Genetics of aerobic and anaerobic performances.
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Biomedical subjects
Publications and source records attributed to J A Simoneau.
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Fast-twitch tibialis anterior muscle of the rabbit was subjected to chronic low-frequency (10 Hz, 10 h/day) stimulation for different time periods up to 28 days. Total cellular activities of carnitine:palmitoyl-CoA transferase, crotonase, 3-hydroxyacyl-CoA dehydrogenase, 3-keto-acyl-CoA thiolase, citrate synthase, NADH:cytochrome c oxidoreductase, succinate: cytochrome c oxidoreductase, and cytochrome c oxidase were measured in contralateral and stimulated muscles at various times. With the exception of crotonase, which increased only 1.6-fold after 28 days of stimulation, the other enzymes increased in parallel displaying 3-fold elevated absolute activities. These results, by supporting and extending our previous findings, indicate that the expression of the enzymes of the main metabolic systems of aerobic substrate oxidation, i.e. the citric acid cycle, the fatty acid oxidation and the respiratory chain, is regulated in a coordinate manner.
The aim of this experiment was to evaluate the effect of different workloads on the relative contribution of the various energy delivery systems during a 90-s ergocycle test. Nine male subjects, 22 +/- 1 (mean +/- SD) years of age and weighing 71.4 +/- 6.8 kg, were submitted to a VO2max test, as 10-s test (0.1 kp/kg) and three 90-s tests at different loads (LO: 0.05, ME: 0.075 and HI: 0.1 kp/kg) on an ergocycle. No difference was found between peak power output during the 10-s and HI tests. No differences were observed in the total work output performed during 90 s at different workloads (between 481 and 495 J/kg) as well as in the contribution of aerobic and anaerobic pathways to total energy production. However, VO2max was reached earlier during the ME and HI tests than during the LO test. These results indicate that variation in workload did not influence the total work output and the total contribution of aerobic and anaerobic systems during maximal 90-s ergocycle performances. However, variation in workload had an impact on the relative aerobic and anaerobic contribution at various time points. It is concluded that a 90-s ergocycle test with a resistance of at least 0.1 kp/kg is required to appropriately assess maximal anaerobic power while anaerobic capacity might be measured with workloads as low as 0.05 kp/kg.
The extent of the growth changes in maximal work output during 10 s (MWO10), 30 s (MWO30), and 90 s (MWO90) of maximal repetitive knee flexions and extensions assessed on a modified Hydra-Gym machine was investigated in 84 boys and 83 girls, 9-19 yr of age. Body weight, fat mass and fat free mass by underwater weighing, and thigh volume and cross-sectional area were also determined. No difference was observed in the absolute MWO10, MWO30, and MWO90 between girls and boys at 9 and 11 yr of age. However, significant differences appeared between genders from 13 yr of age onward, anaerobic performances of the knee extensor muscles of girls representing about 75% or even less of those of boys. The analysis of variance revealed that maximal work ouput during the three knee extension tests was significantly greater in males as well as in females from 9 to 18 yr, regardless how performance was related to morphological characteristics. Performance in absolute values or expressed per unit of body weight, fat free mass, and thigh cross-sectional area for the MWO10, MWO30, and MWO90 tests were almost always significantly lower in both genders when performances of the 9-yr-old group were compared with those of the 13-yr-old group or older groups. Improvement in maximal work output during the 10-s, 30-s, or 90-s knee extension tests with age occurred mainly between 9 and 15 yr in both genders. The results of the present study show that there are gender differences in predominantly anaerobic performances during growth and reveal that increase in muscle mass does not appear to be the only factor responsible for the age-related increment in the anaerobic working capacity of the knee extensor muscles.
Biopsies from the vastus lateralis muscle of seven participants in the Swiss expedition to Mt. Everest and Lhotse in 1986 were taken before departure to and after return from high altitude, and used for measurements of maximal activities of 12 reference enzymes of anaerobic and aerobic-oxidative metabolic pathways. The results indicated that strenuous exercise at high altitude induced increases in enzyme activities of glycolysis and decreases in enzyme activities of terminal substrate oxidation (the citric acid cycle, fatty acid oxidation, ketone body utilization, respiratory chain). The decreases in enzyme activities of aerobic-oxidative metabolism were related to similar decrements in mitochondrial volume density, which suggests that the enzymic changes resulted from a loss of mitochondrial structure rather than from qualitative changes of the mitochondrial population. These changes indicated that strenuous exercise may intensify the stress of high-altitude exposure and, thus, induce an aerobic to anaerobic shift of muscle energy metabolism.
