Gender differences and aging: effects on the human heart

Department of Medicine, New York Medical College, Valhalla 10595, USA.

OBJECTIVES. This study investigated the changes in myocyte size and number in the left and right ventricles that occur with aging in the female and male heart. BACKGROUND. Differences in life span between women and men may be related to a better preservation of myocardial structure in the female heart with aging. On this basis, the hypothesis was advanced that the aging process has a different impact on the integrity of the myocardium in the two genders. METHODS. Morphometric methodologies were applied to analyze the changes in number and size of ventricular myocytes in the hearts of 53 women and 53 men. The changes in mononucleated and binucleated myocytes with age were determined in enzymatically dissociated cells. The age interval examined varied from 17 to 95 years. RESULTS. Aging was associated with a preservation of ventricular myocardial mass, aggregate number of mononucleated and binucleated myocytes, average cell diameter and volume in the female heart. In contrast, nearly 1 g/year of myocardium was lost in the male heart, and this phenomenon accounted for the loss of approximately 64 million cells. This detrimental effect involved the left and right sides of the heart. In the remaining cells, myocyte cell volume increased at a rate of 158 microns3/year in the left and 167 microns3/year in the right ventricle. CONCLUSIONS. Aging does not lead to myocyte cell loss and myocyte cellular reactive hypertrophy in women, indicating that gender differences may play a significant role in the detrimental effects of the aging process on the heart.

This article has been cited by other articles:

				R. Twerenbold, A. Jaffe, T. Reichlin, M. Reiter, and C. Mueller High-sensitive troponin T measurements: what do we gain and what are the challenges? Eur. Heart J., January 19, 2012; (2012) ehr492v1. [Abstract] [Full Text] [PDF]

				J. Kajstura, M. Rota, T. Hosoda, P. Anversa, and A. Leri Response to Bergmann et al: Carbon 14 Birth Dating of Human Cardiomyocytes Circ. Res., January 6, 2012; 110(1): e19 - e21. [Full Text] [PDF]

				R. J. Parks, E. Fares, J. K. MacDonald, M. C. Ernst, C. J. Sinal, K. Rockwood, and S. E. Howlett A Procedure for Creating a Frailty Index Based on Deficit Accumulation in Aging Mice J Gerontol A Biol Sci Med Sci, October 21, 2011; (2011) glr193v1. [Abstract] [Full Text] [PDF]

				A. Leri, J. Kajstura, and P. Anversa Role of Cardiac Stem Cells in Cardiac Pathophysiology: A Paradigm Shift in Human Myocardial Biology Circ. Res., September 30, 2011; 109(8): 941 - 961. [Abstract] [Full Text] [PDF]

				S. M. Kawut, J. A. C. Lima, R. G. Barr, H. Chahal, A. Jain, H. Tandri, A. Praestgaard, E. Bagiella, J. R. Kizer, W. C. Johnson, et al. Sex and Race Differences in Right Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis-Right Ventricle Study Circulation, June 7, 2011; 123(22): 2542 - 2551. [Abstract] [Full Text] [PDF]

				E. Herman, A. Knapton, E. Rosen, J. Zhang, J. Estis, S. J. Agee, Q.-A. Lu, J. A. Todd, and S. E. Lipshultz Baseline Serum Cardiac Troponin I Concentrations in Sprague-Dawley, Spontaneous Hypertensive, Wistar, Wistar-Kyoto, and Fisher Rats as Determined with an Ultrasensitive Immunoassay Toxicol Pathol, June 1, 2011; 39(4): 653 - 663. [Abstract] [Full Text] [PDF]

				M. Mercola, P. Ruiz-Lozano, and M. D. Schneider Cardiac muscle regeneration: lessons from development Genes & Dev., February 15, 2011; 25(4): 299 - 309. [Abstract] [Full Text] [PDF]

				S. Agewall, E. Giannitsis, T. Jernberg, and H. Katus Troponin elevation in coronary vs. non-coronary disease Eur. Heart J., February 2, 2011; 32(4): 404 - 411. [Abstract] [Full Text] [PDF]

				D. J. Campbell, J. B. Somaratne, A. J. Jenkins, D. L. Prior, M. Yii, J. F. Kenny, A. E. Newcomb, D. J. Kelly, and M. J. Black Differences in Myocardial Structure and Coronary Microvasculature Between Men and Women With Coronary Artery Disease Hypertension, February 1, 2011; 57(2): 186 - 192. [Abstract] [Full Text] [PDF]

				W. Shim, A. Mehta, S. Y. Lim, G. Zhang, C. H. Lim, T. Chua, and P. Wong G-CSF for stem cell therapy in acute myocardial infarction: friend or foe? Cardiovasc Res, January 1, 2011; 89(1): 20 - 30. [Abstract] [Full Text] [PDF]

