Mitochondria in the Aging Heart

  • José Marín-García
Chapter

Abstract

Aging is associated with progressive impairment of a variety of vital functions, resulting in an increased vulnerability to environmental challenges and a growing risk of disease and death. Cardiac aging, in particular, reduces cardiac functional reserve and predisposes the heart to stress, serving as one of the major risk factors for cardiovascular diseases (e.g., left ventricular hypertrophy, fibrosis, diastolic dysfunction). Thus, aging contributes to increased cardiovascular mortality in the elderly. During the last two decades, several different molecular pathways involved in the aging process have been revealed, and mitochondria were pointed out as one of the key regulators of longevity. Aging of cardiac tissue is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, deterioration of the respiratory chain function, and changes in mitochondrial biogenesis. Respiratory chain-deficient cells are more susceptible to undergo apoptosis, and increased cell loss is likely to be associated with the age-associated mitochondrial dysfunction.

Keywords

Cholesterol Ischemia Lymphoma Attenuation Glutathione 

References

  1. 1.
    Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115(5):e69–171.PubMedCrossRefGoogle Scholar
  2. 2.
    Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.PubMedGoogle Scholar
  3. 3.
    Bandy B, Davison AJ. Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Radic Biol Med. 1990;8(6):523–39.PubMedCrossRefGoogle Scholar
  4. 4.
    Hiona A, Leeuwenburgh C. The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Exp Gerontol. 2008;43(1):24–33.PubMedCrossRefGoogle Scholar
  5. 5.
    Kujoth GC, Leeuwenburgh C, Prolla TA. Mitochondrial DNA mutations and apoptosis in mammalian aging. Cancer Res. 2006;66(15):7386–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Kujoth GC, Hiona A, Pugh TD, et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005;309(5733):481–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Trifunovic A, Wredenberg A, Falkenberg M, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429(6990):417–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120(4):483–95.PubMedCrossRefGoogle Scholar
  9. 9.
    Navarro A, Boveris A. The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol. 2007;292(2):C670–86.PubMedCrossRefGoogle Scholar
  10. 10.
    Ago T, Matsushima S, Kuroda J, Zablocki D, Kitazono T, Sadoshima J. The NADPH oxidase Nox4 and aging in the heart. Aging (Albany NY). 2010;2(12):1012–6.Google Scholar
  11. 11.
    Ago T, Kuroda J, Pain J, Fu C, Li H, Sadoshima J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res. 2010;106(7):1253–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, Sadoshima J. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci USA. 2010;107(35):15565–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Dai DF, Rabinovitch PS. Cardiac aging in mice and humans: the role of mitochondrial oxidative stress. Trends Cardiovasc Med. 2009;19(7):213–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Riobo NA, Clementi E, Melani M, et al. Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation. Biochem J. 2001;359(Pt 1):139–45.PubMedCrossRefGoogle Scholar
  15. 15.
    Murray J, Taylor SW, Zhang B, Ghosh SS, Capaldi RA. Oxidative damage to mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass spectrometry. J Biol Chem. 2003;278(39):37223–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Cassina AM, Hodara R, Souza JM, et al. Cytochrome c nitration by peroxynitrite. J Biol Chem. 2000;275(28):21409–15.PubMedCrossRefGoogle Scholar
  17. 17.
    Castro L, Rodriguez M, Radi R. Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem. 1994;269(47):29409–15.PubMedGoogle Scholar
  18. 18.
    Schriner SE, Linford NJ, Martin GM, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005;308(5730):1909–11.PubMedCrossRefGoogle Scholar
  19. 19.
    Dai DF, Santana LF, Vermulst M, et al. Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation. 2009;119(21):2789–97.PubMedCrossRefGoogle Scholar
  20. 20.
    Suh JH, Heath SH, Hagen TM. Two subpopulations of mitochondria in the aging rat heart display heterogenous levels of oxidative stress. Free Radic Biol Med. 2003;35(9):1064–72.PubMedCrossRefGoogle Scholar
  21. 21.
    Judge S, Jang YM, Smith A, Hagen T, Leeuwenburgh C. Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB J. 2005;19(3):419–21.PubMedGoogle Scholar
  22. 22.
    Harper ME, Bevilacqua L, Hagopian K, Weindruch R, Ramsey JJ. Ageing, oxidative stress, and mitochondrial uncoupling. Acta Physiol Scand. 2004;182(4):321–31.PubMedCrossRefGoogle Scholar
  23. 23.
    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(23):14988–93.PubMedCrossRefGoogle Scholar
  24. 24.
    Kumaran S, Subathra M, Balu M, Panneerselvam C. Age-associated decreased activities of mitochondrial electron transport chain complexes in heart and skeletal muscle: role of L-carnitine. Chem Biol Interact. 2004;148(1–2):11–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Rodriguez MI, Carretero M, Escames G, et al. Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice. Free Radic Res. 2007;41(1):15–24.PubMedCrossRefGoogle Scholar
  26. 26.
    Kumaran S, Subathra M, Balu M, Panneerselvam C. Supplementation of l-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats. Exp Aging Res. 2005;31(1):55–67.PubMedCrossRefGoogle Scholar
  27. 27.
    Yarian CS, Toroser D, Sohal RS. Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice. Mech Ageing Dev. 2006;127(1):79–84.PubMedCrossRefGoogle Scholar
  28. 28.
    Phaneuf S, Leeuwenburgh C. Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol Regul Integr Comp Physiol. 2002;282(2):R423–30.PubMedGoogle Scholar
  29. 29.
    Preston CC, Oberlin AS, Holmuhamedov EL, et al. Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart. Mech Ageing Dev. 2008;129(6):304–12.PubMedCrossRefGoogle Scholar
  30. 30.
