E. Todd Schroeder

Satellite cell numbers in young and older men 24 hours after eccentric exercise

We tested the hypothesis that the expansion of satellite cell numbers, 24 h after maximal eccentric knee extensor exercise, is blunted in older men. Muscle biopsies were obtained from the vastus lateralis of 10 young (23–35 years) and 9 older (60–75 years) men. Satellite cells were identified immunohistochemically using an antibody to neural cell adhesion molecule. After 92 maximal eccentric contractions, the mean number of satellite cells per muscle fiber increased to a greater extent among the young men (141%; P < 0.001) than older men (51%; P = 0.002) from preexercise levels. Similar results were obtained when satellite cells were expressed as a proportion of all sublaminar nuclei. We conclude that a single bout of maximal eccentric exercise increases satellite cell numbers in both age groups, with a significantly greater response among the young men. These data suggest that age‐related changes in satellite cell recruitment may contribute to muscle regeneration deficits among the elderly. Muscle Nerve 2006

Testosterone and Growth Hormone Improve Body Composition and Muscle Performance in Older Men

CONTEXT Impairments in the pituitary-gonadal axis with aging are associated with loss of muscle mass and function and accumulation of upper body fat. OBJECTIVES We tested the hypothesis that physiological supplementation with testosterone and GH together improves body composition and muscle performance in older men. DESIGN, SETTING, AND PARTICIPANTS One hundred twenty-two community-dwelling men 70.8 +/- 4.2 yr of age with body mass index of 27.4 +/- 3.4 kg/m2, testosterone of 550 ng/dl or less, and IGF-I in lower adult tertile (< or =167 ng/dl) were randomized to receive transdermal testosterone (5 or 10 g/d) during a Leydig cell clamp plus GH (0, 3, or 5 microg/kg . d) for 16 wk. MAIN OUTCOME MEASURES Body composition by dual-energy x-ray absorptiometry, muscle performance, and safety tests were conducted. RESULTS Total lean body mass increased (1.0 +/- 1.7 to 3.0 +/- 2.2 kg) as did appendicular lean tissue (0.4 +/- 1.4 to 1.5 +/- 1.3 kg), whereas total fat mass decreased by 0.4 +/- 0.9 to 2.3 +/- 1.7 kg as did trunk fat (0.5 +/- 0.9 to 1.5 +/- 1.0 kg) across the six treatment groups and by dose levels for each parameter (P < or = 0.0004 for linear trend). Composite maximum voluntary strength of upper and lower body muscles increased by 14 +/- 34 to 35 +/- 31% (P < 0.003 in the three highest dose groups) that correlated with changes in appendicular lean mass. Aerobic endurance increased in all six groups (average 96 +/- 137 sec longer). Systolic and diastolic blood pressure increased similarly in each group with mean increases of 12 +/- 14 and 8 +/- 8 mm Hg, respectively. Other predictable adverse events were modest and reversible. CONCLUSIONS Supplemental testosterone produced significant gains in total and appendicular lean mass, muscle strength, and aerobic endurance with significant reductions in whole-body and trunk fat. Outcomes appeared to be further enhanced with GH supplementation.

Validity and reliability of body composition analysers in children and adults

We tested the validity and reliability of the BioSpace InBody 320, Omron and Bod-eComm body composition devices in men and women (n 254; 21-80 years) and boys and girls (n 117; 10-17 years). We analysed percentage body fat (%BF) and compared the results with dual-energy X-ray absorptiometry (DEXA) in adults and compared the results of the InBody with underwater weighing (UW) in children. All body composition devices were correlated (r 0.54-0.97; P< or =0.010) to DEXA except the Bod-eComm in women aged 71-80 years (r 0.54; P=0.106). In girls, the InBody %BF was correlated with UW (r 0.79; P< or =0.010); however, a more moderate correlation (r 0.69; P< or =0.010) existed in boys. Bland-Altman plots indicated that all body composition devices underestimated %BF in adults (1.0-4.8 %) and overestimated %BF in children (0.3-2.3 %). Lastly, independent t tests revealed that the mean %BF assessed by the Bod-eComm in women (aged 51-60 and 71-80 years) and in the Omron (age 18-35 years) were significantly different compared with DEXA (P< or =0.010). In men, the Omron (aged 18-35 years), and the InBody (aged 36-50 years) were significantly different compared with DEXA (P=0.025; P=0.040 respectively). In addition, independent t tests indicated that the InBody mean %BF in girls aged 10-17 years was significantly different from UW (P=0.001). Pearsons correlation analyses demonstrated that the Bod-eComm (men and women) and Omron (women) had significant mean differences compared with the reference criterion; therefore, the %BF output from these two devices should be interpreted with caution. The repeatability of each body composition device was supported by small CV (<3.0 %).

