada S, Komuro I. Cellular senescence impairs circadian expression of clock genes in vitro and in vivo. Circ Res 2006;98:532–539PubMedGoogle Scholar
  26. 26.
    Edwards MG, Sarkar D, Klopp R, Morrow JD, Weindruch R, Prolla TA. Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart. Physiol Genomics 2003;13:119–127PubMedGoogle Scholar
  27. 27.
    Takahashi T, Schunkert H, Isoyama S, Wei JY, Nadal-Ginard B, Grossman W, Izumo S. Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium. J Clin Invest 1992;89:939–946PubMedGoogle Scholar
  28. 28.
    Ashton KJ, Willems L, Holmgren K, Ferreira L, Headrick JP. Age-associated shifts in cardiac gene transcription and transcriptional responses to ischemic stress. Exp Gerontol 2006;41:189–204PubMedGoogle Scholar
  29. 29.
    Park SK, Prolla TA. Gene expression profiling studies of aging in cardiac and skeletal muscles. Cardiovasc Res 2005;66:205–212PubMedGoogle Scholar
  30. 30.
    Dhahbi JM, Tsuchiya T, Kim HJ, Mote PL, Spindler SR. Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction. J Gerontol A Biol Sci Med Sci 2006;61:218–231PubMedGoogle Scholar
  31. 31.
    Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science 1999:285:1390–1393Google Scholar
  32. 32.
    Kayo T, Allison DB, Weindruch R, Prolla TA. Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc Natl Acad Sci USA 2001;98:5093–5098PubMedGoogle Scholar
  33. 33.
    Hwang JJ, Allen PD, Tseng GC, Lam CW, Fananapazir L, Dzau VJ, Liew CC. Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol Genomics 2002;10:31–44PubMedGoogle Scholar
  34. 34.
    Stanton LW, Garrard LJ, Damm D, Garrick BL, Lam A, Kapoun AM, Zheng Q, Protter AA, Schreiner GF, White RT. Altered patterns of gene expression in response to myocardial infarction. Circ Res 2000:86:939–945Google Scholar
  35. 35.
    Archacki SR, Angheloiu G, Tian XL, Tan FL, DiPaola N, Shen GQ, Moravec C, Ellis S, Topol EJ, Wang Q. Identification of new genes differentially expressed in coronary artery disease by expression profiling. Physiol Genomics 2003;15:65–74PubMedGoogle Scholar
  36. 36.
    Kim YH, Lim do S, Lee JH, Shim WJ, Ro YM, Park GH, Becker KG, Cho-Chung YS, Kim MK. Gene expression profiling of oxidative stress on atrial fibrillation in humans. Exp Mol Med 2003;35:336–349PubMedGoogle Scholar
  37. 37.
    Ueno S, Ohki R, Hashimoto T, Takizawa T, Takeuchi K, Yamashita Y, Ota J, Choi YL, Wada T, Koinuma K, Yamamoto K, Ikeda U, Shimada K, Mano H. DNA microarray analysis of in vivo progression mechanism of heart failure. Biochem Biophys Res Commun 2003;307:771–777PubMedGoogle Scholar
  38. 38.
    Boheler KR, Volkova M, Morrell C, Garg R, Zhu Y, Margulies K, Seymour AM, Lakatta EG. Sex- and age-dependent human transcriptome variability: implications for chronic heart failure. Proc Natl Acad Sci USA 2003;100:2754–2759PubMedGoogle Scholar
  39. 39.
    Csiszar A, Ungvari Z, Koller A, Edwards JG, Kaley G. Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging. Physiol Genomics 2004;17:21–30PubMedGoogle Scholar
  40. 40.
    Csiszar A, Ungvari Z, Koller A, Edwards JG, Kaley G. Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. FASEB J 2003;17:1183–1185PubMedGoogle Scholar
  41. 41.
    Vazquez-Padron RI, Lasko D, Li S, Louis L, Pestana IA, Pang M, Liotta C, Fornoni A, Aitouche A, Pham SM. Aging exacerbates neointimal formation, and increases proliferation and reduces susceptibility to apoptosis of vascular smooth muscle cells in mice. J Vasc Surg 2004;40:1199–1207PubMedGoogle Scholar
  42. 42.
    Kiri AN, Tran HC, Drahos KL, Lan W, McRorie DK, Horn MJ. Proteomic changes in bovine heart mitochondria with age: using a novel technique for organelle separation and enrichment. J Biomol Tech 2005;16:371–379PubMedGoogle Scholar
  43. 43.