    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(2):181–90.PubMedCrossRefGoogle Scholar
  31. 31.
    Cocco T, Sgobbo P, Clemente M, et al. 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(6):796–805.PubMedCrossRefGoogle Scholar
  32. 32.
    Choksi KB, Papaconstantinou J. Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes. Free Radic Biol Med. 2008;44(10):1795–805.PubMedCrossRefGoogle Scholar
  33. 33.
    Tatarkova Z, Kuka S, Racay P, et al. Effects of aging on activities of mitochondrial electron transport chain complexes and oxidative damage in rat heart. Physiol Res. 2011;60(2):281–9.PubMedGoogle Scholar
  34. 34.
    Kwong LK, Sohal RS. Age-related changes in activities of mitochondrial electron transport complexes in various tissues of the mouse. Arch Biochem Biophys. 2000;373(1):16–22.PubMedCrossRefGoogle Scholar
  35. 35.
    Leeuwenburgh C, Wagner P, Holloszy JO, Sohal RS, Heinecke JW. Caloric restriction attenuates dityrosine cross-linking of cardiac and skeletal muscle proteins in aging mice. Arch Biochem Biophys. 1997;346(1):74–80.PubMedCrossRefGoogle Scholar
  36. 36.
    Babusikova E, Kaplan P, Lehotsky J, Jesenak M, Dobrota D. Oxidative modification of rat cardiac mitochondrial membranes and myofibrils by hydroxyl radicals. Gen Physiol Biophys. 2004;23(3):327–35.PubMedGoogle Scholar
  37. 37.
    Chen J, Schenker S, Frosto TA, Henderson GI. Inhibition of cytochrome c oxidase activity by 4-hydroxynonenal (HNE). Role of HNE adduct formation with the enzyme subunits. Biochim Biophys Acta. 1998;1380(3):336–44.PubMedCrossRefGoogle Scholar
  38. 38.
    Humphries KM, Szweda LI. Selective inactivation of alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase: reaction of lipoic acid with 4-hydroxy-2-nonenal. Biochemistry. 1998;37(45):15835–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaplan P, Tatarkova Z, Racay P, Lehotsky J, Pavlikova M, Dobrota D. Oxidative modifications of cardiac mitochondria and inhibition of cytochrome c oxidase activity by 4-hydroxynonenal. Redox Rep. 2007;12(5):211–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Long J, Wang X, Gao H, et al. Malonaldehyde acts as a mitochondrial toxin: inhibitory effects on respiratory function and enzyme activities in isolated rat liver mitochondria. Life Sci. 2006;79(15):1466–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Gomez LA, Monette JS, Chavez JD, Maier CS, Hagen TM. Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart. Arch Biochem Biophys. 2009;490(1):30–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Pepe S, Tsuchiya N, Lakatta EG, Hansford RG. PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH. Am J Physiol. 1999;276(1 Pt 2):H149–58.PubMedGoogle Scholar
  43. 43.
    McLennan PL, Abeywardena MY, Charnock JS. The influence of age and dietary fat in an animal model of sudden cardiac death. Aust N Z J Med. 1989;19(1):1–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Pepe S, McLennan PL. Dietary fish oil confers direct anti­arrhythmic properties on the myocardium of rats. J Nutr. 1996;126(1):34–42.PubMedGoogle Scholar
  45. 45.
    Pepe S, McLennan PL. Cardiac membrane fatty acid composition modulates myocardial oxygen consumption and postischemic recovery of contractile function. Circulation. 2002;105(19):2303–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Hallman M, Kankare P. Mitochondrial and microsomal phospholipid phosphorus metabolism during postnatal growth in rat heart and liver. Lipids. 1979;14(5):435–40.PubMedCrossRefGoogle Scholar
  47. 47.
    Nagatomo T, Hattori K, Ikeda M, Shimada K. Lipid composition of sarcolemma, mitochondria and sarcoplasmic reticulum from newborn and adult rabbit cardiac muscle. Biochem Med. 1980;23(1):108–18.PubMedCrossRefGoogle Scholar
  48. 48.
    McMurchie EJ, Raison JK. Membrane lipid fluidity and its effect on the activation energy of membrane-associated enzymes. Biochim Biophys Acta. 1979;554(2):364–74.PubMedCrossRefGoogle Scholar
  49. 49.
    Innis SM, Clandinin MT. Dynamic modulation of mitochondrial membrane physical properties and ATPase activity by diet lipid. Biochem J. 1981;198(1):167–75.PubMedGoogle Scholar
  50. 50.
    Innis SM, Clandinin MT. Dynamic modulation of mitochondrial inner-membrane lipids in rat heart by dietary fat. Biochem J. 1981;193(1):155–67.PubMedGoogle Scholar
  51. 51.
    Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1991;11(1):81–128.PubMedCrossRefGoogle Scholar
  52. 52.
    Lucas DT, Szweda LI. Cardiac reperfusion injury: aging, lipid peroxidation, and mitochondrial dysfunction. Proc Natl Acad Sci USA. 1998;95(2):510–4.PubMedCrossRefGoogle Scholar
  53. 53.
    Lucas DT, Szweda LI. Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-­ketoglutarate dehydrogenase. Proc Natl Acad Sci USA. 1999;96(12):6689–93.PubMedCrossRefGoogle Scholar
  54. 54.
    Droge W. Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp Gerontol. 2002;37(12):1333–45.PubMedCrossRefGoogle Scholar
  55. 55.
    Quiles JL, Pamplona R, Ramirez-Tortosa MC, et al. Coenzyme Q addition to an n-6 PUFA-rich diet resembles benefits on age-related mitochondrial DNA deletion and oxidative stress of a MUFA-rich diet in rat heart. Mech Ageing Dev. 2010;131(1):38–47.PubMedCrossRefGoogle Scholar
  56. 56.
