Advertisement

Translational Research: Gene, Pharmacogenomics and Cell-Based Therapy in the Aging Heart

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

Keywords

Ischemic Precondition Peptide Nucleic Acid Premature Aging Replicative Senescence Physiol Heart Circ 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ratta SI, Clark BF. Understanding and modulating ageing. IUBMB Life 2005;57:297–304Google Scholar
  2. 2.
    Duque G. Apoptosis in cardiovascular aging research: future directions. Am J Geriatr Cardiol 2000;9:263–264PubMedGoogle Scholar
  3. 3.
    Hampel B, Malisan F, Niederegger H, Testi R, Jansen-Durr P. Differential regulation of apoptotic cell death in senescent human cells. Exp Gerontol 2004;39:1713–1721PubMedGoogle Scholar
  4. 4.
    Solary E, Bettaieb A, Dubrez-Daloz L, Corcos L. Mitochondria as a target for inducing death of malignant hematopoietic cells. Leuk Lymphoma 2003;44:563–574PubMedGoogle Scholar
  5. 5.
    Vieira HL, Boya P, Cohen I, El Hamel C, Haouzi D, Druillenec S, Belzacq AS, Brenner C, Roques B, Kroemer G. Cell permeable BH3-peptides overcome the cytoprotective effect of Bcl-2 and Bcl-X(L). Oncogene 2002;21:1963–1977PubMedGoogle Scholar
  6. 6.
    Tsujimoto Y, Nakagawa T, Shimizu S. Mitochondrial membrane permeability transition and cell death. Biochim Biophys Acta 2006;1757:1297–1300PubMedGoogle Scholar
  7. 7.
    Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 2005;434:658–662PubMedGoogle Scholar
  8. 8.
    Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, Inohara H, Kubo T, Tsujimoto Y. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 2005;434:652–658PubMedGoogle Scholar
  9. 9.
    Halestrap AP, McStay GP, Clarke SJ. The permeability transition pore complex: another view. Biochimie 2002;84:153–166PubMedGoogle Scholar
  10. 10.
    Waldmeier PC, Zimmermann K, Qian T, Tintelnot-Blomley M, Lemasters JJ. Cyclophilin D as a drug target. Curr Med Chem 2003;10:1485–1506PubMedGoogle Scholar
  11. 11.
    Zheng Y, Shi Y, Tian C, Jiang C, Jin H, Chen J, Almasan A, Tang H, Chen Q. Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial permeability transition pore opening and cytochrome c release induced by arsenic trioxide. Oncogene 2004;23:1239–1247PubMedGoogle Scholar
  12. 12.
    Veenman L, Gavish M. The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development. Pharmacol Ther 2006;110:503–524PubMedGoogle Scholar
  13. 13.
    Deniaud A, Hoebeke J, Briand JP, Muller S, Jacotot E, Brenner C. Peptido-targeting of the mitochondrial transition pore complex for therapeutic apoptosis induction. Curr Pharm Des 2006;12:4501–4511PubMedGoogle Scholar
  14. 14.
    Weisleder N, Taffet GE, Capetanaki Y. Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. Proc Natl Acad Sci USA 2004;101:769–774PubMedGoogle Scholar
  15. 15.
    Verrier F, Mignotte B, Jan G, Brenner C. Study of PTPC composition during apoptosis for identification of viral protein target. Ann NY Acad Sci 2003;1010:126–142PubMedGoogle Scholar
  16. 16.
    McCully JD, Wakiyama H, Hsieh YJ, Jones M, Levitsky S. Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2004;286:H1923–H1935PubMedGoogle Scholar
  17. 17.
    Yamamura T, Otani H, Nakao Y, Hattori R, Osako M, Imamura H. IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart. Am J Physiol Heart Circ Physiol 2001;280:H1191–H1200PubMedGoogle Scholar
  18. 18.
    Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y, Kajstura J, Baserga R, Anversa P. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest 1997;100:1991–1999PubMedGoogle Scholar
  19. 19.
    Yamashita K, Kajstura J, Discher DJ, Wasserlauf BJ, Bishopric NH, Anversa P, Webster KA. Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1. Circ Res 2001;88:609–614PubMedGoogle Scholar
  20. 20.
    Fujio Y, Nguyen T, Wencker D, Kitsis RN, Walsh K. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 2000:101:660–667Google Scholar
  21. 21.
    Ren J, Samson WK, Sowers JR. Insulin-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease. J Mol Cell Cardiol 1999;31:2049–2061PubMedGoogle Scholar
  22. 22.
    Burgess W, Liu Q, Zhou J, Tang Q, Ozawa A, VanHoy R, Arkins S, Dantzer R, Kelley KW. The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I. Neuroimmunomodulation 1999;6:56–68PubMedGoogle Scholar
  23. 23.
    Pugazhenth S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem 2000;275:10761–10766Google Scholar
  24. 24.
    Mehrhof FB, Muller FU, Bergmann MW, Li P, Wang Y, Schmitz W, Dietz R, von Harsdorf R. In cardiomyocyte hypoxia, insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein. Circulation 2001;104:2088–2094PubMedGoogle Scholar
  25. 25.
    Fernandez M, Sanchez-Franco F, Palacios N, Sanchez I, Fernandez C, Cacicedo L. IGF-I inhibits apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway in pituitary cells. J Mol Endocrinol 2004;33:155–163PubMedGoogle Scholar
  26. 26.
    Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I, Zias E, Walsh K, Rosenzweig A, Sussman MA, Urbanek K, Nadal-Ginard B, Kajstura J, Anversa P, Leri A. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res 2004;94:514–524PubMedGoogle Scholar
  27. 27.
    Li Q, Wu S, Li SY, Lopez FL, Du M, Kajstura J, Anversa P, Ren J. Cardiac specific overexpression of insulin-like growth factor-1 (IGF-1) attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage. Am J Physiol Heart Circ Physiol 2007;292:H1398–H1403PubMedGoogle Scholar
  28. 28.
    Jin H, Wyss JM, Yang R, Schwall R. The therapeutic potential of hepatocyte growth factor for myocardial infarction and heart failure. Curr Pharm Des 2004;10:2525–2533PubMedGoogle Scholar
  29. 29.
    Fan S, Ma YX, Wang JA, Yuan RQ, Meng Q, Cao Y, Laterra JJ, Goldberg ID, Rosen EM. The cytokine hepatocyte growth factor/scatter factor inhibits apoptosis and enhances DNA repair by a common mechanism involving signaling through phosphatidyl inositol 3’ kinase. Oncogene 2000;19:2212–2223PubMedGoogle Scholar
  30. 30.
    Khan AS, Sane DC, Wannenburg T, Sonntag WE. Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system. Cardiovasc Res 2002;54:25–35PubMedGoogle Scholar
  31. 31.
    Groban L, Pailes NA, Bennett CD, Carter CS, Chappell MC, Kitzman DW, Sonntag WE. Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats. J Gerontol A Biol Sci Med Sci 2006;61:28–35PubMedGoogle Scholar
  32. 32.
    Rossoni G, De Gennaro Colonna V, Bernareggi M, Polvani GL, Muller EE, Berti F. Protectant activity of hexarelin or growth hormone against postischemic ventricular dysfunction in hearts from aged rats. J Cardiovasc Pharmacol 1998;32:260–265PubMedGoogle Scholar
  33. 33.
    Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124–1136PubMedGoogle Scholar
  34. 34.
    Riksen NP, Smits P, Rongen GA. Ischaemic preconditioning: from molecular characterisation to clinical application – part I. Neth J Med 2004;62:353–363PubMedGoogle Scholar
  35. 35.
    Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124–1136PubMedGoogle Scholar
  36. 36.
    Bolli R. The late phase of preconditioning. Circ Res 2000:87:972–983Google Scholar
  37. 37.
    Yellon DM, Downey JM. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 2003;83:1113–1151PubMedGoogle Scholar
  38. 38.
    Cohen MV, Baines CP, Downey JM. Ischemic preconditioning: from adenosine receptor of KATP channel. Annu Rev Physiol 2000;62:79–109PubMedGoogle Scholar
  39. 39.
    Murphy E. Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection. Circ Res 2004;94:7–16PubMedGoogle Scholar
  40. 40.
    Vinten-Johansen J, Zhao ZQ, Zatta AJ, Kin H, Halkos ME, Kerendi F. Postconditioning – A new link in nature’s armor against myocardial ischemia-reperfusion injury. Basic Res Cardiol 2005;100:295–310PubMedGoogle Scholar
  41. 41.
    Hausenloy DJ, Tsang A, Yellon DM. The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 2005:15:69–75Google Scholar
  42. 42.
    Fenton RA, Dickson EW, Meyer TE, Dobson JG Jr. Aging reduces the cardioprotective effect of ischemic preconditioning in the rat heart. J Mol Cell Cardiol 2003;32:1371–1375Google Scholar
  43. 43.
    Abete P, Ferrara N, Cioppa A, Ferrara P, Bianco S, Calabrese C, Cacciatore F, Longobardi G, Rengo F. Preconditioning does not prevent postischemic dysfunction in aging heart. J Am Coll Cardiol 1996;7:1777–1786Google Scholar
  44. 44.
    Przyklenk K, Li G, Whittaker P. No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits. J Am Coll Cardiol 2001;38:1741–1747PubMedGoogle Scholar
  45. 45.
    Burns PG, Krunkenkamp IB, Calderone CA, Kirvaitis RJ, Gaudette GR, Levitsky S. Is the preconditioning response conserved in senescent myocardium? Ann Thorac Surg 1996;61:925–929PubMedGoogle Scholar
  46. 46.
    Abete P, Ferrara N, Cacciatore F, Madrid A, Bianco S, Calabrese C, Napoli C, Scognamiglio P, Bollella O, Cioppa A, Longobardi G, Rengo F. Angina-induced protection against myocardial infarction in adult and elderly patients: a loss of preconditioning mechanism in the aging heart? J Am Coll Cardiol 1997;30:947–954PubMedGoogle Scholar
  47. 47.
    Lee TM, Su SF, Chou TF, Lee YT, Tsai CH. Loss of preconditioning by attenuated activation of myocardial ATP-sensitive potassium channels in elderly patients undergoing coronary angioplasty. Circulation 2002;105: 334–340PubMedGoogle Scholar
  48. 48.
    Bartling B, Friedrich I, Silber RE, Simm A. Ischemic preconditioning is not cardioprotective in senescent human myocardium. Ann Thorac Surg 2003;76:105–111PubMedGoogle Scholar
  49. 49.
