Circulation Research, Vol 68, 1560-1568, Copyright © 1991 by American Heart Association

ARTICLES

Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy

G Olivetti, M Melissari, JM Capasso and P Anversa
Department of Pathology, University of Parma, Italy.

To determine the effects of aging on the human myocardium, 67 hearts were obtained from individuals who died from causes other than cardiovascular disease. The age interval examined was 17-90 years. Regression analysis demonstrated that the aging process was characterized by a loss of 38 million and 14 million myocyte nuclei/yr in the left and right ventricular myocardium, respectively. This loss in muscle mass was accompanied by a progressive increase in myocyte cell volume per nucleus in both ventricles. Left ventricular myocytes enlarged by 110 microns3/yr, whereas right ventricular myocytes increased by 118 microns3/yr, resulting in a preservation of ventricular wall thickness. However, the cellular hypertrophic response was unable to maintain normal cardiac mass. Left and right ventricular weights decreased by 0.70 and 0.21 g/yr, respectively. In conclusion, loss of cells and enlargement of the remaining myocytes may represent the structural basis for the reduced compensatory capacity of the aged heart and together may contribute to the development of myocardial dysfunction and failure in the elderly.

This article has been cited by other articles:

				S. Cheng, V. R.S. Fernandes, D. A. Bluemke, R. L. McClelland, R. A. Kronmal, and J. A.C. Lima Age-Related Left Ventricular Remodeling and Associated Risk for Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis Circ Cardiovasc Imaging, May 1, 2009; 2(3): 191 - 198. [Abstract] [Full Text] [PDF]

				J. M. Lawler, H.-B. Kwak, J.-H. Kim, and M.-H. Suk Exercise training inducibility of MnSOD protein expression and activity is retained while reducing prooxidant signaling in the heart of senescent rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1496 - R1502. [Abstract] [Full Text] [PDF]

				O. Bergmann, R. D. Bhardwaj, S. Bernard, S. Zdunek, F. Barnabe-Heider, S. Walsh, J. Zupicich, K. Alkass, B. A. Buchholz, H. Druid, et al. Evidence for Cardiomyocyte Renewal in Humans Science, April 3, 2009; 324(5923): 98 - 102. [Abstract] [Full Text] [PDF]

				G Perseghin, F De Cobelli, A Esposito, E Belloni, G Lattuada, T Canu, P L Invernizzi, F Ragogna, A La Torre, P Scifo, et al. Left ventricular function and energy metabolism in middle-aged men undergoing long-lasting sustained aerobic oxidative training Heart, April 1, 2009; 95(8): 630 - 635. [Abstract] [Full Text] [PDF]

				C. Chimenti, N. Hamdani, N. M. Boontje, F. DeCobelli, A. Esposito, J. G.F. Bronzwaer, G. J.M. Stienen, M. A. Russo, W. J. Paulus, A. Frustaci, et al. Myofilament Degradation and Dysfunction of Human Cardiomyocytes in Fabry Disease Am. J. Pathol., June 1, 2008; 172(6): 1482 - 1490. [Abstract] [Full Text] [PDF]

				Y. Yang, Y. Ma, W. Han, J. Li, Y. Xiang, F. Liu, X. Ma, J. Zhang, Z. Fu, Y.-D. Su, et al. Age-related differences in postinfarct left ventricular rupture and remodeling Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1815 - H1822. [Abstract] [Full Text] [PDF]

				H.-C. Lee and Y.-H. Wei Oxidative Stress, Mitochondrial DNA Mutation, and Apoptosis in Aging Experimental Biology and Medicine, May 1, 2007; 232(5): 592 - 606. [Abstract] [Full Text] [PDF]

				Y. Notomi, G. Srinath, T. Shiota, M. G. Martin-Miklovic, L. Beachler, K. Howell, S. J. Oryszak, D. G. Deserranno, A. D. Freed, N. L. Greenberg, et al. Maturational and Adaptive Modulation of Left Ventricular Torsional Biomechanics: Doppler Tissue Imaging Observation From Infancy to Adulthood Circulation, May 30, 2006; 113(21): 2534 - 2541. [Abstract] [Full Text] [PDF]