    Vieira HL, Belzacq AS, Haouzi D, et al. The adenine nucleotide translocator: a target of nitric oxide, peroxynitrite, and 4-hydroxynonenal. Oncogene. 2001;20(32):4305–16.PubMedCrossRefGoogle Scholar
  57. 57.
    Quiles JL, Martinez E, Ibanez S, et al. Ageing-related tissue-specific alterations in mitochondrial composition and function are modulated by dietary fat type in the rat. J Bioenerg Biomembr. 2002;34(6):517–24.PubMedCrossRefGoogle Scholar
  58. 58.
    Quiles JL, Ochoa JJ, Ramirez-Tortosa C, et al. Dietary fat type (virgin olive vs. sunflower oils) affects age-related changes in DNA double-strand-breaks, antioxidant capacity and blood lipids in rats. Exp Gerontol. 2004;39(8):1189–98.PubMedCrossRefGoogle Scholar
  59. 59.
    Quiles JL, Ochoa JJ, Ramirez-Tortosa MC, Huertas JR, Mataix J. Age-related mitochondrial DNA deletion in rat liver depends on dietary fat unsaturation. J Gerontol A Biol Sci Med Sci. 2006;61(2):107–14.PubMedCrossRefGoogle Scholar
  60. 60.
    Ochoa JJ, Quiles JL, Ibanez S, et al. Aging-related oxidative stress depends on dietary lipid source in rat postmitotic tissues. J Bioenerg Biomembr. 2003;35(3):267–75.PubMedCrossRefGoogle Scholar
  61. 61.
    Pamplona R, Barja G, Portero-Otin M. Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation? Ann N Y Acad Sci. 2002;959:475–90.PubMedCrossRefGoogle Scholar
  62. 62.
    Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA. Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev. 2007;87(4):1175–213.PubMedCrossRefGoogle Scholar
  63. 63.
    Paradies G, Petrosillo G, Paradies V, Ruggiero FM. Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease. Cell Calcium. 2009;45(6):643–50.PubMedCrossRefGoogle Scholar
  64. 64.
    Schlame M, Rua D, Greenberg ML. The biosynthesis and functional role of cardiolipin. Prog Lipid Res. 2000;39(3):257–88.PubMedCrossRefGoogle Scholar
  65. 65.
    Houtkooper RH, Vaz FM. Cardiolipin, the heart of mitochondrial metabolism. Cell Mol Life Sci. 2008;65(16):2493–506.PubMedCrossRefGoogle Scholar
  66. 66.
    Lesnefsky EJ, Stoll MS, Minkler PE, Hoppel CL. Separation and quantitation of phospholipids and lysophospholipids by high-performance liquid chromatography. Anal Biochem. 2000;285(2):246–54.PubMedCrossRefGoogle Scholar
  67. 67.
    Lesnefsky EJ, Slabe TJ, Stoll MS, Minkler PE, Hoppel CL. Myocardial ischemia selectively depletes cardiolipin in rabbit heart subsarcolemmal mitochondria. Am J Physiol Heart Circ Physiol. 2001;280(6):H2770–8.PubMedGoogle Scholar
  68. 68.
    Sevanian A, Wratten ML, McLeod LL, Kim E. Lipid peroxidation and phospholipase A2 activity in liposomes composed of unsaturated phospholipids: a structural basis for enzyme activation. Biochim Biophys Acta. 1988;961(3):316–27.PubMedCrossRefGoogle Scholar
  69. 69.
    Iwase H, Sakurada K, Hatanaka K, Kobayashi M, Takatori T. Effect of cytochrome c on the linoleic acid-degrading activity of porcine leukocyte 12-lipoxygenase. Free Radic Biol Med. 2000;28(6):912–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Iwase H, Takatori T, Nagao M, et al. Formation of keto and hydroxy compounds of linoleic acid in submitochondrial particles of bovine heart. Free Radic Biol Med. 1998;24(9):1492–503.PubMedCrossRefGoogle Scholar
  71. 71.
    Moghaddas S, Stoll MS, Minkler PE, Salomon RG, Hoppel CL, Lesnefsky EJ. Preservation of cardiolipin content during aging in rat heart interfibrillar mitochondria. J Gerontol A Biol Sci Med Sci. 2002;57(1):B22–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Lesnefsky EJ, Minkler P, Hoppel CL. Enhanced modification of cardiolipin during ischemia in the aged heart. J Mol Cell Cardiol. 2009;46(6):1008–15.PubMedCrossRefGoogle Scholar
  73. 73.
    Petrosillo G, Moro N, Paradies V, Ruggiero FM, Paradies G. Increased susceptibility to Ca(2+)-induced permeability transition and to cytochrome c release in rat heart mitochondria with aging: effect of melatonin. J Pineal Res. 2010;48(4):340–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Paradies G, Ruggiero FM, Petrosillo G, Quagliariello E. Age-dependent decline in the cytochrome c oxidase activity in rat heart mitochondria: role of cardiolipin. FEBS Lett. 1997;406(1–2):136–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Paradies G, Ruggiero FM, Petrosillo G, Quagliariello E. Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin alterations. FEBS Lett. 1998;424(3):155–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S. Cytochrome c release from mitochondria proceeds by a two-step process. Proc Natl Acad Sci USA. 2002;99(3):1259–63.PubMedCrossRefGoogle Scholar
  77. 77.
    Shidoji Y, Hayashi K, Komura S, Ohishi N, Yagi K. Loss of molecular interaction between cytochrome c and cardiolipin due to lipid peroxidation. Biochem Biophys Res Commun. 1999;264(2):343–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Kagan VE, Tyurin VA, Jiang J, et al. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol. 2005;1(4):223–32.PubMedCrossRefGoogle Scholar
  79. 79.
