Whole-body & muscle responses to aerobic exercise training and withdrawal in ageing & COPD

COPD patients exhibit lower peak oxygen consumption (V̇O2PEAK), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic exercise training (AET) at a matched relative intensity and subsequent exercise withdrawal period (EW) we aimed to elucidate the whole-body and muscle mitochondrial responsiveness of healthy-young (HY), healthy-older (HO) and COPD volunteers to whole-body exercise.The HY (n=10), HO (n=10) and COPD (n=20) volunteers were studied before, after eight-weeks AET (65% V̇O2PEAK) and after four-weeks EW. V̇O2PEAK, muscle maximal mitochondrial ATP production rates (MAPR), mitochondrial content, mitochondrial DNA copy number and abundance of 59 targeted fuel metabolism mRNAs were determined at all time-points.Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mitochondrial DNA copy number relative to a nuclear-encoded house-keeping gene was greater in HY (mean±sd) (804±67) than in HO (631±69), p=0.041. AET increased V̇O2PEAK in HO (17%, p=0.002) and HY (21%, p<0.001) but not COPD (p=0.603). Muscle MAPR for palmitate increased with training in HO (57%, p=0.041) and HY (56%, p=0.003) and decreased with EW in HO (−45%, p=0.036) and HY (−30%, p=0.016), but was unchanged in COPD (p=0.594). Mitochondrial DNA copy number increased with AET in HY (66%, p=0.001) but not HO (p=0.081) or COPD (p=0.132). The observed changes in muscle mRNA abundance were similar in all groups after AET and EW.Intrinsic mitochondrial function was not impaired by ageing or COPD in the untrained state. Whole-body and muscle mitochondrial responses to AET were robust in HY, evident in HO, but deficient in COPD. All showed robust muscle mRNA responses. Higher relative exercise intensities during whole-body training may be needed to maximise whole-body and muscle mitochondrial adaptation in COPD.