Rat models of intrinsic aerobic capacity differ in longevity

Abstract

The evolution of complexity associated closely with the development of oxygen metabolic pathways, suggesting that deficiencies in aerobic capacity may underlie disease risk and age-related changes. Based on the strong statistical linkage of low aerobic exercise capacity with all-cause morbidity and mortality, we predicted that rats selectively bred over many generations for low and high intrinsic aerobic running capacity would also contrast for longevity. We evaluated treadmill running endurance across lifespan in a small population of low capacity runners (LCR: 10 females and 6 males) and high capacity runners (HCR: 11 females and 12 males) from generations 15 and 16 of selection. At age 3 months LCR ran for 200 meters (m) and HCR rats for 2500 m on a treadmill running test to exhaustion. At middle age (15 months), running capacity declined significantly in both LCR and HCR but no further change was noted at 20 months in either strain. At age 27 months running capacity decreased to 463 m in HCR (n= 18) and 93 m for LCR (n=8). Survival curves between the strains are different by 32% (Kaplan-Meier; p < 0.01). Median lifespan for HCR is 32.1 months compared to 24.3 months for LCR. The hazard ratio (0.43 CI 0.16 – 0.79) along with initial pathology suggests that LCR are at 57% greater risk over HCR for dying of similar aging lesions. The LCR and HCR strains may be of value for mechanistic investigation of age-related capacity and longevity.