Advertisement

Oxidative Stress in Vascular Aging

  • Anna Csiszar
  • Zoltan Ungvari
Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

The free radical theory of aging postulates that macromolecular damage due to the increased production of reactive oxygen species (ROS) drives the aging process. While many of the original assumptions of the theory are currently debated, there is convincing evidence for the crucial role of ROS in the development of many age-associated diseases. Advancing age is one of the most significant risk factors for the development of atherosclerosis in the Western world. The theme that emerges from this overview is that aging is associated with both NAD(P)H oxidase- and mitochondria-derived ROS overproduction, which promotes inflammatory phenotypic alterations in the vascular wall, facilitating the development of atherosclerosis. We also discuss some of the possible therapeutic strategies by which age-related vascular oxidative stress and inflammation can be delayed or reversed, improving cardiovascular health in the elderly.

Keywords

Aging Oxidative stress Free radical Senescence Cardiovascular disease 

Notes

Acknowledgments

This work was supported by grants from the American Diabetes Association (to ZU), the American Federation for Aging Research (to AC) and the NIH (HL077256 and HL43023 to ZU and AC).

References

  1. 1.
    Lakatta EG (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part III: cellular and molecular clues to heart and arterial aging. Circulation 107:490–497PubMedGoogle Scholar
  2. 2.
    Lakatta EG, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease. Circulation 107:346–354PubMedGoogle Scholar
  3. 3.
    Lakatta EG, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a “set up” for vascular disease. Circulation 107:139–146PubMedGoogle Scholar
  4. 4.
    Harman D, Aging: A (1956) Theory based on free radical and radiation chemistry. J Gerontol 11:298–300PubMedGoogle Scholar
  5. 5.
    Van Remmen H, Richardson A (2001) Oxidative damage to mitochondria and aging. Exp Gerontol 36:957–968PubMedGoogle Scholar
  6. 6.
    Van Remmen H, Hamilton ML, Richardson A (2003) Oxidative damage to DNA and aging. Exerc Sport Sci Rev 31:149–153PubMedGoogle Scholar
  7. 7.
    Hamilton ML, Van Remmen H, Drake JA et al (2001) Does oxidative damage to DNA increase with age? Proc Natl Acad Sci USA 98:10469–10474PubMedGoogle Scholar
  8. 8.
    Csiszar A, Ungvari Z, Edwards JG et al (2002) Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res 90:1159–1166PubMedGoogle Scholar
  9. 9.
    Csiszar A, Pacher P, Kaley G et al (2005) Role of oxidative and nitrosative stress, longevity genes and poly(ADP-ribose) polymerase in cardiovascular dysfunction associated with aging. Curr Vasc Pharmacol 3:285–291PubMedGoogle Scholar
  10. 10.
    Hamilton CA, Brosnan MJ, McIntyre M et al (2001) Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension 37:529–534PubMedGoogle Scholar
  11. 11.
    Sun D, Huang A, Yan EH et al (2004) Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats. Am J Physiol Heart Circ Physiol 286:H2249–H2256PubMedGoogle Scholar
  12. 12.
    van der Loo B, Labugger R, Skepper JN et al (2000) Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med 192:1731–1744PubMedGoogle Scholar
  13. 13.
    Francia P, delli Gatti C, Bachschmid M et al (2004) Deletion of p66shc gene protects against age-related endothelial dysfunction. Circulation 110:2889–2895PubMedGoogle Scholar
  14. 14.
    Ungvari Z, Buffenstein R, Austad SN et al (2008) Oxidative stress in vascular senescence: lessons from successfully aging species. Front Biosci 13:5056–5070PubMedGoogle Scholar
  15. 15.
    Ungvari Z, Krasnikov BF, Csiszar A et al (2008) Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways and DNA repair efficiency. Age 30:121–133PubMedGoogle Scholar
  16. 16.
    Labinskyy N, Csiszar A, Orosz Z et al (2006) Comparison of endothelial function, O2 • – and H2O2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice. Am J Physiol 291:H2698–H2704Google Scholar
  17. 17.
