, Volume 19, Issue 4, pp 129–139 | Cite as

Glutathione, oxidative stress and aging

  • Juan Sastre
  • Federico V. Pallardó
  • Jose ViñaEmail author


The free radical theory of aging proposes that the impairment in physiological performance associated with aging is caused by the detrimental effects of oxygen free radicals. This is interesting because it provides us with a theoretical framework to understand aging and because it suggests a rationale for intervention, i.e., antioxidant administration. Thus, the study of antioxidant systems of the cell may be very important in gerontological studies. Glutathione is one of the main nonprotein antioxidants in the cell which, together with its related enzymes, constitute the “glutathione system.” The involvement of glutathione in aging has been known since the early seventies. Several studies have reported that reduced glutathione is decreased in cells from old animals, whereas oxidized glutathione tends to be increased. Recent experiments from our laboratory have underscored the importance of cellular compartmentation of glutathione. Mitochondrial glutathione plays a key role in the protection against free radical damage associated with aging. Oxidative damage to mitochondrial DNA is directly related to an oxidation of mitochondrial glutathione. In fact, aging is associated with oxidative damage to proteins, nucleic acids, and lipids. These molecular lesions may be responsible for the low physiological performance of aged cells. Thus, antioxidant supplementation may be a rational way to partially protect against age-associated impairment in performance. Apoptosis, a programmed cell death, is an area of research which has seen an explosive growth. Glutathione is involved in apoptosis: apoptotic cells have lower levels of reduced glutathione, and administration of glutathione precursors prevent, or at least delay, apoptosis. Age-associated diseases constitute a major concern for researchers involved in aging. Free radicals are involved in many such diseases; for instance, cancer, diabetes or atherosclerosis. The key role of glutathione and other antioxidants in the pathophysiology of aging and age-associated diseases is discussed in this review.


Glutathione aging mitochondria oxidative stress 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allen, R.G., Sohal, R.S.: Role ofglutathione in the aging and development of insects. In Insect aging. Collatz, K.G. and Sohal, R.S., Eds. Springer Verlag. Berlin Heidelberg. 1986 pp.168–181.Google Scholar
  2. Al-Turk, W., Stohs, S.J., El-Rashidy F.H., Othman, S.: Changes in glutathione and its metabolizing enzymes in human erythrocytes and lymphocytes with age J. Pharm. Pharmacol, 39: 13–16, 1987.PubMedGoogle Scholar
  3. Ames, B.N., Shigenaga, M., Hagen, T.M.: Oxidants, antioxidants and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA, 90: 7915–7922, 1993.PubMedGoogle Scholar
  4. Barja, G., Pérez-Campo, R., López-Torres, L., Cadenas, S., Rojas, C.: Low mitochondrial free radical production as a longevity determinant in species following or not the rate of living theory. Mech. Aging Dev., 1996 (in press).Google Scholar
  5. Beal, M.F., Hyman, B.T., Koroshetz, W.: Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? TINS, 16: 125–131, 1993.PubMedGoogle Scholar
  6. Benzi, G., Marzatico, F., Pastoris, O., Villa, R.F.: Relationship between aging, drug treatment and the cerebral enzymatic antioxidant system. Exp. Gerontol., 24: 137–148, 1989.PubMedCrossRefGoogle Scholar
  7. Buja, L.M., Eigenbrodt, M.L., Eigenbrodt, E.H.: Apoptosis and Necrosis. Basic Types and Mechanisms of Cell Death. Arch. Pathol. Lab. Med. 117, 1208–1214, 1993.PubMedGoogle Scholar
