Skip to main content

Myocardial aging

A stem cell problem

Basic Research in Cardiology volume 100, pages 482–493 (2005)Cite this article

Abstract

This review questions the old paradigm that describes the heart as a post–mitotic organ and introduces the notion of the heart as a self–renewing organ regulated by a compartment of multipotent cardiac stem cells (CSCs) capable of regenerating myocytes and coronary vessels throughout life. Because of this dramatic change in cardiac biology, the objective is to provide an alternative perspective of the aging process of the heart and stimulate research in an area that pertains to all of us without exception. The recent explosion of the field of stem cell biology, with the recognition that the possibility exists for extrinsic and intrinsic regeneration of myocytes and coronary vessels, necessitates reevaluation of cardiac homeostasis and myocardial aging. From birth to senescence, the mammalian heart is composed of non–dividing and dividing cells. Loss of telomeric DNA is minimal in fetal and neonatal myocardium but rather significant in the senescent heart. Aging affects the growth and differentiation potential of CSCs interfering not only with their ability to sustain physiological cell turnover but also with their capacity to adapt to increases in pressure and volume loads. The recognition of factors enhancing the activation of the CSC pool, their mobilization, and translocation, however, suggests that the detrimental effects of aging on the heart might be prevented or reversed by local stimulation of CSCs or the intramyocardial delivery of CSCs following their expansion and rejuvenation in vitro. CSC therapy may become, perhaps, a novel strategy for the devastating problem of heart failure in the old population.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Adams KF, Sueta CA, Gheorghiade M, O’Connor CM, Schwartz TA, Koch GG, Uretsky B, Swedberg K, McKenna W, Soler–Soler J, Califf RM (1999) Gender differences in survival in advanced heart failure. Circulation 99:1816–1821

    PubMed  Google Scholar 

  2. Anversa P, Palackal T, Sonnenblick EH, Olivetti G, Meggs LG, Capasso JM (1990) Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ Res 67:871–885

    PubMed  Google Scholar 

  3. Anversa P, Li P, Sonnenblick EH, Olivetti G (1994) Effects of aging on quantitive structural properties of coronary vasculature and microvasculature in rats. Am J Physiol 267:H1062–H1073

    PubMed  Google Scholar 

  4. Anversa P, Kajstura J (1998) Ventricular myocytes are not terminally differentiated in the adult mammalian heart. Circ Res 83:1–14

    PubMed  Google Scholar 

  5. Anversa P, Leri A, Beltrami CA, Guerra S, Kajstura J (1998) Myocyte death and growth in the failing heart. Laboratory Investigation 78:767–786

    PubMed  Google Scholar 

  6. Anversa P, Leri A, Kajstura J, Nadal–Ginard B (2002) Myocyte growth and cardiac repair. J Mol Cell Cardiol 34:91–105

    Article  PubMed  Google Scholar 

  7. Anversa P, Olivetti G (2002) Cellular basis of physiological and pathological myocardial growth. In: Page E, Fozzard HA, Solaro RJ (eds) Handbook of Physiology: the Cardiovascular System. The Heart. Oxford University Press, New York, pp 75–144

  8. Anversa P, Sussman MA, Bolli R (2004) Molecular genetic advances in cardiovascular medicine: focus on the myocyte. Circulation 109:2832–2838

    Article  PubMed  Google Scholar 

  9. Aschoff L (1921) Pathologische anatomie. Berlin/Leipzig

  10. Baserga R (1985) The biology of cell reproduction. Harvard University Press, Cambridge London

  11. Becker A, McCulloch E, Till J (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454

    PubMed  Google Scholar 

  12. Belair GD, Yeager TR, Lopez PM, Reznikoff CA (1997) Telomerase activity: a biomarker of cell proliferation, not malignant transformation. Proc Natl Acad Sci USA 94:13677–13682

    Article  PubMed  Google Scholar 

  13. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal–Ginard B, Silvestri F, Leri A, Beltrami A, Anversa P (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 344:1750–1757

    Article  PubMed  Google Scholar 

  14. Bishop AE, Buttery LD, Polak JM (2002) Embryonic stem cells. J Pathol 197:424–429

    Article  PubMed  Google Scholar 

  15. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal–Ginard B, Anversa P (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776