Hormone therapy attenuates exercise-induced skeletal muscle damage in postmenopausal women

Hormone therapy (HT) is a potential treatment to relieve symptoms of menopause and prevent the onset of disease such as osteoporosis in postmenopausal women. We evaluated changes in markers of exercise-induced skeletal muscle damage and inflammation [serum creatine kinase (CK), serum lactate dehydrogenase (LDH), and skeletal muscle mRNA expression of IL-6, IL-8, IL-15, and TNF-alpha] in postmenopausal women after a high-intensity resistance exercise bout. Fourteen postmenopausal women were divided into two groups: women not using HT (control; n = 6, 59 +/- 4 yr, 63 +/- 17 kg) and women using traditional HT (HT; n = 8, 59 +/- 4 yr, 89 +/- 24 kg). Both groups performed 10 sets of 10 maximal eccentric repetitions of single-leg extension on the Cybex dynamometer at 60 degrees /s with 20-s rest periods between sets. Muscle biopsies of the vastus lateralis were obtained from the exercised leg at baseline and 4 h after the exercise bout. Gene expression was determined by RT-PCR for IL-6, IL-8, IL-15, and TNF-alpha. Blood draws were performed at baseline and 3 days after exercise to measure CK and LDH. Independent t-tests were performed to test group differences (control vs. HT). A probability level of P <or= 0.05 was used to determine statistical significance. We observed significantly greater changes in mRNA expression of IL-6, IL-8, IL-15, and TNF-alpha (P <or= 0.01) in the control group compared with the HT group after the exercise bout. CK and LDH levels were significantly greater after exercise (P <or= 0.01) in the control group. Postmenopausal women not using HT experienced greater muscle damage after maximal eccentric exercise, indicating a possible protective effect of HT against exercise-induced skeletal muscle damage.

Utility of multifrequency bioelectrical impedance compared with dual-energy x-ray absorptiometry for assessment of total and regional body composition varies between men and women

Multifrequency bioelectrical impedance analysis of body composition may be an appropriate alternative to dual-energy x-ray absorptiometry. We hypothesized that there would be no significant differences between dual-energy x-ray absorptiometry and either the Biospace (Los Angeles, CA, USA) InBody 520 or 720 multifrequency bioelectrical impedance analysis devices for total lean body mass (LBM), appendicular lean mass (ALM), trunk lean mass (TM), and total fat mass (FM) in 25 men and 25 women (including lean, healthy, and obese individuals according to body mass index), age 18 to 49 years, weight of 73.6 ± 15.4 kg. Both devices overestimated LBM in women (~2.5 kg, P < .001) and underestimated ALM in men (~3.0 kg, P < .05) and women (~1.0 kg, P < .05). The 720 overestimated FM in men (1.6 kg, P < .05) and underestimated TM in women (0.6 kg, P ≤ .05). Regression analyses in men revealed R² (0.87-0.91), standard error of the estimate (SEE; 2.3-2.8 kg), and limits of agreement (LOAs; 4.5-5.7 kg) for LBM; R(2) (0.62-0.87), SEE (1.5-2.6 kg), and LOA (3.2-6.0 kg) for ALM; R² (0.52-0.71), SEE (2.4-3.0 kg), and LOA (4.6-6.1 kg) for TM; and R(2) (0.87-0.93), SEE (1.9-2.6 kg), and LOA (5.9-6.2 kg) for FM. Regression analyses in women revealed R² (0.87-0.88), SEE (1.8-1.9 kg), and LOA (4.1-4.2 kg) for LBM; R² (0.78-0.79), SEE (1.4-1.5 kg), and LOA (2.7-2.9 kg) for ALM; R² (0.76-0.77), SEE (1.0 kg), and LOA (2.2-2.3 kg) for TM; and R² (0.95), SEE (2.2 kg), and LOA (4.3-4.4 kg) for FM. The InBody 520 and 720 are valid estimators of LBM and FM in men and of LBM, ALM, and FM in women; the 720 and 520 are valid estimators of TM in men and women, respectively.

