Cardiorespiratory and muscle molecular responses to exercise training in advanced age and chronic obstructive pulmonary disease

INTRODUCTION: Maintenance of cardiorespiratory fitness is important for health in advanced age and in chronic obstructive pulmonary disease (COPD). Aerobic training increases peak oxygen uptake (V̇O2PEAK) in health. Quadriceps weakness is common in COPD. Non-volitional neuromuscular electrical stimulation (NMES) may improve muscle mass and strength as an alternative or adjunct to voluntary resistance exercise (RE). This thesis examines the impact of aerobic exercise training and withdrawal on cardiorespiratory and skeletal muscle molecular markers of adaptation to exercise in advanced age and in COPD and the acute mRNA responses to RE and NMES in COPD. METHODS: Young and older healthy individuals and patients with COPD performed eight weeks aerobic cycling exercise training followed by four weeks exercise withdrawal. Exercise tests and quadriceps muscle biopsies were performed at baseline, after four and eight weeks training and after four weeks exercise withdrawal. Separately, patients with COPD had quadriceps muscle biopsies before and 24 hours after a single bout of RE or NMES. RESULTS: V̇O2PEAK increased similarly in young and older sedentary volunteers after training, but was unchanged in patients with COPD. Cardiorespiratory adaptations were not reversed by four weeks exercise withdrawal in healthy volunteers but V̇O2PEAK decreased in patients with COPD. Change in abundance of targeted mRNA transcripts in quadriceps muscle was strikingly similar in all three groups, predicted influence over the same biological functions and was maintained after exercise withdrawal. Voluntary RE influenced the abundance of a broader range of mRNA targets that NMES; a small number of transcripts were influenced similarly by both interventions. CONCLUSIONS: Young and older sedentary volunteers and patients with COPD experienced the same muscle molecular responses to aerobic training and subsequent exercise withdrawal. Training did not increase V̇O2PEAK in COPD patients suggesting that the limitation to aerobic training adaptations is either downstream of muscle mRNA signalling or due to central limitations. Contractions evoked by neuromuscular electrical stimulation are sufficient to change the abundance of skeletal muscle mRNA targets but voluntary resistance exercise exerts a broader influence.