title: A rat model system to study complex disease risks, fitness, aging, and longevity.
abstract: The association between low exercise capacity and all-cause morbidity and mortality is statistically strong yet mechanistically unresolved. By connecting clinical observation with a theoretical base, we developed a working hypothesis that variation in capacity for oxygen metabolism is the central mechanistic determinant between disease and health (aerobic hypothesis). As an unbiased test, we show that two-way artificial selective breeding of rats for low and high intrinsic endurance exercise capacity also produces rats that differ for numerous disease risks, including the metabolic syndrome, cardiovascular complications, premature aging, and reduced longevity. This contrasting animal model system may prove to be translationally superior relative to more widely used simplistic models for understanding geriatric biology and medicine.
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA. lgkoch@med.umich.edu
authors.forename: Lauren Gerard
authors.initials: LG
authors.lastname: Koch
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D017079:Exercise Tolerance / Q000502:physiology; D008136:Longevity / Q000502:physiology*; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D018570:Risk Assessment / Q000379:methods