Large energetic adaptations of elderly muscle to resistance and endurance training.

This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training. Forty male and female subjects (69.2 +/- 0.6 yr) were assigned to a control group or 6 mo of endurance (ET) or resistance training (RT). We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle. The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties, glycolytic ATP synthesis, and contractile ATP demand. Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms, metabolite concentrations, and mitochondrial volume densities. The ET group showed changes in all energetic pathways: oxidative capacity (+31%), contractile ATP demand (-21%), and glycolytic ATP supply (-56%). The RT group had a large increase in oxidative capacity (57%). Only the RT group exhibited change in structural properties: a rise in mitochondrial volume density (31%) and muscle size (10%). These results demonstrate large energetic, but smaller structural, adaptations by elderly muscle with exercise training. The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle. Thus elderly muscle remains adaptable to chronic exercise, with large energetic changes accompanying both ET and RT.

Oxidative capacity and ageing in human muscle.

This study determined the decline in oxidative capacity per volume of human vastus lateralis muscle between nine adult (mean age 38.8 years) and 40 elderly (mean age 68.8 years) human subjects (age range 25-80 years). We based our oxidative capacity estimates on the kinetics of changes in creatine phosphate content ([PCr]) during recovery from exercise as measured by (31)P magnetic resonance (MR) spectroscopy. A matched muscle biopsy sample permitted determination of mitochondrial volume density and the contribution of the loss of mitochondrial content to the decline in oxidative capacity with age. The maximal oxidative phosphorylation rate or oxidative capacity was estimated from the PCr recovery rate constant (k(PCr)) and the [PCr] in accordance with a simple electrical circuit model of mitochondrial respiratory control. Oxidative capacity was 50 % lower in the elderly vs. the adult group (0.61 +/- 0.04 vs. 1.16 +/- 0.147 mM ATP s(-1)). Mitochondrial volume density was significantly lower in elderly compared with adult muscle (2.9 +/- 0.15 vs. 3.6 +/- 0.11 %). In addition, the oxidative capacity per mitochondrial volume (0.22 +/- 0.042 vs. 0.32 +/- 0.015 mM ATP (s %)(-1)) was reduced in elderly vs. adult subjects. This study showed that elderly subjects had nearly 50 % lower oxidative capacity per volume of muscle than adult subjects. The cellular basis of this drop was a reduction in mitochondrial content, as well as a lower oxidative capacity of the mitochondria with age.

Ageing, muscle properties and maximal O(2) uptake rate in humans.

This paper asks how the decline in maximal O(2) uptake rate (VO(2),max) with age is related to the properties of a key muscle group involved in physical activity - the quadriceps muscles. Maximal oxygen consumption on a cycle ergometer was examined in nine adult (mean age 38.8 years) and 39 elderly subjects (mean age 68.8 years) and compared with the oxidative capacity and volume of the quadriceps. VO(2),max declined with age between 25 and 80 years and the increment in oxygen consumption from unloaded cycling to VO(2),max (delta VO(2)) in the elderly was 45 % of the adult value. The cross-sectional areas of the primary muscles involved in cycling - the hamstrings, gluteus maximus and quadriceps - were all lower in the elderly group. The quadriceps volume was reduced in the elderly to 67 % of the adult value. Oxidative capacity per quadriceps volume was reduced to 53 % of the adult value. The product of oxidative capacity and muscle volume - the quadriceps oxidative capacity - was 36 % of the adult value in the elderly. Quadriceps oxidative capacity was linearly correlated with delta VO(2) among the subjects with the slope indicating that the quadriceps represented 36 % of the VO(2) increase during cycling. The decline in quadriceps oxidative capacity with age resulted from reductions in both muscle volume and oxidative capacity per volume in the elderly and appears to be an important determinant of the age-related reduction in delta VO(2) and VO(2),max found in this study.

Glycolysis is independent of oxygenation state in stimulated human skeletal muscle in vivo.

1. We tested the hypothesis that the cytoplasmic control mechanism for glycolysis is affected by the presence of oxygen during exercise. We used a comparison of maximal twitch stimulation under ischaemic and intact circulation in human wrist flexor and ankle dorsiflexor muscles. 31P magnetic resonance spectroscopy followed the phosphocreatine (PCr), Pi and pH dynamics at 6-9 s intervals. Glycolytic PCr synthesis was determined during stimulation from pH and tissue buffer capacity, as well as the oxidative phosphorylation rate. 2. Ischaemic vs. aerobic stimulation resulted in similar glycolytic fluxes in the two muscles. The onset of glycolysis occured after fifty to seventy stimulations and the extent of glycolytic PCr synthesis was directly proportional to the number of stimulations thereafter. 3. Two-fold differences in the putative feedback regulators of glycolysis, [Pi] and [ADP], were found between aerobic and ischaemic stimulation. The similar glycolytic fluxes in the face of these differences in metabolite levels eliminates feedback as a control mechanism in glycolysis. 4. These results demonstrate that glycolytic flux is independent of oxygenation state and metabolic feedback, but proportional to muscle activation. These results show a key role for muscle stimulation in the activation and maintenance of glycolysis. Further, this glycolytic control mechanism is independent of the feedback control mechanism that governs oxidative phosphorylation.

Decline in isokinetic force with age: muscle cross-sectional area and specific force.

