Single muscle fiber adaptations to resistance training in old (>80 yr) men: evidence for limited skeletal muscle plasticity

The purpose of this study was to investigate whole muscle and single muscle fiber adaptations in very old men in response to progressive resistance training (PRT). Six healthy independently living old men (82 +/- 1 yr; range 80-86 yr, 74 +/- 4 kg) resistance-trained the knee extensors (3 sets, 10 repetitions) at approximately 70% one repetition maximum 3 days/wk for 12 wk. Whole thigh muscle cross-sectional area (CSA) was assessed before and after PRT using computed tomography (CT). Muscle biopsies were obtained from the vastus lateralis before and after the PRT program. Isolated myosin heavy chain (MHC) I and IIa single muscle fibers (n = 267; 142 pre; 125 post) were studied for diameter, peak tension, shortening velocity, and power. An additional set of isolated single muscle fibers (n = 2,215; 1,202 pre; 1,013 post) was used to identify MHC distribution. One repetition maximum knee extensor strength increased (P < 0.05) 23 +/- 4 kg (56 +/- 4 to 79 +/- 7 kg; 41%). Muscle CSA increased (P < 0.05) 3 +/- 1 cm2 (120 +/- 7 to 123 +/- 7 cm2; 2.5%). Single muscle fiber contractile function and MHC distribution were unaltered with PRT. These data indicate limited muscle plasticity at the single-muscle fiber level with a resistance-training program among the very old. The minor increases in whole muscle CSA coupled with the static nature of the myocellular profile indicate that the strength gains were primarily neurological. These data contrast typical muscle responses to resistance training in young ( approximately 20 yr) and old ( approximately 70 yr) humans and indicate that the physiological regulation of muscle remodeling is adversely modified in the oldest old.     

自发性高血压大鼠心肌肥厚和心肌MAPK、AngⅡ的关系

放免法测定自发性高血压大鼠（ＳＨＲ）血浆及心肌血管紧张素Ⅱ（ＡｎｇⅡ）含量,凝胶内磷酸化法测定心肌丝裂素活化蛋白激酶活性（ＭＡＰＫ）,以心脏重／体重表示心肌肥厚程度。结果表明：与４个月的ＷＫＹ大鼠比较,４个月的ＳＨＲ血浆和心肌组织ＡｎｇⅡ及心肌ＭＡＰＫ活性分别增加了２１８．６％、１０１．２％和１０７．０％,心肌肥大程度严重,其中ＭＡＰＫ活性与心肌肥大程度呈明显正相关。提示４个月ＳＨＲ心肌肥厚可能是     

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.     

Resistance exercise load does not determine training-mediated hypertrophic gains in young men

We have reported that the acute postexercise increases in muscle protein synthesis rates, with differing nutritional support, are predictive of longer-term training-induced muscle hypertrophy. Here, we aimed to test whether the same was true with acute exercise-mediated changes in muscle protein synthesis. Eighteen men (21 ± 1 yr, 22.6 ± 2.1 kg/m(2); means ± SE) had their legs randomly assigned to two of three training conditions that differed in contraction intensity [% of maximal strength (1 repetition maximum)] or contraction volume (1 or 3 sets of repetitions): 30%-3, 80%-1, and 80%-3. Subjects trained each leg with their assigned regime for a period of 10 wk, 3 times/wk. We made pre- and posttraining measures of strength, muscle volume by magnetic resonance (MR) scans, as well as pre- and posttraining biopsies of the vastus lateralis, and a single postexercise (1 h) biopsy following the first bout of exercise, to measure signaling proteins. Training-induced increases in MR-measured muscle volume were significant (P < 0.01), with no difference between groups: 30%-3 = 6.8 ± 1.8%, 80%-1 = 3.2 ± 0.8%, and 80%-3= 7.2 ± 1.9%, P = 0.18. Isotonic maximal strength gains were not different between 80%-1 and 80%-3, but were greater than 30%-3 (P = 0.04), whereas training-induced isometric strength gains were significant but not different between conditions (P = 0.92). Biopsies taken 1 h following the initial resistance exercise bout showed increased phosphorylation (P < 0.05) of p70S6K only in the 80%-1 and 80%-3 conditions. There was no correlation between phosphorylation of any signaling protein and hypertrophy. In accordance with our previous acute measurements of muscle protein synthetic rates a lower load lifted to failure resulted in similar hypertrophy as a heavy load lifted to failure.     

Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle.

We examined intramuscular endomysial collagen, cross-linking, and advanced glycation end products, as well as the general and contractile protein concentration of 20 young (25 +/- 3 yr) and 22 old (78 +/- 6 yr, range: 70-93 yr) sedentary men and women to better understand the underlying basis of changes in skeletal muscle mass and function that occur with aging. The old individuals had an impaired ability (increased time) (P < 0.05) to climb stairs (80%), rise from a chair (56%), and walk (44%), as well as lower (P < 0.05) quadriceps muscle volume (-29%), muscle strength (-35%), muscle power (-48%), and strength (-17%) and power (-33%) normalized to muscle size. Vastus lateralis muscle biopsies revealed that intramuscular endomysial collagen (young: 9.6 +/- 1.1, old: 10.2 +/- 1.2 microg/mg muscle wet wt) and collagen cross-linking (hydroxylysylpyridinoline) (young: 395 +/- 65, old: 351 +/- 45 mmol hydroxylysylpyridinoline/mol collagen) were unchanged (P > 0.05) with aging. The advanced glycation end product, pentosidine, was increased (P < 0.05) by approximately 200% (young: 5.2 +/- 1.3, old: 15.9 +/- 4.5 mmol pentosidine/mol collagen) with aging. While myofibrillar protein concentration was lower (-5%, P < 0.05), the concentration of the main contractile proteins myosin and actin were unchanged (P > 0.05) with aging. These data suggest that the synthesis and degradation of proteins responsible for the generation (myosin and actin) and transfer (collagen and pyridinoline cross-links) of muscle force are tightly regulated in aging muscle. Glycation-related cross-linking of intramuscular connective tissue may contribute to altered muscle force transmission and muscle function with healthy aging.     

Normalized force, activation, and coactivation in the arm muscles of young and old men.

The purpose of this study was to determine whether the loss of muscle strength in the elderly could be explained entirely by a decline in the physiological cross-sectional area (PCSA) of muscle. Isometric force, muscle activation (twitch interpolation), and coactivation (surface electromyograph) were measured during maximal voluntary contractions (MVCs) of the elbow flexors (EFs) and extensors (EEs) in 20 young (23 +/- 3 yr) and 13 older (81 +/- 6 yr) healthy men. PCSA was determined using magnetic resonance imaging, and normalized force (NF) was calculated as the MVC/PCSA ratio. The PCSA was smaller in the old compared with the young men, more so in the EEs (28%) compared with the EFs (19%) (P < 0.001); however, the decline in MVC (approximately 30%) with age was similar in the two muscle groups. Muscle activation was not different between the groups, but coactivation was greater (5%) (P < 0.001) in the old men for both muscles. NF was less (11%) in the EFs (P < 0.01) and tended to be unchanged in the EEs of the old compared with young subjects. The relative maintenance of NF in the EEs compared with the EFs may be related to age-associated changes in the architecture of the triceps brachii muscle. In conclusion, although the decline in PCSA explained the majority of strength loss in the old men, additional factors such as greater coactivation or reduced specific tension also may have contributed to the age-related loss of isometric strength.     

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.     

Influence of aging on sex differences in muscle fatigability.