    Drahos KL, Tran HC, Kiri AN, Lan W, McRorie DK, Horn MJ. Comparison of Golgi apparatus and endoplasmic reticulum proteins from livers of juvenile and aged rats using a novel technique for separation and enrichment of organelles. J Biomol Tech 2005;16:347–355PubMedGoogle Scholar
  44. 44.
    Devreese B, Vanrobaeys F, Smet J, Van Beeumen J, Van Coster R. Mass spectrometric identification of mitochondrial oxidative phosphorylation subunits separated by two-dimensional blue-native polyacrylamide gel electrophoresis. Electrophoresis 2002;23:2525–2533PubMedGoogle Scholar
  45. 45.
    Reifschneider NH, Goto S, Nakamoto H, Takahashi R, Sugawa M, Dencher NA, Krause F. Defining the mitochondrial proteomes from five rat organs in a physiologically significant context using 2D blue-native/SDS-PAGE. J Proteome Res 2006;5:1117–1132PubMedGoogle Scholar
  46. 46.
    Dencher NA, Goto S, Reifschneider NH, Sugawa M, Krause F. Unraveling age-dependent variation of the mitochondrial proteome. Ann N Y Acad Sci 2006;1067:116–119PubMedGoogle Scholar
  47. 47.
    Kanski J, Behring A, Pelling J, Schoneich C. Proteomic identification of 3-nitrotyrosine-containing rat cardiac proteins: effects of biological aging. Am J Physiol Heart Circ Physiol 2005;288:H371–H381PubMedGoogle Scholar
  48. 48.
    Aulak KS, Koeck T, Crabb JW, Stuehr DJ. Dynamics of protein nitration in cells and mitochondria. Am J Physiol Heart Circ Physiol 2004;286:H30–H38PubMedGoogle Scholar
  49. 49.
    Elfering SI, Haynes VL, Traaseth NJ, Ettl A, Giulivi C. Aspects, mechanism, and biological relevance of mitochondrial protein nitration sustained by mitochondrial nitric oxide synthase. Am J Physiol Heart Circ Physiol 2004;286:H22–H29PubMedGoogle Scholar
  50. 50.
    Turko IV, Li L, Aulak KS, Stuehr DJ, Chang JY, Murad F. Protein tyrosine nitration in the mitochondria from diabetic mouse heart. Implications to dysfunctional mitochondria in diabetes. J Biol Chem 2003;278:33973–3977Google Scholar
  51. 51.
    Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H. Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 1994;74:121–133PubMedGoogle Scholar
  52. 52.
    Bejma J, Ramires P, Ji LL. Free radical generation and oxidative stress with ageing and exercise: differential effects in the myocardium and liver. Acta Physiol Scand 2000;169:343–351PubMedGoogle Scholar
  53. 53.
    Davies SM, Poljak A, Duncan MW, Smythe GA, Murphy MP. Measurements of protein carbonyls, ortho- and meta-tyrosine and oxidative phosphorylation complex activity in mitochondria from young and old rats. Free Radic Biol Med 2001;31:181–190PubMedGoogle Scholar
  54. 54.
    Cocco T, Sgobbo P, Clemente M, Lopriore B, Grattagliano I, Di Paola M, Villani G. Tissue-specific changes of mitochondrial functions in aged rats: effect of a long-term dietary treatment with N-acetylcysteine. Free Radic Biol Med 2005;38:796–805PubMedGoogle Scholar
  55. 55.
    Colotti C, Cavallini G, Vitale RL, Donati A, Maltinti M, Del Ry S, Bergamini E, Giannessi D. Effects of aging and anti-aging caloric restrictions on carbonyl and heat shock protein levels and expression. Biogerontology 2005;6:397–406PubMedGoogle Scholar
  56. 56.
    Forster MJ, Sohal BH, Sohal RS. Reversible effects of long-term caloric restriction on protein oxidative damage. J Gerontol A Biol Sci Med Sci 2000;55:B522–B529PubMedGoogle Scholar
  57. 57.
    Judge S, Judge A, Grune T, Leeuwenburgh C. Short-term CR decreases cardiac mitochondrial oxidant production but increases carbonyl content. Am J Physiol Regul Integr Comp Physiol 2004;286:R254–R259PubMedGoogle Scholar
  58. 58.
    Opii WO, Joshi G, Head E, Milgram NW, Muggenburg BA, Klein JB, Pierce WM, Cotman CW, Butterfield DA. Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer’s disease. Neurobiol Aging 2006 Oct 19Google Scholar
  59. 59.
