Regeneration and transplantation of muscles in old rats and between young and old rats.

In order to compare the regenerative ability of skeletal muscle between young (5 month) and old (26 month) rats, sliced or intact extensor digitorum longus muscles were freely autografted into young and old rats and also reciprocally grafted from young to old inbred animals and vice versa. Sixty days after grafting, the transplants were analyzed for contractile and histochemical properties. There was a relative similarity between the contraction times of both normal control muscles and of all groups of transplants, although the contraction time tended to be prolonged and histochemical fiber pattern was more often found to be uniform in grafts of senescent animals. All groups of transplants possessed histochemically heterogeneous fiber types at 60 days. The experiments demonstrate that skeletal muscle in old rats possesses a substantial degree of regenerative ability and that the free tranpllantation of entire muscles in old animals is feasible.     

Sex differences in the fatigability of arm muscles depends on absolute force during isometric contractions.

Women are capable of longer endurance times compared with men for contractions performed at low to moderate intensities. The purpose of the study was 1) to determine the relation between the absolute target force and endurance time for a submaximal isometric contraction and 2) to compare the pressor response and muscle activation patterns of men [26.3 +/- 1.1 (SE) yr] and women (27.5 +/- 2.3 yr) during a fatiguing contraction performed with the elbow flexor muscles. Maximal voluntary contraction (MVC) force was greater for men (393 +/- 23 vs. 177 +/- 7 N), which meant that the average target force (20% of MVC) was greater for men (79.7 +/- 6.5 vs. 36.7 +/- 2.0 N). The endurance time for the fatiguing contractions was 118% longer for women (1,806 +/- 239 vs. 829 +/- 94 s). The average of the rectified electromyogram (%MVC) for the elbow flexor muscles at exhaustion was similar for men (31 +/- 2%) and women (30 +/- 2%). In contrast, the heart rate and mean arterial pressure (MAP) were less at exhaustion for women (94 +/- 6 vs. 111 +/- 7 beats/min and 121 +/- 5 vs. 150 +/- 6 mmHg, respectively). The target force and change in MAP during the fatiguing contraction were exponentially related to endurance time (r(2) = 0.68 and r(2) = 0.64, respectively), whereas the change in MAP was linearly related to target force (r(2) = 0.51). The difference in fatigability of men and women when performing a submaximal contraction was related to the absolute contraction intensity and was limited by mechanisms that were distal to the activation of muscle.     

Muscle endurance is greater for old men compared with strength-matched young men.

The purpose was to compare the time to task failure for a sustained isometric contraction performed at a submaximal intensity with the elbow flexor muscles by young and old men who were matched for strength. Eight young men (18-31 yr) and eight old men (67-76 yr) sustained an isometric contraction at 20% of maximal voluntary contraction (MVC) torque until the target torque could no longer be achieved for at least 5 s. The maximal torque exerted at the wrist was similar for the young and old men before the fatiguing task (65.9 +/- 8.0 vs. 65.4 +/- 8.7 N x m; P > 0.05), and they experienced similar reductions in MVC torque after the fatiguing contraction (31.4 +/- 10.6%; P < 0.05). The time to task failure was longer for the old men (22.6 +/- 7.4 min) compared with the strength-matched young men (13.0 +/- 5.2 min; P < 0.05), despite each group sustaining a similar torque during the fatiguing contraction (P > 0.05). The increases in torque fluctuations, electromyographic (EMG) bursting activity, and heart rate were greater for young men compared with the old men, and they were less at task failure for the old men (P < 0.05). Mean arterial pressure increased at a similar rate for both groups of men (P > 0.05), whereas the averaged EMG activity and rating of perceived exertion reached similar values at task failure for the young and old men (P > 0.05). These findings indicate that the longer time to task failure for the old men when performing the submaximal contraction was not due the absolute target torque exerted during the contraction.     

Structure and function of the ankle dorsiflexor muscles in young and moderately active men and women.

