Abstract
Biochemical and structural changes occurring in the myocardium with aging are mainly resulting from the association of a general tissue atrophy with the hypertrophy of the remaining myocytes. Whilst hypertrophy seems to be a compensatory process to the loss of cardiomyocytes and to a mild systolic hypertensive condition that accompanies elderly people, atrophy should be the modification more closely related to aging ‘per se.’ In support to the free radical theory of aging, several signs of oxidative damage have been shown in the aged heart, such as lipofuscin accumulation, decreased phospholipid unsaturation index, greater formation of both hydrogen peroxide and 8-hydroxy-2′deoxyguanosine. As a compensatory reaction, the activities of the main oxygen-radical scavenger enzymes are stimulated in the mitochondria of aged rat heart. Endothelium-mediated vasoregulation is more susceptible to oxidative stress in aged with respect to young rats, suggesting that also the vasculature can be negatively influenced by the oxygen free radicals generated during aging. The possible primary role of oxygen free radicals in the development of myocardial atrophy is also discussed.
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Rosentahal J: Aging and the cardiovascular system. Gerontology 33 (suppl 1): 3–8, 1987
Walsh R: Cardiovascular effects of the aging process. Am J Med 82 (suppl 13): 34–40, 1987
Lakatta EG: Myocardial adaptations in advanced age. Basic Res Cardiol 88 (suppl 2): 125–133, 1993
Jullien T, Verdetti J: Comparative electrophysiological response of young and old rat myocardium to pharmacological agents. Gen Pharmacol 19: 759–766, 1988
Besse S, Assayag P, Delcayre C, Carre F, Cheav SL, Lecarpentier Y, Swynghedauw B: Normal and hypertrophied senescent rat heart: mechanical and molecular characteristics. Am J Physiol 265 (1 Pt 2): H183-H190, 1993
Maciel LMZ, Polikar R, Rohrer D, Popovich BK, Dillmann WH: Age induced decreases in the messenger RNA coding for the sarcoplasmic reticulum Ca2+-ATPase of the rat heart. Circ Res 67: 230–234, 1990
Lakatta EG, Yin CP: Myocardial aging: functional alterations and related cellular mechanisms. Am J Physiol 242: H927-H941, 1982
Rengo F, Ferrara N, Leosco D: Ventricular function in the elderly. Aging 3: 9–17, 1991
Merino A, Alegria E, Castello R, Martinez-Caro D: Influence of age on left ventricular contractility. Am J Cardiol 62: 1103–1108, 1988
Willems JL, Roelandt H, De Greest H, Kesteloot H, Joossems JV: The left ventricular ejection time in elderly subjects. Circulation 42: 37–42, 1970
Spirito P, Maron B: Influence of aging on Doppler echocardiographic indices of left ventricular diastolic function. Br Heart J 59: 672–679, 1988
Fleg JL: Alterations in cardiovascular structure and function with advancing age. Am J Cardiol 57: 33C-44C, 1986
Safar M: Ageing and its effects on the cardiovascular system. Drugs 39 (suppl 1): 1–8, 1990
Lakatta EG, Gerstenblith G, Angell CS, Shock NW, Weisfeldt ML: Diminished inotropic response of aged myocardium to catecholamines. Cir Res 36: 262–269, 1975
Amerini S, Fusi F, Piazzesi G, Mantelli L, Ledda F, Mugelli A: Influence of age on the positive inotropic effect mediated by alpha-and beta-adrenoceptors in rat ventricular strips. Dev Pharmacol Ther 8: 34–42, 1985
Carrier L, Chassagne C, Boheler KR, Schwartz K: Molecular basis of cardiac aging. Presse Med 21: 1196–1198, 1992
Crie JS, Milliward DJ, Bates PC, Griffin EE, Wildenthal K:Age-related alterations in cardiac protein turnover. J Mol Cell Cardiol 13: 589–598, 1981
Starnes JW, Edington DW, Beyer RE: Myocardial protein synthesis during ageing and endurance exercise in rats. J Gerontol 38: 660–665, 1983
Anversa P, Palankal T, Sonnenblick EH, Olivetti G, Meggs LG, Capasso JM: Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Cite Res 67: 871–885, 1990
Eghbali Me, Eghbali Ma, Robinson TF, Sester S, Blumenfeld OO, Cohen-Gould L, Geraci M, Valentine M: Collagen accumulation in heart ventricles as a function of growth and aging. Cardiov Res 23: 723–729, 1989
Harman D: Prolongation of life: role of free radical reaction in aging. Am Geriat Soc 8: 721–735, 1969