				E. R. Porrello and E. N. Olson Building a New Heart From Old Parts: Stem Cell Turnover in the Aging Heart Circ. Res., November 26, 2010; 107(11): 1292 - 1294. [Full Text] [PDF]

				J. Kajstura, N. Gurusamy, B. Ogorek, P. Goichberg, C. Clavo-Rondon, T. Hosoda, D. D'Amario, S. Bardelli, A. P. Beltrami, D. Cesselli, et al. Myocyte Turnover in the Aging Human Heart Circ. Res., November 26, 2010; 107(11): 1374 - 1386. [Abstract] [Full Text] [PDF]

				G. Petrov, V. Regitz-Zagrosek, E. Lehmkuhl, T. Krabatsch, A. Dunkel, M. Dandel, E. Dworatzek, S. Mahmoodzadeh, C. Schubert, E. Becher, et al. Regression of Myocardial Hypertrophy After Aortic Valve Replacement: Faster in Women? Circulation, September 14, 2010; 122(11_suppl_1): S23 - S28. [Abstract] [Full Text] [PDF]

				S. Cheng, V. Xanthakis, L. M. Sullivan, W. Lieb, J. Massaro, J. Aragam, E. J. Benjamin, and R. S. Vasan Correlates of Echocardiographic Indices of Cardiac Remodeling Over the Adult Life Course: Longitudinal Observations From the Framingham Heart Study Circulation, August 10, 2010; 122(6): 570 - 578. [Abstract] [Full Text] [PDF]

				D. Fliegner, C. Schubert, A. Penkalla, H. Witt, G. Kararigas, E. Dworatzek, E. Staub, P. Martus, P. R. Noppinger, U. Kintscher, et al. Female sex and estrogen receptor-{beta} attenuate cardiac remodeling and apoptosis in pressure overload Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2010; 298(6): R1597 - R1606. [Abstract] [Full Text] [PDF]

				M. Piro, R. Della Bona, A. Abbate, L. M. Biasucci, and F. Crea Sex-Related Differences in Myocardial Remodeling J. Am. Coll. Cardiol., March 16, 2010; 55(11): 1057 - 1065. [Abstract] [Full Text] [PDF]

				S. E. Howlett Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats Am J Physiol Heart Circ Physiol, February 1, 2010; 298(2): H659 - H670. [Abstract] [Full Text] [PDF]

				A. Itzhaki-Alfia, J. Leor, E. Raanani, L. Sternik, D. Spiegelstein, S. Netser, R. Holbova, M. Pevsner-Fischer, J. Lavee, and I. M. Barbash Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells Circulation, December 22, 2009; 120(25): 2559 - 2566. [Abstract] [Full Text] [PDF]

				B. Ostadal, I. Netuka, J. Maly, J. Besik, and I. Ostadalova Gender Differences in Cardiac Ischemic Injury and Protection--Experimental Aspects Exp Biol Med, September 1, 2009; 234(9): 1011 - 1019. [Abstract] [Full Text] [PDF]

				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. Sundstrom, E. Ingelsson, L. Berglund, B. Zethelius, L. Lind, P. Venge, and J. Arnlov Cardiac troponin-I and risk of heart failure: a community-based cohort study Eur. Heart J., April 1, 2009; 30(7): 773 - 781. [Abstract] [Full Text] [PDF]

				K. M. Eggers, A. S. Jaffe, L. Lind, P. Venge, and B. Lindahl Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making Clin. Chem., January 1, 2009; 55(1): 85 - 92. [Abstract] [Full Text] [PDF]

				A. Mingels, L. Jacobs, E. Michielsen, J. Swaanenburg, W. Wodzig, and M. van Dieijen-Visser Reference Population and Marathon Runner Sera Assessed by Highly Sensitive Cardiac Troponin T and Commercial Cardiac Troponin T and I Assays Clin. Chem., January 1, 2009; 55(1): 101 - 108. [Abstract] [Full Text] [PDF]

				P. D. Chantler, E. G. Lakatta, and S. S. Najjar Arterial-ventricular coupling: mechanistic insights into cardiovascular performance at rest and during exercise J Appl Physiol, October 1, 2008; 105(4): 1342 - 1351. [Abstract] [Full Text] [PDF]

				S. Barnes, M. Gott, S. Payne, C. Parker, D. Seamark, S. Gariballa, and N. Small Predicting mortality among a general practice-based sample of older people with heart failure Chronic Illness, March 1, 2008; 4(1): 5 - 12. [Abstract] [PDF]