The aim was to investigate determinants of ankle dorsiflexor muscle (DF) strength and size in moderately active young men and women (n = 30; age 20-31 yr). Concentric (Con) and eccentric (Ecc) strength were measured isokinetically. Magnetic resonance imaging was used to determine the muscle cross-sectional area (CSA). Multiple biopsies were obtained from the tibialis anterior muscle to determine total numbers, areas (Area I and II) and proportions (Prop I and II) of type I and II fibers, respectively, and relative contents of myosin heavy chain (MHC) isoforms MHC1, MHC2a, and MHC2x. Women had lower Con and Ecc strength (24 and 27%; P < 0.01), smaller CSA (19%; P < 0.001), lower Ecc DF specific strength (strength/CSA) (10%; P < 0.01), and smaller Area I and Area II (21 and 31%; P < 0.01) than men. Prop I, MHC1, estimated total number of fibers, and Con DF specific strength were similar for both sexes. Con DF strength was up to 72% determined by CSA and Prop I, and Ecc DF strength was up to 81% determined by CSA, Prop I, and sex; variables other than CSA explained at most 9%. Body weight and fiber areas explained >50% of the variation in CSA. In conclusion, CSA was the predominant determinant of DF strength, CSA was to a great extent determined by the body weight and the sizes of muscle fibers, and sex differences in Ecc specific strength require further study.     

Strength training reduces force fluctuations during anisometric contractions of the quadriceps femoris muscles in old adults.

The greater fluctuations in motor output that are often exhibited by old adults can be reduced with strength training. The purpose of the study was to determine the effect of strength and steadiness training by old adults on fluctuations in force and position during voluntary contractions with the quadriceps femoris muscle. Healthy old adults (65-80 yr) completed 16 wk of heavy-load (80% of maximum, n = 11) strength training, heavy-load steadiness training (n = 6), or no training (n = 9). Steadiness training required subjects to match the angular displacement about the knee joint to a constant-velocity template. The Heavy-Load group experienced a 5.5% increase in muscle volume, a 25% increase in maximal voluntary contraction force, and a 26% increase in the one-repetition (1-RM) load. The Heavy-Load Steady group experienced increases of 11.5, 31, and 36%, respectively. The maximal electromyogram signal of quadriceps femoris increased by 51% in the two training groups. The coefficient of variation (CV) for force during submaximal isometric contractions did not change with training for any group. Although both training groups also experienced a reduction in CV for force during anisometric contractions with a 50% 1-RM load, the standard deviation of position did not change with time for any group. The Heavy-Load Steady group also experienced a reduction in CV for force during the training contractions performed with the 80% 1-RM load. Thus strength training reduced the force fluctuations of the quadriceps femoris muscles during anisometric contractions but not during isometric contractions.     

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.     

Spinal reflexes and coactivation of ankle muscles during a submaximal fatiguing contraction.

This study examined the involvement of spinal mechanisms in the control of coactivation during a sustained contraction of the ankle dorsiflexors at 50% of maximal voluntary contraction. Changes in the surface electromyogram (EMG) of the tibialis anterior and of two antagonist muscles, the soleus and lateral gastrocnemius, were investigated during and after the fatigue task. Concurrently, the compound action potential (M-wave) and the Hoffmann reflex of the soleus and lateral gastrocnemius were recorded. The results showed that the torque of the ankle dorsiflexors and the average EMG of the tibialis anterior during maximal voluntary contraction declined by 40.9 +/- 17.7% (mean +/- SD; P < 0.01) and 37.0 +/- 19.9% (P < 0.01), respectively, at task failure. During the submaximal fatiguing contraction, the average EMG of both the agonist and antagonist muscles increased, leading to a nearly constant ratio at the end of the contraction when normalized to postfatigue values. In contrast to the monotonic increase in average EMG of the antagonist muscles, the excitability of their spinal reflex pathways exhibited a biphasic modulation. The amplitude of the Hoffman reflexes in the soleus and lateral gastrocnemius increased to 147.5 +/- 52.9% (P < 0.05) and 166.7 +/- 74.9% (P < 0.01), respectively, during the first 20% of the contraction and then subsequently declined to 66.3 +/- 44.8 and 74.4 +/- 44.2% of their initial values. In conclusion, the results show that antagonist coactivation did not contribute to task failure. The different changes in voluntary EMG activity and spinal reflex excitability in the antagonist muscles during the fatiguing contraction support the concept that the level of coactivation is controlled by supraspinal rather than spinal mechanisms. The findings indicate, however, that antagonist coactivation cannot simply be mediated by a central descending "common drive" to the motor neuron pools of the agonist-antagonist muscle pairs. Rather, they suggest a more subtle regulation of the drive, possibly through presynaptic mechanisms, to the motoneurons that innervate the antagonist muscles.     

