title: Intrinsic aerobic capacity sets a divide for aging and longevity.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).
  
  
  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 (VO(2max)), 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(2max), 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(2+) 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(2)), 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 are useful for deeper mechanistic exploration of aging.
authors.affiliation: Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA. lgkoch@med.umich.edu
authors.forename: Lauren Gerard
authors.initials: LG
authors.lastname: Koch
authors.forename: Ole J
authors.initials: OJ
authors.lastname: Kemi
authors.forename: Nathan
authors.initials: N
authors.lastname: Qi
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
authors.forename: Piter
authors.initials: P
authors.lastname: Bijma
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Gilligan
authors.forename: John E
authors.initials: JE
authors.lastname: Wilkinson
authors.forename: Helene
authors.initials: H
authors.lastname: Wisløff
authors.forename: Morten A
authors.initials: MA
authors.lastname: Høydal
authors.forename: Natale
authors.initials: N
authors.lastname: Rolim
authors.forename: Peter M
authors.initials: PM
authors.lastname: Abadir
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: van Grevenhof
authors.forename: Godfrey L
authors.initials: GL
authors.lastname: Smith
authors.forename: Charles F
authors.initials: CF
authors.lastname: Burant
authors.forename: Oyvind
authors.initials: O
authors.lastname: Ellingsen
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D001823:Body Composition; D001835:Body Weight; D020013:Calcium Signaling; D004734:Energy Metabolism; D005260:Female; D005838:Genotype; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D008297:Male; D009200:Myocardial Contraction; D010101:Oxygen Consumption; D010641:Phenotype; D010807:Physical Endurance / Q000235:genetics; D051381:Rats; D012420:Running; D016277:Ventricular Function, Left