    Bartling B, Hilgefort C, Friedrich I, Silber RE, Simm A. Cardioprotective determinants are conserved in aged human myocardium after ischemic preconditioning. FEBS Lett 2003;555:539–544PubMedGoogle Scholar
  50. 50.
    Taylor RP, Starnes JW. Age, cell signalling and cardioprotection. Acta Physiol Scand 2003;178:107–116PubMedGoogle Scholar
  51. 51.
    Lakatta EG, Yin FC. Myocardial aging: functional alterations and related cellular mechanisms. Am J Physiol 1992;242:H927–H941Google Scholar
  52. 52.
    Przyklenk K, Li G, Simkhovich BZ, Kloner RA. Mechanisms of myocardial ischemic preconditioning are age related: PKC-epsilon does not play a requisite role in old rabbits. J Appl Physiol 2003;95:2563–2569PubMedGoogle Scholar
  53. 53.
    Kristo G, Yoshimura Y, Keith BJ, Mentzer RM Jr, Lasley RD. Aged rat myocardium exhibits normal adenosine receptor-mediated bradycardia and coronary vasodilation but increased adenosine agonist-mediated cardioprotection. J Gerontol A Biol Sci Med Sci 2005;60:1399–1404PubMedGoogle Scholar
  54. 54.
    McCully JD, Uematsu M, Parker RA, Levitsky S. Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in the aged heart. Ann Thorac Surg 1998;66:2037–2043PubMedGoogle Scholar
  55. 55.
    Willems L, Ashton KJ, Headrick JP. Adenosine-mediated cardioprotection in the aging myocardium. Cardiovasc Res 2005;66:245–255PubMedGoogle Scholar
  56. 56.
    Ashton KJ, Nilsson U, Willems L, Holmgren K, Headrick JP. Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium. Biochem Biophys Res Commun 2003;312:367–372PubMedGoogle Scholar
  57. 57.
    Headrick JP, Willems L, Ashton KJ, Holmgren K, Peart J, Matherne GP. Ischaemic tolerance in aged mouse myocardium: the role of adenosine and effects of A1 adenosine receptor overexpression. J Physiol 2003;549:823–833PubMedGoogle Scholar
  58. 58.
    Shinmura K, Nagai M, Tamaki K, Bolli R. Gender and aging do not impair opioid-induced late preconditioning in rats. Basic Res Cardiol 2004;99:46–55PubMedGoogle Scholar
  59. 59.
    Loubani M, Ghosh S, Galinanes M. The aging human myocardium: tolerance to ischemia and responsiveness to ischemic preconditioning. J Thorac Cardiovasc Surg 2003;126:143–147PubMedGoogle Scholar
  60. 60.
    Peart JN, Gross GJ. Chronic exposure to morphine produces a marked cardioprotective phenotype in aged mouse hearts. Exp Gerontol 2004;39:1021–1026PubMedGoogle Scholar
  61. 61.
    Sniecinski R, Liu H. Reduced efficacy of volatile anesthetic preconditioning with advanced age in isolated rat myocardium. Anesthesiology 2004;100:589–597PubMedGoogle Scholar
  62. 62.
    Zheng J, Chin A, Duignan I, Won KH, Hong MK, Edelberg JM. Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection. Am J Physiol Heart Circ Physiol 2006;290:H525–H530PubMedGoogle Scholar
  63. 63.
    Juhaszova M, Rabuel C, Zorov DB, Lakatta EG, Sollott SJ. Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res 2005;66:233–244PubMedGoogle Scholar
  64. 64.
    Brown KA, Chu Y, Lund DD, Heistad DD, Faraci FM. Gene transfer of extracellular superoxide dismutase protects against vascular dysfunction with aging. Am J Physiol Heart Circ Physiol 2006;290:H2600–H2605PubMedGoogle Scholar
  65. 65.
    Iida S, Chu Y, Francis J, Weiss RM, Gunnett CA, Faraci FM, Heistad DD. Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure. Am J Physiol Heart Circ Physiol 2005;289:H525–H532PubMedGoogle Scholar
  66. 66.
    Grzenkowicz-Wydra J, Cisowski J, Nakonieczna J, Zarebski A, Udilova N, Nohl H, Jozkowicz A, Podhajska A, Dulak J. Gene transfer of CuZn superoxide dismutase enhances the synthesis of vascular endothelial growth factor. Mol Cell Biochem 2004;264:169–181PubMedGoogle Scholar
  67. 67.
    Abunasra HJ, Smolenski RT, Morrison K, Yap J, Sheppard MN, O’Brien T, Suzuki K, Jayakumar J, Yacoub MH. Efficacy of adenoviral gene transfer with manganese superoxide dismutase and endothelial nitric oxide synthase in reducing ischemia and reperfusion injury. Eur J Cardiothorac Surg 2001;20:153–158PubMedGoogle Scholar
  68. 68.
    Woo YJ, Zhang JC, Vijayasarathy C, Zwacka RM, Englehardt JF, Gardner TJ, Sweeney HL. Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction. Circulation 1998;98:II255–II260PubMedGoogle Scholar
  69. 69.
    Li Q, Bolli R, Qiu Y, Tang XL, Guo Y, French BA. Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. Circulation 2001;103:1893–1898PubMedGoogle Scholar
  70. 70.