Motor unit firing rates and contractile properties in tibialis anterior of young and old men.

The effects of aging on motoneuron firing rates and muscle contractile properties were studied in tibialis anterior muscle by comparing results from six young (20.8 +/- 0.8 yr) and six old men (82.0 +/- 1.7 yr). For each subject, data were collected from repeated tests over a 2-wk period. Contractile tests included maximal voluntary contraction (MVC) with twitch interpolation and stimulated twitch contractions. The old men had 26% lower MVC torque (P < 0.01) than did the young men, but percent activation was not different (99.1 and 99.3%, respectively). Twitch contraction durations were 23% longer (P < 0.01) in the old compared with the young men. During a series of repeated brief steady-state contractions at 10, 25, 50, 75, and 100% MVC, motor unit firing rates were recorded. Results from approximately 950 motor unit trains in each subject group indicated that at all relative torque levels mean firing rates were 30-35% lower (P < 0.01) in the old subjects. Comparisons between young and old subjects' mean firing rates at each of 10%, 50%, and MVC torques and their corresponding mean twitch contraction duration yielded a range of moderate-to-high correlations (r = -0.67 to -0.84). That lower firing rates were matched to longer twitch contraction durations in the muscle of old men, and relatively higher firing rates were matched with shorter contraction times from the young men, indirectly supports the neuromuscular age-related remodeling principle.     

Preferred ambient temperature for old and young men in summer and winter

To investigate the effects of age on thermal sensitivity, preferred ambient temperature (T _pref) was compared between old (71–76 years) and young (21–30 years) groups, each consisting of six male subjects in summer and winter. The air temperature (T _a) was set at either 20° C or 40° C at commencement. The subject was directed to adjust theT _a for 45 min by manipulating a remote control switch to the level at which he felt most comfortable. In the older group, theT _pref was significantly lower in trials starting at 20° C than that starting at 40° C in summer. The fluctuation ofT _pref (temperature difference between maximum and minimumT _a during the last 10 min) was significantly wider in the older group in both summer and winter. Repetition of the same experiment on each subject showed a poorer reproducibility ofT _pref in the older group than in the younger group in summer. Tympanic and esophageal temperatures of the older group kept falling throughout the trial starting at 20° C in summer. These results suggest that thermal sensitivity is decreased with advancing age and that thermal perception in the elderly, especially to cold, is less sensitive in summer.     

Phosphomannosyl receptors of lysosomal enzymes in cardiac and skeletal muscles of young and old mice

The endogenous activity and the binding of high-uptake beta-N-acetylglucosaminidase were assayed in the membranes of heart and skeletal muscles of young (2 months) and old (15 months) NMRI-mice (Mus musculus) to evaluate the age-related changes in the phosphomannosyl receptors of lysosomal enzymes in muscular membranes. The total activities of beta-N-acetylglucosaminidase were significantly higher in cardiac and skeletal muscles of old than young mice. The total and the specific (inhibited by mannose-6-phosphate) binding of beta-N-acetylglucosaminidase to the membranes of cardiac muscle, but not to those of skeletal muscle, were higher in old mice than in young ones. The endogenous activity of beta-N-acetylglucosaminidase was significantly higher in the membranes of skeletal muscles of old mice than in those of young mice. The membranes of heart muscles did not show any difference in the endogenous activities. The saturation properties of the binding of beta-N-acetylglucosaminidase to the phosphomannosyl receptors were very similar in the membranes of heart and skeletal muscles of both age groups. We conclude that during aging the number of phosphomannosyl receptors of lysosomal enzymes increases in the membranes of heart muscle while the occupancy of phosphomannosyl receptors with endogenous ligands increases in the membranes of skeletal muscle.     

