title: Myocyte turnover in the aging human heart.
abstract: BACKGROUND
  The turnover of cardiomyocytes in the aging female and male heart is currently unknown, emphasizing the need to define human myocardial biology.
  
  
  OBJECTIVE
  The effects of age and gender on the magnitude of myocyte regeneration and the origin of newly formed cardiomyocytes were determined.
  
  
  RESULTS
  The interaction of myocyte replacement, cellular senescence, growth inhibition, and apoptosis was measured in normal female (n=32) and male (n=42) human hearts collected from patients 19 to 104 years of age who died from causes other than cardiovascular diseases. A progressive loss of telomeric DNA in human cardiac stem cells (hCSCs) occurs with aging and the newly formed cardiomyocytes inherit short telomeres and rapidly reach the senescent phenotype. Our data provide novel information on the superior ability of the female heart to sustain the multiple variables associated with the development of the senescent myopathy. At all ages, the female heart is equipped with a larger pool of functionally competent hCSCs and younger myocytes than the male myocardium. The replicative potential is higher and telomeres are longer in female hCSCs than in male hCSCs. In the female heart, myocyte turnover occurs at a rate of 10%, 14%, and 40% per year at 20, 60, and 100 years of age, respectively. Corresponding values in the male heart are 7%, 12%, and 32% per year, documenting that cardiomyogenesis involves a large and progressively increasing number of parenchymal cells with aging. From 20 to 100 years of age, the myocyte compartment is replaced 15 times in women and 11 times in men.
  
  
  CONCLUSIONS
  The human heart is a highly dynamic organ regulated by a pool of resident hCSCs that modulate cardiac homeostasis and condition organ aging.
authors.affiliation: Department of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. jkajstura@partners.org
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Narasimman
authors.initials: N
authors.lastname: Gurusamy
authors.forename: Barbara
authors.initials: B
authors.lastname: Ogórek
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.forename: Carlos
authors.initials: C
authors.lastname: Clavo-Rondon
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoda
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Amario
authors.forename: Silvana
authors.initials: S
authors.lastname: Bardelli
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Beltrami
authors.forename: Daniela
authors.initials: D
authors.lastname: Cesselli
authors.forename: Rossana
authors.initials: R
authors.lastname: Bussani
authors.forename: Federica
authors.initials: F
authors.lastname: del Monte
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
authors.forename: Marcello
authors.initials: M
authors.lastname: Rota
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Beltrami
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Buchholz
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D012727:Sex Characteristics; D055815:Young Adult