Blunted cardiomyocyte remodeling response in exercise-resistant rats

Increasing a subject’s aerobic exercise capacity with training decreases cardiovascular morbidity and mortality. Of major concern is the key observation that up to 20% of subjects demonstrate little or no change in maximal oxygen consumption (VO2max) with exercise training (1) and can be considered exercise resistant. Our goal with the current research was to test the hypothesis that variation in training response is associated with cardiomyocyte functional response to training

Intrinsic aerobic capacity sets a divide for aging and longevity

<p><b>Rationale:</b> 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.</p> <p><b>Objectives:</b> Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).</p> <p><b>Methods and Results:</b> 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 (VO<sub>2max</sub>), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO<sub>2max</sub>, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca<sup>2+</sup> 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 (Vo<sub>2</sub>), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.</p> <p><b>Conclusions:</b> 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 are useful for deeper mechanistic exploration of aging.</p&gt

Aerobic capacity, oxidant stress, and chronic obstructive pulmonary disease--a new take on an old hypothesis.

Chronic obstructive pulmonary disease (COPD) is a smoking-related disorder that is a leading cause of death worldwide. It is associated with an accelerated rate of age-related decline in lung function due to the occurrence of destructive pathological changes such as emphysema, small airway remodeling, and mucus hypersecretion. Smokers are exposed to trillions of radicals and thousands of reactive chemicals and particles with every cigarette, thus oxidant stress is believed to be a central factor in the pathogenesis of COPD. The molecular activities of radicals, reactive oxygen, and nitrogen species can, over time, lead to a number of the detrimental changes in the lung. For instance, smoke can directly damage the mitochondrion, an organelle that has long been linked to age-related diseases associated with oxidant stress. Mitochondria are involved in a number of important cellular processes and are the largest source of endogenous reactive oxygen species (ROS) in the cell; therefore, any impairment of mitochondrial function can lead to greater oxidant damage, cellular dysfunction, and eventually to disease. Only a subset of smokers (15-50%) develops COPD, suggesting that there are polygenetic and/or environmental susceptibility factors involved in this complex disease. Here, we propose that the aerobic capacity for an individual may determine whether one is susceptible to developing COPD. Aerobic capacity is a polygenetic trait closely associated with mitochondrial function, and we suggest antioxidant defenses. Thus, those smokers who have the greatest aerobic capacity will be most resistant to the effects of chronic cigarette smoke exposure and be less likely to develop COPD

Body mass index measures in children with cerebral palsy related to gross motor function classification: a clinic-based study.

OBJECTIVE: To investigate the prevalence of overweight in a clinic-based population of children with cerebral palsy (CP) and its association with gross motor function status. DESIGN: Retrospective chart review. We calculated body mass index (BMI; kg/m2) from charted height and weight and recorded Gross Motor Function Classification Scale (GMFCS levels I-V) on the basis of clinical descriptions in clinic notes for 137 children (2-18 yrs old) with CP seen in a pediatric rehabilitation clinic at an academic medical center. BMI percentiles were reported according to sex-specific age group standards for growth set by the U.S. Centers for Disease Control and Prevention (CDC). Associations were modeled by Pearson\u27s chi2 distribution. RESULTS: Out of the total CP subject group, 29.1% were considered overweight (\u3e95th percentile) or at risk for overweight (85th to 95th percentile). Ambulatory children (GMFCS levels I and II) showed a trend (Pearson\u27s chi2, P = 0.06) toward higher prevalence of overweight (22.7%) compared with nonambulatory children (levels IV and V, 9.6%). Underweight was more prevalent in nonambulatory children (P \u3c 0.01). Logistic regression analysis did not identify any significant predictors for overweight. CONCLUSIONS: In our patient population, analysis of BMI suggests that children with CP have a high rate of overweight and are at risk of overweight, particularly among ambulatory children. More study is needed, using measures more accurate than BMI, to clarify risk