Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men.

Growth hormone (GH), insulin-like growth factor I (IGF-I), and testosterone (T) are important mediators of muscle protein synthesis, and thus muscle mass, all of which decline with age. We hypothesized that circulating hormones would be related to the transcriptional levels of their respective receptors and that this expression would be negatively related to expression of the myostatin gene. We therefore determined content of mRNA transcripts (by RT-PCR) for GH receptor (GHR), IGF-I, androgen receptor (AR), and myostatin in skeletal muscle biopsy samples from 27 healthy men >65 yr of age. There were no significant relationships between age, lean body mass, or percent body fat and transcript levels of GHR, IGF-I, AR, or myostatin. Moreover, there were no significant correlations of serum GH, IGF-I, or T with their corresponding target mRNA levels (GHR, intramuscular IGF-I, or AR) in skeletal muscle. However, GHR was negatively correlated (r = -0.60, P = 0.001) with myostatin mRNA levels. The lack of apparent relationships of muscle transcripts with their respective ligands in healthy older adults suggests that age-related deficits in both GH and T may lead to an increase in myostatin expression and a disassociation in autocrine IGF-I effects on muscle protein synthesis, both of which could contribute to age-related sarcopenia.

A longitudinal assessment of change in VO2max and maximal heart rate in master athletes.

PURPOSE: The purpose of this study was to determine the longitudinal change in VO2max and HRmax in male and female master endurance runners and to compare these changes based upon gender, age, and change in training volume. METHODS: Eighty-six male (53.9 +/- 1.1 yr) and 49 female (49.1 +/- 1.2 yr) master endurance runners were tested an average of 8.5 yr apart. Subjects were grouped by age at first visit, change in VO2max, and change in training volume. Measurements included body composition by hydrostatic weighing, maximal exercise testing on a treadmill, and training history by questionnaire. Data were analyzed by ANOVA and multiple regression. RESULTS: VO2max and HRmax declined significantly regardless of gender or age group (P < 0.05). The rate of change in VO2max by age group ranged from -1% to -4.6% per year for men and -0.5% to 2.4% per year for women. Men with the greatest loss in VO2max had the greatest loss in LBM (-2.8 +/- 0.7 kg), whereas women with the greatest loss in VO2max demonstrated the greatest change in training volume (-24.1 +/- 3.0 km.wk-1). Additionally, women with the greatest loss in VO2max (-9.6 +/- 2.6 mL.kg-1.min-1) did not replace estrogen after menopause independent of age. HRmax change did not differ by VO2max change or training volume change in either gender. CONCLUSIONS: In conclusion, these data suggest that VO2max declines in male and female master athletes at a rate similar to or greater than that expected in sedentary older adults. Additionally, these data suggest that maintenance of LBM and VO2max were associated in men, whereas in women, estrogen replacement and maintenance of training volume were associated with maintained VO2max.

Recombinant human growth hormone and recombinant human insulin-like growth factor I diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects.

Severe gonadal androgen deficiency can have profound catabolic effects in man. Hypogonadal men develop a loss of lean body mass, increased adiposity, and decreased muscle strength despite normal GH and insulin-like growth factor I (IGF-I) concentrations. We designed these studies to investigate whether GH or IGF-I administration to male subjects with profound hypogonadism can diminish or abolish the catabolic effects of testosterone deficiency. Moreover, we also examined the nature of the interactions among GH, IGF-I, and androgens in specific genes of the im system. A group of 13 healthy subjects (mean age, 22 +/- 1 yr) was studied at baseline (D1) and 10 weeks after being made hypogonadal using a GnRH analog (GnRHa; D2). At 6 weeks from baseline they were started on either recombinant human (rh) IGF-I (60 microg/kg, sc, twice daily) or rhGH (12.5 microg/kg, sc, daily) for 4 weeks. On each study day subjects had infusions of L-[(13)C]leucine; indirect calorimetry; isokinetic dynamometry of the knee extensors; determination of body composition (dual energy x-ray absortiometry) and hormone and growth factor concentrations, as well as percutaneous muscle biopsies. Their data were compared with those of previously studied male subjects who received only GNRHA: Administration of rhIGF-I and rhGH to the hypogonadal men had similar effects on whole body metabolism, with maintenance of protein synthesis rates, fat oxidation rates, and fat-free mass compared with the eugonadal state, preventing the decline observed with hypogonadism alone. This was further amplified by the molecular assessment of important genes in muscle function. During rhIGF-I treatment, im expression of IGF-I declined, and IGF-binding protein-4 increased, similar to the changes during GnRHa alone. However, rhGH administration was associated with a marked increase in IGF-I and androgen receptor messenger ribonucleic acid concentrations in skeletal muscle with a reciprocal decline in IGF-binding protein-4 expression in the hypogonadal men. The gene expression for myostatin did not change. These effects were accompanied by a much greater increase in plasma IGF-I concentrations after rhIGF-I (225 +/- 32 vs. 768 +/- 117 microg/L) compared with the concentrations achieved during rhGH (217 +/- 20 vs. 450 +/- 19 microg/L). We conclude that 1) rhGH and rhIGF-I both may be beneficial in preserving lean body mass and sustaining rates of protein synthesis during states of severe androgen deficiency in man; 2) GH may affect the im IGF system via an a paracrine, local production of IGF-I; 3) androgens may be necessary for the full anabolic effect of GH/IGF-I in man. These hormones, particularly GH, may play a role in the treatment of hypogonadal men rendered hypogonadal pharmacologically or those unable to take full testosterone replacement. The latter requires further study.