The purpose of this study was to compare time to task failure for a sustained isometric contraction performed at a submaximal intensity with elbow flexor muscles by young and old men and women. Twenty-seven young (14 men and 13 women, 18-35 yr) and 18 old (10 men and 8 women, 65-80 yr) adults sustained an isometric contraction at 20% of maximal voluntary contraction torque until target torque could no longer be achieved for > or = 5 s. Young adults were stronger than old adults (66.8 +/- 17.9 vs. 47.7 +/- 18.1 N x m, P < 0.05), and men were stronger than women (69.8 +/- 17.9 vs. 47.1 +/- 15.3 N x m, P < 0.05), with no interaction between age and sex (P > 0.05). Time to task failure was longer for old than for young adults (22.8 +/- 9.1 vs. 14.4 +/- 7.6 min, P < 0.05) and for young women than for young men (18.3 +/- 8.0 vs. 10.8 +/- 5.2, P < 0.05), but there was no difference between old women and men (21.3 +/- 10.7 and 24.1 +/- 8.0 min, respectively, P > 0.05) or between young women and old adults (P > 0.05). Mean arterial pressure, heart rate, average electromyographic (EMG) activity, and torque fluctuations of elbow flexor muscles increased during the fatiguing contraction (P < 0.05) for all subjects. Rates of increase in mean arterial pressure, heart rate, and torque fluctuations were greater for young men and old adults, with no differences between old men and women (P > 0.05). Similarly, the rate of increase in EMG activity was greater for young men than for the other three groups. EMG bursts were less frequent for old adults (P < 0.05) at the end of the fatiguing contraction, and this was accompanied by reduced fluctuations in torque. Consequently, time to task failure was related to target torque for young, but not old, adults, and differences in task duration were accompanied by parallel changes in the pressor response.     

Short-term high- vs. low-velocity isokinetic lengthening training results in greater hypertrophy of the elbow flexors in young men.

We performed two studies to determine the effect of a resistive training program comprised of fast vs. slow isokinetic lengthening contractions on muscle fiber hypertrophy. In study I, we investigated the effect of fast (3.66 rad/s; Fast) or slow (0.35 rad/s; Slow) isokinetic high-resistance muscle lengthening contractions on muscle fiber and whole muscle cross-sectional area (CSA) of the elbow flexors was investigated in young men. Twelve subjects (23.8 +/- 2.4 yr; means +/- SD) performed maximal resistive lengthening isokinetic exercise with both arms for 8 wk (3 days/wk), during which they trained one arm at a Fast velocity while the contralateral arm performed an equivalent number of contractions at a Slow velocity. Before (Pre) and after (Post) the training, percutaneous muscle biopsies were taken from the midbelly of the biceps brachii and analyzed for fiber type and CSA. Type I muscle fiber size increased Pre to Post (P < 0.05) in both Fast and Slow arms. Type IIa and IIx muscle fiber CSA increased in both arms, but the increases were greater in the Fast- vs. the Slow-trained arm (P < 0.05). Elbow flexor CSA increased in Fast and Slow arms, with the increase in the Fast arm showing a trend toward being greater (P = 0.06). Maximum torque-generating capacity also increased to a greater degree (P < 0.05) in the Fast arm, regardless of testing velocity. In study II, we attempted to provide some explanation of the greater hypertrophy observed in study I by examining an indicator of protein remodeling (Z-line streaming), which we hypothesized would be greater in the Fast condition. Nine men (21.7 +/- 2.4 yr) performed an acute bout (n = 30, 3 sets x 10 repetitions/set) of maximal lengthening contractions at Fast and Slow velocities used in the training study. Biopsies revealed that Fast lengthening contractions resulted in more (185 +/- 1 7%; P < 0.01) Z-band streaming per millimeter squared muscle vs. the Slow arm. In conclusion, training using Fast (3.66 rad/s) lengthening contractions leads to greater hypertrophy and strength gains than Slow (0.35 rad/s) lengthening contractions. The greater hypertrophy seen in the Fast-trained arm (study I) may be related to a greater amount of protein remodeling (Z-band streaming; study II).     