    Csiszar A, Labinskyy N, Orosz Z et al (2007) Vascular aging in the longest-living rodent, the naked mole rat. Am J Physiol 293:H919–H927Google Scholar
  18. 18.
    Sampayo JN, Olsen A, Lithgow GJ (2003) Oxidative stress in Caenorhabditis elegans: protective effects of superoxide dismutase/catalase mimetics. Aging Cell 2:319–326PubMedGoogle Scholar
  19. 19.
    Sentman ML, Granstrom M, Jakobson H et al (2006) Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase. J Biol Chem 281:6904–6909PubMedGoogle Scholar
  20. 20.
    Mansouri A, Muller FL, Liu Y et al (2006) Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging. Mech Ageing Dev 127:298–306PubMedGoogle Scholar
  21. 21.
    Van Remmen H, Ikeno Y, Hamilton M et al (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16:29–37PubMedGoogle Scholar
  22. 22.
    Schriner SE, Linford NJ, Martin GM et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911PubMedGoogle Scholar
  23. 23.
    Mele J, Van Remmen H, Vijg J et al (2006) Characterization of transgenic mice that overexpress both copper zinc superoxide dismutase and catalase. Antioxid Redox Signal 8:628–638PubMedGoogle Scholar
  24. 24.
    Huang TT, Carlson EJ, Gillespie AM et al (2000) Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. J Gerontol 55:B5–B9Google Scholar
  25. 25.
    Ungvari Z, Csiszar A, Kaley G (2004) Vascular inflammation in aging. Herz 29:733–740PubMedGoogle Scholar
  26. 26.
    Labinskyy N, Csiszar A, Veress G et al (2006) Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Curr Med Chem 13:989–996PubMedGoogle Scholar
  27. 27.
    Donato AJ, Eskurza I, Silver AE et al (2007) Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circ Res 100:1659–1666PubMedGoogle Scholar
  28. 28.
    Eskurza I, Kahn ZD, Seals DR (2006) Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing. J Physiol (Lond) 571:661–668Google Scholar
  29. 29.
    Eskurza I, Monahan KD, Robinson JA et al (2004) Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol (Lond) 556:315–324Google Scholar
  30. 30.
    Jablonski KL, Seals DR, Eskurza I et al (2007) High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men. J Appl Physiol 103:1715–1721PubMedGoogle Scholar
  31. 31.
    Gates PE, Boucher ML, Silver AE et al (2006) Impaired flow-mediated dilation with age is not explained by L-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression. J Appl Physiol 291:H985–H1002Google Scholar
  32. 32.
    Adler A, Messina E, Sherman B et al (2003) NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats. Am J Physiol Heart Circ Physiol 285:H1015–H1022PubMedGoogle Scholar
  33. 33.
    Ungvari Z, Parrado-Fernandez C, Csiszar A et al (2008) Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging. Circ Res 102:519–528PubMedGoogle Scholar
  34. 34.
    Tanabe T, Maeda S, Miyauchi T et al (2003) Exercise training improves ageing-induced decrease in eNOS expression of the aorta. Acta Physiol Scand 178:3–10PubMedGoogle Scholar
  35. 35.
    Woodman CR, Price EM, Laughlin MH (2002) Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries. J Appl Physiol 93:1685–1690PubMedGoogle Scholar
  36. 36.
    Matsushita H, Chang E, Glassford AJ et al (2001) eNOS activity is reduced in senescent human endothelial cells: Preservation by hTERT immortalization. Circ Res 89:793–798PubMedGoogle Scholar
  37. 37.
    Hoffmann J, Haendeler J, Aicher A et al (2001) Aging enhances the sensitivity of endothelial cells toward apoptotic stimuli: important role of nitric oxide. Circ Res 89:709–715PubMedGoogle Scholar
  38. 38.
    Berkowitz DE, White R, Li D et al (2003) Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 108:2000–2006PubMedGoogle Scholar
  39. 39.
    Jacobson A, Yan C, Gao Q et al (2007) Aging enhances pressure-induced arterial superoxide formation. Am J Physiol Heart Circ Physiol 293:H1344–H1350PubMedGoogle Scholar
  40. 40.