    Okubo S, Wildner O, Shah MR, Chelliah JC, Hess ML, Kukreja RC. Gene transfer of heat-shock protein 70 reduces infarct size in vivo after ischemia/reperfusion in the rabbit heart. Circulation 2001;103:877–881PubMedGoogle Scholar
  71. 71.
    Zhu HL, Stewart AS, Taylor MD, Vijayasarathy C, Gardner TJ, Sweeney HL. Blocking free radical production via adenoviral gene transfer decreases cardiac ischemia-reperfusion injury. Mol Ther 2000;2:470–475PubMedGoogle Scholar
  72. 72.
    Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 2005;308:1909–1911PubMedGoogle Scholar
  73. 73.
    Abraham NG. Therapeutic applications of human heme oxygenase gene transfer and gene therapy. Curr Pharm Des 2003;9:2513–2524PubMedGoogle Scholar
  74. 74.
    Pachori AS, Melo LG, Zhang L, Solomon SD, Dzau VJ. Chronic recurrent myocardial ischemic injury is significantly attenuated by pre-emptive adeno-associated virus heme oxygenase-1 gene delivery. J Am Coll Cardiol 2006;47:635–643PubMedGoogle Scholar
  75. 75.
    Melo LG, Agrawal R, Zhang L, Rezvani M, Mangi AA, Ehsan A, Griese DP, Dell’Acqua G, Mann MJ, Oyama J, Yet SF, Layne MD, Perrella MA, Dzau VJ. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 2002;105:602–607PubMedGoogle Scholar
  76. 76.
    Liu X, Pachori AS, Ward CA, Davis JP, Gnecchi M, Kong D, Zhang L, Murduck J, Yet SF, Perrella MA, Pratt RE, Dzau VJ, Melo LG. Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function. FASEB J 2006;20:207–216PubMedGoogle Scholar
  77. 77.
    Tang YL, Qian K, Zhang YC, Shen L, Phillips MI. A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo. J Cardiovasc Pharmacol Ther 2005;10: 251–263PubMedGoogle Scholar
  78. 78.
    Tang Y, Schmitt-Ott K, Qian K, Kagiyama S, Phillips MI. Vigilant vectors: adeno-associated virus with a biosensor to switch on amplified therapeutic genes in specific tissues in life-threatening diseases. Methods 2002;28:259–266PubMedGoogle Scholar
  79. 79.
    Tang YL, Tang Y, Zhang YC, Qian K, Shen L, Phillips MI. Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system. Hypertension 2004;43:746–751PubMedGoogle Scholar
  80. 80.
    Dulak J, Zagorska A, Wegiel B, Loboda A, Jozkowicz A. New strategies for cardiovascular gene therapy: regulatable pre-emptive expression of pro-angiogenic and antioxidant genes. Cell Biochem Biophys 2006;44:31–42PubMedGoogle Scholar
  81. 81.
    Kruger AL, Peterson SJ, Schwartzman ML, Fusco H, McClung JA, Weiss M, Shenouda S, Goodman AI, Goligorsky MS, Kappas A, Abraham NG. Up-regulation of heme oxygenase provides vascular protection in an animal model of diabetes through its antioxidant and antiapoptotic effects. J Pharmacol Exp Ther 2006;319:1144–1152PubMedGoogle Scholar
  82. 82.
    Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, Chau LY. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2001;104:1519–1525PubMedGoogle Scholar
  83. 83.
    Hoekstra KA, Godin DV, Cheng KM. Protective role of heme oxygenase in the blood vessel wall during atherogenesis. Biochem Cell Biol 2004;82:351–359PubMedGoogle Scholar
  84. 84.
    Bouche D, Chauveau C, Roussel JC, Mathieu P, Braudeau C, Tesson L, Soulillou JP, Iyer S, Buelow R, Anegon I. Inhibition of graft arteriosclerosis development in rat aortas following heme oxygenase-1 gene transfer. Transpl Immunol 2002;9:235–238PubMedGoogle Scholar
  85. 85.
    Yang X, Doser TA, Fang CX, Nunn JM, Janardhanan R, Zhu M, Sreejayan N, Quinn MT, Ren J. Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: role of oxidative stress. FASEB J 2006;20:1024–1026PubMedGoogle Scholar
  86. 86.
    Fang CX, Doser TA, Yang X, Sreejayan N, Ren J. Metallothionein antagonizes aging-induced cardiac contractile dysfunction: role of PTP1B, insulin receptor tyrosine phosphorylation and Akt. Aging Cell 2006;5:177–185PubMedGoogle Scholar
  87. 87.
    Storz P. Mitochondrial ROS-radical detoxification, mediated by protein kinase D. Trends Cell Biol 2007;17:13–18PubMedGoogle Scholar
  88. 88.
    Storz P, Doppler H, Toker A. Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. Mol Cell Biol 2005;25:8520–8530PubMedGoogle Scholar
  89. 89.
    Sanz A, Caro P, Barja G. Protein restriction without strong caloric restriction decreases mitochondrial oxygen radical production and oxidative DNA damage in rat liver. J Bioenerg Biomembr 2004;36:545–552PubMedGoogle Scholar
  90. 90.
    Sanz A, Caro P, Ayala V, Portero-Otin M, Pamplona R, Barja G. Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins. FASEB J 2006;20:1064–1073PubMedGoogle Scholar
  91. 91.
    Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005;309:481–484PubMedGoogle Scholar
  92. 92.
    Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA 2005;102:17993–17998PubMedGoogle Scholar
  93. 93.
    Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly Y-M, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 2004;429:417–423PubMedGoogle Scholar
  94. 94.
    Zhang D, Mott JL, Farrar P, Ryerse JS, Chang SW, Stevens M, Denniger G, Zassenhaus HP. Mitochondrial DNA mutations activate the mitochondrial apoptotic pathway and cause dilated cardiomyopathy. Cardiovasc Res 2003;57:147–157PubMedGoogle Scholar
  95. 95.
    Takao M, Aburatani H, Kobayashi K, Yasui A. Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage. Nucleic Acids Res 1998;26:2917–2922PubMedGoogle Scholar
  96. 96.
    Hudson EK, Hogue BA, Souza-Pinto NC, Croteau DL, Anson RM, Bohr VA, Hansford RG. Age-associated change in mitochondrial DNA damage. Free Radic Res 1998;29:573–579PubMedGoogle Scholar
  97. 97.
    Souza-Pinto NC, Croteau DL, Hudson EK, Hansford RG, Bohr VA. Age-associated increase in 8-oxo-deoxyguanosine glycosylase/AP lyase activity in rat mitochondria. Nucleic Acids Res 1999;27:1935–1942PubMedGoogle Scholar
  98. 98.
    Dobson AW, Xu Y, Kelley MR, LeDoux SP, Wilson GL. Enhanced mitochondrial DNA repair and cellular survival after oxidative stress by targeting the human 8-oxoguanine glycosylase repair enzyme to mitochondria. J Biol Chem 2000;275:37518–37523PubMedGoogle Scholar
  99. 99.
    Rachek LI, Grishko VI, Musiyenko SI, Kelley MR, LeDoux SP, Wilson GL. Conditional targeting of the DNA repair enzyme hOGG1 into mitochondria. J Biol Chem 2002;277:44932–44937PubMedGoogle Scholar
  100. 100.
    Chatterjee A, Mambo E, Zhang Y, Deweese T, Sidransky D. Targeting of mutant hogg1 in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress. BMC Cancer 2006;6:235Google Scholar
  101. 101.
    Rachek LI, Grishko VI, Alexeyev MF, Pastukh VV, LeDoux SP, Wilson GL. Endonuclease III and endonuclease VIII conditionally targeted into mitochondria enhance mitochondrial DNA repair and cell survival following oxidative stress. Nucleic Acids Res 2004;32:3240–3247PubMedGoogle Scholar
  102. 102.
    Druzhyna NM, Hollensworth SB, Kelley MR, Wilson GL, Ledoux SP. Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress. Glia 2003;42:370–378PubMedGoogle Scholar
  103. 103.
    Muratovska A, Lightowlers RN, Taylor RW, Turnbull DM, Smith RA, Wilce JA, Martin SW, Murphy MP. Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations: Implications for mitochondrial DNA replication, expression and disease. Nucleic Acids Res 2001;29:1852–1863PubMedGoogle Scholar
  104. 104.
    Geromel V, Cao A, Briane D, Vassy J, Rotig A, Rustin P, Coudert R, Rigaut JP, Munnich A, Taillandier E. Mitochondria transfection by oligonucleotides containing a signal peptide and vectorized by cationic liposomes. Antisense Nucleic Acid Drug Dev 200;11:175–180Google Scholar
  105. 105.
    Flierl A, Jackson C, Cottrell B, Murdock D, Seibel P, Wallace DC. Targeted delivery of DNA to the mitochondrial compartment via import sequence-conjugated peptide nucleic acid. Mol Ther 2003;7:550–557PubMedGoogle Scholar
  106. 106.
    Weissig V, Lasch J, Erdos G, Meyer HW, Rowe TC, Hughes J. DQAsomes: a novel potential drug and gene delivery system made from Dequalinium. Pharm Res 1998;15:334–337PubMedGoogle Scholar
  107. 107.
    D’Souza GG, Boddapati SV, Weissig V. Mitochondrial leader sequence – plasmid DNA conjugates delivered into mammalian cells by DQAsomes co-localize with mitochondria. Mitochondrion 2005;5:352–358PubMedGoogle Scholar
  108. 108.
    D’Souza GG, Rammohan R, Cheng SM, Torchilin VP, Weissig V. DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells. J Control Release 2003;92:189–197PubMedGoogle Scholar
  109. 109.
    Guy J, Qi X, Pallotti F, Schon EA, Manfredi G, Carelli V, Martinuzzi A, Hauswirth WW, Lewin AS. Rescue of a mitochondrial deficiency causing leber hereditary optic neuropathy. Ann Neurol 2002;52:534–542PubMedGoogle Scholar
  110. 110.
    Zullo SJ, Parks WT, Chloupkova M, Wei B, Weiner H, Fenton WA, Eisenstadt JM, Merril CR. Stable transformation of CHO Cells and human NARP cybrids confers oligomycin resistance (oli(r)) following transfer of a mitochondrial DNA-encoded oli(r) ATPase6 gene to the nuclear genome: a model system for mtDNA gene therapy. Rejuvenation Res 2005;8:18–28PubMedGoogle Scholar
  111. 111.
    Manfredi G, Fu J, Ojaimi J, Sadlock JE, Kwong JQ, Guy J, Schon EA. Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. Nat Genet 2002;30:394–399PubMedGoogle Scholar
  112. 112.
