Youth is wasted on the young

Following acute myocardial infarction, the human heart can lose over a billion cardiac myocytes. The injured tissue undergoes fibrosis, leading to significant loss of contractile function, adverse left ventricular remodeling and ultimately chronic heart failure. Adult mammalian cardiac myocytes are multinucleated and it has been well documented that only a limited number of cardiac myocytes enter the cell cycle following myocardial repair [1]. Scientists at the bench have known for decades that cardiac myocytes isolated from adult mammalian myocardium do not enter the cell cycle and actively divide, whereas cardiac myocytes from neonatal myocardium do have a limited capacity to divide in culture. The limited proliferative capacity of adult cardiac myocytes correlates with the limited capacity of the adult myocardium to regenerate itself following acute myocardial infarction, and is in distinct contrast to the regenerative capacity of the myocardium in lower life forms, including zebrafish [2].The recent publication by Porrello and colleagues sought to answer the question of whether the neonatal mammalian heart has the capacity for regeneration that is lost with aging [3]. To answer this question they resected the apex of the hearts of 1-day-old neonatal mice and found that the myocardium does regenerate. The regenerative process is accompanied by proliferation of cardiac myocytes that peaked at 7 days after resection. By 21 days after resection the apex of experimental animals was indistinguishable from that of sham animals, without any evidence of significant scar. Furthermore, cardiac function and chamber dimensions were similarly unchanged between experimental and sham-treated animals. In distinct contrast, apical resection in 7-day-old mice did not lead to cardiac myocyte proliferation or regeneration of the lost apical tissue. Rather, the apex in the 7-day-old mice was markedly fibrotic, suggesting that the regenerative capacity of neonatal myocardium is lost w