The purpose of this study was to 1) examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older women (n = 7; 74 +/- 2 yr) and 2) to compare these results to our previously completed single cell PRT work with older men (n = 7; 74 +/- 2 yr) (Trappe S, Williamson D, Godard M, Porter D, Rowden G, and Costill D. J Applied Physiol 89:143--152, 2000). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsies were obtained from the vastus lateralis before and after the PRT. Chemically skinned single muscle fibers (n = 313) were studied at 15 degrees C for peak tension (P(o)), unloaded shortening velocity (V(o)), and power. Due to the low number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 24% (90 +/- 2 to 112 +/- 6 microm; P < 0.05) in MHC I fibers with no change in MHC IIa fibers. P(o) increased (P < 0.05) 33% in MHC I (0.76 +/- 0.04 to 1.01 +/- 0.09 mN) and 14% in MHC IIa (0.73 +/- 0.04 to 0.83 +/- 0.05 mN) fibers. Muscle fiber V(o) was unaltered in both fiber types with PRT. MHC I and IIa fiber power increased (P < 0.05) 50% [11 +/- 2 to 17 +/- 2 microN. fiber length (FL). s(-1)] and 25% (40 +/- 8 to 51 +/- 6 microN. FL. s(-1)), respectively. However, when peak power was normalized to cell size, no pre- to postimprovements were observed. These data indicate that PRT in elderly women increases muscle cell size, strength, and peak power in both slow and fast muscle fibers, which was similar to the older men. However, in contrast to the older men, no change in fiber V(o) or normalized power was observed in the older women. These data suggest that older men and women respond differently at the muscle cell level to the same resistance-training stimulus.

These results indicate that a resistance-training paradigm employed every third day during 21 d of unloading was effective in maintaining skeletal muscle strength (static and dynamic) and size of the KE and PF.

Although the IRM strength gains were not significantly different, HMB supplementation appears to increase peak isometric and various isokinetic torque values, and increase FFM and decrease plasma CPK activity. Lastly, it appears that higher doses of HMB (i.e., > 38 mg x kg(-1) x d(-1)) do not promote strength or FFM gains.

The purpose of this investigation was to examine the effects of 12 wk of progressive resistance training (PRT) on single muscle fiber myosin heavy chain (MHC; I, I/IIa, I/IIa/IIx, IIa, IIa/IIx, IIx) isoform proportions in young individuals. Young, untrained men (YM; n = 6) and women (YW; n = 6) (age = 22 +/- 1 and 25 +/- 2 yr for YW and YM, respectively) received pre- and post-PRT muscle biopsies from the right vastus lateralis for single muscle fiber MHC distribution by electrophoretic analysis (192 +/- 5 pre- and 183 +/- 6 post-fibers/subject analyzed; 4,495 fibers total). Data are presented as percentages of the total fibers analyzed per subject. The PRT protocol elicited an increase in the pure MHC IIa (Delta = + 24 and + 27; YW and YM, respectively; P < 0.05) with no change in the pure MHC I distribution. The hybrid MHC distributions decreased I/IIa/IIx (Delta = -2; YM and YW; P < 0.05), IIa/IIx (Delta = -13 and -19 for YM and YW, respectively; P < 0.05), and total hybrid fiber proportion (I/IIa + I/IIa/IIx + IIa/IIx) decreased (Delta = -19 and -30 for YM and YW, respectively; P < 0.05) with the training, as did the MHC IIx distribution (Delta = -2; YW only; P < 0.05). Alterations in the predominance of MHC isoforms within hybrid fibers (decrease in MHC I-dominant I/IIa and nondominant MHC IIa/IIx, increase in MHC IIa-dominant IIa/IIx; P < 0.05) appeared to contribute to the increase in the MHC IIa proportion. Electrophoresis of muscle cross sections revealed an approximately 7% increase (P < 0.05) in MHC IIa proportion in both groups, whereas the MHC IIx decrease by 7.5 and 11.6% post-PRT in YW and YM, respectively. MHC I proportions increase in YM by 4.8% (P < 0.05) post-PRT. These findings further support previous resistance training data in young adults with respect to the increase in the MHC IIa proportions but demonstrate that a majority of the change can be attributed to the decrease in single-fiber hybrid proportions.

Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients over age 50. Previous therapeutic trials have targeted the inflammatory features of sIBM, but all have failed. Since protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature of the disease. Using rat myoblast cultures, we found that up-regulation of the heat shock response with Arimoclomol reduced key pathological markers of sIBM in vitro. Furthermore, in mutant valosin-containing protein VCP mice, which develop an inclusion body myopathy (IBM), treatment with Arimoclomol ameliorated disease pathology and improved muscle function. We therefore evaluated the safety and tolerability of Arimoclomol in an investigator-lead, randomised, double-blind, placebo-controlled, proof-of-concept patient trial and gathered exploratory efficacy data which showed that Arimoclomol was safe and well tolerated. Although Arimoclomol improved some IBM-like pathology in vitro and in vivo in the mutant VCP mouse, we did not see statistically significant evidence of efficacy in this proof of concept patient trial.

Sex-related differences in mCSA and MUAP of the higher-threshold MUs were likely the result of larger muscle fibres expressing type II characteristics for males.

The purpose of this investigation was to determine the effects of postexercise eucaloric carbohydrate-protein feedings on muscle glycogen restoration after an exhaustive cycle ergometer exercise bout. Seven male collegiate cyclists [age = 25.6 +/- 1.3 yr, height = 180.9 +/- 3.2 cm, wt = 75.4 +/- 4.0 kg, peak oxygen uptake (VO(2 peak)) = 4.20 +/- 0.2 l/min] performed three trials, each separated by 1 wk: 1) 100% alpha-D-glucose [carbohydrate (CHO)], 2) 70% carbohydrate-20% protein (PRO)-10% fat, and 3) 86% carbohydrate-14% amino acid (AA). All feedings were eucaloric, based on 1.0 g. kg body wt(-1). h(-1) of CHO, and administered every 30 min during a 4-h muscle glycogen restoration period in an 18% wt/vol solution. Muscle biopsies were obtained immediately and 4 h after exercise. Blood samples were drawn immediately after the exercise bout and every 0.5 h for 4 h during the restoration period. Increases in muscle glycogen concentrations for the three feedings (CHO, CHO-PRO, CHO-AA) were 118 mmol/kg dry wt; however, no differences among the feedings were apparent. The serum glucose and insulin responses did not differ throughout the restoration period among the three feedings. These results suggest that muscle glycogen restoration does not appear to be enhanced with the addition of proteins or amino acids to an eucaloric CHO feeding after exhaustive cycle exercise.

It is suggested that firing rate characteristics of motor units (MUs) are influenced by the physical properties of the muscle. However, no study has correlated MU firing rates at recruitment, targeted force, or derecruitment with the contractile properties of the muscle in vivo. Twelve participants (age = 20.67 ± 2.35 yr) performed a 40% isometric maximal voluntary contraction of the leg extensors that included linearly increasing, steady force, and decreasing segments. Muscle biopsies were collected with myosin heavy chain (MHC) content quantified, and surface electromyography (EMG) was recorded from the vastus lateralis. The EMG signal was decomposed into the firing events of single MUs. Slopes and y-intercepts were calculated for 1) firing rates at recruitment vs. recruitment threshold, 2) mean firing rates at steady force vs. recruitment threshold, and 3) firing rates at derecruitment vs. derecruitment threshold relationships for each subject. Correlations among type I %MHC isoform content and the slopes and y-intercepts from the three relationships were examined. Type I %MHC isoform content was correlated with MU firing rates at recruitment (y-intercepts: r = -0.577; slopes: r = 0.741) and targeted force (slopes: r = 0.853) vs. recruitment threshold and MU firing rates at derecruitment (y-intercept: r = -0.597; slopes: r = 0.701) vs. derecruitment threshold relationships. However, the majority of the individual MU firing rates vs. recruitment and derecruitment relationships were not significant (P > 0.05) and, thus, revealed no systematic pattern. In contrast, MU firing rates during the steady force demonstrated a systematic pattern with higher firing rates for the lower- than higher-threshold MUs and were correlated with the physical properties of MUs in vivo.