    Pearson KJ, Baur JA, Lewis KN et al (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157–168PubMedGoogle Scholar
  41. 41.
    Csiszar A, Labinskyy N, Smith K et al (2007) Vasculoprotective effects of anti-tumor necrosis factor-{alpha} treatment in aging. Am J Pathol 170:388–698PubMedGoogle Scholar
  42. 42.
    Arenas IA, Xu Y, Davidge ST (2006) Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-{alpha} antagonism. Am J Physiol Heart Circ Physiol 290:H1259–H1263PubMedGoogle Scholar
  43. 43.
    Park L, Anrather J, Girouard H et al (2007) Nox2-derived reactive oxygen species mediate neurovascular dysregulation in the aging mouse brain. J Cereb Blood Flow Metab 27:1908–1918PubMedGoogle Scholar
  44. 44.
    Park L, Anrather J, Zhou P et al (2005) NADPH-oxidase-derived reactive oxygen species mediate the cerebrovascular dysfunction induced by the amyloid beta peptide. J Neurosci 25:1769–1777PubMedGoogle Scholar
  45. 45.
    Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424PubMedGoogle Scholar
  46. 46.
    Szabo C (2003) Multiple pathways of peroxynitrite cytotoxicity. Toxicol Lett 140–141:105–112PubMedGoogle Scholar
  47. 47.
    Turko IV, Murad F (2002) Protein nitration in cardiovascular diseases. Pharmacol Rev 54:619–634PubMedGoogle Scholar
  48. 48.
    Kanski J, Behring A, Pelling J et al (2004) Proteomic identification of 3-nitrotyrosine-containing rat cardiac proteins: effect of biological aging. Am J Physiol Heart Circ Physiol 288:H371–H381PubMedGoogle Scholar
  49. 49.
    Ungvari ZI, Orosz Z, Labinskyy N et al (2007) Increased mitochondrial H2O2 production promotes endothelial NF-kB activation in aged rat arteries. Am J Physiol Heart Circ Physiol 293:H37–H47PubMedGoogle Scholar
  50. 50.
    Ungvari ZI, Labinskyy N, Gupte SA et al (2008) Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats. Am J Physiol Heart Circ Physiol 294:H2121–H2128PubMedGoogle Scholar
  51. 51.
    Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20:145–147PubMedGoogle Scholar
  52. 52.
    Wenzel P, Schuhmacher S, Kienhofer J et al (2008) Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction. Cardiovasc Res 80:280–289PubMedGoogle Scholar
  53. 53.
    Brown KA, Didion SP, Andresen JJ et al (2007) Effect of aging, MnSOD deficiency, and genetic background on endothelial function: evidence for MnSOD haploinsufficiency. Arterioscler Thromb Vasc Biol 27:1941–1946PubMedGoogle Scholar
  54. 54.
    Camici GG, Cosentino F, Tanner FC et al (2008) The role of p66Shc deletion in age-associated arterial dysfunction and disease states. J Appl Physiol 105:1628–1631PubMedGoogle Scholar
  55. 55.
    Cosentino F, Francia P, Camici GG et al (2008) Final common molecular pathways of aging and cardiovascular disease: role of the p66Shc protein. Arterioscler Thromb Vasc Biol 28:622–628PubMedGoogle Scholar
  56. 56.
    Ceda GP, Dall’Aglio E, Maggio M et al (2005) Clinical implications of the reduced activity of the GH-IGF-I axis in older men. J Endocrinol Invest 28:96–100PubMedGoogle Scholar
  57. 57.
    Sonntag WE, Lynch CD, Cooney PT et al (1997) Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology 138:3515–3520PubMedGoogle Scholar
  58. 58.
    Groban L, Pailes NA, Bennett CD et al (2006) Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats. J Gerontol A Biol Sci Med Sci 61:28–35PubMedGoogle Scholar
  59. 59.
    Wannenburg T, Khan AS, Sane DC et al (2001) Growth hormone reverses age-related cardiac myofilament dysfunction in rats. Am J Physiol Heart Circ Physiol 281:H915–H922PubMedGoogle Scholar
  60. 60.
    Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351PubMedGoogle Scholar
  61. 61.