  8. Buttke, T.M., Sandstrom, P.A.: Oxidative stress as a mediator of apoptosis. Immunol. Today, 15: 7–10, 1994.PubMedCrossRefGoogle Scholar
  9. Cand, F. and Verdetti, J.: Superoxide dismutase, glutathione peroxidase, catalase, and lipid peroxidation in the major organs of the aging rats. Free Radical Biol. Med., 7:59–63, 1989.CrossRefGoogle Scholar
  10. Calleja, M., Peña, P., Ugalde, C., Ferreiro, C., Marco, R., Garesse, R.: Mitochondrial DNA remains intact during Drosophila aging, but the levels of mitochondrial transcripts are significantly reduced. J. Biol. Chem., 268:18891–18897, 1993.Google Scholar
  11. Cannon, J.G., Orencole, S.F., Fielding, R.A., Meydani, M., Meydani, S.N., Fiatarone, M.A., Blumberg, J.B., Evans, W.J.: Acute phase response in exercise-interaction of age and vitamin-E on neutrophils and muscle enzyme release. Am. J. Physiol., 259:1990.Google Scholar
  12. Carney, J.M., Starke-Reed, P.E., Oliver, C.N., Landum, R.W., Cheng, M.S., Wu, J.F. and Floyd, R.A.: Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-a-phenylnitrone. Proc. Natl. Acad. Sci. USA, 88:3633–3636, 1991.PubMedGoogle Scholar
  13. Chance, B., Sies, H., Boveris, A.: Hydroperoxide metabolism in mammalian organs. Physiological Rev., 59: 527–604, 1979.Google Scholar
  14. Corbisier, P., Remacle, J.: Involvement of mitochondria in cell degeneration. Eur. J. Cell Biol., 51: 173–182, 1990.PubMedGoogle Scholar
  15. Coyle, J., Puttfaarcken, P.: Oxidative stress, glutamate and neurodegenerative disorders. Science, 262: 689–694, 1993.PubMedGoogle Scholar
  16. Cutler, R.G.: Antioxidants and aging. Am. J. Clin. Nutr., 53: S373–S379, 1991.Google Scholar
  17. De la Cruz, J., Burón, I., Roncero, I.: Morphological and functional studies during aging at mitochondrial level. Action of drugs. Int. J. Biochem., 22:729–735, 1990.PubMedCrossRefGoogle Scholar
  18. Deckwerth, T.L., Johnson, E.M.: Temporal analysis of events associated with programmed cell death (apoptosis) of sympathetic neurons deprived of nerve growth factor. J. Cell Biol., 123: 1207–1222, 1993.PubMedCrossRefGoogle Scholar
  19. Devasagayam, T.P.: Senescence-associated decrease of NADPH-induced lipid peroxidation in rat liver microsomes. FEBS Lett. 205, 246–50, 1986.PubMedCrossRefGoogle Scholar
  20. Devasagayam, T.P. and Tarachand, U.: Decreased lipid peroxidation in the rat kidney during gestation. Biochem. Biophys. Res. Commun. 145, 134–8, 1987.PubMedCrossRefGoogle Scholar
  21. Estrela, J.M., Obrador, E., Navarro, J., Lasso-de-la-Vega, M.C., Pellicer, J.: Elimination of Ehrlich tumors by ATP-induced growth inhibition, glutathione depletion and X-rays. Nature Med. 1, 84–88, 1995.PubMedCrossRefGoogle Scholar
  22. Ferrer, J.V., Gascó, E., Sastre, J., Pallardó, F.V., Asensi, M., Vifia, J.: Age-related changes in glutathione synthesis in the eye lens. Biochem. J., 269: 531–534, 1990.PubMedGoogle Scholar
  23. Fucci, L., Oliver, C.N., Coon, M.J. and Stadtman, E.R.: Inactivation of key metabolic enzymes by mixed-function oxidation reactions: Possible implication in protein turnover and aging. Proc. Natl. Acad. Sci. USA, 80: 1521–1525, 1983.PubMedGoogle Scholar
  24. Furukawa, T., Meydani, S.N., Blumberg, J.B.: Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mech. Aging Dev., 38: 107–117, 1987.PubMedCrossRefGoogle Scholar
  25. Gadaleta, M.N., 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. 187: 501–506, 1990.PubMedCrossRefGoogle Scholar
  26. Garcia de la Asuncion, J., Millán, A., Pill, R., Bruseghini, L., Esteras, A., Pallardó, F.V., Sastre, J., Viña, J.: Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA. FASEB J., 10: 333–338, 1996.Google Scholar
  27. Garland, D., Russell, P., Zigler, J.S. Jr.: The oxidative modification of lens proteins. Basic Life Sci. 49, 347–52. 1988.PubMedGoogle Scholar