Resistance training alters the response of fed state mixed muscle protein synthesis in young men

Ten healthy young men (21.0 +/- 1.5 yr, 1.79 +/- 0.1 m, 82.7 +/- 14.7 kg, means +/- SD) participated in 8 wk of intense unilateral resistance training (knee extension exercise) such that one leg was trained (T) and the other acted as an untrained (UT) control. After the 8 wk of unilateral training, infusions of L-[ring-d(5)]phenylalanine, L-[ring-(13)C(6)]phenylalanine, and d(3)-alpha-ketoisocaproic acid were used to measure mixed muscle protein synthesis in the T and UT legs by the direct incorporation method [fractional synthetic rate (FSR)]. Protein synthesis was determined at rest as well as 4 h and 28 h after an acute bout of resistance exercise performed at the same intensity relative to the gain in single repetition maximum before and after training. Training increased mean muscle fiber cross-sectional area only in the T leg (type I: 16 +/- 10%; type II: 20 +/- 19%, P < 0.05). Acute resistance exercise increased muscle protein FSR in both legs at 4 h (T: 162 +/- 76%; UT: 108 +/- 62%, P < 0.01 vs. rest) with the increase in the T leg being significantly higher than in the UT leg at this time (P < 0.01). At 28 h postexercise, FSR in the T leg had returned to resting levels; however, the rate of protein synthesis in the UT leg remained elevated above resting (70 +/- 49%, P < 0.01). We conclude that resistance training attenuates the protein synthetic response to acute resistance exercise, despite higher initial increases in FSR, by shortening the duration for which protein synthesis is elevated.     

Aging and acute exercise enhance free radical generation in rat skeletal muscle.

Reactive oxygen species (ROS) are implicated in the mechanism of biological aging and exercise-induced oxidative damage. The present study examined the effect of an acute bout of exercise on intracellular ROS production, lipid and protein peroxidation, and GSH status in the skeletal muscle of young adult (8 mo, n = 24) and old (24 mo, n = 24) female Fischer 344 rats. Young rats ran on a treadmill at 25 m/min and 5% grade until exhaustion (55.4 +/- 2.7 min), whereas old rats ran at 15 m/min and 5% grade until exhaustion (58.0 +/- 2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an indication of ROS and other intracellular oxidants production in the homogenate of deep vastus lateralis, was 77% (P < 0.01) higher in rested old vs. young rats. Exercise increased DCFH oxidation by 38% (P < 0.09) and 50% (P < 0.01) in the young and old rats, respectively. DCFH oxidation in isolated deep vastus lateralis mitochondria with site 1 substrates was elevated by 57% (P < 0.01) in old vs. young rats but was unaltered with exercise. Significantly higher DCFH oxidation rate was also found in aged-muscle mitochondria (P < 0.01), but not in homogenates, when ADP, NADPH, and Fe(3+) were included in the assay medium without substrates. Lipid peroxidation in muscle measured by malondialdehyde content showed no age effect, but was increased by 20% (P < 0.05) with exercise in both young and old rats. Muscle protein carbonyl formation was unaffected by either age or exercise. Mitochondrial GSH/ GSSG ratio was significantly higher in aged vs. young rats (P < 0.05), whereas exercise increased GSSG content and decreased GSH/GSSG in both age groups (P < 0.05). These data provided direct evidence that oxidant production in skeletal muscle is increased in old age and during prolonged exercise, with both mitochondrial respiratory chain and NADPH oxidase as potential sources. The alterations of muscle lipid peroxidation and mitochondrial GSH status were consistent with these conclusions.     

An age-related shift in the force-frequency relationship affects quadriceps fatigability in old adults.

