Olaf Bergmann,1* Ratan D. Bhardwaj,1* Samuel Bernard,2 Sofia Zdunek,1 Fanie Barnabé-Heider,1 Stuart Walsh,3 Joel Zupicich,1 Kanar Alkass,4 Bruce A. Buchholz,5 Henrik Druid,4 Stefan Jovinge,3,6 Jonas Frisén1

1 Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
2 CNRS UMR5208, Institut Camille Jordan, Université Claude Bernard Lyon 1, 69622 Villeurbanne cedex, France.
3 Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, SE-221 84 Lund, Sweden.
4 Department of Forensic Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
5 Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, 7000 East Avenue, L-397, Livermore, CA 94551, USA.
6 Department of Cardiology, Lund University Hospital, SE-221 85 Lund, Sweden.

* These authors contributed equally to this work.

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.