John A. Carrithers

Single Muscle Fibre Contractile Properties in Young and Old Men and Women

The purpose of this study was to determine whether there was an age‐related decline in the isometric and isotonic contractile function of permeabilized slow (MHC I) and fast (MHC IIa) single muscle fibres. Vastus lateralis muscle fibres from six young men (YM; 25 ± 1 years), six young women (YW; 25 ± 1 years), six old men (OM; 80 ± 4 years) and six old women (OW; 78 ± 2 years) were studied at 15 °C for in vitro force‐velocity properties, peak force and contractile velocity. Peak power was 23‐28 % lower (P < 0.05) in MHC I fibres of YW compared to the other three groups. MHC IIa peak power was 25–40 % lower (P < 0.05) in OW compared to the other three groups. No difference was found in MHC I and IIa normalized peak power among any of the groups. Peak force was lower (P < 0.05) in the YW (MHC I fibres) and OW (MHC IIa fibres) compared to the other groups. Differences in peak force with ageing were negated when normalized to cell size. No age‐related differences were observed in single fibre contractile velocity of MHC I and IIa fibres. These data show that YW (MHC I) and OW (MHC IIa) have lower single fibre absolute peak power and peak force compared to men; however, these differences are negated when normalized to cell size. General muscle protein concentrations (i.e. total, sarcoplasmic and myofibrillar) from the same biopsies were lower (4–9 %, P < 0.05) in the OM and OW. However, myosin and actin concentrations were not different (P > 0.05) among the four groups. These data suggest that differences in whole muscle strength and function that are often observed with ageing appear to be regulated by quantitative rather than qualitative parameters of single muscle fibre contractile function.

β-hydroxy-β-methylbutyrate ingestion, Part I : effects on strength and fat free mass

PURPOSE The purpose of this investigation was 1) to determine whether HMB supplementation results in an increase in strength and FFM during 8 wk of resistance training and 2) determine whether a higher dose of HMB provides additional benefits. METHODS Thirty-seven, untrained, college-aged men were assigned to one of three groups: 0, 38, or 76 mg x kg(-1) x d(-1) of HMB (approximately equal to 3 and 6 g x d(-1), respectively). Resistance training consisted of 10 different exercises performed 3 d x wk(-1) for 8 wk at 80% of 1-repetition maximum (1RM). The 1RM was reevaluated every 2 wk with workloads adjusted accordingly. RESULTS No differences were observed in 1RM strength among the groups at any time. However, the 38 mg x kg (-1) x d(-1) group showed a greater increase in peak isometric torque than the 0 or 76 mg.kg(-1) x d(-1) groups (P < 0.05). The 76 mg x kg(-1) x d(-1) group had a greater increase in peak isokinetic torque than the 0 or 38 mg x kg(-1) x d(-1) groups at 2.1, -3.15, and -4.2 rad x s(-1) (P < 0.05). Plasma creatine phosphokinase (CPK) activity was greater for the 0 mg x kg(-1) x d(-1) versus the 38 or 76 mg x kg(-1) x d(-1) groups at 48 h after the initial training bout (P < 0.05). In addition, no differences were observed in body fat between the three groups. However, the 38 mg x kg(-1) x d(-1) group exhibited a greater increase in FFM (P < 0.05). CONCLUSIONS 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.

β-hydroxy-β-methylbutyrate ingestion, Part II : effects on hematology, hepatic and renal function

PURPOSE The purpose of this investigation was to examine the effects of differing amounts of beta-hydroxy-beta-methylbutyrate (HMB), 0, 36, and 76 mg x kg(-1) x d(-1), on hematology, hepatic and renal function during 8 wk of resistance training. METHODS Thirty-seven, untrained collegiate males and were randomly assigned to one of the three groups, 0, 38, or 76 mg x kg(-1) x d(-1). Resistance training consisted of 10 exercises, performed 3 d x wk(-1) for 8 wk at 80% of their 1-repetition maximum. Blood and urine was obtained before training, 48 h after the initial session, 1 wk, 2 wk, 4 wk, and at 8 wk of resistance training. Blood was analyzed for glucose, blood urea nitrogen, hemoglobin, hepatic enzymes, lipid profile, total leukocytes, and individual leukocytes. Urine was analyzed for pH, glucose, and protein excretion. RESULTS The 38 mg x kg(-1) x d(-1) group had a greater increase in basophils compared with 0 or 76 mg x kg(-1) x d(-1) groups (P < 0.05). No difference occurred in any other blood and urine measurements. CONCLUSION These data indicate that 8 wk of HMB supplementation (< or = 76 mg x kg(-1) x d(-1)) during resistance training had no adverse affects on hepatic enzyme function, lipid profile, renal function, or the immune system.