  28. Goldschmidt, L.: Seasonal variations in red cell glutathione levels with aging in mental patients and normal controls. Proc. Soc. Exp. Biol. Med., 133: 555–559, 1970.PubMedGoogle Scholar
  29. Gordillo, E., Ayala, A., Lobato, M., Bautista, J., Machado, A.: Possible involvement of histidine residues in the loss of enzymatic activity of rat liver malic enzyme during aging. J. Biol. Chem., 263, 8053–8056, 1988.PubMedGoogle Scholar
  30. Gotz, M.E., Freyberger, A., Riederer, P.: Oxidative Stress — A Role in the Pathogenesis of Parkinsons Disease. J. Neur. Transmission, 29: 241–249, 1990.Google Scholar
  31. Gutteridge, J.M.C.: Copper-phenanthroline induced site specific oxygen radical damage to DNA. Detection of loosely bound trace copper in biological fluids. Biochem. J., 218: 983–985, 1984.PubMedGoogle Scholar
  32. Gutteridge, J.M.C., Westermarck, T., and Halliwell, B.: Oxygen radical damage in biological systems. In: Free Radicals, Aging and Degenerative Diseases, pp: 99–139. eds J.E. Johson Jr., R. Walford, D. Harman, J. Miquel. Alan R. Liss, 1986.Google Scholar
  33. Halliwell, B., Gutteridge, J.M.C.: Free Radicals in Biology and Medicine. Claredon, Oxford. 1989.Google Scholar
  34. Hansford, R.G.: Lipid oxidation by heart mitochondria from young adult and senescent rats. Biochem J;170: 285–295, 1978.PubMedGoogle Scholar
  35. Harman, D.: Aging: a theory based on free radical and radiation chemistry J. Gerontol, 11: 298–300, 1956.PubMedGoogle Scholar
  36. Harman, D.: The aging process-Major risk factor for disease and death. Proc. Nat. Acad. Sci. USA, 88: 5360–5363, 1991.PubMedGoogle Scholar
  37. Hazelton, G.A., Lang, C.A.: Glutathione contents of tissues in the aging mouse. Biochem. J;188: 25–30, 1980.PubMedGoogle Scholar
  38. Hockenbery, D.M., Oltvai, Z.N., Yin, X.M., Milliman, C.L., Korsmeyer, S.J.: Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241–251, 1993.PubMedCrossRefGoogle Scholar
  39. Ikebe, S., Tanaka, M., Ohno, K., Sato, W., Hattori, K., Kondo, T., Mizuno, Y., Ozawa, T.: Increase of deleted mitochondrial DNA in the striatum in Parkinsons Disease and senescence. Biochem. Biophys. Res. Commun; 170: 1044–1048, 1990.PubMedCrossRefGoogle Scholar
  40. Jankovic, B.D.: Neuromodulation. From phenomenology to molecular evidence. Ann. N.Y. Acad. Sci. 741, 1–38, 1994.PubMedGoogle Scholar
  41. Johns, D.R.: Mitochondrial DNA and disease. New Engl. J. Med; 333:638–644, 1995.PubMedCrossRefGoogle Scholar
  42. Kalra, J., Rajput, A.H., Mantha, S.V., Chaudhary, A.K., Prasad, K.: Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson’s disease. Moll. Cell. Biochem. 112, 181–6, 1992.CrossRefGoogle Scholar
  43. Knekt, P., Heliovaara, M., Rissanen, A., Aromaa, A., Aaran, R.-K.: Serum antioxidant vitamins and risk of cataract. Br. Med. J. 305: 1392–1394, 1992.CrossRefGoogle Scholar
  44. Kroemer, G., Petit, P., Zamzami, N., Vaysiere, J.L. and Mignotte, B.: The biochemistry of programmed cell death. FASEB J; 9:1277–1287, 1995.PubMedGoogle Scholar
  45. Ku, H., Brunk, U.T., Sohal, R.S.: Relationship between mitochondrial superoxide and hydroperoxide production and longevity of mammalian species. Free Radical Biol. Med; 15: 621–627, 1993.CrossRefGoogle Scholar
  46. Leske, M.C., Chylack, L.T. Jr., Wu, S.Y.: The lens opacities case-control study. Risk factors for cataract. Arch. Ophthalmol. 109: 244–251, 1991.PubMedGoogle Scholar
  47. Levine, R.L.: Oxidative modification of glutamine synthetase II. Characterization of the ascorbate model system. J. Biol. Chem; 258:11828–11833, 1983.Google Scholar
  48. Linnane, A., Marzuki, S., Ozawa, T., Tanaka, M.: Mitochondrial DNA mutations as an important contributor to aging and degenerative diseases. Lancet, 642–645, 1989.Google Scholar