Decay of force transients following active stretch is slower in older than young men: Support for a structural mechanism contributing to residual force enhancement in old age

Following active lengthening of muscle, force reaches an isometric steady state above that which would be achieved for a purely isometric contraction at the same muscle length. This fundamental property of muscle, termed “residual force enhancement (RFE),” cannot be predicted by the force-length relationship, and is unexplained by the cross-bridge theory of muscle contraction. Recently, we showed that older adults experience higher RFE than young for the ankle dorsiflexors primarily owing to a greater reliance on passive force enhancement (PFE) and similar RFE for the knee extensors but a greater contribution of PFE to total RFE. Natural adult aging may prove a useful model in exploring mechanisms of RFE which may reside in the dissipation of force transients following stretch. A post-hoc analysis was conducted on previously described RFE experiments in young (~26 years) and old (~77 years) men for the dorsiflexors and knee extensors to fit the force following stretch with a biexponential decay. In both muscle groups the decay half-life of the first exponential was two times slower in the older compared with young men. There were significant associations between PFE and the decay in force, suggesting a greater “non-active” contribution to total RFE across muscles in older compared with young men. The greater “non-active” component of RFE in older adults could be due to structural age-related changes causing increased muscle stiffness during and following stretch.     

Cardiorespiratory and subjective responses to prolonged arm and leg exercise in healthy young and older men

Ten young (aged 23–30 years) and nine older (aged 54–59 years) healthy men with a similar size of limb muscle mass performed arm crank and leg cycle exercise for 30 min at relative exercise intensities of 50% and 75% of maximal oxygen uptake for the corresponding muscle group. In the tests, heart rate, blood pressure, gas exchange variables, rating of perceived exertion and blood lactate concentration were measured. The limb muscle mass was determined by anthropometric measurements. At the 75% target exercise level, four of the older men and two of the young men could not complete the arm-cranking test, and one of the older men and two of the young men could not complete the leg-cycle test. During arm-cranking the absolute exercise intensity was similar for the young and older men because of similar maximal values during arm-cranking. But during leg-cycling the absolute excercise intensity was higher for the young men than for the older men due to the difference in corresponding maximal values. During arm-cranking there were no significant differences in the physiological responses between the age groups except that a higher ventilatory response was noted among the older compared to the young men. During leg-cycling the heart rate values were higher among the young compared to the older men. But, when the heart rate values were expressed as a percentage of maximal heart rate in the corresponding maximal tests, no significant differences between the age groups were found. The results indicated that 30-min of arm or leg exercise at the same relative submaximal excercise intensity produces a similar degree of physiological strain in healthy older compared to young men. During arm-cranking, the young and the older men exercised at the same external intensity, indicating a similar ability to perform prolonged excercise using smaller muscle groups expressed both in absolute and relative terms. Accepted: 7 October 1996     

Versatile stem cells, young and old. A review

Both embryonic and somatic stem cells have been studied in recent years with particular regard to their differentiation potential. In vitro studies allow a considerable amplification of such cells in culture as well as the induction of commitment in different directions under proper stimulating factors. Moreover, a surprising versatility has been discovered,which makes possible a `reprogramming' of stem cells into a lineage pathway which may be completely different from the expected direction: for instance, a production of brain cells from blood progenitors has been obtained. It is thus possible to envisage methods of producing in culture sufficient amounts of stem cells, committed to a certain pathway, which can be transplanted in vivo to replace damaged tissues and organs. This revised version was published online in July 2006 with corrections to the Cover Date.     

Adaptations in muscular activation of the knee extensor muscles with strength training in young and older adults

The purpose of this study was to compare the extent of muscular activation during maximal voluntary knee extension contractions in old and young individuals and to examine the effects of resistance training on muscular activation in each group. The interpolated twitch technique was used to estimate muscular activation during two pre-training baseline tests, and after two and six weeks of resistance training. Throughout the study, the older group was 30% less strong than the young group (p=0.02). The training protocol was effective in both groups with overall isometric strength gains of 30 and 36% in the older (p=0.01) and young (p<0.01) groups, respectively. 10-RM training loads increased by 66% in the old group (p<0.01) and by 77% in the young group (p<0.01) throughout training. At the first baseline test, a 2% difference in muscular activation between groups (p=0.3) did not explain the large disparity in strength. Muscular activation increased by 2% in both groups throughout training (p<0.01). Despite considerably less muscular strength in the older group, muscular activation was greater than 95% of maximum and appears to be equal in both young and older individuals. Both groups demonstrated similar but small increases in muscular activation throughout training.