    Rytomaa M, Kinnunen PK. Evidence for two distinct acidic phospholipid-binding sites in cytochrome c. J Biol Chem. 1994;269(3):1770–4.PubMedGoogle Scholar
  80. 80.
    Salamon Z, Tollin G. Interaction of horse heart cytochrome c with lipid bilayer membranes: effects on redox potentials. J Bioenerg Biomembr. 1997;29(3):211–21.PubMedCrossRefGoogle Scholar
  81. 81.
    Spooner PJ, Watts A. Cytochrome c interactions with cardiolipin in bilayers: a multinuclear magic-angle spinning NMR study. Biochemistry. 1992;31(41):10129–38.PubMedCrossRefGoogle Scholar
  82. 82.
    Liu L, Azhar G, Gao W, Zhang X, Wei JY. Bcl-2 and Bax expression in adult rat hearts after coronary occlusion: age-associated differences. Am J Physiol. 1998;275(1 Pt 2):R315–22.PubMedGoogle Scholar
  83. 83.
    Tani M, Suganuma Y, Hasegawa H, et al. Decrease in ischemic tolerance with aging in isolated perfused Fischer 344 rat hearts: relation to increases in intracellular Na+ after ischemia. J Mol Cell Cardiol. 1997;29(11):3081–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Frolkis VV, Frolkis RA, Mkhitarian LS, Fraifeld VE. Age-dependent effects of ischemia and reperfusion on cardiac function and Ca2+ transport in myocardium. Gerontology. 1991;37(5):233–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Ataka K, Chen D, Levitsky S, Jimenez E, Feinberg H. Effect of aging on intracellular Ca2+, pHi, and contractility during ischemia and reperfusion. Circulation. 1992;86(5 Suppl):II371–6.PubMedGoogle Scholar
  86. 86.
    Azhar G, Gao W, Liu L, Wei JY. Ischemia-reperfusion in the adult mouse heart influence of age. Exp Gerontol. 1999;34(5):699–714.PubMedCrossRefGoogle Scholar
  87. 87.
    Lesnefsky EJ, Lundergan CF, Hodgson JM, et al. Increased left ventricular dysfunction in elderly patients despite successful thrombolysis: the GUSTO-I angiographic experience. J Am Coll Cardiol. 1996;28(2):331–7.PubMedCrossRefGoogle Scholar
  88. 88.
    Monette JS, Gomez LA, Moreau RF, Bemer BA, Taylor AW, Hagen TM. Characteristics of the rat cardiac sphingolipid pool in two mitochondrial subpopulations. Biochem Biophys Res Commun. 2010;398(2):272–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Monette JS, Gomez LA, Moreau RF, et al. (R)-alpha-Lipoic acid treatment restores ceramide balance in aging rat cardiac mitochondria. Pharmacol Res. 2011;63(1):23–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Futerman AH, Hannun YA. The complex life of simple sphingolipids. EMBO Rep. 2004;5(8):777–82.PubMedCrossRefGoogle Scholar
  91. 91.
    Lang PA, Schenck M, Nicolay JP, et al. Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. Nat Med. 2007;13(2):164–70.PubMedCrossRefGoogle Scholar
  92. 92.
    Birbes H, El Bawab S, Obeid LM, Hannun YA. Mitochondria and ceramide: intertwined roles in regulation of apoptosis. Adv Enzyme Regul. 2002;42:113–29.PubMedCrossRefGoogle Scholar
  93. 93.
    Gudz TI, Tserng KY, Hoppel CL. Direct inhibition of mitochondrial respiratory chain complex III by cell-permeable ceramide. J Biol Chem. 1997;272(39):24154–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Di Paola M, Cocco T, Lorusso M. Ceramide interaction with the respiratory chain of heart mitochondria. Biochemistry. 2000;39(22):6660–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Garcia-Ruiz C, Colell A, Mari M, Morales A, Fernandez-Checa JC. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. J Biol Chem. 1997;272(17):11369–77.PubMedCrossRefGoogle Scholar
  96. 96.
    Rutkute K, Asmis RH, Nikolova-Karakashian MN. Regulation of neutral sphingomyelinase-2 by GSH: a new insight to the role of oxidative stress in aging-associated inflammation. J Lipid Res. 2007;48(11):2443–52.PubMedCrossRefGoogle Scholar
  97. 97.
    Liu B, Hannun YA. Inhibition of the neutral magnesium-dependent sphingomyelinase by glutathione. J Biol Chem. 1997;272(26):16281–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Suh JH, Wang H, Liu RM, Liu J, Hagen TM. (R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Arch Biochem Biophys. 2004;423(1):126–35.PubMedCrossRefGoogle Scholar
  99. 99.
    Cortopassi GA, Arnheim N. Detection of a specific mitochondrial DNA deletion in tissues of older humans. Nucleic Acids Res. 1990;18(23):6927–33.PubMedCrossRefGoogle Scholar
  100. 100.
    Corral-Debrinski M, Shoffner JM, Lott MT, Wallace DC. Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutat Res. 1992;275(3–6):169–80.PubMedGoogle Scholar
  101. 101.
    Sugiyama S, Hattori K, Hayakawa M, Ozawa T. Quantitative analysis of age-associated accumulation of mitochondrial DNA with deletion in human hearts. Biochem Biophys Res Commun. 1991;180(2):894–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell. 1990;61(6):931–7.PubMedCrossRefGoogle Scholar
  103. 103.
    Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990;348(6302):651–3.PubMedCrossRefGoogle Scholar
  104. 104.