    Brown-Borg HM, Borg KE, Meliska CJ et al (1996) Dwarf mice and the ageing process. Nature 384:33PubMedGoogle Scholar
  62. 62.
    Sornson MW, Wu W, Dasen JS et al (1996) Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 384:327–333PubMedGoogle Scholar
  63. 63.
    Flurkey K, Papaconstantinou J, Miller RA et al (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA 98:6736–6741PubMedGoogle Scholar
  64. 64.
    Hauck SJ, Aaron JM, Wright C et al (2002) Antioxidant enzymes, free-radical damage, and response to paraquat in liver and kidney of long-living growth hormone receptor/binding protein gene-disrupted mice. Horm Metab Res 34:481–486PubMedGoogle Scholar
  65. 65.
    Al-Regaiey KA, Masternak MM, Bonkowski M et al (2005) Long-lived growth hormone receptor knockout mice: interaction of reduced insulin-like growth factor i/insulin signaling and caloric restriction. Endocrinology 146:851–860PubMedGoogle Scholar
  66. 66.
    Csiszar A, Labinskyy N, Perez V et al (2008) Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol 295:H1882–H1894PubMedGoogle Scholar
  67. 67.
    Abu-Erreish GM, Neely JR, Whitmer JT et al (1977) Fatty acid oxidation by isolated perfused working hearts of aged rats. Am J Physiol 232:E258–E262PubMedGoogle Scholar
  68. 68.
    Hulsmann WC, Dubelaar ML (1992) Carnitine requirement of vascular endothelial and smooth muscle cells in imminent ischemia. Mol Cell Biochem 116:125–129PubMedGoogle Scholar
  69. 69.
    Imesch E, Nef P, Giacobino JP (1984) Study in pig coronary smooth muscle cell subcellular fractions of the activity of various enzymes involved in lipid metabolism and of the beta-receptor adenylate cyclase couple. Comp Biochem Physiol B 77:501–506PubMedGoogle Scholar
  70. 70.
    Gillies PJ, Bell FP (1979) Carnitine palmitoyltransferase activity in mitochondrial fractions isolated from aortas of rabbits fed cholesterol-supplemented diets. Atherosclerosis 34:25–34PubMedGoogle Scholar
  71. 71.
    Csiszar A, Labinskyy N, Orosz Z et al (2006) Altered mitochondrial energy metabolism may play a role in vascular aging. Med Hypotheses 67:904–908PubMedGoogle Scholar
  72. 72.
    Weir CJ, Gibson IF, Martin W (1991) Effects of metabolic inhibitors on endothelium-dependent and endothelium-independent vasodilatation of rat and rabbit aorta. Br J Pharmacol 102:162–166PubMedGoogle Scholar
  73. 73.
    Rodman DM, Mallet J, McMurtry IF (1991) Difference in effect of inhibitors of energy metabolism on endothelium-dependent relaxation of rat pulmonary artery and aorta. Am J Respir Cell Mol Biol 4:237–242PubMedGoogle Scholar
  74. 74.
    Griffith TM, Edwards DH, Newby AC et al (1986) Production of endothelium derived relaxant factor is dependent on oxidative phosphorylation and extracellular calcium. Cardiovasc Res 20:7–12PubMedGoogle Scholar
  75. 75.
    Dionisi O, Galeotti T, Terranova T et al (1975) Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues. Biochim Biophys Acta 403:292–300PubMedGoogle Scholar
  76. 76.
    Csiszar A, Wang M, Lakatta EG et al (2008) Inflammation and endothelial dysfunction during aging: role of NF-{kappa}B. J Appl Physiol 105:1333–1341PubMedGoogle Scholar
  77. 77.
    Csiszar A, Ungvari Z, Koller A et al (2003) Aging-induced proinflammatory shift in cytokine expression profile in rat coronary arteries. FASEB J 17:1183–1185PubMedGoogle Scholar
  78. 78.
    Csiszar A, Ungvari Z, Koller A et al (2004) Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging. Physiol Genomics 17:21–30PubMedGoogle Scholar
  79. 79.