    Nabeshi H, Oikawa S, Inoue S, Nishino K, Kawanishi S. Proteomic analysis for protein carbonyl as an indicator of oxidative damage in senescence-accelerated mice. Free Radic Res 2006;40:1173–1181PubMedGoogle Scholar
  60. 60.
    Chaudhuri AR, de Waal EM, Pierce A, Van Remmen H, Ward WF, Richardson A. Detection of protein carbonyls in aging liver tissue: a fluorescence-based proteomic approach. Mech Ageing Dev 2006;127:849–861PubMedGoogle Scholar
  61. 61.
    Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med 1995:46; 223–234PubMedGoogle Scholar
  62. 62.
    Reiser KM. Influence of age and long-term dietary restriction on enzymatically mediated crosslinks and nonenzymatic glycation of collagen in mice. J Gerontol 1994;49:B71–B79PubMedGoogle Scholar
  63. 63.
    Norton GR, Candy G, Woodiwiss AJ. Aminoguanidine prevents the decreased myocardial compliance produced by streptozotocin-induced diabetes mellitus in rats. Circulation 1996;93:1905–1912PubMedGoogle Scholar
  64. 64.
    Li SY, Du M, Dolence EK, Fang CX, Mayer GE, Ceylan-Isik AF, LaCour KH, Yang X, Wilbert CJ, Sreejayan N, Ren J. Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification. Aging Cell 2005;4:57–64PubMedGoogle Scholar
  65. 65.
    Brett J, Schmidt AM, Yan SD, Zou YS, Weidman E, Pinsky D, Nowygrod R, Neeper M, Przysiecki C, Shaw A, Migheli A, Stern D. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 1993;143:1699–1712PubMedGoogle Scholar
  66. 66.
    Bucciarelli LG, Kaneko M, Ananthakrishnan R, Harja E, Lee LK, Hwang YC, Lerner S, Bakr S, Li Q, Lu Y, Song F, Qu W, Gomez T, Zou YS, Yan SF, Schmidt AM, Ramasamy R. Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury. Circulation 2006;113:1226–1234PubMedGoogle Scholar
  67. 67.
    Simm A, Casselmann C, Schubert A, Hofmann S, Reimann A, Silber RE. Age associated changes of AGE-receptor expression: RAGE upregulation is associated with human heart dysfunction. Exp Gerontol 2004;39:407–413PubMedGoogle Scholar
  68. 68.
    Clark WA, Rudnick SJ, Simpson DG, LaPres JJ, Decker RS. Cultured adult cardiac myocytes maintain protein synthetic capacity of intact adult hearts. Am J Physiol 1993;264:H573–H582PubMedGoogle Scholar
  69. 69.
    Nag AC, Cheng M. Biochemical evidence for cellular dedifferentiation in adult rat cardiac muscle cells in culture: expression of myosin isozymes. Biochem Biophys Res Commun 1986;137:855–862PubMedGoogle Scholar
  70. 70.
    Bugaisky LB, Zak R. Differentiation of adult rat cardiac myocytes in cell culture. Circ Res 1989;64:493–500PubMedGoogle Scholar
  71. 71.
    He Q, Cahill CJ, Spiro MJ. Suspension culture of differentiated rat heart myocytes on non-adhesive surfaces. J Mol Cell Cardiol 1996;28:1177–1186PubMedGoogle Scholar
  72. 72.
    Bird SD, Doevendans PA, van Rooijen MA, Brutel de la Riviere A, Hassink RJ, Passier R, Mummery CL. The human adult cardiomyocyte phenotype. Cardiovasc Res 2003;58:423–434Google Scholar
  73. 73.
    Kamino H, Hiratsuka M, Toda T, Nishigaki R, Osaki M, Ito H, Inoue T, Oshimura M. Searching for genes involved in arteriosclerosis: proteomic analysis of cultured human umbilical vein endothelial cells undergoing replicative senescence. Cell Struct Funct 2003;28:495–503PubMedGoogle Scholar
  74. 74.
    Eman MR, Regan-Klapisz E, Pinkse MW, Koop IM, Haverkamp J, Heck AJ, Verkleij AJ, Post JA. Protein expression dynamics during replicative senescence of endothelial cells studied by 2-D difference in-gel electrophoresis. Electrophoresis 2006;27:1669–1682PubMedGoogle Scholar
  75. 75.