    Vermulst M, Wanagat J, Kujoth GC, et al. DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat Genet. 2008;40(4):392–4.PubMedCrossRefGoogle Scholar
  105. 105.
    Edgar D, Shabalina I, Camara Y, et al. Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab. 2009;10(2):131–8.PubMedCrossRefGoogle Scholar
  106. 106.
    Zhang C, Bills M, Quigley A, Maxwell RJ, Linnane AW, Nagley P. Varied prevalence of age-associated mitochondrial DNA deletions in different species and tissues: a comparison between human and rat. Biochem Biophys Res Commun. 1997;230(3):630–5.PubMedCrossRefGoogle Scholar
  107. 107.
    Corral-Debrinski M, Stepien G, Shoffner JM, Lott MT, Kanter K, Wallace DC. Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease. JAMA. 1991;266(13):1812–6.PubMedCrossRefGoogle Scholar
  108. 108.
    Muller-Hocker J. Cytochrome-c-oxidase deficient cardiomyocytes in the human heart–an age-related phenomenon. A histochemical ultracytochemical study. Am J Pathol. 1989;134(5):1167–73.PubMedGoogle Scholar
  109. 109.
    Trifunovic A, Larsson NG. Mitochondrial dysfunction as a cause of ageing. J Intern Med. 2008;263(2):167–78.PubMedCrossRefGoogle Scholar
  110. 110.
    Zheng W, Khrapko K, Coller HA, Thilly WG, Copeland WC. Origins of human mitochondrial point mutations as DNA polymerase gamma-mediated errors. Mutat Res. 2006;599(1–2):11–20.PubMedGoogle Scholar
  111. 111.
    Stuart JA, Bourque BM, de Souza-Pinto NC, Bohr VA. No evidence of mitochondrial respiratory dysfunction in OGG1-null mice deficient in removal of 8-oxodeoxyguanine from mitochondrial DNA. Free Radic Biol Med. 2005;38(6):737–45.PubMedCrossRefGoogle Scholar
  112. 112.
    Wang J, Silva JP, Gustafsson CM, Rustin P, Larsson NG. Increased in vivo apoptosis in cells lacking mitochondrial DNA gene expression. Proc Natl Acad Sci USA. 2001;98(7):4038–43.PubMedCrossRefGoogle Scholar
  113. 113.
    Trifunovic A, Hansson A, Wredenberg A, et al. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA. 2005;102(50):17993–8.PubMedCrossRefGoogle Scholar
  114. 114.
    Anversa P, Hiler B, Ricci R, Guideri G, Olivetti G. Myocyte cell loss and myocyte hypertrophy in the aging rat heart. J Am Coll Cardiol. 1986;8(6):1441–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Anversa P, Palackal T, Sonnenblick EH, Olivetti G, Meggs LG, Capasso JM. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ Res. 1990;67(4):871–85.PubMedCrossRefGoogle Scholar
  116. 116.
    Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res. 1991;68(6):1560–8.PubMedCrossRefGoogle Scholar
  117. 117.
    Wanagat J, Wolff MR, Aiken JM. Age-associated changes in function, structure and mitochondrial genetic and enzymatic abnormalities in the Fischer 344 x Brown Norway F(1) hybrid rat heart. J Mol Cell Cardiol. 2002;34(1):17–28.PubMedCrossRefGoogle Scholar
  118. 118.
    Kajstura J, Cheng W, Sarangarajan R, et al. Necrotic and apoptotic myocyte cell death in the aging heart of Fischer 344 rats. Am J Physiol. 1996;271(3 Pt 2):H1215–28.PubMedGoogle Scholar
  119. 119.
    Ljubicic V, Menzies KJ, Hood DA. Mitochondrial dysfunction is associated with a pro-apoptotic cellular environment in senescent cardiac muscle. Mech Ageing Dev. 2010;131(2):79–88.PubMedCrossRefGoogle Scholar
  120. 120.
    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(2):233–44.PubMedCrossRefGoogle Scholar
  121. 121.
    Packer MA, Scarlett JL, Martin SW, Murphy MP. Induction of the mitochondrial permeability transition by peroxynitrite. Biochem Soc Trans. 1997;25(3):909–14.PubMedGoogle Scholar
  122. 122.
    Petrosillo G, Casanova G, Matera M, Ruggiero FM, Paradies G. Interaction of peroxidized cardiolipin with rat-heart mitochondrial membranes: induction of permeability transition and cytochrome c release. FEBS Lett. 2006;580(27):6311–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Petrosillo G, Moro N, Ruggiero FM, Paradies G. Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release. Free Radic Biol Med. 2009;47(7):969–74.PubMedCrossRefGoogle Scholar
  124. 124.
    Hofer T, Servais S, Seo AY, et al. Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: effects of aging and lifelong calorie restriction. Mech Ageing Dev. 2009;130(5):297–307.PubMedCrossRefGoogle Scholar
  125. 125.
    Primeau AJ, Adhihetty PJ, Hood DA. Apoptosis in heart and skeletal muscle. Can J Appl Physiol. 2002;27(4):349–95.PubMedCrossRefGoogle Scholar
  126. 126.
    Gustafsson AB, Gottlieb RA. Heart mitochondria: gates of life and death. Cardiovasc Res. 2008;77(2):334–43.PubMedCrossRefGoogle Scholar
  127. 127.
    Tuominen EK, Wallace CJ, Kinnunen PK. Phospholipid-cytochrome c interaction: evidence for the extended lipid anchorage. J Biol Chem. 2002;277(11):8822–6.PubMedCrossRefGoogle Scholar
  128. 128.