    Sung B, Park S, Yu BP et al (2006) Amelioration of age-related inflammation and oxidative stress by PPARgamma activator: suppression of NF-kappaB by 2,4-thiazolidinedione. Exp Gerontol 41:590–599PubMedGoogle Scholar
  80. 80.
    Chung HY, Sung B, Jung KJ et al (2006) The molecular inflammatory process in aging. Antioxid Redox Signal 8:572–581PubMedGoogle Scholar
  81. 81.
    Helenius M, Hanninen M, Lehtinen SK et al (1996) Aging-induced up-regulation of nuclear binding activities of oxidative stress responsive NF-kB transcription factor in mouse cardiac muscle. J Mol Cell Cardiol 28:487–498PubMedGoogle Scholar
  82. 82.
    Cernadas MR, Sanchez de Miguel L, Garcia-Duran M et al (1998) Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats. Circ Res 83:279–286PubMedGoogle Scholar
  83. 83.
    Hajra L, Evans AI, Chen M et al (2000) The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA 97:9052–9057PubMedGoogle Scholar
  84. 84.
    Zhang J, Dai J, Lu Y et al (2004) In vivo visualization of aging-associated gene transcription: evidence for free radical theory of aging. Exp Gerontol 39:239–247PubMedGoogle Scholar
  85. 85.
    Korhonen P, Helenius M, Salminen A (1997) Age-related changes in the regulation of transcription factor NF-kappa B in rat brain. Neurosci Lett 225:61–64PubMedGoogle Scholar
  86. 86.
    Radak Z, Chung HY, Naito H et al (2004) Age-associated increase in oxidative stress and nuclear factor kappaB activation are attenuated in rat liver by regular exercise. FASEB J 18:749–750PubMedGoogle Scholar
  87. 87.
    Yan ZQ, Sirsjo A, Bochaton-Piallat ML et al (1999) Augmented expression of inducible NO synthase in vascular smooth muscle cells during aging is associated with enhanced NF-kappaB activation. Arterioscler Thromb Vasc Biol 19:2854–2862PubMedGoogle Scholar
  88. 88.
    Lee CK, Allison DB, Brand J et al (2002) Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci USA 99:14988–14993PubMedGoogle Scholar
  89. 89.
    Belmin J, Bernard C, Corman B et al (1995) Increased production of tumor necrosis factor and interleukin-6 by arterial wall of aged rats. Am J Physiol 268:H2288–H2293PubMedGoogle Scholar
  90. 90.
    Pelletier C, Varin-Blank N, Rivera J et al (1998) Fc epsilonRI-mediated induction of TNF-alpha gene expression in the RBL- 2H3 mast cell line: regulation by a novel NF-kappaB-like nuclear binding complex. J Immunol 161:4768–4776PubMedGoogle Scholar
  91. 91.
    Bruunsgaard H, Skinhoj P, Pedersen AN et al (2000) Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol 121:255–260PubMedGoogle Scholar
  92. 92.
    Schulz S, Schagdarsurengin U, Suss T et al (2004) Relation between the tumor necrosis factor-alpha (TNF-alpha) gene and protein expression, and clinical, biochemical, and genetic markers: age, body mass index and uric acid are independent predictors for an elevated TNF-alpha plasma level in a complex risk model. Eur Cytokine Netw 15:105–111PubMedGoogle Scholar
  93. 93.
    Yamamoto K, Shimokawa T, Yi H et al (2002) Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse. Blood 100:4011–4018PubMedGoogle Scholar
  94. 94.
    Spaulding CC, Walford RL, Effros RB (1997) Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-alpha and IL-6 in C3B10RF1 mice. Mech Ageing Dev 93:87–94PubMedGoogle Scholar
  95. 95.
    Harris TB, Ferrucci L, Tracy RP et al (1999) Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 106:506–512PubMedGoogle Scholar
  96. 96.
    Ungvari Z, Csiszar A, Edwards JG et al (2003) Increased superoxide production in coronary arteries in hyperhomocysteinemia: role of tumor necrosis factor-alpha, NAD(P)H oxidase, and inducible nitric oxide synthase. Arterioscler Thromb Vasc Biol 23:418–424PubMedGoogle Scholar
  97. 97.
