Inherited physical capacity: Widening divergence from young to adult to old

Cardiorespiratory performance segregates into rat strains of inherited low- and high-capacity runners (LCRs and HCRs); during adulthood, this segregation remains stable, but widens in senescence and is followed by segregated function, health, and mortality. However, this segregation has not been investigated prior to adulthood. We, therefore, assessed cardiorespiratory performance and cardiac cell (cardiomyocyte) structure-function in 1- and 4-month-old LCRs and HCRs. Maximal oxygen uptake was 23% less in LCRs at 1-month compared to HCRs at 1-month, and 72% less at 4 months. Cardiomyocyte contractility was 37-56% decreased, and Ca2+ release was 34-62% decreased, in 1- and 4-month LCRs versus HCRs. This occurred because HCRs had improved contractility and Ca2+ release during maturation, whereas LCRs did not. In quiescent cardiomyocytes, LCRs displayed 180% and 297% more Ca2+ sparks and 91% and 38% more Ca2+ waves at 1 and 4 months versus HCRs. Cell sizes were not different between LCRs and HCRs, but LCRs showed reduced transverse-tubules versus HCRs, though no discrepant transverse-tubule generation occurred during maturation. In conclusion, LCRs show reduced scores for aerobic capacity and cardiomyocyte structure-function compared to HCRs and there is a widening divergence between LCRs and HCRs during juvenile to near-adult maturation. Rat models of inherited low and high exercise capacities segregate for heart structure-function. Towards end-of-life, widening divergence in exercise and heart scores leads to a stark difference in health and longevity; high exercise capacity rats have healthier and longer lives. For the first time, we show that this divergence starts early in life, whereby those with low exercise and heart scores mature poorly-setting the scene for lifelong segregation. image