The anaerobic performance characteristics of 15 Black males of African ancestry (25 +/- 2 yr; mean +/- SD) and 17 White males of French Canadian ancestry (22 +/- 2 yr) were compared. All subjects were sedentary. Morphological characteristics and body composition were similar in both groups. They were tested for maximal force during voluntary isometric contraction of the knee extensors and for total work output during 10 s, 30 s, and 90 s of maximal and repetitive knee extensions. Results indicated no significant differences between Blacks and Whites in maximal force of the knee extensors (736 +/- 78 N vs 722 +/- 11 N, respectively) and in total work output during the 10-s (1134 +/- 246 J vs 1124 +/- 207 J) and 30-s (2735 +/- 519 J vs 2779 +/- 647 J) tests. There was a difference of about 400 J between Blacks and Whites in the total work output during the 90-s test, but this difference was not statistically significant. However, significant differences were found between Blacks and Whites in the peak power output decrement during the last 60 s of the 90-s anaerobic test. These differences in peak power output between the two groups ranged between 7 and 10 W during the last 30 s of the 90-s test. The results indicate that knee extensor muscles of sedentary Black and White males have similar anaerobic performance power and capacities. However, the results reveal that sedentary Black subjects experience a greater degree of fatigue than sedentary Whites during an anaerobic exercise lasting longer than 30 s.
Chronic stimulation of rat fast-twitch muscle increased the content of both fatty acid-binding protein (FABP) and myoglobin. The increases in FABP, which reached values close to that of cardiac muscle, exceeded those in myoglobin and those in citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities.
Transitions in the expression of the myosin light chains (LC) were investigated in fast-twitch muscles of the rat during chronic (10 h/day), low-frequency (10 Hz) stimulation. Changes were followed at the mRNA level by Northern blot analysis and in vitro translation, as well as at the protein level by electrophoresis under denaturing and nondenaturing conditions. In vivo synthesis of the light chains was assessed by measuring the incorporation of intramuscularly injected [35S]methionine. Chronic stimulation induced a transition in the isomyosin pattern with an increase of FM3, a concomitant decrease in FM1 and, after longer stimulation periods, the appearance of low concentrations of the slow isomyosin. These changes were accompanied by an elevated LC1f/LC3f ratio and increases in the amounts of both the LC1sb and, to a lesser degree, LC2s proteins. Alterations in the amounts of specific mRNAs were the same whether determined by Northern blot analysis or by in vitro translation of total RNA preparations from the same muscles. Generally, the changes in the relative concentrations of fast and slow light-chain proteins agreed with the changes detected at the mRNA level and the alterations in protein synthesis detected with the use of an in vivo labeling assay. An exception was the elevated tissue content of LC2s where no changes were detectable in the concentration of its mRNA as determined by in vitro translation or in vivo synthesis. The increase in LC2s protein may, therefore, have been due to reduced degradation. In addition, the decrease in LC3f was more pronounced at the protein level than at the mRNA level. This might indicate an increased turnover of LC3f or the existence of additional post-transcriptional regulations of LC3f expression.
Fast-twitch tibialis anterior muscle of the rat was chronically stimulated for periods of 18 days, 28 days and 56 days. Changes in the myosin light-chain (LC) pattern consisted in an increase in LC1f, concomitant with a decrease in LC3f. In contrast to previous findings in chronically stimulated fast-twitch tibialis anterior muscle of the rabbit, no substantial increases occurred in the slow myosin light-chain isoforms. In vivo labeling using [35S]methionine incorporation revealed differences in relative turnover between the fast myosin light chains. The relative turnover of the fast myosin light chains appeared to increase in normal muscle in the order LC2f less than LC1f less than LC3f. As judged from [35S]methionine incorporation, the changes in light-chain tissue content mainly resulted from altered synthesis rates. However, in the case of LC3f the decrease in protein content could not only be explained by a reduced synthesis, but, additionally, appeared to be due to enhanced degradation. Parvalbumin, which was included in the present study, was also found to decrease in the stimulated muscle. However, its decrease appeared to result primarily from reduced synthesis.
Analyses of lactate dehydrogenase (LDH) isozymes were performed in normal and chronically stimulated (10 Hz, 10 h/d) tibialis anterior (TA) muscles of the mouse, rat, guinea pig, and rabbit. The electrophoretic mobilities of the individual LDH isozymes of normal muscles revealed species-specific patterns. Stimulation up to 28 days evoked increases in the percentage of the H-subunit of LDH. The absolute increase was highest in the rabbit, intermediate in the guinea pig and rat, and lowest in the mouse. The extent of the M- to H-subunit exchange, thus, appeared to be inversely correlated with the basal aerobic-oxidative capacities of the investigated muscles. In addition, a relationship between the expression of the H-subunit of LDH and the increase in aerobic-oxidative capacity became evident from these stimulation-induced processes of metabolic adaptation.
