Stem cells regulate myocyte growth in the aging rat heart

Whether aging affects the number of primitive cells in the heart is currently unknown. Therefore, the numerical density of undifferentiated cells was measured quantitatively in the left ventricular myocardium of rats at 4 and 27 months of age. The numbers of c-kit, MDR1 and Sca-1-like positive cells per 100 mm2 of tissue were 10±3, 20±9 and 4±1 in rats at 4 months. Corresponding values in rats at 27 months, were 29±8, 84±32 and 16±5. These increases with age were statistically significant. Stem cell surface antigens were maintained in cardiac progenitors expressing the transcription factor GATA-4. The frequency of cardiac progenitors was 4-7-fold higher in older rats. Similarly, myocyte precursors, expressing stem cell antigens, MEF2 and a thin cytoplasmic layer of cardiac myosin heavy chain were more numerous in the senescent heart. Importantly, a 6-fold higher myocyte mitotic index was found in old, 620±96/10e6, than in young, 95±31/10e6, rats. In conclusion, the loss of myocytes with age is, at least in part, counterbalanced by myocyte regeneration. Myocyte division is triggered by activation of resident cardiac stem cells, which increases in the senescent heart.