				P D Chantler, D F Goldspink, R E Clements, L Sharp, D Schlosshan, and L-B Tan Congestive heart failure: extent of cardiac functional changes caused by aging and organ dysfunction. Heart, May 1, 2006; 92(5): 686 - 688. [Full Text] [PDF]

				P. Anversa, J. Kajstura, A. Leri, and R. Bolli Life and Death of Cardiac Stem Cells: A Paradigm Shift in Cardiac Biology Circulation, March 21, 2006; 113(11): 1451 - 1463. [Full Text] [PDF]

				A. Leri, J. Kajstura, and P. Anversa Cardiac Stem Cells and Mechanisms of Myocardial Regeneration Physiol Rev, October 1, 2005; 85(4): 1373 - 1416. [Abstract] [Full Text] [PDF]

				J.-Y. Min, Y. Chen, S. Malek, A. Meissner, M. Xiang, Q. Ke, X. Feng, M. Nakayama, E. Kaplan, and J. P. Morgan Stem cell therapy in the aging hearts of Fisher 344 rats: Synergistic effects on myogenesis and angiogenesis J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 547 - 553. [Abstract] [Full Text] [PDF]

				D. de Santis, P. Abete, G. Testa, F. Cacciatore, G. Galizia, D. Leosco, L. Viati, V. D. Villano, D. D. Morte, F. Mazzella, et al. Echocardiographic evaluation of left ventricular end-systolic elastance in the elderly Eur J Heart Fail, August 1, 2005; 7(5): 829 - 833. [Abstract] [Full Text] [PDF]

				T. Iwasaki, K. Mukasa, M. Yoneda, S. Ito, Y. Yamada, Y. Mori, N. Fujisawa, T. Fujisawa, K. Wada, H. Sekihara, et al. Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1222 - E1228. [Abstract] [Full Text] [PDF]

				S.-K. Park and T. A. Prolla Gene expression profiling studies of aging in cardiac and skeletal muscles Cardiovasc Res, May 1, 2005; 66(2): 205 - 212. [Abstract] [Full Text] [PDF]

				F. Syed, A. Odley, H. S. Hahn, E. W. Brunskill, R. A. Lynch, Y. Marreez, A. Sanbe, J. Robbins, and G. W. Dorn II Physiological Growth Synergizes With Pathological Genes in Experimental Cardiomyopathy Circ. Res., December 10, 2004; 95(12): 1200 - 1206. [Abstract] [Full Text] [PDF]

				A. Orlandi, A. Francesconi, M. Marcellini, A. Ferlosio, and L. G. Spagnoli Role of ageing and coronary atherosclerosis in the development of cardiac fibrosis in the rabbit Cardiovasc Res, December 1, 2004; 64(3): 544 - 552. [Abstract] [Full Text] [PDF]

				R. Fincke, J. S. Hochman, A. M. Lowe, V. Menon, J. N. Slater, J. G. Webb, T. H. LeJemtel, G. Cotter, and SHOCK Investigators Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: A report from the SHOCK trial registry J. Am. Coll. Cardiol., July 21, 2004; 44(2): 340 - 348. [Abstract] [Full Text] [PDF]

				J. J. Magner and D. Royston Heart failure Br. J. Anaesth., July 1, 2004; 93(1): 74 - 85. [Abstract] [Full Text] [PDF]

				O. O. Aalami, T. D. Fang, H. M. Song, and R. P. Nacamuli Physiological Features of Aging Persons Arch Surg, October 1, 2003; 138(10): 1068 - 1076. [Full Text] [PDF]

				X. Zhang, G. Azhar, M. C. Furr, Y. Zhong, and J. Y. Wei Model of functional cardiac aging: young adult mice with mild overexpression of serum response factor Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R552 - R560. [Abstract] [Full Text] [PDF]

				H. Oxenham and N. Sharpe Cardiovascular aging and heart failure Eur J Heart Fail, August 1, 2003; 5(4): 427 - 434. [Abstract] [Full Text] [PDF]