Influence of weight training exercise and modification of hormonal response on skeletal muscle growth.

To investigate the influence of carbohydrate (CHO) consumption on the acute hormonal response, and chronic adaptation to weight lifting exercise, two studies were conducted. Following a four-hour fast, seven young men (21.3 +/- 3.5 y) performed (on two occasions) a nine-station weight lifting protocol, completing 3 sets of 10 repetitions at 75% of 1RM (series 1). Randomly assigned, one session included the ingestion of a non-caloric placebo, and the other, a 6% CHO solution. For series 2, two groups of young men (21.3 +/- 1.5 y) participated in 12 weeks of progressive resistance weight training. Training for one group included the ingestion of a non-caloric placebo, and the other, a 6% CHO solution. In series 1, weight lifting exercise with CHO ingestion significantly (p < 0.05) elevated blood glucose and plasma insulin levels above baseline, as well as that occurring with the placebo. This resulted in a significant blunting of the cortisol response (7% with CHO compared to 99% with placebo). These findings indicate that CHO consumption during weight lifting exercise can modify the acute hormonal response to exercise. With series 2, CHO consumption continued to blunt the cortisol response to exercise during the twelve weeks of training. This is in contrast to significantly elevated cortisol levels observed for the placebo control group. Corresponding with the modified response patterns were differences in muscle growth. Weight training exercise with CHO ingestion resulted in significantly greater gains in both type I (19.1%) and type II (22.5%) muscle fibre area than weight training exercise alone. The difference in the cortisol response accounted for 74% of the variance (r = 0.8579, p = 0.006) of change in type I muscle fibre area, and 52.3% of the variance (r = 0.7231, p = 0.043) of change in type II muscle fibre area. These findings suggest that the modification of the cortisol response associated with CHO ingestion can positively impact the skeletal muscle hypertrophic adaptation to weigh training.

Maximal aerobic power, lactate threshold, and running performance in master athletes.

PURPOSE: This study sought to determine how lactate threshold (LT) is related to running performance in older male and female runners, if LT changes significantly with age, and if gender alters the relationship between LT and performance in older runners. METHODS: Subjects were 168 master runners (111 men, 57 women) selected from a longitudinal study, who ran at least 10 miles x wk(-1) for 5 yr or more. VO2max was measured on a treadmill and body composition by hydrostatic weighing. Blood samples taken each minute of exercise were analyzed for lactate concentration and LT determined as the breakpoint in lactate accumulation. Performance times and training histories were self-reported by questionnaire. RESULTS: Men had significantly greater body mass, fat-free mass (FFM), and VO2max (L x min(-1); mL x kg(-1) x min(-1)) than women. FFM and VO2max (L x min(-1); mL x kg(-1) x min(-1)) declined with age in both men and women. Running performance was significantly different between men and women and declined with age in both. LT (L x min(-1); mL x kg(-1) x min(-1)) was significantly different between men and women, and declined significantly with age in men, whereas LT (%VO2max) did not differ between men and women and increased significantly with age in both. VO2max (mL x kg(-1) x min(-1)) was the most significant predictor of performance in both men and women, whereas LT (L x min(-1)) added to the prediction of 5-km and 10-km performance in women. CONCLUSION: The results of this study demonstrate that VO2max (mL x kg(-1) x min(-1)) is a better predictor of performance than LT in older male and female runners. Additionally, LT as a percentage of VO2max increases significantly with age.

The inability of hormone replacement therapy or chronic running to maintain bone mass in master athletes.

BACKGROUND: Previous studies have demonstrated equivocal findings on the effect of chronic running on bone mass in post-menopausal women. The purpose of this study was to determine the effect of chronic running alone and in conjunction with hormone replacement therapy (HRT) on bone mineral density (BMD) in postmenopausal women. METHODS: Forty-three women [15 premenopausal 48.1 +/- .4 yrs (Pre); 13 postmenopausal 57.3 +/- 2.3 yrs (Post); and 15 HRT-treated postmenopausal 56.8 +/- 1.5 yrs (PostE)] served as subjects. All were chronic runners (duration > 5 yrs, > 10 miles per week). BMD was determined by dual energy x-ray absorptiometry, VO2 max on a treadmill, body composition by hydrostatic weighing, knee strength by KinCom dynamometer, and training and menstrual history by questionnaire. Analysis of covariance with Tukey post hoc tests was utilized to compare the groups. RESULTS: The groups were similar in body weight, VO2 max, years training, and miles run per week. Pre and PostE did not differ in total or spine BMD. However, Pre had greater hip BMD than PostE (.973 +/- .03 vs .876 +/- .03 g/cm2; p < .05). As well, Pre had greater BMD of the hip (.973 +/- .03 vs .805 +/- .03 g/cm2; p < .05), spine (1.047 +/- .04 vs .870 +/- .04 g/cm2; p < .05), and total body (1.115 +/- .02 vs .996 +/- .03 g/cm2; p < .05) than Post. CONCLUSIONS: These results suggest that (a) chronic running + HRT is insufficient to protect hip BMD and (b) chronic running alone provides no protection for bone mass in postmenopausal women.