We examined the effect of an age-related leftward shift in the force-frequency relationship on the comparative quadriceps fatigability of nine young (27 +/- 1 yr old) and nine old men (78 +/- 1 yr old) during low-frequency electrical stimulation. Two different protocols of intermittent trains (6 pulses on, 650 ms off) of electrical stimulation at 25% maximum voluntary contraction were performed by both groups: 1) 180 trains at 14.3 Hz [constant frequency (CF) protocol], and 2) 180 trains at the frequency corresponding to 60% of each subject's force-frequency curve [normalized frequency (NF) protocol; young 14.9 +/- 0.4 vs. old 12.7 +/- 0.5 Hz; P < 0.05]. The quadriceps of the old men were weaker (approximately 31%) and relaxation was slower compared with the young men, as assessed by the maximal relaxation rate constant of the 50-Hz tetanus (young 12.1 +/- 0.2 vs. old 9.2 +/- 0.5 s(-1); P < 0.05) and a leftward shift in the force-frequency relationship. The NF protocol revealed a decreased fatigability in the quadriceps with old age (percentage of 1st contraction force remaining at 180th: old 63.4 +/- 1.5 vs. young 58.2 +/- 1.7%; P < 0.05) that was masked during the CF protocol (old 60.7 +/- 1.6 vs. young 58.6 +/- 2.3%; P > 0.05). Irrespective of the protocol, the maximal relaxation rate was reduced to approximately 73 and approximately 57% of the prefatigue value in the young and old men, respectively. The age-related leftward shift in the force-frequency relationship of the quadriceps contributed to an underestimation of the fatigue resistance with old age during the CF protocol. However, when the stimulation frequency used in the NF protocol was adjusted to account for the age-related shift in the force-frequency relationship, the quadriceps muscles of the old men were less fatigable than those of the young men. Thus we suggest that whole muscle fatigability is better examined by electrical stimulation protocols that are adjusted for inter- and intragroup differences in the force-frequency relationship.     

Effect of aging on human muscle architecture.

The effect of aging on human gastrocnemius medialis (GM) muscle architecture was evaluated by comparing morphometric measurements on 14 young (aged 27-42 yr) and on 16 older (aged 70-81 yr) physically active men, matched for height, body mass, and physical activity. GM muscle anatomic cross-sectional area (ACSA) and volume (Vol) were measured by computerized tomography, and GM fascicle length (Lf) and pennation angle (theta) were assessed by ultrasonography. GM physiological cross-sectional area (PCSA) was calculated as the ratio of Vol/Lf. In the elderly, ACSA and Vol were, respectively, 19.1% (P < 0.005) and 25.4% (P < 0.001) smaller than in the young adults. Also, Lf and were found to be smaller in the elderly group by 10.2% (P < 0.01) and 13.2% (P < 0.01), respectively. When the data for the young and elderly adults were pooled together, significantly correlated with ACSA (P < 0.05). Because of the reduced Vol and Lf in the elderly group, the resulting PCSA was found to be 15.2% (P < 0.05) smaller. In conclusion, this study demonstrates that aging significantly affects human skeletal muscle architecture. These structural alterations are expected to have implications for muscle function in old age.     

Semen characteristics, scrotal circumference and bacterial isolates of fine wool range rams

During 1983, 887 fine wool rams were subjected to breeding soundness evaluation to determine effects of age and scrotal circumference on semen characteristics. Of rams evaluated, 94.4, 84.8, and 81.9% of young (6 yr), respectively, were rated as satis-factory. Old rams had fewer (P < 0.05) motile cells and more (P < 0.05) abnormal cells than young rams. Among older rams there was a higher percentage (P < 0.05) with testicular lesions than among young or mature rams. Scrotal circumference was positively correlated (P < 0.01) with semen volume and percentage of motile normal cells. Motility was negatively correlated (P < 0.01) with percentage of abnormal cells. Mature and old rams with large (>/=36.7 cm) testis had more (P < 0.10) abnormal cells than those in the same age groups with smaller testis. Scrotal circumference was positively correlated (P < 0.10) to volume and motility in mature and old rams, while motility was negatively correlated (P < 0.01) to percentage of abnormal cells in all age groups. Previous semen testing reduced (P < 0.05) the percentage of mature rams with leucocytes. Vaccination against epididymitis reduced (P < 0.05) the incidence of mature rams with leucocytes and testicular lesions. Brucella ovis was recovered from 54 (67.5%) of 80 ejaculates cultured. Among rams infected with B . ovis , only three (5.6%) were vaccinated against B . ovis and had their semen tested previously.