  49. Lippman, R.D.: Rapid “in vivo” quantification and comparison of hydroperoxides and oxidized collagen in aging mice, rabbits and man. Exp. Gerontol, 20: 1–5, 1985.PubMedCrossRefGoogle Scholar
  50. Lippman, R.D.: Free radical-induced lipoperoxidation and aging. In: Handbook of Free Radicals and Antioxidants in Biomedicine Vol. I eds J. Miquel, A.T. Quintanilha, and H. Weber, CRC press, Boca Ratón Cal. USA. 1989.Google Scholar
  51. López-Torres, M., Pérez-Campo, R., Rojas, C., Cadenas, S., Barja, G.: Maximum life span in vertebrates: correlation with liver antioxidant enzymes, glutathione system, ascorbate, urate sensitivity to peroxidation, true malondialdehyde, in vivo H2O2 and basal and, maximum aerobic capacity. Mech. Aging and Dev., 70: 177–99, 1993.CrossRefGoogle Scholar
  52. Martensson, J., Steinherz, R., Jain, A., Meister, A.: Glutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage. Proc. Natl. Acad. Sci. USA, 86:8727–8731, 1989.PubMedGoogle Scholar
  53. Medvedev, Z.: An Attempt at a Rational Classification of Theories of Aging. Biological Reviews of the Cambridge Philosophical Society, 65: 375–398, 1990.PubMedCrossRefGoogle Scholar
  54. Meydani, M., Evans, W.J., Handelman, G., Biddle, L., Fielding, R.A., Meydani, S.N., Burrill, J., Fiatarone, M.A., Blumberg, J.B., Cannon, J.G.: Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. Am. J. Physiol., 33: R992–R998, 1993.Google Scholar
  55. Miquel, J., Economos, A.C., Fleming, J., Johnson, J.E. Jr.: Mitochondrial role in cell aging. Exp. Gerontol., 15: 579–91, 1980.CrossRefGoogle Scholar
  56. Miquel, J., Lundgren, P.R., Johnson, J.E.: Spectrophotofluorimetric and electron microscopic study of lipofuscin accumulation in the testis of aging mice, J Gerontol., 33: 5–19, 1978.Google Scholar
  57. Miquel, J., Fleming, J.E.: Theoretical and experimental support for an “oxygen radical-mitochondrial injury” hypothesis of cell aging. In: Free Radicals, Aging and Degenerative Diseases. Johnson, J.E. Jr., Walford, R., Harman, D., Miquel, J. eds. FF. New York: Alan R. Liss 1986, pp: 51–74.Google Scholar
  58. Mizuno, Y., Ohta, K.: Regional distribution of thiobarbituric acid-reactive products, activities of enzymes regulating the metabolism of free radicals and some of the related enzymes. J. Neurochem, 46: 1344–1352, 1986.PubMedGoogle Scholar
  59. Monti, D., Troiano, L., Tropea, F., Grassilli, E., Cossarizza, A., Barozzi, D., Pelloni, M.C., Tamassia, M.G., Bellomo, G., Franceschi, C.: Apoptosis — programmed cell death: a role in the aging process? Am. J. Clin. Nutr. 55: 1208S–14S, 1992.Google Scholar
  60. Muskhelishvili, L., Hart, R.W., Turturro, A., James, S.J.: Age-related changes in the intrinsic rate of apoptosis in livers of diet-restricted and ad tibitum-fed B6C3F1 mice. Am. J. Pathol., 147: 20–24, 1995.PubMedGoogle Scholar
  61. Nohl and Hegner, Do mitochondria produce oxygen radicals in vivo? Eur. J. Biochem. 82, 563–7, 1978.PubMedCrossRefGoogle Scholar
  62. Oliver, C.N., Ahn, B.W., Moerman, E.J., Goldstein, S., Stadtman, E.R.: Age-related changes in oxidized proteins. J. Biol. Chem. 262, 5488–5491, 1987.PubMedGoogle Scholar
  63. Omenn, G.S., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A.: Effect of a combination of b carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 334, 1150–5, 1996PubMedCrossRefGoogle Scholar
  64. Orr, W.C., Sohal, R.S.: The effects of catalase gene overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Arch. Biochem. Biophys. 297: 35–41, 1992.PubMedCrossRefGoogle Scholar
  65. Orr, W.C., Sohal, R.S.: Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263: 1128–30, 1994.PubMedGoogle Scholar
  66. Pallardó, F.V., Mompó, J., Esteve, J.M., Sastre, J., Asensi, M.A., Viña, J.: Glutathione oxidation increases in apoptotic fibroblasts. Role of apoptosis in aging. VIII Biennial Meeting. International Society for Free Radical Research Barcelona 1–5 October 1996.Google Scholar