    Petrosillo G, Ruggiero FM, Pistolese M, Paradies G. Reactive oxygen species generated from the mitochondrial electron transport chain induce cytochrome c dissociation from beef-heart submitochondrial particles via cardiolipin peroxidation. Possible role in the apoptosis. FEBS Lett. 2001;509(3):435–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Kagan VE, Borisenko GG, Tyurina YY, et al. Oxidative lipidomics of apoptosis: redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine. Free Radic Biol Med. 2004;37(12):1963–85.PubMedCrossRefGoogle Scholar
  130. 130.
    Grazette LP, Boecker W, Matsui T, et al. Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes: implications for herceptin-induced cardiomyopathy. J Am Coll Cardiol. 2004;44(11):2231–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Rohrbach S, Muller-Werdan U, Werdan K, Koch S, Gellerich NF, Holtz J. Apoptosis-modulating interaction of the neuregulin/erbB pathway with anthracyclines in regulating Bcl-xS and Bcl-xL in cardiomyocytes. J Mol Cell Cardiol. 2005;38(3):485–93.PubMedCrossRefGoogle Scholar
  132. 132.
    Rohrbach S, Niemann B, Abushouk AM, Holtz J. Caloric restriction and mitochondrial function in the ageing myocardium. Exp Gerontol. 2006;41(5):525–31.PubMedCrossRefGoogle Scholar
  133. 133.
    Gross A, Jockel J, Wei MC, Korsmeyer SJ. Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J. 1998;17(14):3878–85.PubMedCrossRefGoogle Scholar
  134. 134.
    Saikumar P, Dong Z, Patel Y, et al. Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene. 1998;17(26):3401–15.PubMedCrossRefGoogle Scholar
  135. 135.
    Murphy KM, Streips UN, Lock RB. Bax membrane insertion during Fas(CD95)-induced apoptosis precedes cytochrome c release and is inhibited by Bcl-2. Oncogene. 1999;18(44):5991–9.PubMedCrossRefGoogle Scholar
  136. 136.
    Karbowski M, Lee YJ, Gaume B, et al. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. J Cell Biol. 2002;159(6):931–8.PubMedCrossRefGoogle Scholar
  137. 137.
    Arnoult D, Rismanchi N, Grodet A, et al. Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death. Curr Biol. 2005;15(23):2112–8.PubMedCrossRefGoogle Scholar
  138. 138.
    Neuspiel M, Zunino R, Gangaraju S, Rippstein P, McBride H. Activated mitofusin 2 signals mitochondrial fusion, interferes with Bax activation, and reduces susceptibility to radical induced depolarization. J Biol Chem. 2005;280(26):25060–70.PubMedCrossRefGoogle Scholar
  139. 139.
    Karbowski M, Norris KL, Cleland MM, Jeong SY, Youle RJ. Role of Bax and Bak in mitochondrial morphogenesis. Nature. 2006;443(7112):658–62.PubMedCrossRefGoogle Scholar
  140. 140.
    Sheridan C, Delivani P, Cullen SP, Martin SJ. Bax- or Bak-induced mitochondrial fission can be uncoupled from cytochrome C release. Mol Cell. 2008;31(4):570–85.PubMedCrossRefGoogle Scholar
  141. 141.
    Migliaccio E, Giorgio M, Mele S, et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature. 1999;402(6759):309–13.PubMedCrossRefGoogle Scholar
  142. 142.
    Giorgio M, Migliaccio E, Orsini F, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell. 2005;122(2):221–33.PubMedCrossRefGoogle Scholar
  143. 143.
    Orsini F, Moroni M, Contursi C, et al. Regulatory effects of the mitochondrial energetic status on mitochondrial p66Shc. Biol Chem. 2006;387(10–11):1405–10.PubMedGoogle Scholar
  144. 144.
    Pinton P, Rimessi A, Marchi S, et al. Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science. 2007;315(5812):659–63.PubMedCrossRefGoogle Scholar
  145. 145.
    Graiani G, Lagrasta C, Migliaccio E, et al. Genetic deletion of the p66Shc adaptor protein protects from angiotensin II-induced myocardial damage. Hypertension. 2005;46(2):433–40.PubMedCrossRefGoogle Scholar
  146. 146.
    Bianchi G, Di Giulio C, Rapino C, Rapino M, Antonucci A, Cataldi A. p53 and p66 proteins compete for hypoxia-inducible factor 1 alpha stabilization in young and old rat hearts exposed to intermittent hypoxia. Gerontology. 2006;52(1):17–23.PubMedCrossRefGoogle Scholar
  147. 147.
    Obreztchikova M, Elouardighi H, Ho M, Wilson BA, Gertsberg Z, Steinberg SF. Distinct signaling functions for Shc isoforms in the heart. J Biol Chem. 2006;281(29):20197–204.PubMedCrossRefGoogle Scholar
  148. 148.
    Malhotra A, Vashistha H, Yadav VS, et al. Inhibition of p66ShcA redox activity in cardiac muscle cells attenuates hyperglycemia-induced oxidative stress and apoptosis. Am J Physiol Heart Circ Physiol. 2009;296(2):H380–8.PubMedCrossRefGoogle Scholar
  149. 149.
    Craig EE, Hood DA. Influence of aging on protein import into cardiac mitochondria. Am J Physiol. 1997;272(6 Pt 2):H2983–8.PubMedGoogle Scholar
  150. 150.
    Frank S, Gaume B, Bergmann-Leitner ES, et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell. 2001;1(4):515–25.PubMedCrossRefGoogle Scholar
  151. 151.
    Olichon A, Baricault L, Gas N, et al. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem. 2003;278(10):7743–6.PubMedCrossRefGoogle Scholar
  152. 152.
    Lee YJ, Jeong SY, Karbowski M, Smith CL, Youle RJ. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol Biol Cell. 2004;15(11):5001–11.PubMedCrossRefGoogle Scholar
  153. 153.
