Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study.

Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle attenuation coefficient, as determined by computed tomography, is a noninvasive measure of muscle density, and lower values reflect increased muscle lipid content. This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degrees/s in 2,627 men and women aged 70-79 yr participating in baseline studies of the Health ABC Study, a longitudinal study of health, aging, and body composition. Strength was higher in men than in women (132.3 +/- 34.5 vs. 81.4 +/- 22.0 N x m, P < 0.01). Men had greater muscle attenuation values (37.3 +/- 6.5 vs. 34.7 +/- 7.0 Hounsfield units) and muscle cross-sectional area (CSA) at the midthigh than women (132.7 +/- 22.4 vs. 93.3 +/- 17.5 cm(2), P < 0.01 for both). The strength per muscle CSA (specific force) was also higher in men (1.00 +/- 0.21 vs. 0.88 +/- 0.21 N x m x cm(-2)). The attenuation coefficient was significantly lower for hamstrings than for quadriceps (28.7 +/- 8.7 vs. 41.1 +/- 6.9 Hounsfield units, P < 0.01). Midthigh muscle attenuation values were lowest (P < 0.01) in the eldest men and women and were negatively associated with total body fat (r = -0.53, P < 0.01). Higher muscle attenuation values were also associated with greater specific force production (r = 0.26, P < 0.01). Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women. These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity.     

Skeletal muscle: Energy metabolism, fiber types, fatigue and adaptability

Skeletal muscles cope with a large range of activities, from being able to support the body weight during long periods of upright standing to perform explosive movements in response to an unexpected threat. This requires systems for energy metabolism that can provide energy during long periods of moderately increased energy consumption as well as being able to rapidly increasing the rate of energy production more than 100-fold in response to explosive contractions. In this short review we discuss how muscles can deal with these divergent demands. We first outline the major energy metabolism pathways in skeletal muscle. Next we describe metabolic differences between different muscle fiber types. Contractile performance declines during intense activation, i.e. fatigue develops, and we discuss likely underlying mechanisms. Finally, we discuss the ability of muscle fibers to adapt to altered demands, and mechanisms behind these adaptations. The accumulated experimental evidence forces us to conclude that most aspects of energy metabolism involve multiple and overlapping signaling pathways, which indicates that the control of energy metabolism is too important to depend on one single molecule or mechanism.     

Skeletal muscle fatigue in vitro is temperature dependent

Our purpose was to determine the effect of temperature on the fatigability of isolated soleus and extensor digitorum longus (EDL) muscles from rats during repeated isometric contractions. Muscles (70-90 mg) were studied at 20-40 degrees C in vitro. Fatigability was defined with respect to both the time and number of stimuli required to reach 50% of the force (P) developed at the onset of the fatigue test. Fatigue was studied during stimulation protocols of variable [force approximately 70% of maximum force (Po)] and constant frequency (28 Hz). Results for soleus and EDL muscles were qualitatively similar, but fatigue times were longer for soleus than for EDL muscles. During the variable-frequency protocol, development of approximately 70% of Po required an increase in stimulation frequency as temperature increased. During stimulation at these frequencies, fatigue time shortened as temperature increased. For both fatigue protocols, the relationship between temperature and the number of stimuli required to reach fatigue followed a bell-shaped curve, with maximum values at 25-30 degrees C. The temperature optimum for maximizing the number of isometric contractions to reach fatigue reflects direct effects of temperature on muscle function.     

Grip strength, muscle fatigue, and body composition in nomadic Turkana pastoralists

Tests of hand grip strength and hand grip muscle fatigue were conducted on Ngisonyoka Turkana pastoralists of northwest Kenya to explore some of the functional relationships between activity and body composition. The test of maximal voluntary contraction (MVC) of hand grip flexors was conducted on 151 Turkana and 38 U.S. men and women. The fatigue test was conducted on the same number of subjects who were instructed to attempt to maintain 80% of the MVC for 90 seconds. The results of these tests, combined with arm measurements of size and body composition, were used to evaluate muscle size and strength relationships and to estimate muscle fiber type distribution in the forearm. MVC values of Turkana men were low by U.S. and European standards. The low values resulted from smaller Turkana muscle areas. MVC values of Turkana women were comparable to those of U.S. and European women, reflecting comparable muscle areas. The fatigue curves of Turkana and U.S. men and women suggest that slow-twitch aerobic muscle fibers predominate for the hand grip flexors of the Turkana pastoralists.     