				A. Bosy-Westphal, C. Eichhorn, D. Kutzner, K. Illner, M. Heller, and M. J. Muller The Age-Related Decline in Resting Energy Expenditure in Humans Is Due to the Loss of Fat-Free Mass and to Alterations in Its Metabolically Active Components J. Nutr., July 1, 2003; 133(7): 2356 - 2362. [Abstract] [Full Text] [PDF]

				A. Maurel, C. Hernandez, O. Kunduzova, G. Bompart, C. Cambon, A. Parini, and B. Frances Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1460 - H1467. [Abstract] [Full Text] [PDF]

				B. Nadal-Ginard, J. Kajstura, A. Leri, and P. Anversa Myocyte Death, Growth, and Regeneration in Cardiac Hypertrophy and Failure Circ. Res., February 7, 2003; 92(2): 139 - 150. [Abstract] [Full Text] [PDF]

				A. M. Bronikowski, P. A. Carter, T. J. Morgan, T. Garland Jr, N. Ung, T. D. Pugh, R. Weindruch, and T. A. Prolla Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart Physiol Genomics, January 15, 2003; 12(2): 129 - 138. [Abstract] [Full Text] [PDF]

				P. Liu, B. Xu, T. A Cavalieri, and C. E Hock Age-related difference in myocardial function and inflammation in a rat model of myocardial ischemia-reperfusion Cardiovasc Res, December 1, 2002; 56(3): 443 - 453. [Abstract] [Full Text] [PDF]

				C.-K. Lee, D. B. Allison, J. Brand, R. Weindruch, and T. A. Prolla Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts PNAS, November 12, 2002; 99(23): 14988 - 14993. [Abstract] [Full Text] [PDF]

				L. Thomas, K. Levett, A. Boyd, D. Y. C. Leung, N. B. Schiller, and D. L. Ross Compensatory changes in atrial volumes with normal aging: is atrial enlargement inevitable? J. Am. Coll. Cardiol., November 6, 2002; 40(9): 1630 - 1635. [Abstract] [Full Text] [PDF]

				K. Leineweber, T. Wangemann, C. Giessler, H. Bruck, S. Dhein, M. Kostelka, F.-W. Mohr, R.-E. Silber, and O.-E. Brodde Age-dependent changes of cardiac neuronal noradrenaline reuptake transporter (uptake1) in the human heart J. Am. Coll. Cardiol., October 16, 2002; 40(8): 1459 - 1465. [Abstract] [Full Text] [PDF]

				Y.-H. Wei and H.-C. Lee Oxidative Stress, Mitochondrial DNA Mutation, and Impairment of Antioxidant Enzymes in Aging Experimental Biology and Medicine, October 1, 2002; 227(9): 671 - 682. [Abstract] [Full Text] [PDF]

				J. D. Kilts, T. Akazawa, M. D. Richardson, and M. M. Kwatra Age Increases Cardiac Galpha i2 Expression, Resulting in Enhanced Coupling to G Protein-coupled Receptors J. Biol. Chem., August 16, 2002; 277(34): 31257 - 31262. [Abstract] [Full Text] [PDF]

				K. Przyklenk and P. Whittaker Reply J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1701 - 1702. [Full Text] [PDF]

				A. Goette, G. Juenemann, B. Peters, H. U. Klein, A. Roessner, C. Huth, and C. Rocken Determinants and consequences of atrial fibrosis in patients undergoing open heart surgery Cardiovasc Res, May 1, 2002; 54(2): 390 - 396. [Abstract] [Full Text] [PDF]

				J. Ribstein, G. Du Cailar, and A. Zanchetti Cardiac and renal damage in the elderly hypertensive Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1_suppl): S16 - S24. [PDF]

				S. Phaneuf and C. Leeuwenburgh Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R423 - R430. [Abstract] [Full Text] [PDF]

				K. Przyklenk, G. Li, and P. Whittaker No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1741 - 1747. [Abstract] [Full Text] [PDF]

				Z. Mallat, P. Fornes, R. Costagliola, B. Esposito, J. Belmin, D. Lecomte, and A. Tedgui Age and Gender Effects on Cardiomyocyte Apoptosis in the Normal Human Heart J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2001; 56(11): M719 - 723. [Abstract] [Full Text] [PDF]

