Michael A. Tevald

Lower energy cost of skeletal muscle contractions in older humans

Recent studies suggest that the cost of muscle contraction may be reduced in old age, which could be an important mediator of age-related differences in muscle fatigue under some circumstances. We used phosphorus magnetic resonance spectroscopy and electrically elicited contractions to examine the energetic cost of ankle dorsiflexion in 9 young (Y; 26 +/- 3.8 yr; mean +/- SD) and 9 older healthy men (O; 72 +/- 4.6). We hypothesized that the energy cost of twitch and tetanic contractions would be lower in O and that this difference would be greater during tetanic contractions at f(50) (frequency at 50% of peak force from force-frequency relationship) than at 25 Hz. The energy costs of a twitch (O = 0.13 +/- 0.04 mM ATP/twitch, Y = 0.18 +/- 0.06; P = 0.045) and a 60-s tetanus at 25 Hz (O = 1.5 +/- 0.4 mM ATP/s, Y = 2.0 +/- 0.2; P = 0.01) were 27% and 26% lower in O, respectively, while the respective force.time integrals were not different. In contrast, energy cost during a 90-s tetanus at f(50) (O = 10.9 +/- 2.0 Hz, Y = 14.8 +/- 2.1 Hz; P = 0.002) was 49% lower in O (1.0 +/- 0.2 mM ATP/s) compared with Y (1.9 +/- 0.2; P < 0.001). Y had greater force potentiation during the f(50) protocol, which accounted for the greater age difference in energy cost at f(50) compared with 25 Hz. These results provide novel evidence of an age-related difference in human contractile energy cost in vivo and suggest that intramuscular changes contribute to the lower cost of contraction in older muscle. This difference in energetics may provide an important mechanism for the enhanced fatigue resistance often observed in older individuals.

Intracellular energetics and critical Po2 in resting ischemic human skeletal muscle in vivo

During ischemia and some types of muscular contractions, oxygen tension (Po(2)) declines to the point that mitochondrial ATP synthesis becomes limited by oxygen availability. Although this critical Po(2) has been determined in animal tissue in vitro and in situ, there remains controversy concerning potential disparities between values measured in vivo and ex vivo. To address this issue, we used concurrent heteronuclear magnetic resonance spectroscopy (MRS) to determine the critical intracellular Po(2) in resting human skeletal muscle in vivo. We interleaved measurements of deoxymyoglobin using (1)H-MRS with measures of high-energy phosphates and pH using (31)P-MRS, during 15 min of ischemia in the tibialis anterior muscles of 6 young men. ATP production and intramyocellular Po(2) were quantified throughout ischemia. Critical Po(2), determined as the Po(2) corresponding to the point where PCr begins to decline (PCr(ip)) in resting muscle during ischemia, was 0.35 ± 0.20 Torr, means ± SD. This in vivo value is consistent with reported values ex vivo and does not support the notion that critical Po(2) in resting muscle is higher when measured in vivo. Furthermore, we observed a 4.5-fold range of critical Po(2) values among the individuals studied. Regression analyses revealed that time to PCr(ip) was associated with critical Po(2) and the rate of myoglobin desaturation (r = 0.83, P = 0.04) but not the rate of ATP consumption during ischemia. The apparent dissociation between ATP demand and myoglobin deoxygenation during ischemia suggests that some degree of uncoupling between intracellular energetics and oxygenation is a potentially important factor that influences critical Po(2) in vivo.