Humans produce less muscle force (F) as they age. However, the relationship between decreased force and muscle cross-sectional area (CSA) in older humans is not well documented. We examined changes in F and CSA to determine the relative contributions of muscle atrophy and specific force (F/CSA) to declining force production in aging humans. The proportions of myosin heavy chain (MHC) isoforms were characterized to assess whether this was related to changes in specific force with age. We measured the peak force of isokinetic knee extension in 57 males and females aged 23-80 years, and used magnetic resonance imaging to determine the contractile area of the quadriceps muscle. Analysis of MHC isoforms taken from biopsies of the vastus lateralis muscle showed no relation to specific force. F, CSA, and F/CSA decreased with age. Smaller CSA accounted for only about half of the 39% drop in force that occurred between ages 65-80 years. Specific force dropped about 1.5% per year in this age range, for a total decrease of 21%. Thus, quantitative changes in muscle (atrophy) are not sufficient to explain the strength loss associated with aging.

Activation of glycolysis in human muscle in vivo.

We tested the cytoplasmic control mechanisms for glycolytic ATP synthesis in human wrist flexor muscles. The forearm was made ischemic and activated by maximal twitch stimulation of the median and ulnar nerves in 10 subjects. Kinetic changes in phosphocreatine, Pi, ADP, ATP, sugar phosphates, and pH were measured by 31P magnetic resonance spectroscopy at 7.1-s intervals. Proton production was determined from pH and tissue buffer capacity during stimulation. Glycolysis was activated between 30 and 50 stimulations, and the rate did not significantly change through the stimulation period. The independence of glycolytic rate on [Pi], [ADP], or [AMP] indicates that feedback regulation by these metabolites could not account for this activation of glycolysis. However, glycolytic H+ and ATP production increased sixfold from 0.5 to 3 Hz, indicating that glycolytic rate reflected muscle activation frequency. This dependence of glycolytic rate on muscle stimulation frequency and independence on metabolite levels is consistent with control of glycolysis by Ca2+.

From muscle properties to human performance, using magnetic resonance.

Our goal is to show how muscle properties can be used to understand the exercise performance limitations of the elderly. We show that magnetic resonance (MR) imaging and spectroscopy are useful for noninvasively characterizing the structural and energetic properties of muscle in vivo. Determination of muscle volume and cross-sectional area is easily and rapidly accomplished by applying quantitative morphometric methods to MR images. New MR spectroscopic techniques provide a noninvasive "biopsy" of the oxidative, glycolytic, and contractile capacities of muscle fibers. We show how the structural and energetic properties measured by MR can be used to define the functional capacity of muscle and the contribution of this capacity to the performance of the whole body (e.g., VO2max). Finally, we relate these laboratory measures of muscle properties and performance to activities meaningful to the functioning of the elderly in everyday life, such as sustained walking and stair climbing.

Increased incidence of a resonance in the phosphodiester region of 31P nuclear magnetic resonance spectra in the skeletal muscle of fibromyalgia patients.

OBJECTIVE: To determine if patients with fibromyalgia syndrome (FMS) are more susceptible to activity-induced muscle damage than are healthy subjects. METHODS: Eleven FMS patients and 10 healthy subjects performed concentric and eccentric exercise with their dominant and nondominant forearms, respectively. 31P magnetic resonance spectroscopy (to assess inorganic phosphate [P(i)] and phosphocreatine [PCr]) and dolorimetry (to assess pain) were performed before and 20 minutes after exercise and at 4 subsequent 24-hour intervals. RESULTS: Neither group exhibited increased P(i)/PCr ratios or reduced dolorimetry scores following the exercise protocols. FMS patients did display a phosphodiester resonance at a higher rate than healthy subjects (37% versus 12%), but this was not related to the exercise. CONCLUSION: Unchanged P(i)/PCr ratios and dolorimetry scores following acute exercise provide evidence against the hypothesis that FMS patients are more susceptible to activity-induced muscle damage than are healthy subjects, although P(i)/Pcr and pain may not adequately document such damage. The frequent occurrence of phosphodiester in the spectra of FMS patients may indicate a sarcolemmal abnormality in these subjects.

Muscle fatigue: conduction or mechanical failure?

It is well documented that repeated voluntary activity or electrical stimulation of skeletal muscle results in a decline in force production or power output. However, the precise physiological causes of "muscle fatigue" are not yet well understood. It is conceivable that the mechanism(s) may lie either in the conduction of action potentials in the central and peripheral nervous systems or in the transformation of the electrical event into mechanical force production by the muscle itself. In fact, none of the components of the electrical pathway from generation of impulses in the brain to their conduction over the neuron and the excitable membranes of the muscle can as yet be ruled out as potential contributors to the fatigue process. Relative to that on conduction failure, more information exists concerning the possibility that a defect in the excitation contraction coupling process in skeletal muscle, e.g., intracellular acidosis, inadequate supply of energy for contraction, or a disruption in Ca2+ homeostasis may also be significant in compromising force production following sustained activity. Despite this, the amount of conflicting data derived from these experiments has hindered the resolution of this question. In the future more attention must be given to such issues as the type of activity used to elicit fatigue and the fiber composition of the muscles studied. This is imperative as these factors clearly impact the nature of correlations between the biochemical and physiological events in muscle that are required to support prospective fatigue mechanisms.