				T.-H. Lin, H.-C. Chiu, Y.-T. Lee, H.-M. Su, W.-C. Voon, H.-W. Liu, W.-T. Lai, and S.-H. Sheu Association Between Functional Polymorphisms of Renin-Angiotensin System, Left Ventricular Mass, and Geometry Over 4 Years in a Healthy Chinese Population Aged 60 Years and Older J Gerontol A Biol Sci Med Sci, October 1, 2007; 62(10): 1157 - 1163. [Abstract] [Full Text] [PDF]

				C. M. Westerhout, M. S. Lauer, S. James, Y. Fu, L. Wallentin, P. W. Armstrong, and for the GUSTO IV ACS Investigators Electrocardiographic left ventricular hypertrophy in GUSTO IV ACS: an important risk marker of mortality in women Eur. Heart J., September 1, 2007; 28(17): 2064 - 2069. [Abstract] [Full Text] [PDF]

				T. A. Dorfman, B. D. Levine, T. Tillery, R. M. Peshock, J. L. Hastings, S. M. Schneider, B. R. Macias, G. Biolo, and A. R. Hargens Cardiac atrophy in women following bed rest J Appl Physiol, July 1, 2007; 103(1): 8 - 16. [Abstract] [Full Text] [PDF]

				G. Keyhan, S.-F. Chen, and L. Pilote Angiotensin-converting enzyme inhibitors and survival in women and men with heart failure Eur J Heart Fail, June 1, 2007; 9(6-7): 594 - 601. [Abstract] [Full Text] [PDF]

				C. G. Frazier, K. P. Alexander, L. K. Newby, S. Anderson, E. Iverson, M. Packer, J. Cohn, S. Goldstein, and P. S. Douglas Associations of Gender and Etiology With Outcomes in Heart Failure With Systolic Dysfunction: A Pooled Analysis of 5 Randomized Control Trials J. Am. Coll. Cardiol., April 3, 2007; 49(13): 1450 - 1458. [Abstract] [Full Text] [PDF]

				C. F. Deschepper and B. Llamas Hypertensive Cardiac Remodeling in Males and Females: From the Bench to the Bedside Hypertension, March 1, 2007; 49(3): 401 - 407. [Full Text] [PDF]

				S. A. Grandy and S. E. Howlett Cardiac excitation-contraction coupling is altered in myocytes from aged male mice but not in cells from aged female mice Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2362 - H2370. [Abstract] [Full Text] [PDF]

				B. Gruner Svealv, G. Fritzon, and B. Andersson Gender and age related differences in left ventricular function and geometry with focus on the long axis Eur Heart J Cardiovasc Imaging, August 1, 2006; 7(4): 298 - 307. [Abstract] [Full Text] [PDF]

				S. Natori, S. Lai, J. P. Finn, A. S. Gomes, W. G. Hundley, M. Jerosch-Herold, G. Pearson, S. Sinha, A. Arai, J. A. C. Lima, et al. Cardiovascular Function in Multi-Ethnic Study of Atherosclerosis: Normal Values by Age, Sex, and Ethnicity Am. J. Roentgenol., June 1, 2006; 186(6_Supplement_2): S357 - S365. [Abstract] [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]

				G G L Biondi-Zoccai, A Abate, R Bussani, D Camilot, F D Giorgio, M-P D Marino, F Silvestri, F Baldi, L M Biasucci, and A Baldi Reduced post-infarction myocardial apoptosis in women: a clue to their different clinical course? Heart, January 1, 2005; 91(1): 99 - 101. [Full Text] [PDF]

				J. P. Konhilas, A. H. Maass, S. W. Luckey, B. L. Stauffer, E. N. Olson, and L. A. Leinwand Sex modifies exercise and cardiac adaptation in mice Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2768 - H2776. [Abstract] [Full Text] [PDF]

				R. D. Patten, I. Pourati, M. J. Aronovitz, J. Baur, F. Celestin, X. Chen, A. Michael, S. Haq, S. Nuedling, C. Grohe, et al. 17{beta}-Estradiol Reduces Cardiomyocyte Apoptosis In Vivo and In Vitro via Activation of Phospho-Inositide-3 Kinase/Akt Signaling Circ. Res., October 1, 2004; 95(7): 692 - 699. [Abstract] [Full Text] [PDF]

				S. C. Lieber, N. Aubry, J. Pain, G. Diaz, S.-J. Kim, and S. F. Vatner Aging increases stiffness of cardiac myocytes measured by atomic force microscopy nanoindentation Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H645 - H651. [Abstract] [Full Text] [PDF]

				M. Klapholz, M. Maurer, A. M. Lowe, F. Messineo, J. S. Meisner, J. Mitchell, J. Kalman, R. A. Phillips, R. Steingart, E. J. Brown Jr, et al. Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: Results of the New York heart failure registry J. Am. Coll. Cardiol., April 21, 2004; 43(8): 1432 - 1438. [Abstract] [Full Text] [PDF]