Oral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adults.

BACKGROUND: Growth hormone (GH) helps maintain body composition and metabolism in adults. However, basal and peak GH decline with age. Exercise produces a physiologic GH response that is subnormal in elderly people. Arginine (Arg) infusion can augment GH secretion, but the efficacy of oral Arg to improve GH response to exercise has not been explored. We investigated whether oral Arg increases GH secretion in young and old people at rest and during exercise. METHODS: Twenty young (Y: 22.1 +/- 0.9 y; SEM) and 8 old (O: 68.5 +/- 2.1 y) male and female subjects underwent three different trials following determination of their one-repetition maximum strength (1-RM); exercise only (EO; 3 sets, 8-10 reps at 85% of 1-RM; on 12 separate resistive lifts), Arg only (5.0 g), or Arg + exercise. Blood samples were collected between successive lifts, and GH (ng x ml(-1)) was determined via RIA. RESULTS: In Y vs O: Basal GH secreted (area under the curve) was 543.6 +/- 84.0 vs 211.5 +/- 63.0. During EO, values were 986.6 +/- 156.6 and 517.8 +/- 85.5. Both were significantly lower in the older individuals (p < .05). Oral Arg alone did not result in any increase in GH secretion at rest (310.8 +/- 73.2 vs 262.9 +/- 141.2). When Arg was coadministered during exercise, GH release was not affected in either the young or old and appeared to be blunted in the young compared to the exercise only trial in the young. CONCLUSION: Based upon these findings, we concluded that oral Arg does not stimulate GH secretion and may impair GH release during resistive exercise.

Eccentric muscle action increases site-specific osteogenic response.

PURPOSE: Strain magnitude is known to be a primary determinant of the osteogenic response to loading. However, whether bone adaptation to muscle loading is determined primarily by load magnitude is unclear. The purpose of this study was to determine the contribution of load magnitude from muscle action on the site-specific osteogenic response. METHODS: Twenty young women (12 exercise, 8 control) served as subjects. Bone mineral density (BMD) of the whole body and mid-femur segment and body composition were determined by dual-energy x-ray absorptiometry. Knee extension and flexion strengths were determined on a KinCom dynamometer, with surface electromyography of the vastus lateralis muscle. Exercise subjects trained three times weekly for 18 wk on a KinCom. One leg trained using eccentric knee extension and flexion, and the opposite leg trained using concentric knee extension and flexion. RESULTS: Eccentric exercise demonstrated greater force production with lower integrated electromyographic signal (IEMG) compared with concentric exercise. Significant increases in muscle strength occurred in both exercised legs (P < 0.05), which were of similar relative change. However, only the eccentric trained leg significantly increased mid-femur segment BMD (+3.9%, P < 0.05) and mid-thigh segment lean mass (+5.2%, P < 0.05). CONCLUSIONS: These results suggest that eccentric muscle training is more osteogenic than concentric muscle training and that eccentric training is more efficient by attaining higher force production with lower IEMG.

Age-related blunting of growth hormone secretion during exercise may not be soley due to increased somatostatin tone.

Age-related declines in growth hormone (GH) secretion may result from augmented somatostatin (SRIH) tone and/or diminished GH-releasing hormone (GHRH) secretion. We assessed GH release during exercise without and with pyridostigmine (PYR), which indirectly suppresses SRIH. GH levels were measured throughout exercise and recovery in 12 young men (mean +/- SEM, 20.8 +/- 0.4 years) and seven old men (66.1 +/- 1.9). The area under the GH curve (GH-AUC) was greater in young versus old men during a short-term maximal exercise test (12.9 +/- 2.8 v 1.5 +/- 0.2 ng x min(-1) x mL(-1), P = .002) and a 1-hour 60% maximal (submaximal, 10.0 +/- 1.5 v 3.0 +/- 1.0 ng x min(-1) x mL(-1), P = .001) cycle exercise bout. PYR increased the GH-AUC in young and old men during maximal (20.9 +/- 5.2 v 4.9 +/- 1.8) and submaximal (12.3 +/- 1.6 v 4.7 +/- 1.5) exercise (P < .05). The greater GH response to maximal versus submaximal exercise suggests a role for adrenergic modulation of GHRH during exercise. However, the failure of PYR to restore the responses of the old to those of the young suggests that increased SRIH tone does not completely explain the age difference in GH secretion during exercise.