Skeletal muscle fiber quality in older men and women

Wholemuscle strength and cross-sectional area (WMCSA), andcontractile properties of chemically skinned segments from single fibers of the quadriceps were studied in 7 young men (YM, 36.5 ± 3.0 yr), 12 older men (OM, 74.4 ± 5.9 yr), and 12 olderwomen (OW, 72.1 ± 4.3 yr). WMCSA was smaller in OMcompared with YM (56.1 ± 10.1 vs. 79.7 ± 13.1 cm²; P = 0.031) and in OW (44.9 ± 7.5; P < 0.003) compared with OM. Age-related, but notsex-related, differences in strength were eliminated after adjustingfor WMCSA. Maximal force was measured in 552 type I and 230 type IIAfibers. Fibers from YM (type I = 725 ± 221; type IIA = 792 ± 271 µN) were stronger (P < 0.001) thanfibers from OM (I = 505 ± 179; IIA = 577 ± 262 µN) even after correcting for size. Type IIA fibers were stronger(P < 0.005) than type I fibers in YM and OM but not inOW (I = 472 ± 154; IIA = 422 ± 97 µN).Sex-related differences in type I and IIA fibers were dependent onfiber size. In conclusion, differences in WMCSA explain age-relateddifferences in strength. An intrinsic defect in contractile proteinscould explain weakness in single fibers from OM. Sex-relateddifferences exist at the whole muscle and single fiber levels.

     

Hibernating bears conserve muscle strength and maintain fatigue resistance

Black bears spend several months each winter confined to a small space within their den without food or water. In nonhibernating mammals, these conditions typically result in severe muscle atrophy, causing a loss of strength and endurance. However, an initial study indicated that bears appeared to conserve strength while denning. We conducted an in vivo, nonsubjective measurement of strength, resistance to fatigue, and contractile properties on the tibialis anterior muscle of six hibernating bears during both early and late winter using a rigid leg brace and foot force plate. After 110 d of anorexia and confinement, skeletal muscle strength loss in hibernating bears was about one-half that in humans confined to bed rest. Bears lost 29% of muscle strength over 110 d of denning without food, while humans on a balanced diet but confined to bed for 90 d have been reported to lose 54% of their strength. Additionally, muscle contractile properties, including contraction time, half-relaxation time, half-maximum value time, peak rate of development and decay, time to peak force development, and time to peak force decay did not change, indicating that no small-scale alterations in whole-muscle function occurred over the winter. This study further supports our previous findings that black bears have a high resistance to atrophy despite being subjected to long-term anorexia and limited mobility.     

Skeletal muscle acetylcholine receptor. Purification, characterization, and turnover in muscle cell cultures

Acetylcholine receptor has been purified from embryonic skeletal muscle cells grown and allowed to differentiate in tissue culture. The polypeptide composition of purified receptor has been determined by two-dimensional electrophoresis. The purest preparations are composed of a single Mr = 41,000 class of polypeptide which exhibits some charge heterogeneity. By high resolution two-dimensional electrophoresis a spot corresponding to acetylcholine receptor was localized among total proteins of muscle membrane extracts. Synthesis of this component is shown to be developmentally regulated. Quantitative analysis of receptor synthesis and degradation has led to the conclusion that receptor is one of a class of proteins whose synthesis is tightly regulated during terminal steps of myogenesis.     

Specific strength and voluntary muscle activation in young and elderly women and men.

The extents to which decreased muscle size or activation are responsible for the decrease in strength commonly observed with aging remain unclear. Our purpose was to compare muscle isometric strength [maximum voluntary contraction (MVC)], cross-sectional area (CSA), specific strength (MVC/CSA), and voluntary activation in the ankle dorsiflexor muscles of 24 young (32 +/- 1 yr) and 24 elderly (72 +/- 1 yr) healthy men and women of similar physical activity level. Three measures of voluntary muscle activation were used: the central activation ratio [MVC/(MVC + superimposed force)], the maximal rate of voluntary isometric force development, and foot tap speed. Men had higher MVC and CSA than did women. Young men had higher MVC compared with elderly men [262 +/- 19 (SE) vs. 197 +/- 22 N, respectively], whereas MVC was similar in young and elderly women (136 +/- 15 vs. 149 +/- 16 N, respectively). CSA was greater in young compared with elderly subjects. There was no age-related impairment of specific strength, central activation ratio, or the rate of voluntary force development. Foot tap speed was reduced in elderly (34 +/- 1 taps/10 s) compared with young subjects (47 +/- 1 taps/10 s). These results suggest that isometric specific strength and the ability to fully and rapidly activate the dorsiflexor muscles during a single isometric contraction were unimpaired by aging. However, there was an age-related deficit in the ability to perform rapid repetitive dynamic contractions.     

