Late‐life Training in Exercise Resistant vs Exercise Sensitive Rats: VO 2 max Predicts Successful Aging

Aerobic exercise is a primary recommendation for the prevention and treatment of chronic disease with aging. Yet up to 20% of human subjects are considered “exercise resistant”; i.e., demonstrate little or no change in maximal oxygen consumption (VO 2 max) in response to training. Exercise capacity can be divided into 2 components: an intrinsic capacity operating in the untrained state, that sums with an adaptive capacity acquired in response to exercise training. Previously, we developed rat models of low and high intrinsic exercise capacity via 2‐way artificial selective breeding and showed that VO 2 max was a strong predictor of survivability. To further test our thesis that diminished capacity for energy transfer underlies complex disease, accelerated aging, and reduced longevity (Energy Transfer Hypothesis), we developed a second contrasting rat model system of High Response Trainers (HRT) and Low Response Trainers (LRT) using gain in maximal treadmill running distance with training as the selection criterion. The purpose of this study was to track the general fitness in LRT and HRT rats during late‐life to gain an initial understanding of adaptive capacity, successful aging, and survivability. Methods Female and male LRT/HRT rats (n=72) were studied in sedentary control (SED) or endurance trained (TR) conditions between 22–26 months of age. Each individual rat trained on a treadmill 2–3 times a week at 60% of their maximum running speed and distance for 16 wks. Measurements included exercise capacity (speed, distance, and work performed) and changes in body composition (NMR) and VO 2 max using CLAMS. Results All SED rats had a significant decrease in exercise capacity with aging. For females that trained, exercise capacity was significantly lower in LRT‐TR compared to HRT‐TR across aging. HRT‐TR females increased running capacity 190 ± 56 m between 22 and 26 mo whereas LRT‐TR running was unchanged −20 ± 20 m. For males, LRT‐TR and HRT‐TR were different for running capacity at 24 mo (156 ± 22 vs 296 ± 34 m) but not different at 22 and 26 mo. Female LRT‐TR weighed 27 g more and had no change in lean body mass and 12% greater change in body fat compared to HRT‐TR after 16 wks of training. Aged LRT‐TR males were 47 g heavier than HRT‐TR after 16 wks training but with no significant differences in % lean or % fat body composition. At 26 months of age, there was a stronger association between VO 2 max and capacity to perform work in TR rats (r=.79) compared to those in the SED groups (r=.57). During late life (22–26 mo), LRT rats had higher mortality compared to HRT. Conclusion 1) HRT female rats respond to late‐life training better and have a higher final VO 2 max compared to LRT; 2) Females were more successful than males at increasing exercise capacity with late life training; 3) The acquired VO 2 max that occurs as an response to late‐life training (TR groups) has a stronger association with the capacity to perform work than the intrinsic capacity in the untrained state (SED groups). 4) During late‐life, LRT rats had higher mortality compared to the HRT. This study supports our Energy Transfer Hypothesis and shows, using an unbiased paradigm of selective breeding, that acquiring a high VO 2 max is basic for the beneficial effects of exercise for successful aging. Support or Funding Information The Glenn Foundation for Medical Research; NIH ORIP P40OD021331