    Article  PubMed  Google Scholar 

  16. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283:534–537

    Article  PubMed  Google Scholar 

  17. Blackburn EH (2000) Telomere states and cell fates. Nature 408:53–56

    Article  PubMed  Google Scholar 

  18. Blackburn EH (2005) Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett 579:859–862

    Article  PubMed  Google Scholar 

  19. Blasco MA, Hahn WC (2003) Evolving views of telomerase and cancer. Trends Cell Biol 13:289–294

    Article  PubMed  Google Scholar 

  20. Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779

    Article  PubMed  Google Scholar 

  21. Busuttil RA, Dolle M, Campisi J, Vijga J (2004) Genomic instability, aging, and cellular senescence. Ann NY Acad Sci 1019:245–255

    Article  PubMed  Google Scholar 

  22. Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120:513–522

    Article  PubMed  Google Scholar 

  23. Campisi J (2001) From cells to organisms: can we learn about aging from cells in culture? Exp Gerontol 36:607–618

    Article  PubMed  Google Scholar 

  24. Campisi J (1997) The bilogy of replicative senescence. Eur J Cancer 33:703–709

    Article  PubMed  Google Scholar 

  25. Capasso JM, Fitzpatrick D, Anversa P (1992) Cellular mechanisms of ventricular failure: myocyte kinetics and geometry with age. Am J Physiol 262:H1770–H1781

    PubMed  Google Scholar 

  26. Chan SR, Blackburn EH (2004) Telomeres and telomerase. Philos Trans R Soc Lond B Biol Sci 359:109–121

    Article  PubMed  Google Scholar 

  27. Chen J, Astle BA, Harrison DE (1999) Development and aging of primitive hematopoietic stem cells in BALB/cBy mice. Exp Hematol 27:928–935

    Article  PubMed  Google Scholar 

  28. Chen J, Astle CM, Harrison DE (2000) Genetic regulation of primitive hematopoietic stem cell senescence. Exp Hematol 28:442–450

    Article  PubMed  Google Scholar 

  29. Chien KR (2004) Stem cells: lost in translation. Nature 428:607–608

    Article  PubMed  Google Scholar 

  30. Chimenti C, Kajstura J, Torella D, Urbanek K, Heleniak H, Colussi C, Di Meglio F, Nadal–Ginard B, Frustaci A, Leri A, Maseri A, Anversa P (2003) Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res 93:604–613

    Article  PubMed  Google Scholar 

  31. Cristofalo VJ, Allan RG, Pignolo RJ, Martin BG, Beck JC (1998) Relationship between donor age and replicative lifespan in culture, a reevaluation. Proc Natl Acad Sci USA 95:10614–10619

    Article  PubMed  Google Scholar 

  32. de Haan G, Van Zant G (1999) Dynamic changes in mouse hematopoietic stem cell numbers during aging. Blood 93:3294–3301

    PubMed  Google Scholar 

  33. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira–Smith O, Campisi J (1995) A biomarker that indentifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363–9367

    PubMed  Google Scholar 

  34. Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94:4080–4085

    Article  PubMed  Google Scholar 

  35. Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, Jiang H, Wang Y, Keating MT (2005) p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev 19:1175–1187

    Article  PubMed  Google Scholar 

  36. Fallon J, Reid S, Kinyamu R, Opole R, Baratta J, Korc M, Endo TL, Duong A, Nguyen G, Karkehabadhi M, Twardzik D, Loughlin S (2000) In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci USA 97:14686–14691

    Article  PubMed  Google Scholar 

  37. Faragher RGA, Kipling D (1998) How might replicative senescence contribute to human aging? BioEssays 20:985–991

    Article  PubMed  Google Scholar 

  38. Ferrari G, Cusella–DeAngelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F (1998) Muscle regeneration by bone marrow–derived myogenic progenitors. Science 279:1528–1530

    Article  PubMed  Google Scholar 

  39. Fuchs E, Segre JA (2000) Stem cells: a new lease on life. Cell 100:143–155

    Article  PubMed  Google Scholar 

  40. Greider CW (2000–2001) Cellular response to telomere shortening: cellular senescence as a tumor suppressor mechanism. Harvey Lect 96:33–50