  67. Paradies, G., Ruggiero, F.M.: Effect of aging on the activity of the phosphate carrier and on the lipid composition in rat liver mitochondria. Arch. Biochem. Biophys., 284: 332–337, 1978.CrossRefGoogle Scholar
  68. Pinto, R.E., Bartley, WA.: Negative correlation between oxygen uptake and glutathione oxidation in rat liver homogenates. Biochem. J. 114, 5–9, 1969PubMedGoogle Scholar
  69. Pryor, W.: Oxy-radicals and related species: their formation, lifetimes and reactions. Ann. Rev. Physiol. 48: 657–667, 1986.CrossRefGoogle Scholar
  70. Ratan, RR., Murphy, T.H, Baraban, J.M.: Oxidative stress induces apoptosis in embryonic cortical neurons. J. Neurochem., 62: 376–379, 1994.PubMedCrossRefGoogle Scholar
  71. Richter, C., Park, J.W., Ames, B.: Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci. USA, 85: 6465–6467, 1988.PubMedGoogle Scholar
  72. Ritchie, J.P., Leutzinger, Y., Partharsarathy, S., Malloy, V., Orentreich, N., Zimmerman, J.A.: Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J., 8: 1302–1307, 1994.Google Scholar
  73. Rikans, L.E., Moore, D.R.: Effect of aging on aqueous-sphase antioxidants in tissues of male Fischer rats. Biochem. Biophys. Acta, 966: 269–275, 1988.PubMedGoogle Scholar
  74. Saez, G., Thornalley, P.J., Hill, H.A.O., Hems, R., Bannister, JV.: The production of free radicals during the autoxidation of cysteine and their effect on isolated rat hepatocytes. Biochim. Biophys. Acta, 719, 24–31, 1982PubMedGoogle Scholar
  75. Santa Maria, C., Machado, A.: Effects of development and aging on pulmonary NADP-cytochrome c reductase, glutathione peroxidase, glutathione reductase and thioredoxin reductase activities in male and female rats. Mech. Aging Dev., 37: 183–195, 1987.CrossRefGoogle Scholar
  76. Sastre, J., Pallardó, F.V., Pá, R., Pellin, A., Juan, G., O’Connor, E., Estrela, J.M., Miquel, J., Viña, J.: Aging of the liver: Age-associated mitochondrial damage in intact hepatocytes. Hepatology 1996 (In press).Google Scholar
  77. Scalettar, B.A., Abney, J.R., Hackenbrock, C.R.: Dynamics, structure and function are coupled in the mitochondrial matrix. Proc. Natl. Acad. Sci. USA., 88: 8057–8061, 1991.PubMedGoogle Scholar
  78. Schwartzman, R.A. and Cidlowski, J.A.: Apoptosis: The biochemistry and Molecular Biology of Programmed Cell Death. Endocrine Rev. 14, 133–151, 1993.CrossRefGoogle Scholar
  79. Sawada, C.M., Carlson, J.C.: Changes in superoxide radical and lipid peroxide formation in the brain, heart and liver during the lifetime of the rat. Mech. Aging Dev. 41:125–137, 1987.PubMedCrossRefGoogle Scholar
  80. Seto, N.O.L., Hayashi, S., Tener, G.M.: Overexpression of Cu-Zn superoxide dismutase in Drosophila does affect life-span. Proc. Natl. Acad. Sci. USA, 87: 4270–74, 1990.PubMedGoogle Scholar
  81. Sevanian, A., Hochstein, P.: Mechanisms and consequences of lipid peroxidation in biological systems. Ann. Rev. Nutr, 5: 365–390, 1985.CrossRefGoogle Scholar
  82. Shigenaga, M.K., Hagen, T.M., Ames, B.N.: Oxidative damage and mitochondrial decay in aging. Proc. Natl. Acad. Sci. USA, 91: 10771–8, 1994.Google Scholar
  83. Sies, H., Bartoli, G.M., Burk, R.F., Waydhas, C.: Glutathione efflux from perfused rat liver after phenobarbital treatment, during drug oxidations, and in selenium deficiency. Eur. J. Biochem., 89: 113–118, 1978.PubMedCrossRefGoogle Scholar
  84. Sies, H.: Biochemistry of oxidative stress. Angewandte Chemie, 25: 1058–1071, 1986.CrossRefGoogle Scholar
  85. Sohal, R.S.: Hydrogen peroxide production by mitochondria may be a biomarker of aging. Mech. Age Dev., 60: 189–198, 1991.CrossRefGoogle Scholar
