The heat stress response is associated with several beneficial adaptations that promote cell health and survival. Specifically, in vitro and animal investigations suggest that repeated exposures to a mild heat stress (~40°C) elicits positive mitochondrial adaptations in skeletal muscle comparable to those observed with exercise. To assess whether such adaptations translate to human skeletal muscle, we produced local, deep tissue heating of the vastus lateralis via pulsed shortwave diathermy in 20 men (n=10) and women (n=10). Diathermy increased muscle temperature by 3.9 °C within 30 minutes of application. Immediately following a single 2-hr heating session, we observed increased phosphorylation of AMPK and ERK1/2, but not of p38 MAPK nor JNK. Following repeated heat exposures (2-hr daily for 6 consecutive days), we observed a significant cellular heat stress response, as heat shock protein 70 and 90 increased 45% and 38%, respectively. In addition, PGC-1α and mitochondrial electron transport protein complexes I and V expression were increased after heating. These increases were accompanied by augmentation of maximal coupled, and uncoupled, respiratory capacity, measured via high-resolution respirometry. Our data provide the first evidence that mitochondrial adaptation can be elicited in human skeletal muscle in response to repeated exposures to mild heat stress.

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Impaired skeletal muscle efficiency potentially contributes to the age-related decline in exercise capacity and may explain the altered haemodynamic response to exercise in the elderly. Thus we examined whether (i) the ATP cost of contraction increases with age, and (ii) this results in altered convective O(2) delivery to maintain microvascular oxygenation in the calf muscle. To this aim, we used an integrative experimental approach combining (31)P-MRS (magnetic resonance spectroscopy), Doppler ultrasound imaging and NIRS (near-IR spectroscopy) during dynamic plantar flexion exercise at 40% of WR(max) (maximal power output) in 20 healthy young and 20 older subjects matched for physical activity. The ATP cost of contraction was significantly higher in the old (7.2±4.1 mM/min per W) compared with the young (2.4±1.9 mM/min per W; P<0.05) and this was only significantly correlated with the plantar flexion WR(max) value in the old subjects (r=-0.52; P<0.05). Even when differences in power output were taken into account, end-exercise blood flow (old, 259±168 ml/min per W and young, 134±40 ml/min per W; P<0.05) and convective O(2) delivery (old, 0.048±0.031 l/min per W and young, 0.026±0.008 l/min per W; P<0.05) were greater in the old in comparison with the young subjects. In contrast, the NIRS oxyhaemoglobin, deoxyhaemoglobin and microvascular oxygenation indices were not significantly different between the groups (P>0.05). Therefore the present study reveals that, although the peripheral haemodynamic responses to plantar flexion exercise appear to be appropriate, the elevated energy cost of contraction and associated reduction in the WR(max) value in this muscle group may play a role in limiting exercise capacity with age.