Ikeda H, Tauchi H, Shimasaki H, Veta N, Sato T: Age and organ difference in amount and distribution of autofluorescent granules in rats. Mech Ageing Dev 31: 139–146, 1985
Shimasaki H, Nozawa T, Privett OS, Anderson WR: Detection of age related fluorescent substance in rat tissue. Arch Biochem Biophys 183: 443–451, 1977
Gao G, Johansson U, Rundquist I, Ollinger K: Lipofuscin-induced autofluorescence of living neonatal rat cardiomyocytes in culture. Mech Ageing Dev 73: 79–86, 1994
Brunk UT, Jones CB, Sohal RS: A novel hypothesis of lipofuscinogenesis and cellular aging based on interactions between oxidative stress and autophagocytosis. Mutat Res 275: 395–403, 1992
Muscari C, Frascaro M, Guarnieri C, Caldarera CM: Mitochondrial function and superoxide generation from submitochondrial particles of aged rat hearts. Biochim Biophys Acta 1015: 200–204, 1990
Muscari C, Caldarera CM, Guarnieri C: Age-dependent production of mitochondrial hydrogen peroxide, lipid peroxides and fluorescent pigments in the rat heart. Bas Res Cardiol 85: 172–178, 1990
Nohl H, Hegner D: Do mitochondria produce oxygen radicals in vivo? Eur J Biochem 82: 563–567, 1878
Lammi-Keefe CJ, Swan PB, Hegarty PVJ: Copper-zinc and manganese superoxide dismutase activities in cardiac and skeletal muscles during aging in male rats. Gerontology 30: 153–158, 1984
Hazelton GA, Lang CA: Glutathione peroxidase and reductase activities in the aging mouse. Mech Ageing Dev 29: 71–81, 1985
Nohl H, Hegner D, Summer KH: Responses of mitochondrial superoxide dismutase, catalase and glutathione peroxidase activities to aging. Mech Ageing Dev 11: 141–151, 1984
Ji LL, Dillon D, Wu E: Myocardial aging: Antioxidant enzyme systems and related biochemical properties. Am J Physiol 261 (2 Pt 2): R368-R392, 1991
Muscari C, Guarnieri C, Biagetti L, Finelli C, Caldarera CM: Influence of age on oxidative damage in mitochondria of ischemic and reperfused rat hearts. Cardioscience 1: 275–278, 1990
Muscari C, Biagetti L, Stefanelli C, Giordano E, Guarnieri C, Caldarera CM: Adaptive changes in Coenzyme Q biosynthesis to myocardial reperfusion in young and aged rats. J Mol Cell Cardiol 27: 283–289, 1995
Lewin MB, Timiras PS: Lipid changes with aging in cardiac mitochondrial membranes. Mech Ageing Dev 24: 343–351, 1984
Sawada M, Sester U, Carlson JC: Superoxide radical formation and associated biochemical alterations in plasma membrane of brain, heart, and liver during the lifetime of the rat. J Cell Biochem 48: 296–304, 1992
Lopez-Jimenez JA, Bordoni A, Hrelia S, Rossi CA, Turchetto E, Zamora-Navarro S, Biagi PL: Evidence for a detectable delta-6desaturase activity in rat heart microsomes: aging influence on enzyme activity. Biochem Biophys Res Commun 192: 1037–1041, 1993
Gudmundsdottir E, Benediktsdottir VE, Gudbjarnason S: Combined effects of age and dietary fat on beta-receptors and Ca2+ channels in rat hearts. Am J Physiol 260 (1 Pt 2): H66-H72, 1991
Pignatti C, Tantini B, Zanfanti ML, Sacchi P, Clo' C: Influence of Mg2+ on the in vitro responsiveness of adenylate cyclase from hearts of aging rats. Cardioscience 4: 105–109, 1993
Tantini B, Pignatti C, Sacchi P, Zanfanti ML, Mariani F, Clo' C: Influence of spermine on adenylate cyclase responsiveness of cultured cardiomyocytes from aging rats. In: C.M. Caldarera, C. Clo' and M.S. Moruzzi (eds). Polyamines, Biological and Clinical Aspects, CLUEB, Bologna, Italy, 1994, pp 287–294
Holmes GE, Bernstein C, Bernstein H: Oxidative and other DNA damages as the basis of aging: A review. Mutation Res 275: 305–315, 1992
Ames BN, Gold LS: Endogenous mutagens and the causes of aging and cancer. Mutation Res 250: 3–16, 1991
Fraga CG, Shigenaga MK, Park JW, Degan P, Ames BN: Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc NatlAcad Sci (USA) 87: 4533–4537, 1990
Sohal RS, Agarwal S, Candas M, Forster MJ, Lal H: Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice. Mech Ageing Dev 76: 215–224, 1994
Richter C: Reactive oxygen and DNA damage in mitochondria. Mutation Res 275: 249–255, 1992
Richter C: Do mitochondrial DNA fragments promote cancer and aging? FEBS Lett 241: 1–5, 1988
Hayakawa M, Hattori K, Sugiyama S, Ozawa T: Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts. Biochem Biophys Res Commun 189: 979–985, 1992