Concentric and eccentric muscle strength before, during and after fatigue in 13 year-old boys

The purpose of this study was to investigate the force-producing characteristics of boys aged 13 years in relation to fatigue of elbow flexor muscles. Maximal voluntary force in elbow flexion was measured before and after a muscle endurance test (MET) by using an isokinetic dynamometer isometrically, concentrically and eccentrically at three velocities, i.e. 0.21, 0.52, and 1.05 rad · s^–1. The MET consisted of maximal concentric and eccentric muscle actions performed alternately at 0.52 rad · s^–1 for 50 consecutive trials. Muscle cross-sectional area (CSA) of elbow flexor muscles (biceps brachii and brachialis) was measured by a B-mode ultrasound apparatus. Although eccentric force showed significantly higher values than concentric force during MET, there was no significant difference in the rate of decline in force between the two actions. There was no significant difference in the rate of decline in force after MET for each velocity and muscle action. Isometric, concentric and eccentric force before MET was significantly related to muscle CSA whereas, after MET, concentric force significantly correlated with muscle CSA but there was no significant correlation between muscle CSA and isometric or eccentric force. From our study, it is therefore suggested that in development to maturity, isometric, concentric and eccentric force decrease at the same rate with advancing muscle fatigue; however, there might be differences among muscle actions in facors affecting force development.     

Training-induced changes in muscle CSA, muscle strength, EMG, and rate of force development in elderly subjects after long-term unilateral disuse.

The ability to develop muscle force rapidly may be a very important factor to prevent a fall and to perform other tasks of daily life. However, information is still lacking on the range of training-induced neuromuscular adaptations in elderly humans recovering from a period of disuse. Therefore, the present study examined the effect of three types of training regimes after unilateral prolonged disuse and subsequent hip-replacement surgery on maximal muscle strength, rapid muscle force [rate of force development (RFD)], muscle activation, and muscle size. Thirty-six subjects (60-86 yr) were randomized to a 12-wk rehabilitation program consisting of either 1) strength training (3 times/wk for 12 wk), 2) electrical muscle stimulation (1 h/day for 12 wk), or 3) standard rehabilitation (1 h/day for 12 wk). The nonoperated side did not receive any intervention and thereby served as a within-subject control. Thirty subjects completed the trial. In the strength-training group, significant increases were observed in maximal isometric muscle strength (24%, P < 0.01), contractile RFD (26-45%, P < 0.05), and contractile impulse (27-32%, P < 0.05). No significant changes were seen in the two other training groups or in the nontrained legs of all three groups. Mean electromyogram signal amplitude of vastus lateralis was larger in the strength-training than in the standard-rehabilitation group at 5 and 12 wk (P < 0.05). In contrast to traditional physiotherapy and electrical stimulation, strength training increased muscle mass, maximal isometric strength, RFD, and muscle activation in elderly men and women recovering from long-term muscle disuse and subsequent hip surgery. The improvement in both muscle mass and neural function is likely to have important functional implications for elderly individuals.     

Skeletal muscle formation in vertebrates.

Research in the past year has added to our understanding of the signalling systems that specify myogenic identity in the embryo and of the regulation and roles of MyoD family members. New insights into the movement of muscle precursor cells include the demonstration that Lbx1 is essential for their migration from the somite to some but not all sites of muscle formation elsewhere. Later in development, ras as well as calcineurin signalling is now implicated in the definition of slow versus fast fibre types. The myogenic identity of precursor cells in the adult depends on Pax7, the orthologue of Pax3 which is required for early myogenesis; this finding is of major importance for muscle regeneration and the active field of stem cell research.     

Skeletal muscle unweighting: spaceflight and ground-based models.