    Ono T, Isobe K, Nakada K, Hayashi J. Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria. Nat Genet 2001;28:272–275PubMedGoogle Scholar
  113. 113.
    Nakada K, Inoue K, Ono T, Isobe K, Ogura A, Goto YI, Nonaka I, Hayashi JI. Inter-mitochondrial complementation: mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nat Med 2001;7:934–940PubMedGoogle Scholar
  114. 114.
    Khan SM, Smigrodzki RM, Swerdlow R. Cell and animal models of mtDNA biology: progress and prospects. Am J Physiol Cell Physiol 2007;292:C658–C669PubMedGoogle Scholar
  115. 115.
    Clark MA, Shay JW. Mitochondrial transformation of mammalian cells. Nature 1982;295:605–607PubMedGoogle Scholar
  116. 116.
    Enriquez JA, Cabezas-Herrera J, Bayona-Bafaluy MP, Attardi G. Very rare complementation between mitochondria carrying different mitochondrial DNA mutations points to intrinsic genetic autonomy of the organelles in cultured human cells. J Biol Chem 2000;275:11207–11215PubMedGoogle Scholar
  117. 117.
    Attardi G, Enriquez JA, Cabezas-Herrera J. Inter-mitochondrial complementation of mtDNA mutations and nuclear context. Nat Genet 2002;30:360PubMedGoogle Scholar
  118. 118.
    Sato A, Nakada K, Hayashi J. Mitochondrial dynamics and aging: mitochondrial interaction preventing individuals from expression of respiratory deficiency caused by mutant mtDNA. Biochim Biophys Acta 2006;1763: 473–481PubMedGoogle Scholar
  119. 119.
    Spees JL, Olson SD, Whitney MJ, Prockop DJ. Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci USA 2006;103:1283–1288PubMedGoogle Scholar
  120. 120.
    Khrapko K. Mitochondrial DNA gene therapy: a gene therapy for aging? Rejuvenation Res 2005;8:6–8PubMedGoogle Scholar
  121. 121.
    Hansel A, Kuschel L, Hehl S, Lemke C, Agricola HJ, Hoshi T, Heinemann SH. Mitochondrial targeting of the human peptide methionine sulfoxide reductase (MSRA), an enzyme involved in the repair of oxidized proteins. FASEB J 2002;16:911–913PubMedGoogle Scholar
  122. 122.
    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–H1760PubMedGoogle Scholar
  123. 123.
    Sanguino E, Roglans N, Alegret M, Sanchez RM, Vazquez-Carrera M, Laguna JC. Atorvastatin reverses age-related reduction in rat hepatic PPARalpha and HNF-4. Br J Pharmacol 2005;145:853–861PubMedGoogle Scholar
  124. 124.
    Tarnopolsky MA, Beal MF. Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 2001;49:561–574PubMedGoogle Scholar
  125. 125.
    Kelso GF, Porteous CM, Coulter CV, Hughes G, Porteous WK, Ledgerwood EC, Smith RA, Murphy MP. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem 2001;276:4588–4596PubMedGoogle Scholar
  126. 126.
    Smith RA, Porteous CM, Gane AM, Murphy MP. Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci USA 2003;100:5407–5412PubMedGoogle Scholar
  127. 127.
    Adlam VJ, Harrison JC, Porteous CM, James AM, Smith RA, Murphy MP, Sammut IA. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J 2005;19:1088–1095PubMedGoogle Scholar
  128. 128.
    Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death and reperfusion injury. J Biol Chem 2004;279:34682–34690PubMedGoogle Scholar
  129. 129.
    Torchilin VP. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng 2006;8:343–375PubMedGoogle Scholar
  130. 130.
    Farout L, Friguet B. Proteasome function in aging and oxidative stress: implications in protein maintenance failure. Antioxid Redox Signal 2006;8:205–216PubMedGoogle Scholar
  131. 131.
    Grune T, Merker K, Jung T, Sitte N, Davies KJ. Protein oxidation and degradation during postmitotic senescence. Free Radic Biol Med 2005;39:1208–1215PubMedGoogle Scholar
  132. 132.
    Davies KJ. Degradation of oxidized proteins by the 20S proteasome. Biochimie 2001;83:301–310PubMedGoogle Scholar
  133. 133.
    Davies KJ, Shringarpure R. Preferential degradation of oxidized proteins by the 20S proteasome may be inhibited in aging and in inflammatory neuromuscular diseases. Neurology 2006;66:S93–S96PubMedGoogle Scholar
  134. 134.
    Kaushik S, Cuervo AM. Autophagy as a cell-repair mechanism: activation of chaperone-mediated autophagy during oxidative stress. Mol Aspects Med 2006;27:444–454PubMedGoogle Scholar
  135. 135.
    Miyata S, Takemura G, Kawase Y, Li Y, Okada H, Maruyama R, Ushikoshi H, Esaki M, Kanamori H, Li L, Misao Y, Tezuka A, Toyo-Oka T, Minatoguchi S, Fujiwara T, Fujiwara H. Autophagic cardiomyocyte death in cardiomyopathic hamsters and its prevention by granulocyte colony-stimulating factor. Am J Pathol 2006;168:386–397PubMedGoogle Scholar
  136. 136.
    Brunk UT, Terman A. The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 2002;269:1996–2002PubMedGoogle Scholar
  137. 137.
    Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, Kominami E, Tanaka K, Chiba T. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 2005;169:425–434PubMedGoogle Scholar
  138. 138.
    Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 2005;8:3–5PubMedGoogle Scholar
  139. 139.
    Cavallini G, Donati A, Taddei M, Bergamini E. Evidence for selective mitochondrial autophagy and failure in aging. Autophagy 2007;3:26–27PubMedGoogle Scholar
  140. 140.
    Donati A. The involvement of macroautophagy in aging and anti-aging interventions. Mol Aspects Med 2006;27:455–470PubMedGoogle Scholar
  141. 141.
    Bergamini E, Cavallini G, Donati A, Gori Z. The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically. Biomed Pharmacother 2003;57:203–208PubMedGoogle Scholar
  142. 142.
    Abeliovich H, Zhang C, Dunn WA Jr, Shokat KM, Klionsky DJ. Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy. Mol Biol Cell 2003;14:477–490PubMedGoogle Scholar
  143. 143.
    de Grey AD, Alvarez PJ, Brady RO, Cuervo AM, Jerome WG, McCarty PL, Nixon RA, Rittmann BE, Sparrow JR. Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases. Ageing Res Rev 2005;4:315–338PubMedGoogle Scholar
  144. 144.
    de Grey AD. Bioremediation meets biomedicine: therapeutic translation of microbial catabolism to the lysosome. Trends Biotechnol 2002;20:452–455PubMedGoogle Scholar
  145. 145.
    Serrano AL, Andres V. Telomeres and cardiovascular disease: does size matter? Circ Res 2004;94:575–584PubMedGoogle Scholar
  146. 146.
    Liu SC, Wang SS, Wu MZ, Wu DC, Yu FJ, Chen WJ, Chiang FT, Yu MF. Activation of telomerase and expression of human telomerase reverse transcriptase in coronary atherosclerosis. Cardiovasc Pathol 2005;14:232–240PubMedGoogle Scholar
  147. 147.
    Wootton M, Steeghs K, Watt D, Munro J, Gordon K, Ireland H, Morrison V, Behan W, Parkinson EK. Telomerase alone extends the replicative life span of human skeletal muscle cells without compromising genomic stability. Hum Gene Ther 2003;14:1473–1487PubMedGoogle Scholar
  148. 148.
    Di Donna S, Mamchaoui K, Cooper RN, Seigneurin-Venin S, Tremblay J, Butler-Browne GS, Mouly V. Telomerase can extend the proliferative capacity of human myoblasts, but does not lead to their immortalization. Mol Cancer Res 2003;1:643–653PubMedGoogle Scholar
  149. 149.
    Yudoh K, Matsuno H, Nakazawa F, Katayama R, Kimura T. Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts. J Bone Miner Res 2001;16:1453–1464PubMedGoogle Scholar
  150. 150.
    Yang J, Chang E, Cherry AM, Bangs CD, Oei Y, Bodnar A, Bronstein A, Chiu CP, Herron GS. Human endothelial cell life extension by telomerase expression. J Biol Chem 1999;274:26141–26148PubMedGoogle Scholar
  151. 151.
    Oh H, Taffet GE, Youker KA, Entman ML, Overbeek PA, Michael LH, Schneider MD. Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Proc Natl Acad Sci USA 2001;98:10308–10313PubMedGoogle Scholar
  152. 152.
    Samper E, Flores JM, Blasco MA. Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc-/- mice with short telomeres. EMBO Rep 2001;2:800–807PubMedGoogle Scholar
  153. 153.
    Gorbunova V, Seluanov A, Pereira-Smith OM. Expression of human telomerase (hTERT) does not prevent stress-induced senescence in normal human fibroblasts but protects the cells from stress-induced apoptosis and necrosis. J Biol Chem 2002;277:38540–38549PubMedGoogle Scholar
  154. 154.
    von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002;27:339–344Google Scholar
  155. 155.
    Haendeler J, Hoffmann J, Diehl JF, Vasa M, Spyridopoulos I, Zeiher AM, Dimmeler S. Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells. Circ Res 2004;94:768–775PubMedGoogle Scholar
  156. 156.
    Harley CB. Telomerase therapeutics for degenerative diseases. Curr Mol Med 2005;5:205–211PubMedGoogle Scholar
  157. 157.
    Imanishi T, Hano T, Nishio I. Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress. J Hypertens 2005;23:97–104PubMedGoogle Scholar
  158. 158.
    Imanishi T, Hano T, Nishio I. Estrogen reduces endothelial progenitor cell senescence through augmentation of telomerase activity. J Hypertens 2005;23:1699–1706PubMedGoogle Scholar
  159. 159.
    Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadinanos J, Lopez-Otin C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z. Genomic instability in laminopathy-based premature aging. Nat Med 2005;11:780–785PubMedGoogle Scholar
  160. 160.
    Cadinanos J, Varela I, Lopez-Otin C, Freije JM. From immature lamin to premature aging: molecular pathways and therapeutic opportunities. Cell Cycle 2005;4:1732–1735PubMedGoogle Scholar
  161. 161.
    Fong LG, Frost D, Meta M, Qiao X, Yang SH, Coffinier C, Young SG. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 2006;311:1621–1623PubMedGoogle Scholar
  162. 162.
