Sustained cardiac programming by short-term juvenile exercise training in male rats

Cardiac hypertrophy following endurance-training is thought to be due to hypertrophy of existing cardiomyocytes. The benefits of endurance exercise on cardiac hypertrophy are generally thought to be short-lived and regress to sedentary levels within a few weeks of stopping endurance training. We have now established that cardiomyocyte hyperplasia also plays a considerable role in cardiac growth in response to just 4 weeks of endurance exercise in juvenile (5-9 weeks of age) rats. The effect of endurance exercise on cardiomyocyte hyperplasia diminishes with age and is lost by adulthood. We have also established that the effect of juvenile exercise on heart mass is sustained into adulthood.

The aim of this study was to investigate if endurance training during juvenile life 'reprogrammes' the heart and leads to sustained improvements in the structure, function, and morphology of the adult heart. Male Wistar Kyoto rats were exercise trained 5 days week^-1 for 4 weeks in either juvenile (5-9 weeks of age), adolescent (11-15 weeks of age) or adult life (20-24 weeks of age). Juvenile exercise training, when compared to 24-week-old sedentary rats, led to sustained increases in left ventricle (LV) mass (+18%; P < 0.05), wall thickness (+11%; P < 0.05), the longitudinal area of binucleated cardiomyocytes (P < 0.05), cardiomyocyte number (+36%; P < 0.05), and doubled the proportion of mononucleated cardiomyocytes (P < 0.05), with a less pronounced effect of exercise during adolescent life. Adult exercise training also increased LV mass (+11%; P < 0.05), wall thickness (+6%; P < 0.05) and the longitudinal area of binucleated cardiomyocytes (P < 0.05), despite no change in cardiomyocyte number or the proportion of mono- and binucleated cardiomyocytes. Resting cardiac function, LV chamber dimensions and fibrosis levels were not altered by juvenile or adult exercise training. At 9 weeks of age, juvenile exercise significantly reduced the expression of microRNA-208b, which is a known regulator of cardiac growth, but this was not sustained to 24 weeks of age. In conclusion, juvenile exercise leads to physiological cardiac hypertrophy that is sustained into adulthood long after exercise training has ceased. Furthermore, this cardiac reprogramming is largely due to a 36% increase in cardiomyocyte number, which results in an additional 20 million cardiomyocytes in adulthood.