				W. G. Hundley, D. W. Kitzman, T. M. Morgan, C. A. Hamilton, S. N. Darty, K. P. Stewart, D. M. Herrington, K. M. Link, and W. C. Little Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance J. Am. Coll. Cardiol., September 1, 2001; 38(3): 796 - 802. [Abstract] [Full Text] [PDF]

				T. Wannenburg, A. S. Khan, D. C. Sane, M. C. Willingham, T. Faucette, and W. E. Sonntag Growth hormone reverses age-related cardiac myofilament dysfunction in rats Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H915 - H922. [Abstract] [Full Text] [PDF]

				J. Shirani, J. Lee, R. Quigg, R. Pick, S. L. Bacharach, and V. Dilsizian Relation of thallium uptake to morphologic features of chronic ischemic heart disease: evidence for myocardial remodeling in noninfarcted myocardium J. Am. Coll. Cardiol., July 1, 2001; 38(1): 84 - 90. [Abstract] [Full Text] [PDF]

				A. P. Beltrami, K. Urbanek, J. Kajstura, S.-M. Yan, N. Finato, R. Bussani, B. Nadal-Ginard, F. Silvestri, A. Leri, C. A. Beltrami, et al. Evidence That Human Cardiac Myocytes Divide after Myocardial Infarction N. Engl. J. Med., June 7, 2001; 344(23): 1750 - 1757. [Abstract] [Full Text] [PDF]

				M. Ochi, N. Hatori, M. Fujii, Y. Saji, S. Tanaka, and H. Honma Limited flow capacity of the right gastroepiploic artery graft: postoperative echocardiographic and angiographic evaluation Ann. Thorac. Surg., April 1, 2001; 71(4): 1210 - 1214. [Abstract] [Full Text] [PDF]

				A. Frustaci, J. Kajstura, C. Chimenti, I. Jakoniuk, A. Leri, A. Maseri, B. Nadal-Ginard, and P. Anversa Myocardial Cell Death in Human Diabetes Circ. Res., December 8, 2000; 87(12): 1123 - 1132. [Abstract] [Full Text] [PDF]

				H.-J. Priebe The aged cardiovascular risk patient Br. J. Anaesth., November 1, 2000; 85(5): 763 - 778. [Abstract] [Full Text] [PDF]

				M. Lye and C. Donnellan GENERAL CARDIOLOGY: Heart disease in the elderly Heart, November 1, 2000; 84(5): 560 - 566. [Full Text]

				S. J. Liu, R. P. Wyeth, R. B. Melchert, and R. H. Kennedy Aging-associated changes in whole cell K+ and L-type Ca2+ currents in rat ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H889 - H900. [Abstract] [Full Text] [PDF]

				G. Peri, M. Introna, D. Corradi, G. Iacuitti, S. Signorini, F. Avanzini, F. Pizzetti, A. P. Maggioni, T. Moccetti, M. Metra, et al. PTX3, A Prototypical Long Pentraxin, Is an Early Indicator of Acute Myocardial Infarction in Humans Circulation, August 8, 2000; 102(6): 636 - 641. [Abstract] [Full Text] [PDF]

				S G Williams, D J Wright, and L B Tan Management of cardiogenic shock complicating acute myocardial infarction: towards evidence based medical practice Heart, June 1, 2000; 83(6): 621 - 626. [Full Text]

				P. Anversa Myocyte Death in the Pathological Heart Circ. Res., February 4, 2000; 86(2): 121 - 124. [Full Text] [PDF]

				H. N. Sabbah Apoptotic cell death in heart failure Cardiovasc Res, February 1, 2000; 45(3): 704 - 712. [Full Text] [PDF]

				P. Madeddu, C. Emanueli, R. Maestri, M. B. Salis, A. Minasi, M. C. Capogrossi, and G. Olivetti Angiotensin II Type 1 Receptor Blockade Prevents Cardiac Remodeling in Bradykinin B2 Receptor Knockout Mice Hypertension, January 1, 2000; 35(1): 391 - 396. [Abstract] [Full Text] [PDF]