    Scaffidi P, Misteli T. Reversal of the cellular phenotype in the premature aging disease hutchinson-gilford progeria syndrome. Nat Med 2005;11:440–445PubMedGoogle Scholar
  163. 163.
    Columbaro M, Capanni C, Mattioli E, Novelli G, Parnaik VK, Squarzoni S, Maraldi NM, Lattanzi G. Rescue of heterochromatin organization in hutchinson-gilford progeria by drug treatment. Cell Mol Life Sci 2005;62:2669–2678PubMedGoogle Scholar
  164. 164.
    Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA 2006;103:8703–8708PubMedGoogle Scholar
  165. 165.
    Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ, Redon C, Pilch DR, Olaru A, Eckhaus M, Camerini-Otero RD, Tessarollo L, Livak F, Manova K, Bonner WM, Nussenzweig MC, Nussenzweig A. Genomic instability in mice lacking histone H2AX. Science 2002;296:922–927PubMedGoogle Scholar
  166. 166.
    Quiles JL, Ochoa JJ, Huertas JR, Mataix J. Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on. Exp Gerontol 2004;39:189–194PubMedGoogle Scholar
  167. 167.
    de Boer J, Andressoo JO, de Wit J, Huijmans J, Beems RB, van Steeg H, Weeda G, van der Horst GT, van Leeuwen W, Themmen AP, Meradji M, Hoeijmakers JH. Premature aging in mice deficient in DNA repair and transcription. Science 2002;296:1276–1279PubMedGoogle Scholar
  168. 168.
    Armelini MG, Muotri AR, Marchetto MC, de Lima-Bessa KM, Sarasin A, Menck CF. Restoring DNA repair capacity of cells from three distinct diseases by XPD gene-recombinant adenovirus. Cancer Gene Ther 2005;12:389–396PubMedGoogle Scholar
  169. 169.
    Zeng L, Quilliet X, Chevallier-Lagente O, Eveno E, Sarasin A. Mezzina Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C. Gene Ther 1997;4:1077–1084PubMedGoogle Scholar
  170. 170.
    Carreau M, Quilliet X, Eveno E, Salvetti A, Danos O, Heard JM, Mezzina M, Sarasin A. Functional retroviral vector for gene therapy of xeroderma pigmentosum group D patients. Hum Gene Ther 1995;6:1307–1315PubMedGoogle Scholar
  171. 171.
    Erol A. PPARalpha activators may be good candidates as antiaging agents. Med Hypotheses 2005;65:35–38PubMedGoogle Scholar
  172. 172.
    Pineda Torra I, Gervois P, Staels B. Peroxisome proliferator-activated receptor alpha in metabolic disease, inflammation, atherosclerosis and aging. Curr Opin Lipidol 1999;10:151–159PubMedGoogle Scholar
  173. 173.
    Melloul D, Stoffel M. Regulation of transcriptional coactivator PGC-1alpha. Sci Aging Knowledge Environ 2004;2004:pe9Google Scholar
  174. 174.
    Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005;434:113–118PubMedGoogle Scholar
  175. 175.
    Ling C, Poulsen P, Carlsson E, Ridderstrale M, Almgren P, Wojtaszewski J, Beck-Nielsen H, Groop L, Vaag A. Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins. J Clin Invest 2004;114:1518–1526PubMedGoogle Scholar
  176. 176.
    Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004;429:771–776PubMedGoogle Scholar
  177. 177.
    Lemieux ME, Yang X, Jardine K, He X, Jacobsen KX, Staines WA, Harper ME, McBurney MW. The Sirt1 deacetylase modulates the insulin-like growth factor signaling pathway in mammals. Mech Ageing Dev 2005;126:1097–1105PubMedGoogle Scholar
  178. 178.
    Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 2002;21:2383–2396PubMedGoogle Scholar
  179. 179.
    Yu J, Lei L, Liang Y, Hinh L, Hickey RP, Huang Y, Liu D, Yeh JL, Rebar E, Case C, Spratt K, Sessa WC, Giordano FJ. An engineered VEGF-activating zinc finger protein transcription factor improves blood flow and limb salvage in advanced-age mice. FASEB J 2006;20:479–481PubMedGoogle Scholar
  180. 180.
    Bhasin S, Calof OM, Storer TW, Lee ML, Mazer NA, Jasuja R, Montori VM, Gao W, Dalton JT. Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab 2006;2:146–159PubMedGoogle Scholar
  181. 181.
    Schmidt U, del Monte F, Miyamoto MI, Matsui T, Gwathmey JK, Rosenzweig A, Hajjar RJ. Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase. Circulation 2000;101:790–796PubMedGoogle Scholar
  182. 182.
    Schmidt U, Zhu X, Lebeche D, Huq F, Guerrero JL, Hajjar RJ. In vivo gene transfer of parvalbumin improves diastolic function in aged rat hearts. Cardiovasc Res 2005;66:318–323PubMedGoogle Scholar
  183. 183.
    Michele DE, Szatkowski ML, Albayya FP, Metzger JM. Parvalbumin gene delivery improves diastolic function in the aged myocardium in vivo. Mol Ther 2004;10:399–403PubMedGoogle Scholar
  184. 184.
    Huq F, Lebeche D, Iyer V, Liao R, Hajjar RJ. Gene transfer of parvalbumin improves diastolic dysfunction in senescent myocytes. Circulation 2004;109:2780–2785PubMedGoogle 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

Personalised recommendations