Yen TC, Su JH, King KL, Wei YH: Ageing-associated 5Kb deletion in human liver mitochondrial DNA. Biochem Biophys Res Commun 178: 124–131, 1991
Muller-Hoker J: Cytochrome-c-oxidase deficient cardiomyocytes in the human heart. An age-related phenomenon. Am J Pathol 134: 1167–1173, 1989
Holt IJ, Harding AE, Morgan-Huges JA: Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331: 717–719, 1978
Hattori K, Tanaka M, Sujiyama S, Oayashi T, Ito T, Sataket T, Hanaki Y, Asai J, Nagano M, Ozawa T: Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor to presbycardia. Am Heart J 21 (6 Pt 1): 1735–1742, 1991
Katsumata K, Hayakawa M, Tanaka M, Sujiyama S, Ozawa T: Fragmentation of human heart mitochondrial DNA associated with premature aging. Biochem Biophys Res Commun 202: 102–110, 1994
Muscari C, Finelli C, Stefanelli C, Flamigni F, Guarnieri C, Caldarera CM: Age-dependent differences ofATPbreakdown andATP-catabolite release in ischemic and reperfused hearts. Mech Ageing Dev 67: 1–11, 1993
Finelli C, Guarnieri C, Muscari C, Ventura C, Caldarera CM: Incorporation of [14C]hypoxanthine into cardiac adenine nucleosides: Effect of aging and post-ischemic reperfusion. Biochim Biophys Acta 1180, 262–266, 1993
Muscari C, Caldarera I, Rapezzi C, Branzi A, Caldarera CM: Biochemical correlates with myocardial aging. Cardioscience 3: 67–78, 1992
Guarnieri C, Muscari C, Finelli C, Caldarera CM: Age-related changes in cardiac mitochondrial energetics under the influence of calcium in rat. Cardioscience 4: 117–120, 1993
Yin FC: The aging vasculature and its effects on the heart. In: M.L. Weisfeldt (ed.). The Aging Heart. Raven Press, New York, 1980, pp 137–213
De Mey C, Vanhoutte PM: Effect of age and spontaneous hypertension on the tachyphylaxis to 5-hydroxytryptamine and angiontensin II in the isolated rat kidney. Hypertension 3: 718–724, 1981
Moritoki H, Matsugi T, Takase H, Ueda H, Tanioka A: Evidence for the involvement of cyclic GMP in adenosine-induced, age-dependent vasodilation. Br J Pharmacol 100: 569–575, 1990
Katusic ZS, Vanhoutte PM: Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 257: H33-H37, 1989
Tesfamarian B, Cohen RA: Role of superoxide anion and endothelium in vasoconstrictor action of prostaglandin endoperoxide. Am J Physiol 262: H1915-H1919, 1992
Palmer RMJ, Ferrige AG, Moncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526, 1987
Darley-Usmar V, Radomski M: Free radicals in the vasculature: the good, the bad and the ugly. The Biochemist 16(5): 15–18, 1994
Guarnieri C, Giordano E, Muscari C, Grossi L, Caldarera CM: Alphatocopherol pretreatment improves endothelium-dependent vasodilatation in aortic strips of young and aging rats exposed to oxidative stress. Mol Cell Biochem, in press
Persoon-Rothert M, Egas-Kenniphaas JM, van der Valk-Kokshoorm EJ, Buys JP, van der Laarse A: Oxidative stress-induced perturbations of calcium homeostasis and cell death in cultured myocytes: role of extracellular calcium. Mol Cell Biochem 136: 1–9, 1994
Bhatnagar A: Biochemical mechanisms of irreversible cell injury caused by free radical-initiated reactions. Mol Cell Biochem 137: 916, 1994
Yoneda M, Katsumata K, Hayakawa M, Tanaka M, Ozawa T: Oxygen stress induces an apoptotic death associated with fragmentation of mitochondrial genome. Biochem Biophys Res Commun 209: 723–729, 1995
Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H: Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 74: 121–133, 1994
Sohal RS, Brunk UT: Mitochondrial production of pro-oxidants and cellular senescence. Mutation Res 275, 295–304, 1992
Davies KJA: Protein damage and degradation by oxygen radicals. J Biol Chem 262: 9895–9901, 1987
Davies KJA, Quintanilha AT, Brooks GA, Parker L: Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 107: 1198–1205, 1982
Meerson FZ: Development of modern components of the mechanism of cardiac hypertrophy. Cite Res 34 (suppl 2): 5–3, 1974
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Muscari, C., Giaccari, A., Giordano, E. et al. Role of reactive oxygen species in cardiovascular aging. Mol Cell Biochem 160, 159–166 (1996). https://doi.org/10.1007/BF00240046
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DOI: https://doi.org/10.1007/BF00240046