				C. Emanueli, R. Maestri, D. Corradi, R. Marchione, A. Minasi, M. G. Tozzi, M. B. Salis, S. Straino, M. C. Capogrossi, G. Olivetti, et al. Dilated and Failing Cardiomyopathy in Bradykinin B2 Receptor Knockout Mice Circulation, December 7, 1999; 100(23): 2359 - 2365. [Abstract] [Full Text] [PDF]

				O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]

				A. Colao, A. Cuocolo, C. Di Somma, G. Cerbone, A. M. Della Morte, E. Nicolai, R. Lucci, M. Salvatore, and G. Lombardi Impaired Cardiac Performance in Elderly Patients with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3950 - 3955. [Abstract] [Full Text]

				R. M. Oskvig Special Problems in the Elderly Chest, May 1, 1999; 115 (2009): 158S - 164S. [Abstract] [Full Text] [PDF]

				L. A. Megeney, B. Kablar, R. L. S. Perry, C. Ying, L. May, and M. A. Rudnicki Severe cardiomyopathy in mice lacking dystrophin and MyoD PNAS, January 5, 1999; 96(1): 220 - 225. [Abstract] [Full Text] [PDF]

				L. S. Piers, M. J. Soares, L. M. McCormack, and K. O'Dea Is there evidence for an age-related reduction in metabolic rate? J Appl Physiol, December 1, 1998; 85(6): 2196 - 2204. [Abstract] [Full Text] [PDF]

				C.-H. Chen, M. Nakayama, E. Nevo, B. J. Fetics, W. L. Maughan, and D. A. Kass Coupled systolic-ventricular and vascular stiffening with age: Implications for pressure regulation and cardiac reserve in the elderly J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1221 - 1227. [Abstract] [Full Text] [PDF]

				P. Anversa and J. Kajstura Ventricular Myocytes Are Not Terminally Differentiated in the Adult Mammalian Heart Circ. Res., July 13, 1998; 83(1): 1 - 14. [Full Text] [PDF]

				A. Leri, Y. Liu, A. Malhotra, Q. Li, P. Stiegler, P. P. Claudio, A. Giordano, J. Kajstura, T. H. Hintze, and P. Anversa Pacing-Induced Heart Failure in Dogs Enhances the Expression of p53 and p53-Dependent Genes in Ventricular Myocytes Circulation, January 20, 1998; 97(2): 194 - 203. [Abstract] [Full Text] [PDF]

				D. A. Kass, A. Saeki, R. S. Tunin, and F. A. Recchia Adverse Influence of Systemic Vascular Stiffening on Cardiac Dysfunction and Adaptation to Acute Coronary Occlusion Circulation, April 15, 1996; 93(8): 1533 - 1541. [Abstract] [Full Text]

				W. Cheng, K. Reiss, P. Li, M. J. Chun, J. Kajstura, G. Olivetti, and P. Anversa Aging Does Not Affect the Activation of the Myocyte Insulin-Like Growth Factor-1 Autocrine System After Infarction and Ventricular Failure in Fischer 344 Rats Circ. Res., April 1, 1996; 78(4): 536 - 546. [Abstract] [Full Text]

				J. Kajstura, X. Zhang, Y. Liu, E. Szoke, W. Cheng, G. Olivetti, T. H. Hintze, and P. Anversa The Cellular Basis of Pacing-Induced Dilated Cardiomyopathy : Myocyte Cell Loss and Myocyte Cellular Reactive Hypertrophy Circulation, October 15, 1995; 92(8): 2306 - 2317. [Abstract] [Full Text]

				C. A. Caldarone, I. B. Krukenkamp, P. G. Burns, G. R. Gaudette, J. Schulman, and S. Levitsky Blood cardioplegia in the senescent heart J. Thorac. Cardiovasc. Surg., February 1, 1995; 109(2): 269 - 274. [Abstract] [Full Text]

				A. A. Maggioni, A. Maseri, C. Fresco, M. G. Franzosi, F. Mauri, E. Santoro, G. Tognoni, and The Investigators of the Gruppo Italiano por lo St Age-Related Increase in Mortality among Patients with First Myocardial Infarctions Treated with Thrombolysis N. Engl. J. Med., November 11, 1993; 329(20): 1442 - 1448. [Abstract] [Full Text]