				J. K. Ghali, H. J. Krause-Steinrauf, K. F. Adams Jr, S. S. Khan, Y. D. Rosenberg, C. W. Yancy Jr, J. B. Young, S. Goldman, M. A. Peberdy, and J. Lindenfeld Gender differences in advanced heart failure: insights from the BEST study J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2128 - 2134. [Abstract] [Full Text] [PDF]

				J. C. Baldi, K. McFarlane, H. C. Oxenham, G. A. Whalley, H. J. Walsh, and R. N. Doughty Left ventricular diastolic filling and systolic function of young and older trained and untrained men J Appl Physiol, December 1, 2003; 95(6): 2570 - 2575. [Abstract] [Full Text]

				J. Lindenfeld, J. K. Ghali, H. J. Krause-Steinrauf, S. Khan, K. Adams Jr, S. Goldman, M. A. Peberdy, C. Yancy, S. Thaneemit-Chen, R. L. Larsen, et al. Hormone replacement therapy is associated with improved survival in women with advanced heart failure J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1238 - 1245. [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]

				K. L. Golden, J. D. Marsh, Y. Jiang, T. Brown, and J. Moulden Gonadectomy of adult male rats reduces contractility of isolated cardiac myocytes Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E449 - E453. [Abstract] [Full Text] [PDF]

				S. Kostin, L. Pool, A. Elsasser, S. Hein, H. C.A. Drexler, E. Arnon, Y. Hayakawa, R. Zimmermann, E. Bauer, W.-P. Klovekorn, et al. Myocytes Die by Multiple Mechanisms in Failing Human Hearts Circ. Res., April 18, 2003; 92(7): 715 - 724. [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. Drew, S. Phaneuf, A. Dirks, C. Selman, R. Gredilla, A. Lezza, G. Barja, and C. Leeuwenburgh Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R474 - R480. [Abstract] [Full Text] [PDF]

				E. G. Lakatta and D. Levy Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part II: The Aging Heart in Health: Links to Heart Disease Circulation, January 21, 2003; 107(2): 346 - 354. [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]

				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]

				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 - M723. [Abstract] [Full Text] [PDF]

				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]

				S. E. Reis, R. Holubkov, J. B. Young, B. G. White, J. N. Cohn, and A. M. Feldman Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies J. Am. Coll. Cardiol., August 1, 2000; 36(2): 529 - 533. [Abstract] [Full Text] [PDF]

				C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]

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

				G. Olivetti, E. Cigola, R. Maestri, C. Lagrasta, D. Corradi, and F. Quaini Recent advances in cardiac hypertrophy Cardiovasc Res, January 1, 2000; 45(1): 68 - 75. [Full Text] [PDF]

				S. Guerra, A. Leri, X. Wang, N. Finato, C. Di Loreto, C. A. Beltrami, J. Kajstura, and P. Anversa Myocyte Death in the Failing Human Heart Is Gender Dependent Circ. Res., October 29, 1999; 85(9): 856 - 866. [Abstract] [Full Text] [PDF]

				E. O. Weinberg, C. D. Thienelt, S. E. Katz, J. Bartunek, M. Tajima, S. Rohrbach, P. S. Douglas, and B. H. Lorell Gender differences in molecular remodeling in pressure overload hypertrophy J. Am. Coll. Cardiol., July 1, 1999; 34(1): 264 - 273. [Abstract] [Full Text] [PDF]

				M. C. Petrie, N. F. Dawson, D. R. Murdoch, A. P. Davie, and J. J. V. McMurray Failure of Women's Hearts Circulation, May 4, 1999; 99(17): 2334 - 2341. [Full Text] [PDF]

				P. S. Douglas, S. E. Katz, E. O. Weinberg, M. H. Chen, S. P. Bishop, and B. H. Lorell Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload J. Am. Coll. Cardiol., October 1, 1998; 32(4): 1118 - 1125. [Abstract] [Full Text] [PDF]

				J. Kajstura, A. Leri, N. Finato, C. Di Loreto, C. A. Beltrami, and P. Anversa Myocyte proliferation in end-stage cardiac failure in humans PNAS, July 21, 1998; 95(15): 8801 - 8805. [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]

				P. Anversa and J. Kajstura Myocyte Cell Death in the Diseased Heart Circ. Res., June 15, 1998; 82(11): 1231 - 1233. [Full Text] [PDF]

				G. F. Mureddu, G. de Simone, R. Greco, G. F. Rosato, and F. Contaldo Left Ventricular Filling in Arterial Hypertension: Influence of Obesity and Hemodynamic and Structural Confounders Hypertension, February 1, 1997; 29(2): 544 - 550. [Abstract] [Full Text]