When cardiac muscle is lost, the heart mostly heals through the formation of scar tissue.Although the heart cannot undergo large-scale tissue regeneration, stem/progenitor cells with the potential to generate cardiomyocytes in vitro remain in the adult human myocardium, and mature cardiomyocytes have been suggested to have the ability to re-enter the cell cycle and duplicate.
To investigate cardiomyocyte turnover in human hearts, Bergmann et al. used a novel system based on radiocarbon dating of DNA. Following nuclear bomb testing during the early period of the cold war (1945-1963), the levels of 14C (incorporated into 14CO2) in the atmosphere rapidly equalized around the world. After being taken up by plants which are subsequently consumed by humans, the 14C is then incorporated into DNA, and because DNA is stable after a cell has gone through its last cell division, the concentration of 14C in DNA serves as a date mark for when a cell was born, and can be used to retrospectively date cells in humans.A similar approach has been used in rodent models previously, but never implemented in humans due to safety concerns.
Using mathematical modeling, the authors suggest that cardiomyocyte renewal is an age-dependent process, with a gradual decrease from 1% annual turnover at the age of 25, to 0.45% at the age of 75. By contrast, non-myocytes in the heart turn over at an estimated rate of 18% per year. By the age of 50, 55% of human cardiomyocytes remain from birth, while 45% were generated afterward. However, overall fewer than 50% of cardiomyocytes are rejuvenated during a normal life span.
This remarkable piece of work exploits a dark period of recent human history to make a novel and exciting scientific discovery. The next step lies in determining the origins of new cardiac myocytes, and the pathways that lead to their development, before looking at how they are activated in response to injury. Knowledge of this process may in the long term lead to methods of rejuvenating damaged myocardium, and preventing heart failure.
· Evidence of Cardiomyocyte Renewal in Humans. Bergmann O, Bhardwaj RD, Bernard S et al. Science 2009:324;p98-102