Startup Circuit Training Program Reduces Metabolic Risk in Latino Adolescents

PURPOSE This study aimed to test the effects of a circuit training (CT; aerobic + strength training) program, with and without motivational interviewing (MI) behavioral therapy, on reducing adiposity and type 2 diabetes risk factors in Latina teenagers. METHODS Thirty-eight Latina adolescents (15.8 ± 1.1 yr) who are overweight/obese were randomly assigned to control (C; n = 12), CT (n = 14), or CT + MI (n = 12). The CT classes were held twice a week (60-90 min) for 16 wk. The CT + MI group also received individual or group MI sessions every other week. The following were measured before and after intervention: strength by one-repetition maximum; cardiorespiratory fitness (V·O 2max) by submaximal treadmill test; physical activity by accelerometry; dietary intake by records; height, weight, waist circumference; total body composition by dual-energy x-ray absorptiometry; visceral adipose tissue, subcutaneous adipose tissue, and hepatic fat fraction by magnetic resonance imaging; and glucose/insulin indices by fasting blood draw. Across-intervention group effects were tested using repeated-measures ANOVA with post hoc pairwise comparisons. RESULTS CT and CT + MI participants, compared with controls, significantly increased fitness (+16% and +15% vs -6%, P = 0.03) and leg press (+40% vs +20%, P = 0.007). Compared with controls, CT participants also decreased waist circumference (-3% vs +3%; P < 0.001), subcutaneous adipose tissue (-10% vs 8%, P = 0.04), visceral adipose tissue (-10% vs +6%, P = 0.05), fasting insulin (-24% vs +6%, P = 0.03), and insulin resistance (-21% vs -4%, P = 0.05). CONCLUSIONS CT may be an effective starter program to reduce fat depots and improve insulin resistance in Latino youth who are overweight/obese, whereas the additional MI therapy showed no additive effect on these health outcomes.

Musculoskeletal adaptations to 16 weeks of eccentric progressive resistance training in young women.

We investigated the musculoskeletal adaptations and efficacy of a whole-body eccentric progressive resistance-training (PRT) protocol in young women. Subjects (n = 37; mean age, 24.3) were randomly assigned to one of 3 groups: high-intensity eccentric PRT (HRT), low-intensity eccentric PRT (LRT), or control. Subjects performed 3 sets of 6 repetitions at 125% intensity or 3 sets of 10 repetitions at 75% intensity in the HRT and LRT groups, respectively, 2 times per week for 16 weeks. Strength was determined by the concentric 1-repetition maximum (1RM) standard. Bone mass and body composition were measured by dual-energy x-ray absorptiometry (DXA). Blood and urine samples were obtained for deoxypyridinoline, osteocalcin, creatine kinase, and creatinine. Data were analyzed by repeated-measures analysis of variance with post hoc comparisons. Strength increased 20–40% in both training groups. Lean body mass increased in the LRT (0.7 ± 0.6 kg) and HRT (0.9 ± 0.9 kg) groups. Bone mineral content increased (0.855 ± 0.958 g) in the LRT group only. Deoxypyridinoline decreased and osteocalcin increased in the HRT and LRT groups, respectively. These findings suggest that submaximal eccentric training is optimal for musculoskeletal adaptations and that the intensity of eccentric training influences the early patterns of bone adaptation.

Influence of hormone replacement therapy on eccentric exercise induced myogenic gene expression in postmenopausal women

Hormone replacement therapy (HRT) is used in postmenopausal women to relieve symptoms of menopause and prevent osteoporosis. We sought to evaluate changes in mRNA expression of key myogenic factors in postmenopausal women taking and not taking HRT following a high-intensity eccentric resistance exercise. Fourteen postmenopausal women were studied and included 6 control women not using HRT (59 +/- 4 years, 63 +/- 17 kg) and 8 women using traditional HRT (59 +/- 4 yr, 89 +/- 24 kg). Both groups performed 10 sets of 10 maximal eccentric repetitions of single-leg extension on a Cybex dynamometer at 60 degrees /s. Muscle biopsies of the vastus lateralis were obtained from the exercised leg at baseline and 4 h after the exercise bout. Gene expression was determined using RT-PCR for follistatin, forkhead box 3A (FOXO3A), muscle atrophy F-box (MAFbx), muscle ring finger-1 (MuRF-1), myogenic differentiation factor (MyoD), myogenin, myostatin, myogenic factor 5 (Myf5), and muscle regulatory factor 4 (MRF4). At rest, the HRT group expressed higher levels of MyoD, myogenin, Myf5, MRF4, and follistatin (P < 0.05). In response to eccentric exercise, follistatin, MyoD, myogenin, Myf5, and MRF4 were significantly increased (P <or= 0.05) and FOXO3A, MAFbx, MuRF-1, and myostatin were significantly decreased in the control and HRT groups (P <or= 0.05). Significantly greater changes in mRNA expression of follistatin, FOXO3A, MAFbx, MuRF-1, MyoD, myogenin, myostatin, Myf5, and MRF4 (p<or=0.05) occurred in the HRT group than in the control group after exercise. These data suggest that postmenopausal women using HRT express higher myogenic regulatory factor gene expression, which may reflect an attempt to preserve muscle mass. Furthermore, postmenopausal women using HRT experienced a greater myogenic response to maximal eccentric exercise.

