Article thumbnail

Intrinsic aerobic capacity sets a divide for aging and longevity

By Lauren Gerard Koch, Ole J. Kemi, Nathan Qi, Sean X. Leng, Piter Bijma, Lori J. Gilligan, John E. Wilkinson, Helene Wisløff, Morten A. Høydal, Natale Rolim, Peter M. Abadir, Elizabeth M. van Grevenhof, Godfrey L. Smith, Charles F. Burant, Øyvind Ellingsen, Steven L. Britton and Ulrik Wisløff

Abstract

<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

Topics: RC1200
Publisher: 'Ovid Technologies (Wolters Kluwer Health)'
Year: 2011
DOI identifier: 10.1161/CIRCRESAHA.111.253807
OAI identifier: oai:eprints.gla.ac.uk:57344
Provided by: Enlighten

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circ Res.
  2. Aerobic capacity-dependent differences in cardiac gene expression. Physiol Genomics.
  3. Aerobic metabolism underlies complexity and capacity.
  4. Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance.
  5. Artificial selection for intrinsic aerobic endurance running capacity in rats. Physiol Genomics.
  6. Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability.
  7. Calmodulin and ca2+/calmodulin kinases in the heart -physiology and pathophysiology. Cardiovasc Res.
  8. Cardiorespiratory fitness and adiposity as mortality predictors in older adults.
  9. Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.
  10. Computation of inbreeding and relationship coefficients - in populations with a relatively small number of different male ancestors.
  11. Daily activity energy expenditure and mortality among older adults.
  12. Development of the national institutes of health genetically heterogeneous rat stock. Alcohol Clin Exp Res.
  13. Disease-specific mortality among elite athletes.
  14. Exercise capacity and body composition as predictors of mortality among men with diabetes. Diabetes Care.
  15. Exercise capacity and mortality among men referred for exercise testing.
  16. Exercise capacity and mortality in black and white men.
  17. Exercise capacity and the risk of death in women: The st james women take heart project.
  18. for the Cardiovascular Health Study Collaborative Research Group. Risk factors for 5-year mortality in older adults: The cardiovascular health study.
  19. Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk.
  20. Gibbons LW. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men
  21. (1996). Introduction to quantitative genetics.
  22. Modifiable risk factors as predictors of all-cause mortality: The roles of genetics and childhood environment.
  23. Obesity paradox and cardiorespiratory fitness in 12,417 male veterans aged 40 to 70 years.
  24. (2010). Perls TT. Genetic signatures of exceptional longevity in humans. Science.
  25. Physical fitness and all-cause mortality. A prospective study of healthy men
  26. Physical fitness as a predictor of mortality among healthy, middle-aged norwegian men.
  27. Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury.
  28. Recent results: Biomarkers of aging. Exp Gerontol.
  29. Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction.
  30. Signals of recent positive selection in a worldwide sample of human populations. Genome Res.
  31. The aging process and potential interventions to extend life expectancy. Clin Interv Aging.
  32. The failing heart--an engine out of fuel.
  33. The role of mitochondrial uncoupling proteins in lifespan. Pflugers Arch.
  34. Transcriptional control of mitochondrial biogenesis: The central role of pgc-1alpha. Cardiovasc Res.
  35. Understanding the odd science of aging.