    Google Scholar 

  41. Geiger H, Van Zant G (2002) The aging of lympho–hematopoietic stem cells. Nature Immunol 4:329–333

    Article  Google Scholar 

  42. Guarente L, Kenyon C (2000) Genetic pathways that regulate aging in model organisms. Nature 408:255–262

    Article  PubMed  Google Scholar 

  43. Guerra S, Leri A, Wang X, Finato N, Di Loreto C, Beltrami CA, Kajstura J, Anversa P (1999) Myocyte death in the failing human heart is gender dependent. Circ Res 85:856–866

    PubMed  Google Scholar 

  44. Hachamovitch R, Wicker P, Capasso JM, Anversa P (1989) Alterations in coronary blood flow and reserve with aging in Fischer 344 rats. Am J Physiol 256:H66–H73

    PubMed  Google Scholar 

  45. Haunstetter A, Izumo S (1998) Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ Res 82:1111–1129

    PubMed  Google Scholar 

  46. Hierlihy AM, Seale P, Lobe CG, Rudnicki MA, Megeney LA (2002) The post–natal heart contains a myocardial stem cell population. FEBS Lett 530:239–243

    Article  PubMed  Google Scholar 

  47. Horner PJ, Gage FH (2000) Regenerating the damaged central nervous system. Nature 407:963–970

    Article  PubMed  Google Scholar 

  48. James SE, Faragher RG, Burke JF, Shall S, Mayne LV (2000) Werner's syndrome T lymphocytes display a normal in vitro life–span. Mech Aging Dev 121:139–149

    Article  PubMed  Google Scholar 

  49. Jazwinski SM, Kim S, Lai CY, Benguria A (1998) Epigenetic stratification: the role of individual change in the biological aging process. Exp Gerontol 33:571–580

    Article  PubMed  Google Scholar 

  50. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96:25–34

    Article  PubMed  Google Scholar 

  51. Kajstura J, Cheng W, Sarangarajan R, Li P, Li B, Nitahara JA, Chapnick S, Reiss K, Olivetti G, Anversa P (1996) Necrotic and apoptotic myocyte cell death in the aging heart of Fischer 344 rats. Am J Physiol 271:H1215–H1228

    Google Scholar 

  52. Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P (1998) Myocyte proliferation in end–stage cardiac failure in humans. Proc Natl Acad Sci USA 95:8801–8805

    Article  PubMed  Google Scholar 

  53. Kajstura J, Pertoldi B, Leri A, Beltrami CA, Deptala A, Darzynkiewicz Z, Anversa P (2000) Telomere shortening is an in vivo marker of myocyte replication and aging. Am J Pathol 156:813–819

    PubMed  Google Scholar 

  54. Kajstura J, Rota M, Whang C, Cascapera S, Hosoda T, Bearzi C, Nurzynska D, Kasahara H, Zias E, Bonafe M, Nadal– Ginard B, Torella D, Nascimbene A, Quaini F, Urbanek K, Leri A, Anversa P (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 96:127–137

    Article  PubMed  Google Scholar 

  55. Kang PM, Izumo S (2000) Apoptosis and heart failure: A critical review of the literature. Circ Res 86:1107–1113

    PubMed  Google Scholar 

  56. Karsner HT, Saphir O, Todd TW (1925) The state of the cardiac muscle in hypertrophy and atrophy. Am J Pathol 1:351–371

    Google Scholar 

  57. Kaufmann E (1922) Specielle pathologische anatomie. Berlin/Leipzig

  58. Kim H, You S, Farris J, Kong BW, Christman SA, Foster LK, Foster DN (2002) Expression profiles of p53–, p16(INK4a)–, and telomere–regulating genes in replicative senescent primary human, mouse, and chicken fibroblasts cells. Exp Cell Res 272:199–208

    Article  PubMed  Google Scholar 

  59. Kuro–o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Lida A, Shiraki–lida T, Nishikawa S, Nagai R, Nabeshima Y (1997) Mutation of the mouse klotho gene leads to a syndrome resembling aging. Nature 390:45–52

    Article  PubMed  Google Scholar 

  60. Kuro–o M (2001) Disease model: human aging. Trends Mol Med 7:179–181

    Article  PubMed  Google Scholar 

  61. Lagasse E, Connors H, Al–Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M (2000) Purified Hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229–1234

    Article  PubMed  Google Scholar 

  62. Lakatta EG (1993) Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 73:413–467

    PubMed  Google Scholar 

  63. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR (2005) Postnatal isl+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433:647–653

