Aerobic exercise training reduces regulators of denervation in exercise resistant and exercise sensitive old rats
Authors: Brown Lemuel A. , MacPherson Peter C. , Koch Lauren G. , Qi Nathan R. , Britton Steven L. , Brooks Susan V. 
Published: June 2021

Aerobic exercise training is a primary approach to reduce the risk of metabolic disease and disability in older adults. Specifically, exercise training can improve whole body metabolism and reduce the declines in muscle mass and strength associated with aging; however, close to a fifth of the human population show little to no adaptations to exercise training. To further examine the basis for these inherent differences amongst individuals, a selective breeding approach has been used for over 20 generations to generate rats that show high (HRT) or low (LRT) gain in exercise capacity in response to treadmill training. A trend for reduced survivability has been reported in LRT compared with HRT rats, but whether LRT rats display earlier onset or faster rate of age‐associated physiological declines is not known.PurposeTo test the hypothesis that exercise initiated late in life will slow the progression of age associated muscle deficits in HRT but not LRT rats.MethodsYoung female sedentary LRT and HRT rats (n=12) and old female LRT and HRT rats (n=31) were selected for this study. Old rats either remained sedentary (SED) or were endurance trained (TR) between 22–26 months of age. TR rats ran on a treadmill 2–3 times a week at 60% of their maximum running speed and distance for 16 weeks. Contractile properties of extensor digitorum longus (EDL) were tested in vitro and additional hind limb muscles were excised for analysis of motor endplate structure and mRNA levels for genes associated with denervation.ResultsThere were no changes with exercise in absolute or specific force or in average area or perimeter of endplates in the LRT and HRT rats, but end plate fragmentation was 5 fold greater in the old LRT rats compared to the young LRT rats and 8–9 fold greater in the old HRT rats compared to the young HRT rats. Acetylcholine receptor (AChR) expression was 17 fold greater in old LRT‐SED rats and remained elevated 24 fold in old LRT‐TR rats compared to young LRT‐SED rats. AChR expression in old HRT‐SED rats was also elevated compared with young HRT‐SED rats but by only 5‐fold and following exercise AChR expression was reduced such that levels were not different between old HRT‐TR and young HRT‐SED rats. Similarly, myogenin expression in old LRT‐SED rats was 14 fold greater than in young LRT‐SED rats but no differences were detected between LRT‐SED and old LRT‐TR rats. Myogenin expression in old HRT‐SED rats was also elevated 2 fold compared with young HRT‐SED with no differences detected between HRT‐SED and old HRT‐TR rats.ConclusionsAs previously shown in mice, rats and humans, all old rats show evidence of disruption of innervation as suggested by the fragmentation of endplates. The observation that exercise prevented the age‐associated increase in myogenin in LRT rats and in both myogenin and AChR in HRT rats is consistent with our hypothesis that exercise has a greater protective effect in HRT rats.Support or Funding InformationThis study was supported by The Glenn Foundation for Medical Research, National Institutes of Health ORIP P40OD021331 and P01 AG051442.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.