    Arnoult D, Grodet A, Lee YJ, Estaquier J, Blackstone C. Release of OPA1 during apoptosis participates in the rapid and complete release of cytochrome c and subsequent mitochondrial fragmentation. J Biol Chem. 2005;280(42):35742–50.PubMedCrossRefGoogle Scholar
  154. 154.
    Frezza C, Cipolat S, Martins de Brito O, et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell. 2006;126(1):177–89.PubMedCrossRefGoogle Scholar
  155. 155.
    Estaquier J, Arnoult D. Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis. Cell Death Differ. 2007;14(6):1086–94.PubMedCrossRefGoogle Scholar
  156. 156.
    Youle RJ, Karbowski M. Mitochondrial fission in apoptosis. Nat Rev Mol Cell Biol. 2005;6(8):657–63.PubMedCrossRefGoogle Scholar
  157. 157.
    Iemitsu M, Miyauchi T, Maeda S, et al. Aging-induced decrease in the PPAR-alpha level in hearts is improved by exercise training. Am J Physiol Heart Circ Physiol. 2002;283(5):H1750–60.PubMedGoogle Scholar
  158. 158.
    Dinardo MM, Musicco C, Fracasso F, et al. Acetylation and level of mitochondrial transcription factor A in several organs of young and old rats. Biochem Biophys Res Commun. 2003;301(1):187–91.PubMedCrossRefGoogle Scholar
  159. 159.
    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(1–3):302–8.PubMedCrossRefGoogle Scholar
  160. 160.
    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(2):191–8.PubMedCrossRefGoogle Scholar
  161. 161.
    Jian B, Yang S, Chen D, Chaudry I, Raju R. Influence of aging and hemorrhage injury on Sirt1 expression: possible role of myc-Sirt1 regulation in mitochondrial function. Biochim Biophys Acta. 2011;1812(11):1446–51.PubMedCrossRefGoogle Scholar
  162. 162.
    Bodyak N, Kang PM, Hiromura M, et al. Gene expression profiling of the aging mouse cardiac myocytes. Nucleic Acids Res. 2002;30(17):3788–94.PubMedCrossRefGoogle Scholar
  163. 163.
    Andreu AL, Arbos MA, Perez-Martos A, et al. Reduced mitochondrial DNA transcription in senescent rat heart. Biochem Biophys Res Commun. 1998;252(3):577–81.PubMedCrossRefGoogle Scholar
  164. 164.
    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(3):501–6.PubMedCrossRefGoogle Scholar
  165. 165.
    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(2):179–93.PubMedCrossRefGoogle Scholar
  166. 166.
    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(5):3343–7.PubMedCrossRefGoogle Scholar
  167. 167.
    Goyns MH, Charlton MA, Dunford JE, et al. Differential display analysis of gene expression indicates that age-related changes are restricted to a small cohort of genes. Mech Ageing Dev. 1998;101(1–2):73–90.PubMedCrossRefGoogle Scholar
  168. 168.
    Gadaleta MN, Rainaldi G, Lezza AM, Milella F, Fracasso F, Cantatore P. Mitochondrial DNA copy number and mitochondrial DNA deletion in adult and senescent rats. Mutat Res. 1992;275(3–6):181–93.PubMedGoogle Scholar
  169. 169.
    Frahm T, Mohamed SA, Bruse P, Gemund C, Oehmichen M, Meissner C. Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart. Mech Ageing Dev. 2005;126(11):1192–200.PubMedCrossRefGoogle Scholar
  170. 170.
    Miller FJ, Rosenfeldt FL, Zhang C, Linnane AW, Nagley P. Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. Nucleic Acids Res. 2003;31(11):e61.PubMedCrossRefGoogle Scholar
  171. 171.
    Hoppel CL, Moghaddas S, Lesnefsky EJ. Interfibrillar cardiac mitochondrial complex III defects in the aging rat heart. Biogerontology. 2002;3(1–2):41–4.PubMedCrossRefGoogle Scholar
  172. 172.
    Lesnefsky EJ, Gudz TI, Moghaddas S, et al. Aging decreases electron transport complex III activity in heart interfibrillar mitochondria by alteration of the cytochrome c binding site. J Mol Cell Cardiol. 2001;33(1):37–47.PubMedCrossRefGoogle Scholar
  173. 173.
    Fannin SW, Lesnefsky EJ, Slabe TJ, Hassan MO, Hoppel CL. Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria. Arch Biochem Biophys. 1999;372(2):399–407.PubMedCrossRefGoogle Scholar
  174. 174.
    Liesa M, Palacin M, Zorzano A. Mitochondrial dynamics in mammalian health and disease. Physiol Rev. 2009;89(3):799–845.PubMedCrossRefGoogle Scholar
  175. 175.
    Crane JD, Devries MC, Safdar A, Hamadeh MJ, Tarnopolsky MA. The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure. J Gerontol A Biol Sci Med Sci. 2010;65(2):119–28.PubMedCrossRefGoogle Scholar
  176. 176.
    Cartoni R, Leger B, Hock MB, et al. Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. J Physiol. 2005;567(Pt 1):349–58.PubMedCrossRefGoogle Scholar
  177. 177.
    Soriano FX, Liesa M, Bach D, Chan DC, Palacin M, Zorzano A. Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2. Diabetes. 2006;55(6):1783–91.PubMedCrossRefGoogle Scholar
  178. 178.
    Bergmann O, Bhardwaj RD, Bernard S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324(5923):98–102.PubMedCrossRefGoogle Scholar
  179. 179.
    Anversa P, Rota M, Urbanek K, et al. Myocardial aging—a stem cell problem. Basic Res Cardiol. 2005;100(6):482–93.PubMedCrossRefGoogle Scholar
  180. 180.
    Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458–60.PubMedCrossRefGoogle Scholar
  181. 181.
    Bodnar AG, Ouellette M, Frolkis M, et al. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279(5349):349–52.PubMedCrossRefGoogle Scholar
  182. 182.
    von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci. 2002;27(7):339–44.CrossRefGoogle Scholar
  183. 183.
    Passos JF, von Zglinicki T. Mitochondria, telomeres and cell senescence. Exp Gerontol. 2005;40(6):466–72.PubMedCrossRefGoogle Scholar
  184. 184.
    Saretzki G, Murphy MP, von Zglinicki T. MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress. Aging Cell. 2003;2(2):141–3.PubMedCrossRefGoogle Scholar
  185. 185.
    Liu L, Trimarchi JR, Smith PJ, Keefe DL. Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell. 2002;1(1):40–6.PubMedCrossRefGoogle Scholar
  186. 186.
    Jahangir A, Ozcan C, Holmuhamedov EL, Terzic A. Increased calcium vulnerability of senescent cardiac mitochondria: protective role for a mitochondrial potassium channel opener. Mech Ageing Dev. 2001;122(10):1073–86.PubMedCrossRefGoogle Scholar
  187. 187.
    Vitorica J, Cano J, Satrustegui J, Machado A. Comparison between developmental and senescent changes in enzyme activities linked to energy metabolism in rat heart. Mech Ageing Dev. 1981;16(2):105–16.PubMedCrossRefGoogle Scholar
  188. 188.
    De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 2011;476(7360):336–40.PubMedCrossRefGoogle Scholar
  189. 189.
    Di Lisa F, Bernardi P. Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition. Cardiovasc Res. 2005;66(2):222–32.PubMedCrossRefGoogle Scholar
  190. 190.
    Garlid KD, Dos Santos P, Xie ZJ, Costa AD, Paucek P. Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K(+) channel in cardiac function and cardio­protection. Biochim Biophys Acta. 2003;1606(1–3):1–21.PubMedGoogle Scholar
  191. 191.
    Lesnefsky EJ, Gallo DS, Ye J, Whittingham TS, Lust WD. Aging increases ischemia-reperfusion injury in the isolated, buffer-­perfused heart. J Lab Clin Med. 1994;124(6):843–51.PubMedGoogle Scholar
  192. 192.
    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(3):334–40.PubMedCrossRefGoogle Scholar
  193. 193.
    Schulman D, Latchman DS, Yellon DM. Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-­reperfusion injury. Am J Physiol Heart Circ Physiol. 2001;281(4):H1630–6.PubMedGoogle Scholar
  194. 194.
    Fenton RA, Dickson EW, Meyer TE, Dobson Jr JG. Aging reduces the cardioprotective effect of ischemic preconditioning in the rat heart. J Mol Cell Cardiol. 2000;32(7):1371–5.PubMedCrossRefGoogle Scholar
  195. 195.
    Goodell S, Cortopassi G. Analysis of oxygen consumption and mitochondrial permeability with age in mice. Mech Ageing Dev. 1998;101(3):245–56.PubMedCrossRefGoogle Scholar
  196. 196.
    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(1):H371–81.PubMedCrossRefGoogle Scholar
  197. 197.
    Madesh M, Hajnoczky G. VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J Cell Biol. 2001;155(6):1003–15.PubMedCrossRefGoogle Scholar
  198. 198.
    Nohl H, Kramer R. Molecular basis of age-dependent changes in the activity of adenine nucleotide translocase. Mech Ageing Dev. 1980;14(1–2):137–44.PubMedCrossRefGoogle Scholar
  199. 199.
    Crompton M. Mitochondrial intermembrane junctional complexes and their role in cell death. J Physiol. 2000;529(Pt 1):11–21.PubMedCrossRefGoogle Scholar
  200. 200.
    Chen JJ, Bertrand H, Yu BP. Inhibition of adenine nucleotide translocator by lipid peroxidation products. Free Radic Biol Med. 1995;19(5):583–90.PubMedCrossRefGoogle Scholar
  201. 201.
    Kristal BS, Park BK, Yu BP. 4-Hydroxyhexenal is a potent inducer of the mitochondrial permeability transition. J Biol Chem. 1996;271(11):6033–8.PubMedCrossRefGoogle Scholar
  202. 202.
    Chorna SV, Dosenko V, Strutyns’ka NA, Vavilova HL, Sahach VF. Increased expression of voltage-dependent anion channel and adenine nucleotide translocase and the sensitivity of calcium-induced mitochondrial permeability transition opening pore in the old rat heart. Fiziol Zh. 2010;56(4):19–25.PubMedGoogle Scholar
  203. 203.
    Woodfield K, Ruck A, Brdiczka D, Halestrap AP. Direct demonstration of a specific interaction between cyclophilin-D and the adenine nucleotide translocase confirms their role in the mitochondrial permeability transition. Biochem J. 1998;336(Pt 2):287–90.PubMedGoogle Scholar
  204. 204.
    Liu L, Zhu J, Brink PR, Glass PS, Rebecchi MJ. Age-associated differences in the inhibition of mitochondrial permeability transition pore opening by cyclosporine A. Acta Anaesthesiol Scand. 2011;55(5):622–30.PubMedCrossRefGoogle Scholar
  205. 205.
    Zhu J, Rebecchi MJ, Tan M, Glass PS, Brink PR, Liu L. Age-associated differences in activation of Akt/GSK-3beta signaling pathways and inhibition of mitochondrial permeability transition pore opening in the rat heart. J Gerontol A Biol Sci Med Sci. 2010;65(6):611–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • José Marín-García
    • 1
  1. 1.The Molecular Cardiology and Neuromuscular InstituteHighland ParkUSA

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