    Article  PubMed  Google Scholar 

  64. Leri A, Barlucchi L, Limana F, Deptala A, Darzynkiewicz Z, Hintze TH, J, Nadal– Ginard B, Anversa P (2001) Telomerase expression and activity are coupled with myocyte proliferation and preservation of telomeric length in the failing heart. Proc Natl Acad Sci USA 98:8626–8631

    Article  PubMed  Google Scholar 

  65. Leri A, Malhotra A, Liew CC, Kajstura J, Anversa P (2000) Telomerase activity in rat cardiac myocytes is age and gender dependent. J Mol Cell Cardiol 32:385–390

    Article  PubMed  Google Scholar 

  66. Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, Nadal–Ginard B, Kajstura J, Anversa P, Blasco MA (2003) Ablation of telomerase and telomere loss leads to cardiac dilation and heart failure associated with p53 upregulation. EMBO J 22:131–139

    Article  PubMed  Google Scholar 

  67. Limana F, Urbanek K, Chimenti S, Quaini F, Leri A, Kajstura J, Nadal– Ginard B, Izumo S, Anversa P (2002) bcl–2 overexpression promotes myocyte proliferation. Proc Natl Acad Sci USA 99:6257–6262

    Article  PubMed  Google Scholar 

  68. MacLellan WR, Schneider MD (2000) Genetic dissection of cardiac growth control pathways. Annu Rev Physiol 62:289–319

    Article  PubMed  Google Scholar 

  69. Maggioni AP, Maseri A, Fresco C, Franzosi MG, Mauri F, Santoro E, Tognoni G (1993) Age–related increase in mortality amoung patients with first myocardial infarctions treated with thrombolysis. N Engl J Med 329:1442–1448

    Article  PubMed  Google Scholar 

  70. Mallat Z, Tedgui A, Fontaliran F, Frank R, Durigon M, Fontaine G (1996) Evidence of apoptosis in arrhythmogenic right ventricular dysplasia. N Engl J Med 335:1190–1196

    Article  PubMed  Google Scholar 

  71. Martin CM, Meeson AP, Robertson SM, Hawke TJ, Richardson JA, Bates S, Goetsch SC, Gallardo TD, Garry DJ (2004) Persistent expression of the ATPbiding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol 265:262–275

    Article  PubMed  Google Scholar 

  72. Martin GM, Oshima J (2000) Lessons from human progeroid syndromes. Nature 408:263–266

    Article  PubMed  Google Scholar 

  73. Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I (2004) Adult cardiac Sca–1 positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384–11391

    Article  PubMed  Google Scholar 

  74. McKinney–Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F, Goodell MA (2002) Muscle–derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci USA 99:1341–1346

    Article  PubMed  Google Scholar 

  75. Mezey E (2004) Commentary: on bone marrow stem cells and openmindedness. Stem Cells Dev 13:147–152

    Article  PubMed  Google Scholar 

  76. Mondello C, Scovassi AI (2004) Telomeres, telomerase, and apoptosis. Biochem Cell Biol 82:498–507

    Article  PubMed  Google Scholar 

  77. Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL (1996) The aging of hematopoietic stem cells. Nat Med 2:1011–1016

    Article  PubMed  Google Scholar 

  78. Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL (1997) Identification of a lineage of multipotent hematopoietic progenitors. Development 124:1929–1939

    PubMed  Google Scholar 

  79. Nakamura T, Schneider MD (2003) The way to a human’s heart is through the stomach. Circulation 107:2638–2639

    Article  PubMed  Google Scholar 

  80. Narula J, Haider N, Virmani R, Di Salvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA (1996) Apoptosis in myocytes in end–stage heart failure. N Engl J Med 335:1182–1189

    Article  PubMed  Google Scholar 

  81. Ogawa M, Matsuzaki Y, Nishikawa S, Hayashi S, Kunisada T, Sudo T, Kina T, Nakauchi H, Nishikawa S (1991) Expression and function of c–kit in hematopoietic progenitor cells. J Exp Med 174:63–71

    Article  PubMed  Google Scholar 

  82. Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD (2003) Cardiac progenitor cells form adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 100:12313–12318

    Article  PubMed  Google Scholar 

  83. Okada S, Nakauchi H, Nagayoshi K, Nishikawa S, Nishikawa S, Miura Y, Suda T (1991) Enrichment and characterization of murine hematopoietic stem cells that express c–kit molecule. Blood 78:1706–1712