    Bozkurt B, Kribbs SB, Clubb FJ Jr et al (1998) Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats. Circulation 97:1382–1391PubMedGoogle Scholar
  98. 98.
    Bozkurt B, Torre-Amione G, Warren MS et al (2001) Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation 103:1044–1047PubMedGoogle Scholar
  99. 99.
    Arenas IA, Armstrong SJ, Xu Y et al (2005) Chronic tumor necrosis factor-alpha inhibition enhances NO modulation of vascular function in estrogen-deficient rats. Hypertension 46:76–81PubMedGoogle Scholar
  100. 100.
    Csiszar A, Smith K, Labinskyy N et al (2006) Resveratrol attenuates TNF-{alpha}-induced activation of coronary arterial endothelial cells: role of NF-{kappa}B inhibition. Am J Physiol 291:H1694–H1699Google Scholar
  101. 101.
    Austad SN (1989) Life extension by dietary restriction in the bowl and doily spider, Frontinella pyramitela. Exp Gerontol 24:83–92PubMedGoogle Scholar
  102. 102.
    Spencer RP (1990) Relationship of reproductive success and median longevity to food intake, in the captive female spider Frontinella pyramitela. Mech Ageing Dev 55:9–13PubMedGoogle Scholar
  103. 103.
    Weindruch R, Kayo T, Lee CK et al (2002) Gene expression profiling of aging using DNA microarrays. Mech Ageing Dev 123:177–193PubMedGoogle Scholar
  104. 104.
    Kayo T, Allison DB, Weindruch R et al (2001) Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc Natl Acad Sci USA 98:5093–5098PubMedGoogle Scholar
  105. 105.
    Weindruch R, Kayo T, Lee CK et al (2001) Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice. J Nutr 131:918S–923SPubMedGoogle Scholar
  106. 106.
    Zainal TA, Oberley TD, Allison DB et al (2000) Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle. FASEB J 14:1825–1836PubMedGoogle Scholar
  107. 107.
    Lee CK, Weindruch R, Prolla TA (2000) Gene-expression profile of the ageing brain in mice. Nat Genet 25:294–297PubMedGoogle Scholar
  108. 108.
    Lee CM, Aspnes LE, Chung SS et al (1998) Influences of caloric restriction on age-associated skeletal muscle fiber characteristics and mitochondrial changes in rats and mice. Ann N Y Acad Sci 854:182–191PubMedGoogle Scholar
  109. 109.
    Lass A, Sohal BH, Weindruch R et al (1998) Caloric restriction prevents age-associated accrual of oxidative damage to mouse skeletal muscle mitochondria. Free Radic Biol Med 25:1089–1097PubMedGoogle Scholar
  110. 110.
    Edwards IJ, Rudel LL, Terry JG et al (1998) Caloric restriction in rhesus monkeys reduces low density lipoprotein interaction with arterial proteoglycans. J Gerontol A Biol Sci Med Sci 53:B443–B448PubMedGoogle Scholar
  111. 111.
    Moore WA, Davey VA, Weindruch R et al (1995) The effect of caloric restriction on lipofuscin accumulation in mouse brain with age. Gerontology 41(Suppl 2):173–185PubMedGoogle Scholar
  112. 112.
    Feuers RJ, Weindruch R, Hart RW (1993) Caloric restriction, aging, and antioxidant enzymes. Mutat Res 295:191–200PubMedGoogle Scholar
  113. 113.
    Weindruch R (1992) Effect of caloric restriction on age-associated cancers. Exp Gerontol 27:575–581PubMedGoogle Scholar
  114. 114.
    Harper ME, Bevilacqua L, Hagopian K et al (2004) Ageing, oxidative stress, and mitochondrial uncoupling. Acta Physiol Scand 182:321–331PubMedGoogle Scholar
  115. 115.
    Higami Y, Barger JL, Page GP et al (2006) Energy restriction lowers the expression of genes linked to inflammation, the cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue. J Nutr 136:343–352PubMedGoogle Scholar
  116. 116.
    Pearson KJ, Lewis KN, Price NL et al (2008) Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction. Proc Natl Acad Sci USA 105:2325–2330PubMedGoogle Scholar
  117. 117.
    Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273:59–63PubMedGoogle Scholar
  118. 118.
    Csiszar A, Labinskyy N, Jimenez R et al (2009) Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. Mech Ageing Dev 130:518–527PubMedGoogle Scholar
  119. 119.
    Lambert AJ, Merry BJ (2004) Effect of caloric restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin. Am J Physiol Regul Integr Comp Physiol 286:R71–R79PubMedGoogle Scholar
  120. 120.
    Zou Y, Yoon S, Jung KJ et al (2006) Upregulation of aortic adhesion molecules during aging. J Gerontol 61:232–244Google Scholar
  121. 121.
    de Cabo R, Furer-Galban S, Anson RM et al (2003) An in vitro model of caloric restriction. Exp Gerontol 38:631–639PubMedGoogle Scholar
  122. 122.
    Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580PubMedGoogle Scholar
  123. 123.
    Wood JG, Rogina B, Lavu S et al (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689PubMedGoogle Scholar
  124. 124.
    Howitz KT, Bitterman KJ, Cohen HY et al (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196PubMedGoogle Scholar
  125. 125.
    Brunet A, Sweeney LB, Sturgill JF et al (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–2015PubMedGoogle Scholar
  126. 126.
    Cohen HY, Miller C, Bitterman KJ et al (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305:390–392PubMedGoogle Scholar
  127. 127.
    Anderson RM, Bitterman KJ, Wood JG et al (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423:181–185PubMedGoogle Scholar
  128. 128.
    Milne JC, Lambert PD, Schenk S et al (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450:712–716PubMedGoogle Scholar
  129. 129.
    Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230PubMedGoogle Scholar
  130. 130.
    Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998–16003PubMedGoogle Scholar
  131. 131.
    Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289:2126–2128PubMedGoogle Scholar
  132. 132.
    Csiszar A, Labinskyy N, Podlutsky A et al (2008) Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. Am J Physiol Heart Circ Physiol 294:H2721–H2735PubMedGoogle Scholar
  133. 133.
    Shinmura K, Tamaki K, Bolli R (2008) Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1. Am J Physiol Heart Circ Physiol 295:H2348–H2355PubMedGoogle Scholar
  134. 134.
    Allard JS, Heilbronn LK, Smith C et al (2008) In vitro cellular adaptations of indicators of longevity in response to treatment with serum collected from humans on calorie restricted diets. PLoS ONE 3:e3211PubMedGoogle Scholar
  135. 135.
    Porcu M, Chiarugi A (2005) The emerging therapeutic potential of sirtuin-interacting drugs: from cell death to lifespan extension. Trends Pharmacol Sci 26:94–103PubMedGoogle Scholar
  136. 136.
    Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev 5:493–506Google Scholar
  137. 137.
    Yang H, Baur JA, Chen A et al (2007) Design and synthesis of compounds that extend yeast replicative lifespan. Aging Cell 6:35–43PubMedGoogle Scholar
  138. 138.
    Mai A, Massa S, Lavu S et al (2005) Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors. J Med Chem 48:7789–7795PubMedGoogle Scholar
  139. 139.
    Firestein R, Blander G, Michan S et al (2008) The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE 3:e2020PubMedGoogle Scholar
  140. 140.
    Viswanathan M, Kim SK, Berdichevsky A et al (2005) A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell 9:605–615PubMedGoogle Scholar
  141. 141.
    Bauer JH, Goupil S, Garber GB et al (2004) An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster. Proc Natl Acad Sci USA 101:12980–12985PubMedGoogle Scholar
  142. 142.
    Valenzano DR, Terzibasi E, Genade T et al (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16:296–300PubMedGoogle Scholar
  143. 143.
    Baur JA, Pearson KJ, Price NL et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342PubMedGoogle Scholar
  144. 144.
    Orosz Z, Csiszar A, Labinskyy N et al (2007) Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. Am J Physiol 292:H130–H139Google Scholar
  145. 145.
    Ungvari Z, Orosz Z, Rivera A et al (2007) Resveratrol increases vascular oxidative stress resistance. Am J Physiol 292:H2417–H2424Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Reynolds Oklahoma Center on Aging, Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

Personalised recommendations