  86. Sohal, R.S., Arnold, L.A., Sohal, B,H.: Age-related changes in antioxidant enzymes and prooxidant generation in tissues of the rat with special reference to parameters in two insect species. Free Rad. Biol. Med., 9: 495–500, 1990.PubMedCrossRefGoogle Scholar
  87. Sohal, R.S., Dubey, A.: Mitochondrial oxidative damage, hydrogen peroxide release, and aging. Free Radical. Biol. Med., 16: 621–626, 1994.CrossRefGoogle Scholar
  88. Stadtman, E.R.: Protein oxidation and aging. Science, 257: 1220–1224, 1992.PubMedGoogle Scholar
  89. Starke-Reed, P.E., Oliver, C.N.: Protein oxidation and proteolysis during aging and oxidative stress. Arch. Biochem. Biophys., 275: 559–567, 1989.PubMedCrossRefGoogle Scholar
  90. Smith, C.D., Carney, J.M., Starke-Reed, P.E., Oliver, C.N., Stadtman, E.R., Floyd, R.A., Markesbery, W.R.: Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc. Natl. Acad. Sci. USA, 88: 10540–10543, 1991.Google Scholar
  91. Takeyama, N., Matsuo, N., Tanaka, T.: Oxidative damage to mitochondria is mediated by the Ca2+ inner membrane permeability transition. Biochem. J., 294: 719–25, 1993.PubMedGoogle Scholar
  92. Trounce, I., Byrne, E., Marzuki, S.: Decline in skeletal muscle mitochondrial chain function: possible factor in aging. Lancet, 25 March: 637–639, 1989.Google Scholar
  93. Tummino, P.J., Gafni, A.: A comparative study of succinate-supported respiration and ATP/ADP translocation in liver mitochondrial from adult and old rats. Mech Age. Dev., 59: 177–188, 1991.CrossRefGoogle Scholar
  94. Vaux, D.L.: Toward an understanding of the molecular mechanisms of physiological cell death. Proc. Natl. Acad. Sci. USA 90, 786–789, 1993.PubMedGoogle Scholar
  95. Viña, J. (Editor). Glutathione: Metabolism and Physiological Functions. CRC Press, Boston, 1990Google Scholar
  96. Viña, J., Hems, R., Krebs, H.A.: Maintenance of glutathione content in isolated hepatocytes. Biochem. J. 170, 627–630, 1978PubMedGoogle Scholar
  97. Viña, J., Sastre, J., Anton, V., Bruseghini, L., Esteras, A., Asensi, M.: Effect of aging on glutathione metabolism. Protection by antioxidants. In Free Radicals and Aging. Emerit, I. and Chance, B. eds. Birkhauser Verlag. Basel. Switzerland 1992, pp. 136–144.Google Scholar
  98. Vladimirov, Y.A., Archakov, A.I.: Lipid peroxidation in biomembranes (in Russian) Moscow: Nauka 1972.Google Scholar
  99. Vladimirov, Y.A.: Free radical lipid peroxidation in biomembranes: Mechanism, regulation, and biological consequences. In: Free Radicals, Aging and Degenerative Diseases, eds.: J.E. Johnson Jr., R. Walford, D. Harman, J. Miquel. Alan R. Liss, pp: 141–195, 1986.Google Scholar
  100. Wallace, D.C.: Mitochondrial DNA sequence variation in human evolution and disease. Proc. Natl. Acad. Sci. USA, 91: 8739–8746, 1994.PubMedGoogle Scholar
  101. Wolman, M.: Oxidation of lipids and membranes I: in vivo formation of peroxidative lipid polymers. J. Supramol. struct. 3, 80–9, 1975.PubMedCrossRefGoogle Scholar
  102. Yen, T.C., Chen, Y.S., King, K.L., Yeh, S.H., Wei, Y.H.: Liver mitochondrial respiratory functions decline with age. Biochem. Biophys. Res. Commun., 165: 994–1003, 1989.CrossRefGoogle Scholar
  103. Zamzami, N., Marchetti, P., Castedo, M., Hirsch, T., Susin, S.A., Masse, B., Kroemer, G.: Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis. FEBS lett. 384: 53–57, 1996a.PubMedCrossRefGoogle Scholar
  104. Zamzami, N.P., Susin, S.A., Marchetti, P., Hirsch, T., Castedo, M., Kroemer, G.: Mitochondrial control of nuclear apoptosis. J. Exp. Med., 183: 1533–1544, 1996b.PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association, Inc. 1996

Authors and Affiliations

  • Juan Sastre
    • 1
  • Federico V. Pallardó
    • 1
  • Jose Viña
    • 1
    Email author
  1. 1.Department of Physiology, Faculty of MedicineUniversity of ValenciaSpain

Personalised recommendations