    Hampel B, Fortschegger K, Ressler S, Chang MW, Unterluggauer H, Breitwieser A, Sommergruber W, Fitzky B, Lepperdinger G, Jansen-Durr P, Voglauer R, Grillari J. Increased expression of extracellular proteins as a hallmark of human endothelial cell in vitro senescence. Exp Gerontol 2006;41:474–481PubMedGoogle Scholar
  76. 76.
    Chang MW, Grillari J, Mayrhofer C, Fortschegger K, Allmaier G, Marzban G, Katinger H, Voglauer R. Comparison of early passage, senescent and hTERT immortalized endothelial cells. Exp Cell Res 2005;309:121–136PubMedGoogle Scholar
  77. 77.
    Lee JH, Chung KY, Bang D, Lee KH. Searching for aging-related proteins in human dermal microvascular endothelial cells treated with anti-aging agents. Proteomics 2006;6:1351–1361PubMedGoogle Scholar
  78. 78.
    Cremona O, Muda M, Appel RD, Frutiger S, Hughes GJ, Hochstrasser DF, Geinoz A, Gabbiani G. Differential protein expression in aortic smooth muscle cells cultured from newborn and aged rats. Exp Cell Res 1995;217:280–287PubMedGoogle Scholar
  79. 79.
    Perls T, Shea-Drinkwater M, Bowen-Flynn J, Ridge SB, Kang S, Joyce E, Daly M, Brewster SJ, Kunkel L, Puca AA. Exceptional familial clustering for extreme longevity in humans. J Am Geriatr Soc 2000;48:1483–1485PubMedGoogle Scholar
  80. 80.
    Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel JW. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum Genet 1996;97:319–323PubMedGoogle Scholar
  81. 81.
    Christensen K, Johnson TE, Vaupel JW. The quest for genetic determinants of human longevity: challenges and insights. Nat Rev Genet 2006;7:436–448PubMedGoogle Scholar
  82. 82.
    Reed T, Dick DM, Uniacke SK, Foroud T, Nichols WC. Genome-wide scan for a healthy aging phenotype provides support for a locus near D4S1564 promoting healthy aging. J Gerontol A Biol Sci Med Sci 2004;59:227–232PubMedGoogle Scholar
  83. 83.
    Puca AA, Daly MJ, Brewster SJ, Matise TC, Barrett J, Shea-Drinkwater M, Kang S, Joyce E, Nicoli J, Benson E, Kunkel LM, Perls T. A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proc Natl Acad Sci USA 2001;98:10505–10508PubMedGoogle Scholar
  84. 84.
    Geesaman BJ, Benson E, Brewster SJ, Kunkel LM, Blanche H, Thomas G, Perls TT, Daly MJ, Puca AA. Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan. Proc Natl Acad Sci USA 2003;100:14115–14120PubMedGoogle Scholar
  85. 85.
    Juo SH, Han Z, Smith JD, Colangelo L, Liu K. Common polymorphism in promoter of microsomal triglyceride transfer protein gene influences cholesterol, ApoB, and triglyceride levels in young african american men: results from the coronary artery risk development in young adults (CARDIA) study. Arterioscler Thromb Vasc Biol 2000;20:1316–1322PubMedGoogle Scholar
  86. 86.
    Nebel A, Croucher PJ, Stiegeler R, Nikolaus S, Krawczak M, Schreiber S. No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans. Proc Natl Acad Sci USA 2005;102:7906–7909PubMedGoogle Scholar
  87. 87.
    Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 1994;6:29–32PubMedGoogle Scholar
  88. 88.
    Blanche H, Cabanne L, Sahbatou M, Thomas G. A study of French centenarians: are ACE and APOE associated with longevity? C R Acad Sci III 2001;324:129–135PubMedGoogle Scholar
  89. 89.
    Rea IM, Mc Dowell I, McMaster D, Smye M, Stout R, Evans A. MONICA group (Belfast). Monitoring of Cardiovascular trends study group. Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST). Mech Ageing Dev 2001;122:1367–1372PubMedGoogle Scholar
  90. 90.
    Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 2003;290:2030–2040PubMedGoogle Scholar
  91. 91.
    Stessman J, Maaravi Y, Hammerman-Rozenberg R, Cohen A, Nemanov L, Gritsenko I, Gruberman N, Ebstein RP. Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study. Mech Ageing Dev 2005;126:333–339PubMedGoogle Scholar
  92. 92.
    Todesco L, Angst C, Litynski P, Loehrer F, Fowler B, Haefeli WE. Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age. Eur J Clin Invest 1999;29:1003–1009PubMedGoogle Scholar
  93. 93.
