Intrinsic Aerobic Capacity Sets a Divide for Aging and Longevity

Abstract

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.

Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function

“…Thus the cardiomyocyte hypertrophy observed in this phenotype more closely resembles a pathological (as opposed to a physiological) cardiac growth response (31), even at 12 wk of age. This is also in agreement with the loss of myocardial transverse T tubules (19,21) and blunted cardiomyocyte contractile function (15) evident in older LCR rats, as well as the cardiac phenotype of rodent models of insulin resistance/type 2 diabetes (15, 39, 42). There is strong evidence that maintaining an increased level of physical activity is a key intervention favoring health benefits and longevity in patients with insulin resistance and diabetes (5,14).…”

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

“…Such a model might more closely mimic the large percentage of the US population with low level of daily physical activity (44). As human physical activity is a polygenic condition (29), we and others (25,35) contend that a selectively bred model of low daily physical activity will be more realistic to the biological basis of human sedentarism than would a transgenic model of lazy behavior produced by knockout or overexpression of a single gene. We also chose to pursue a model utilizing voluntary wheel running to study potential motivational differences for low physical activity given the following commentary by two reports: 1) Leasure and Jones (26) wrote: "ѧstudies suggest that forced and voluntary exercise may not be equivalent in their effects on the brain and behavior"; and 2) Fleshner et al (13) stated: ".…”

“…Koch and Britton (23) first reported in 2001 a similarly developed selective breeding model of rats that intrinsically possessed high (HCR) vs. low aerobic endurance capacity (LCR) using forced treadmill running to an operationally defined level of exhaustion. After 23 generations, LCRs had numerous greater disease risks, including metabolic syndrome and cardiovascular complications (24), as well as premature aging and a remarkable 28 -45% reduction in average lifespan (25) compared with HCR rats. In justifying their rationale for selective breeding, Koch et al (25) wrote, "This contrasting animal model system may prove to be translationally superior relative to more widely used simplistic models for understanding geriatric biology and medicine."…”

Prevalência de dislipidemia e sua relação com consumo de oxigênio entre servidores públicos

“…Outro fator que pode explicar o fato de as pessoas com maior idade terem menor nível de TG pode ser a sobrevida de quem possui esses níveis baixos, pois quem possui altos índices de CT, TG e outras variáveis que incrementam o risco cardíaco tendem a viver menos (11,(15)(16)(17) . Com relação à capacidade aeróbica (VO 2máx ), níveis baixos têm sido considerados um importante preditor de morbidade e mortalidade prematura em adultos saudáveis (24) , e, em combinação com outros fatores de risco, podem agravar a situação. A maioria dos avaliados do atual estudo se encontrou com níveis adequados de aptidão cardiorrespiratória, mesmo com idade média de 46,6+10,4 anos, o que levou os autores a acreditarem em uma superestimação dos valores de VO 2máx obtidos no teste de esforço.…”