    PubMed  Google Scholar 

  84. Olivetti G, Melissari M, Capasso JM, Anversa P (1991) Cardiomyopathy of the aging human heart Circ Res 68:1560–1568

    PubMed  Google Scholar 

  85. Olivetti G, Giordano G, Corradi D, Melissari M, Lagrasta C, Gambert SR, Anversa P (1995) Gender differences and aging: effects on the human heart. J Am Coll Cardiol 26:1068–1079

    Article  PubMed  Google Scholar 

  86. Olivetti G, Cigola E, Maestri R, Corradi D, Lagrasta C, Gambert SR, Anversa P (1996) Aging, cardiac hypertrophy and ischemic cardiomyopathy do not affect the proportion of mononucleated and multinucleated myocytes in the human heart. J Mol Cell Cardiol 28:1463–1477

    Article  PubMed  Google Scholar 

  87. Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Di Loreto C, Beltrami CA, Krajewski S, Reed JC, Anversa P (1997) Apoptosis in the failing human heart. N Engl J Med 336:1131–1141

    Article  PubMed  Google Scholar 

  88. Orlic D, Fischer R, Nishikawa SI, Nienhuis AW, Bodine DM (1985) Purification and characterization of heterogeneous pluripotent hematopoietic stem cell populations expressing high levels of c–kit receptor. Blood 82:762–770

    Google Scholar 

  89. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal–Ginard B, Bodine DM, Leri A, Anversa P (2001) Mobilized bone marrow cells repair the infracted heart, improving function and survival. Proc Natl Acad Sci USA 98:10344–10349

    Article  PubMed  Google Scholar 

  90. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal–Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infracted myocardium. Nature 410:701–705

    Article  PubMed  Google Scholar 

  91. Ostler EL, Wallis CV, Sheerin AN, Faragher RGA (2002) A model for the phenotypic presentation of Werner’s syndrome. Exp Gerontol 37:285–292

    Article  PubMed  Google Scholar 

  92. Postiglione A, Soricelli A, Covelli EM, Lazzetta N, Ruocco A, Milan G, Santoro L, Alfano B, Brunetti A (1996) Premature aging in Werner’s syndrome spares the central nervous system. Neurobiol Aging 17:325–330

    Article  PubMed  Google Scholar 

  93. Rakusan K (1984) Cardiac growth, maturation, and aging. In: Zak R (ed) Growth of the heart in health and disease. Raven Press Publishers, pp 131–164

  94. Rakusan K, Flanagan MF, Geve T, Southern J, Van Praagh R (1992) Morphometry of human coronary capillaries during normal growth and the effects of age in left ventricular pressure overload hypertrophy. Circulation 86:38–46

    PubMed  Google Scholar 

  95. Rubin H (1997) Cell aging in vivo and in vitro. Mech Aging Dev 98:1–35

    Article  PubMed  Google Scholar 

  96. Rubin H (2002) The disparity between human cell senescence in vitro and lifelong replication in vivo. Nat Biotechnol 20:675–681

    Article  PubMed  Google Scholar 

  97. Schneider EL, Mitsui Y (1976) The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci USA 73:3584–3588

    PubMed  Google Scholar 

  98. Schwarze SR, Shi Y, Fu VX, Watson PA, Jarrad DF (2001) Role of cyclin–dependent kinase inhibitors in the growth arrest at senescence in human prostate epithelial and uroepithelial cells. Oncogene 20:8184–8192

    Article  PubMed  Google Scholar 

  99. Setoguchi M, Leri A, Wang S, Liu Y, De Luca A, Giordano A, Hintze TH, Kajstura J, Anversa P (1999) Activation of cyclins and cyclin–dependent kinases, DNA synthesis, and myocyte mitotic division in pacing–induced heart failure in dogs. Lab Invest 79:1545–1558

    PubMed  Google Scholar 

  100. Severino J, Allen RG, Balin S, Balin A, Christofalo VJ (2000) is B–galactosidase staing a marker of senescence in vivo and in vitro? Exp Cell Res 257:162–171