    Kohara K, Fujisawa M, Ando F, Tabara Y, Niino N, Miki T, Shimokata H. NILS-LSA Study. MTHFR gene polymorphism as a risk factor for silent brain infarcts and white matter lesions in the Japanese general population: the NILS-LSA Study. Stroke 2003;34:1130–1135Google Scholar
  94. 94.
    Atzmon G, Rincon M, Schechter CB, Shuldiner AR, Lipton RB, Bergman A, Barzilai N. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 2006;4:e113PubMedGoogle Scholar
  95. 95.
    Luft FC. Bad genes, good people, association, linkage, longevity and the prevention of cardiovascular disease. Clin Exp Pharmacol Physiol 1999;26:576–579PubMedGoogle Scholar
  96. 96.
    Frederiksen H, Gaist D, Bathum L, Andersen K, McGue M, Vaupel JW, Christensen K. Angiotensin I-converting enzyme (ACE) gene polymorphism in relation to physical performance, cognition and survival-a follow-up study of elderly Danish twins. Ann Epidemiol 2003;13:57–65PubMedGoogle Scholar
  97. 97.
    Bladbjerg EM, Andersen-Ranberg K, de Maat MP, Kristensen SR, Jeune B, Gram J, Jespersen J. Longevity is independent of common variations in genes associated with cardiovascular risk. Thromb Haemost 1999;82:1100–1105PubMedGoogle Scholar
  98. 98.
    Hamdi HK, Castellon R. A genetic variant of ACE increases cell survival: a new paradigm for biology and disease. Biochem Biophys Res Commun 2004;318:187–191PubMedGoogle Scholar
  99. 99.
    Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci USA 2002;99:856–861PubMedGoogle Scholar
  100. 100.
    Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC. Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circ Res 2005;96:412–418PubMedGoogle Scholar
  101. 101.
    Mooijaart SP, van Heemst D, Schreuder J, van Gerwen S, Beekman M, Brandt BW, Eline Slagboom P, Westendorp RG. ‘Long Life’ Study Group. Variation in the SHC1 gene and longevity in humans. Exp Gerontol 2004;39:263–268PubMedGoogle Scholar
  102. 102.
    Post WS, Goldschmidt-Clermont PJ, Wilhide CC, Heldman AW, Sussman MS, Ouyang P, Milliken EE, Issa JP. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovasc Res 1999;43:985–991PubMedGoogle Scholar
  103. 103.
    Kim J, Kim JY, Song KS, Lee YH, Seo JS, Jelinek J, Goldschmidt-Clermont PJ, Issa JP. Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. Biochim Biophys Acta 2007;1772:72–80PubMedGoogle Scholar
  104. 104.
    Lopatina N, Haskell JF, Andrews LG, Poole JC, Saldanha S, Tollefsbol T. Differential maintenance and de novo methylating activity by three DNA methyltransferases in aging and immortalized fibroblasts. J Cell Biochem 2002;84:324–334PubMedGoogle Scholar
  105. 105.
    Lopatina N, Haskell JF, Andrews LG, Poole JC, Saldanha S, Tollefsbol T. Differential maintenance and de novo methylating activity by three DNA methyltransferases in aging and immortalized fibroblasts. J Cell Biochem 2002;84:324–334PubMedGoogle Scholar
  106. 106.
    Trapp J, Jung M. The role of NAD+ dependent histone deacetylases (sirtuins) in ageing. Curr Drug Targets 2006;7:1553–1560PubMedGoogle Scholar
  107. 107.
    Longo VD, Kennedy BK. Sirtuins in aging and age-related disease. Cell 2006;126:257–268PubMedGoogle Scholar
  108. 108.
    Rose G, Dato S, Altomare K, Bellizzi D, Garasto S, Greco V, Passarino G, Feraco E, Mari V, Barbi C, BonaFe M, Franceschi C, Tan Q, Boiko S, Yashin AI, De Benedictis G. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp Gerontol 2003;38:1065–1070PubMedGoogle Scholar
  109. 109.
    Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics 2005;85:258–263PubMedGoogle Scholar
  110. 110.
    Haigis MC, Guarente LP. Mammalian sirtuins – emerging roles in physiology, aging, and calorie restriction. Genes Dev 2006;20:2913–2921PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • José Marín-García
    • 1
  • Michael J. Goldenthal
    • 2
  • Gordon W. Moe
    • 3
  1. 1.The Molecular Cardiology and Neuromuscular InstituteHighland Park
  2. 2.The Molecular Cardiology and Neuromuscular InstituteHighland Park
  3. 3.University of TorontoTorontoCanada

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