The capacity of the heart to regenerate functional myocardium is extremely limited or absent. This lack of regenerative capacity contrasts with that of many other organs and tissues. Heart failure remains the leading cause of hospitalization in the United States, and its prevalence continues to grow as the population ages. In most patients, the underlying cause of heart failure is a loss of cardiomyocytes, accompanied by functional derangements in contraction and relaxation. The traditional view has held that the reparative ability of the heart is limited by the inability of terminally differentiated cardiomyocytes to undergo cell division after the first weeks of life and a failure in the mobilization of cardiac stem cells (if they exist). However, a recent study by Bergmann and colleagues1 calls this time-tested view into question.

The investigators performed a virtual pulse-chase experiment by measuring the incorporation of carbon-14, which was released during above-ground nuclear-bomb tests, into genomic DNA of human cardiomyocytes to calculate rates of turnover in these cells. Levels of carbon-14 in the atmosphere rose sharply as a result of nuclear testing and dropped precipitously once the Limited Nuclear Test Ban Treaty was signed in 1963. As a result, cells that were “born” during times of high carbon-14 levels can be precisely dated because subjects living during this period incorporated carbon-14 into the DNA of newly generated cardiomyocytes. The results indicate that, contrary to traditional teaching, cardiomyocytes renew throughout life at a very low rate. At the age of 25 years, approximately 1% of cardiomyocytes turn over annually, and the turnover rate decreases to 0.45% at the age of 75 years. During an average life span, fewer than 50% of cardiomyocytes renew. Remarkably, despite the substantial functional and metabolic demands placed on cardiomyocytes during the course of a lifetime, some of these cells survive for more than half a century.