    Article  PubMed  Google Scholar 

  101. Sherr CJ, De Pinho RA (2000) Cellular senescence: mitotic clock or culture shock. Cell 102:407–410

    Article  PubMed  Google Scholar 

  102. Smith JR, Whitney JR (1980) Intraclonal variation in proliferative potential of human diploid fibroblasts: stochastic mechanism for cellular aging. Science 207:82–84

    PubMed  Google Scholar 

  103. Soonpaa MH, Field LJ (1994) Assessment of cardiomyocyte DNA synthesis during hypertrophy in adult mice. Am J Physiol 266:H1439–H1445

    PubMed  Google Scholar 

  104. Soonpaa MH, Koh GY, Klug MG, Field LJ (1994) Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science 264:98–101

    PubMed  Google Scholar 

  105. Sudo K, Ema H, Morita Y, Nakauchi H (2000) Age–associated characteristics of murine hematopoietic stem cells. J Exp Hematol 192:1273–1280

    Google Scholar 

  106. Sussman MA, Anversa P (2004) Myocardial aging and senescence: where have the stem cells gone? Annu Rev Physiol 66:29–48

    Article  PubMed  Google Scholar 

  107. Takahashi Y, Kuro–o M, Ishikawa F (2000) Aging mechanisms. Proc Natl Acad Sci USA 97:12407–12408

    Article  PubMed  Google Scholar 

  108. Tomanek RJ, Aydelotte MR, Torry RJ (1991) Remodeling of coronary vessels during aging in purebred beagles. Circ Res 69:1068–1074

    PubMed  Google Scholar 

  109. Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I, Zias E, Walsh K, Rosenzweig A, Sussman MA, Urbanek K, Nadal–Ginard B, Kajstura J, Anversa P, Leri A (2004) Cardiac stem cell and myocyte aging, heart failure, and insulin–like growth factor–1 overexpression. Circ Res 94:514–524

    Article  PubMed  Google Scholar 

  110. Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal–Ginard B, Leri A, Kajstura J, Quaini E, Anversa P (2003) Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA 100:10440–10445

    Article  PubMed  Google Scholar 

  111. Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F, Beltrami CA, Bussani R, Beltrami AP, Quaini F, Bolli R, Leri A, Kajstura J, Anversa P (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci USA 102:8692–8697

    Article  PubMed  Google Scholar 

  112. Vogel H, Lim DS, Karsenty G, Finegold M, Hasty P (1999) Deletion of Ku86 causes early onset of senescence in mice. Proc Natl Acad Sci USA 96:10770–10775

    Article  PubMed  Google Scholar 

  113. Wagers AJ, Weissman IL (2004) Plasticity of stem cells. Cell 116:639–648

    Article  PubMed  Google Scholar 

  114. Wei JY (1992) Age and the cardiovascular system. N Engl J Med 237:1735–1739

    Google Scholar 

  115. Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157–168

    Article  PubMed  Google Scholar 

  116. Wood WB (1998) Aging of C. elegans: mosaics and mechanisms. Cell 95:147–150

    Article  PubMed  Google Scholar 

  117. Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K, Hanley A, Scadova H, Qin G, Cha DH, Johnson KL, Aikawa R, Asahara T, Losordo DW (2005) Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 115:326–338

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Cardiovascular Research Institute, Department of Medicine, New York Medical College, Vosburgh Pavilion, Valhalla, NY 10595, USA

    P. Anversa M.D., M. Rota, K. Urbanek, T. Hosoda, A. Leri & J. Kajstura

  2. Albert Einstein College of Medicine, New York, NY 10461, USA

    E. H. Sonnenblick

  3. Institute of Molecular Cardiology, University of Louisville, Louisville, Ky 40292, USA

    R. Bolli

Authors
  1. P. Anversa M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Rota
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Urbanek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Hosoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. H. Sonnenblick
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Leri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Kajstura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. Bolli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Anversa M.D..

Additional information

Dr. M. Sussman, San Diego, USA, served as guest editor for the manuscript and was reponsible for all editorial decisions, including the selection of reviewers. The policy applies to all manuscripts with authors from the editor's institution.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Anversa, P., Rota, M., Urbanek, K. et al. Myocardial aging. Basic Res Cardiol 100, 482–493 (2005). https://doi.org/10.1007/s00395-005-0554-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-005-0554-3

Keywords

  • Coronary Vessel
  • Volume Load
  • Cell Turnover
  • Stem Cell Biology
  • Mammalian Heart