Testosterone Threshold Levels and Lean Tissue Mass Targets Needed to Enhance Skeletal Muscle Strength and Function: The HORMA Trial

BACKGROUND In the HORMA (Hormonal Regulators of Muscle and Metabolism in Aging) Trial, supplemental testosterone and recombinant human growth hormone (rhGH) enhanced lean body mass, appendicular skeletal muscle mass, muscle performance, and physical function, but there was substantial interindividual variability in outcomes. METHODS One hundred and twelve men aged 65-90 years received testosterone gel (5 g/d vs 10 g/d via Leydig cell clamp) and rhGH (0 vs 3 vs 5 μg/kg/d) in a double-masked 2 × 3 factorial design for 16 weeks. Outcomes included lean tissue mass by dual energy x-ray absorptiometry, one-repetition maximum strength, Margaria stair power, and activity questionnaires. We used pathway analysis to determine the relationship between changes in hormone levels, muscle mass, strength, and function. RESULTS Increases in total testosterone of 1046 ng/dL (95% confidence interval = 1040-1051) and 898 ng/dL (95% confidence interval = 892-904) were necessary to achieve median increases in lean body mass of 1.5 kg and appendicular skeletal muscle mass of 0.8 kg, respectively, which were required to significantly enhance one-repetition maximum strength (≥ 30%). Co-treatment with rhGH lowered the testosterone levels (quantified using liquid chromatography-tandem mass spectrometry) necessary to reach these lean mass thresholds. Changes in one-repetition maximum strength were associated with increases in stair climbing power (r = .26, p = .01). Pathway analysis supported the model that changes in testosterone and insulin-like growth factor 1 levels are related to changes in lean body mass needed to enhance muscle performance and physical function. Testosterones effects on physical activity were mediated through a different pathway because testosterone directly affected Physical Activity Score of the Elderly. CONCLUSIONS To enhance muscle strength and physical function, threshold improvements in lean body mass and appendicular skeletal muscle mass are necessary and these can be achieved by targeting changes in testosterone levels. rhGH augments the effects of testosterone. To maximize functional improvements, the doses of anabolic hormones should be titrated to achieve target blood levels.

N-Terminal Propeptide of Type III Procollagen as a Biomarker of Anabolic Response to Recombinant Human GH and Testosterone

CONTEXT Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (LBM) and muscle strength gains in response to testosterone and GH. DESIGN Community-dwelling older men received GnRH agonist plus 5 or 10 g testosterone gel plus 0, 3, or 5 microg recombinant human GH daily. P3NP levels were measured at baseline and wk 4, 8, 12, and 16. LBM and appendicular skeletal muscle mass (ASM) were measured by dual-energy x-ray absorptiometry. RESULTS One hundred twelve men completed treatment; 106 underwent serum P3NP measurements. P3NP levels were higher at wk 4 than baseline (6.61 +/- 2.14 vs. 4.51 +/- 1.05, P < 0.0001) and reached plateau by wk 4 in men receiving testosterone alone. However, wk 8 P3NP levels were higher than wk 4 levels in men receiving testosterone plus recombinant human GH. Increases in P3NP from baseline to wk 4 and 16 were significantly associated with gains in LBM (r = 0.26, P = 0.007; r = 0.53, P < 0.001) and ASM (r = 0.17, P = 0.07; r = 0.40, P < 0.0001). Importantly, for participants receiving only testosterone, P3NP increases at wk 4 and 16 were related to muscle strength gains (r = 0.20, P = 0.056 and r = 0.36, P = 0.04). In stepwise regression, change in P3NP explained 28 and 30% of the change in ASM and LBM, respectively, whereas change in testosterone but not IGF-I and age provided only small improvements in the models. CONCLUSION Early changes in serum P3NP levels are associated with subsequent changes in LBM and ASM during testosterone and GH administration. Serum P3NP may be a useful early predictive biomarker of anabolic response to GH and testosterone.