Influence of age and resistance exercise on human skeletal muscle proteolysis: a microdialysis approach

We combined the interstitial sampling method of microdialysis with the natural tracer qualities (i.e. non‐recyclability) of the amino acid 3‐methylhistidine (3MH) to uniquely study in vivo degradation of the two most abundant skeletal muscle proteins, myosin and actin. Interstitial 3MH concentration was measured before and for 24 h following a single bout of resistance exercise in eight young (27 ± 2 years) and eight old (75 ± 4 years) men. The exercise bout consisted of four exercises (3 sets of 8 repetitions at 80% one‐repetition maximum (1RM) per exercise) emphasizing the quadriceps. Interstitial 3MH concentration was calculated using the internal reference method from microdialysate samples that were obtained from two microdialysis probes placed in the vastus lateralis. Resting interstitial 3MH concentration was 44% higher (P < 0.05) in the old (6.16 ± 0.56 nmol ml−1) as compared with the young (4.28 ± 0.27 nmol ml−1). Interstitial 3MH was not different (P > 0.05) from preexercise at any time point within the 24 h following exercise in both the young and the old. Leg arteriovenous exchange measurements in a separate group of young subjects also showed no increase in 3MH release during the 4 h following a resistance exercise bout compared with a non‐exercised control leg (control leg: –28 ± 6, exercise leg: –28 ± 11 nmol min−1). These results suggest that myosin and actin proteolysis are not increased in the first 24 h following a standard bout of resistance exercise, and this response is not altered with ageing. The higher interstitial 3MH concentration in the old suggests an increased proteolysis of the two main contractile proteins in the rested and fasted state, which is consistent with a decrease in muscle mass with ageing. Microdialysis is an appropriate methodology for use in ageing individuals and is compatible with high‐intensity resistance exercise.

No difference in the skeletal muscle angiogenic response to aerobic exercise training between young and aged men

Ischaemia‐induced skeletal muscle angiogenesis is impaired in aged compared with young mice. In humans, vascular endothelial growth factor (VEGF) mRNA and protein following an acute exercise bout are lower in aged compared with young untrained men. We hypothesized that exercise‐induced skeletal muscle angiogenesis would be attenuated in aged compared with young men. In eight aged (mean age: 64 years) and six young (mean age: 25 years) sedentary men, muscle biopsies were obtained from the vastus lateralis prior to (Pre), after 1 week and after 8 weeks of an aerobic exercise training program for the measurement of capillarization and VEGF mRNA. Dialysate VEGF protein collected from the muscle interstitial space was measured at rest and during submaximal exercise at Pre, 1 week and 8 weeks. Exercise training increased capillary contacts (CC) and capillary‐to‐fibre perimeter exchange index (CFPE) of type I and IIA fibres similarly in young and aged. The CC of type IIA and IIB fibres was lower in aged compared with young independent of training status. Exercise‐induced interstitial VEGF protein was lower in aged compared with young independent of training status. In untrained, greater exercise‐induced interstitial VEGF protein during exercise was associated with greater type I, IIA and IIB CC. Exercise training increased VEGF mRNA similarly in young and aged. These results demonstrate that the angiogenic response to aerobic exercise training is not altered during the ageing process in humans. In addition, muscular activity‐associated increases in interstitial VEGF protein may play an important role in the maintenance of skeletal muscle capillarization across the life span.

No difference in the skeletal muscle angiogenic response

Ischaemia‐induced skeletal muscle angiogenesis is impaired in aged compared with young mice. In humans, vascular endothelial growth factor (VEGF) mRNA and protein following an acute exercise bout are lower in aged compared with young untrained men. We hypothesized that exercise‐induced skeletal muscle angiogenesis would be attenuated in aged compared with young men. In eight aged (mean age: 64 years) and six young (mean age: 25 years) sedentary men, muscle biopsies were obtained from the vastus lateralis prior to (Pre), after 1 week and after 8 weeks of an aerobic exercise training program for the measurement of capillarization and VEGF mRNA. Dialysate VEGF protein collected from the muscle interstitial space was measured at rest and during submaximal exercise at Pre, 1 week and 8 weeks. Exercise training increased capillary contacts (CC) and capillary‐to‐fibre perimeter exchange index (CFPE) of type I and IIA fibres similarly in young and aged. The CC of type IIA and IIB fibres was lower in aged compared with young independent of training status. Exercise‐induced interstitial VEGF protein was lower in aged compared with young independent of training status. In untrained, greater exercise‐induced interstitial VEGF protein during exercise was associated with greater type I, IIA and IIB CC. Exercise training increased VEGF mRNA similarly in young and aged. These results demonstrate that the angiogenic response to aerobic exercise training is not altered during the ageing process in humans. In addition, muscular activity‐associated increases in interstitial VEGF protein may play an important role in the maintenance of skeletal muscle capillarization across the life span.