Long-term manned spaceflight requires that flight crews be exposed to extended periods of unweighting of antigravity skeletal muscles. This exposure will result in adaptations in these muscles that have the potential to debilitate crew members on return to increased gravity environments. Therefore, the development of countermeasures to prevent these unwanted adaptations is an important requirement. The limited access to microgravity environments for the purpose of studying muscle adaptation and evaluating countermeasure programs has necessitated the use of ground-based models to conduct both basic and applied muscle physiology research. In this review, the published results from ground-based models of muscle unweighting are presented and compared with the results from related spaceflight research. The models of skeletal muscle unweighting with a sufficient body of literature included bed rest, cast immobilization, and unilateral lower limb suspension. Comparisons of changes in muscle strength and size between these models in the context of the limited results available from spaceflight suggest that each model may be useful for the investigation of certain aspects of the skeletal muscle unweighting that occur in microgravity.     

Skeletal muscle energy metabolism during prolonged, fatiguing exercise.

A depletion of phosphocreatine (PCr), fall in the total adenine nucleotide pool (TAN = ATP + ADP + AMP), and increase in TAN degradation products inosine 5'-monophosphate (IMP) and hypoxanthine are observed at fatigue during prolonged exercise at 70% maximal O(2) uptake in untrained subjects [J. Baldwin, R. J. Snow, M. F. Carey, and M. A. Febbraio. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R295-R300, 1999]. The present study aimed to examine whether these metabolic changes are also prevalent when exercise is performed below the blood lactate threshold (LT). Six healthy, untrained humans exercised on a cycle ergometer to voluntary exhaustion at an intensity equivalent to 93 +/- 3% of LT ( approximately 65% peak O(2) uptake). Muscle biopsy samples were obtained at rest, at 10 min of exercise, approximately 40 min before fatigue (F-40 =143 +/- 13 min), and at fatigue (F = 186 +/- 31 min). Glycogen concentration progressively declined (P < 0.01) to very low levels at fatigue (28 +/- 6 mmol glucosyl U/kg dry wt). Despite this, PCr content was not different when F-40 was compared with F and was only reduced by 40% when F was compared with rest (52. 8 +/- 3.7 vs. 87.8 +/- 2.0 mmol/kg dry wt; P < 0.01). In addition, TAN concentration was not reduced, IMP did not increase significantly throughout exercise, and hypoxanthine was not detected in any muscle samples. A significant correlation (r = 0.95; P < 0. 05) was observed between exercise time and glycogen use, indicating that glycogen availability is a limiting factor during prolonged exercise below LT. However, because TAN was not reduced, PCr was not depleted, and no correlation was observed between glycogen content and IMP when glycogen stores were compromised, fatigue may be related to processes other than those involved in muscle high-energy phosphagen metabolism.     

Contralateral muscle activity and fatigue in the human first dorsal interosseous muscle.

During effortful unilateral contractions, muscle activation is not limited to the target muscles but activity is also observed in contralateral muscles. The amount of this associated activity is depressed in a fatigued muscle, even after correction for fatigue-related changes in maximal force. In the present experiments, we aimed to compare fatigue-related changes in associated activity vs. parameters that are used as markers for changes in central nervous system (CNS) excitability. Subjects performed brief maximal voluntary contractions (MVCs) with the index finger in abduction direction before and after fatiguing protocols. We followed changes in MVCs, associated activity, motor-evoked potentials (MEP; transcranial magnetic stimulation), maximal compound muscle potentials (M waves), and superimposed twitches (double pulse) for 20 min after the fatiguing protocols. During the fatiguing protocols, associated activity increased in contralateral muscles, whereas afterwards the associated force was reduced in the fatigued muscle. This force reduction was significantly larger than the decline in MVC. However, associated activity (force and electromyography) remained depressed for only 5-10 min, whereas the MVCs stayed depressed for over 20 min. These decreases were accompanied by a reduction in MEP, MVC electromyography activity, and voluntary activation in the fatigued muscle. According to these latter markers, the decrease in CNS motor excitability lasted much longer than the depression in associated activity. Differential effects of fatigue on (associated) submaximal vs. maximal contractions might contribute to these differences in postfatigue behavior. However, we cannot exclude differences in processes that are specific to either voluntary or to associated contractions.     

Skeletal muscle adaptations to microgravity exposure in the mouse.

To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to approximately 11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced (P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb (P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.