Rationale Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity. Objectives Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis). Methods and Results Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15 and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO2max), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28-45% shorter than high capacity rats (hazard ratio, 0.06; P<.001). VO2max, measured across adulthood was a reliable predictor of lifespan (P<.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca2+ handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (VO2), and lean body mass were all better sustained with age in rats bred for high aerobic capacity. Conclusions These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and useful for deeper mechanistic exploration.

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The study was conducted to compare effects of different dietary Se sources (sodium selenite [NaSe], Se-enriched yeast [Se yeast] or L-selenomethionine [SeMet]) and one Se-deficient control diet on the expression of selected genes, hematological and clinical biochemical parameters, and muscle morphology in two parallel trials with finisher pigs. Se concentrations in blood plasma and tissues were also monitored. From the pigs in one of the parallel groups, muscle samples obtained from Musculus longissimus dorsi (LD) before and during the trial were examined. The pigs in the other parallel group were challenged once with lipopolysaccharide (LPS) intravenously. Transcriptional analyses of LD showed that selenogenes SelenoW and H were higher expressed in pigs fed Se-supplemented diets compared with control. Furthermore, the expression of interferon gamma and cyclooxygenase 2 was lower in the Se-supplemented pigs versus control. In whole blood samples prior to LPS, SelenoN, SelenoS and thioredoxin reductase 1 were higher expressed in pigs fed NaSe supplemented feed compared with the other groups, possibly indicating a higher level of oxidative stress. After LPS exposure glutathione peroxidase 1 and SelenoN were more reduced in pigs fed NaSe compared with pigs fed organic Se. Products of most above-mentioned genes are intertwined with the oxidant-antioxidant system. No significant effects of Se-source were found on hematologic parameters or microscopic anatomy. The Se-concentrations in various skeletal muscles and heart muscle were significantly different between the groups, with highest concentrations in pigs fed SeMet, followed by those fed Se yeast, NaSe, and control diet. Consistent with previous reports our results indicate that dietary Se at adequate levels can support the body's antioxidant system. Our results indicate that muscle fibers of pigs fed organic Se are less vulnerable to oxidative stress compared with the other groups.