Titin and nebulin content in human skeletal muscle following eccentric resistance exercise.

We measured titin and nebulin content in muscle biopsies from the vastus lateralis before and 24 h after one bout of high‐intensity eccentric knee extensor resistance exercise in seven men (26 ± 3 years). Titin and nebulin content were significantly (P < 0.05) reduced after exercise by 30 and 15%, respectively. These results suggest that the structural components of the myofibrillar apparatus are degraded following high‐intensity eccentric resistance exercise in humans. Loss of these proteins may have important implications for the mechanisms regulating the adaptive response of skeletal muscle to resistance exercise.

Contractile protein concentrations in human single muscle fibers.

The intent of this investigation was twofold:(1) to develop a convenient method for analyzing skeletal muscle protein concentrations in a large number of individual human single fibers and (2) to compare the myosin heavy chain (MHC) and actin concentrations in fibers expressing pure MHC I or MHC IIa. Individual vastus lateralis fibers were dissected from five individuals (3 M, 2 F; 24 ± 1 year) and used to determine single fiber total protein (TP) concentration and MHC distribution. Fibers expressing pure MHC I and MHC IIa were further analyzed for MHC (252 fibers; mean of 50/subject) and actin (160 fibers; mean of 32/subject) concentration relative to TP. Single fiber MHC concentration was 26 ± 4% greater (P < 0.05) in MHC IIa (364 ± 39 μg MHC/mg TP) vs. MHC I (266 ± 29 μg MHC/mg TP) fibers. No differences (P > 0.05) were noted in single fiber actin concentration (MHC I: 171 ± 17 μg actin/mg TP; MHC IIa: 165 ± 17 μg actin/mg TP). These data indicate that within the TP fraction, skeletal muscle fibers contain differing amounts of MHC, and this appears to be fiber type specific. These data and methods have implications for the study of human muscle fiber type specific alterations in various protein concentrations in response to exercise, models of unloading, and aging.

Aging and the Skeletal Muscle Angiogenic Response to Exercise in Women

Whether aging lowers skeletal muscle basal capillarization and angiogenesis remains controversial. To investigate the effects of aging on skeletal muscle capillarization, eight young (YW) and eight aged (AW) women completed 8 weeks of exercise training. The response and relationships of muscle capillarization, interstitial vascular endothelial growth factor (VEGF), and microvascular blood flow to aerobic exercise training were investigated. Vastus lateralis biopsies were obtained before and after exercise training for the measurement of capillarization. Muscle interstitial VEGF protein and microvascular blood flow were measured at rest and during submaximal exercise at PRE, 1-WK, and 8-WKS by microdialysis. Exercise training increased (20%-25%) capillary contacts of type I, IIA, and IIB fibers in YW and AW. Interstitial VEGF protein was higher in AW than YW at rest and was higher in YW than AW during exercise independent of training status. Differences in muscle capillarization were not explained by secreted VEGF nor were differences in VEGF explained by microvascular blood flow. These results confirm that aging (57-76 years age range) does not impair the muscle angiogenic response to exercise training, although sex differences may exist in similarly trained women and men.

Influence of creatine monohydrate ingestion on muscle metabolites and intense exercise capacity in individuals with multiple sclerosis11No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated.

OBJECTIVE To evaluate the effectiveness of ingesting creatine monohydrate in elevating intramuscular creatine stores and improving exercise capacity in individuals with multiple sclerosis (MS). DESIGN Randomized, double-blind, placebo-controlled, pre-posttrial. SETTING A university-based exercise physiology laboratory. PARTICIPANTS Sixteen individuals with relapsing-remitting MS (median Expanded Disability Status Scale score, 4.75; range, 1.5-6.0). INTERVENTION Eight individuals with MS were randomized to the creatine group (20g/d of creatine monohydrate for 5d), and 8 others were randomized to the placebo group. Needle biopsies were performed on the vastus lateralis at rest before and after treatment. Subjects performed 3 bouts of 30 maximal knee extensions and flexions at 180 degrees /s with 1 minute of recovery between bouts before and after treatment. MAIN OUTCOME MEASURES Intramuscular total creatine, phosphocreatine, free creatine, and total work output. RESULTS Creatine ingestion did not significantly elevate intramuscular total creatine, phosphocreatine, or free creatine or improve total work production. CONCLUSION Creatine ingestion had no significant effect on muscle creatine stores or high-intensity exercise capacity in individuals with MS.