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Abstract

It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.
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We thank R. Lee, K. Spalding, and members of the Frisén lab for valuable discussions; M. Toro and K. Hamrin for help with flow cytometry; P. Reimer for assistance with radiocarbon interpretation; R. Cassidy, M. Müller, and E. Klaile for technical advice; M. Stahlberg and T. Bergman for help with high-performance liquid chromatography; and D. Kurdyla and P. Zermeno for producing graphite. This study was supported by grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, Knut och Alice Wallenbergs Stiftelse, Human Frontiers Science Program, the Swedish Cancer Society, the Foundation for Strategic Research, the Karolinska Institutet, the Juvenile Diabetes Research Foundation, NIH/NCRR (RR13461), European Commission FP7 CardioCell, and the Tobias Foundation. This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. R.D.B. and F.B.-H. were supported by fellowships from the Canadian Institutes of Health Research, and F.B.-H. was also supported by a fellowship from the Christopher and Dana Reeve Foundation.

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Published In

Science
Volume 324 | Issue 5923
3 April 2009

Submission history

Received: 14 August 2008
Accepted: 29 January 2009
Published in print: 3 April 2009

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Authors

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Olaf Bergmann*
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Ratan D. Bhardwaj*
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Samuel Bernard
CNRS UMR5208, Institut Camille Jordan, Université Claude Bernard Lyon 1, 69622 Villeurbanne cedex, France.
Sofia Zdunek
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Fanie Barnabé-Heider
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Stuart Walsh
Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, SE-221 84 Lund, Sweden.
Joel Zupicich
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Kanar Alkass
Department of Forensic Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Bruce A. Buchholz
Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, 7000 East Avenue, L-397, Livermore, CA 94551, USA.
Henrik Druid
Department of Forensic Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Stefan Jovinge
Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, SE-221 84 Lund, Sweden.
Department of Cardiology, Lund University Hospital, SE-221 85 Lund, Sweden.
Jonas Frisén
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Notes

† To whom correspondence should be addressed. E-mail: [email protected]

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