This study compares changes in contractile properties, parvalbumin content, and Ca2+-uptake by the sarcoplasmic reticulum (SR) of low-frequency stimulated rat and rabbit tibialis anterior (TA) muscles. Time to peak tension increased 1.8-fold in 35-day stimulated rabbit TA, while no change occurred in rat TA. Isometric twitch tension increased 2-fold in rabbit TA, but was unaltered in rat TA. Parvalbumin (PA) content was more than 90% reduced in rabbit TA, but only 60% in rat TA after 35 days. At this time, PA content of the stimulated rat TA was still higher than that of normal rabbit TA. Taking into account the suggested role of PA as a cytosolic Ca2+ buffer, its decrease could lead to an impaired free Ca2+-decay with a prolonged active state and a higher tension output during a single twitch. This would explain why chronic stimulation led to an increase in isometric twitch tension in rabbit TA, but not in rat TA. The 1.6-fold rise in half-relaxation time of 35-day stimulated rat and rabbit TA most likely resulted from a 50% reduced Ca2+-uptake by the SR, due to a still unknown modification of the Ca2+-transport ATPase.
The present study was designed to assess the efficacy and reliability of a method (Anal. Biochem. 162: 156-59, 1987) of total RNA isolation from small muscle samples. The RNA content of skeletal muscles in mouse, rabbit, guinea pig, rat, and human was also investigated. Enough RNA was extractable from muscle samples as small as 25 mg in weight to provide material for the analysis of specific mRNA sequences using RNA blot hybridization with a cDNA probe for a mitochondrially encoded subunit of cytochrome-c oxidase. The RNA was free of detectable levels of protein or DNA. Gel electrophoresis and cDNA probe hybridization indicated that the RNA was relatively undegraded. Significant differences (P less than 0.05) in RNA content were found among fiber types (type I fibers greater than type II fibers) and among the soleus muscles of various species (guinea pig greater than rat = mouse greater than rabbit). Human muscle possessed the lowest RNA content (350 ng/mg) among the species investigated. The results indicate that intact RNA can be rapidly and reliably isolated from small skeletal muscle, including samples typically obtained from human muscle biopsies. This technique should permit the analysis of gene expression in muscle subject to a variety of physiological treatments.
The purpose of the present study was to describe the extent of the variation in some of the common characteristics of human skeletal muscle. A total of 418 biopsies was obtained from the vastus lateralis muscle of 270 healthy sedentary and 148 physically active individuals of both sexes. The lowest and highest proportion of type I muscle fiber observed were 15 and 85%, respectively. Coefficients of variation (CV) reached approximately 30% for the proportion of types I and IIA fibers and were two times higher for the proportion of type IIB fiber. The smallest and largest mean muscle fiber cross-sectional areas (CSA) were approximately 1,100 microns 2 and 9,500 microns 2, respectively. Mean CSA of the various fiber types exhibited CV of approximately 23%. CV reached 30% for the activity of creatine kinase, ranged between 28 and 41% for the glycolytic enzyme markers, and between 34 and 44% for the aerobic-oxidative enzyme markers. The mean proportion of type I fiber was lower in male than in female muscles, whereas the mean CSA of all fiber types was smaller in female than in male muscles. Levels of glycolytic enzyme markers were higher in male than in female skeletal muscles. However, activities of aerobic-oxidative enzyme markers were similar in males and females. These results reveal the existence of large interindividual variability and gender differences in the most common characteristics of the human skeletal muscle.
Samples were obtained in a maximum of 295 males and females from the vastus lateralis muscle and proteins fractionated by thin-layer isoelectric focusing. Muscle creatine kinase (CKM) and adenylate kinase (myokinase) (AK1M) were studied for the presence of variants. Six individuals exhibited a CKM variant described here for the first time, for a frequency of the variant gene of 1%. For AK1M, 21 individuals were heterozygotes for an inherited variant protein, an allele frequency of 3.5%. CKM (N = 5) and AK1M (N = 18) variant individuals were paired with control subjects who had the common CKM or AK1M muscle phenotype and compared for several performance indicators. There was no significant difference between the CKM and AK1M common and variant phenotypes for any of the performance measurements. However, the CKM variant subjects tended to be more effective than controls in a 90-min performance test (by about 22%) and had less percent decline over 60 s in force generation (by about 26%). In a subsequent experiment, a few variant subjects could be compared to controls in terms of response to exercise training. Although trends were observed, the CKM and AK1M variant subjects had a response to training generally comparable to that of the nonvariant individuals. While human variation in performance and trainability cannot be accounted for by the genetic polymorphism of the two kinase enzymes, the trends in the data suggest that allelic variation at these two gene loci may be of some functional significance.
The objective of this report was to compare the performance of sedentary individuals, physical education students, and athletes of various disciplines in 10 s and 90 s maximal cycle ergometer tests. The 10 s power was the highest power output in one second from the 10 s test, while capacities were defined as the total work output during the best 10 s trial and the 90 s test. ANOVA and Duncan multiple range test indicated that the mean values of the 10 S power and capacity and the 90 S capacity tests were significantly higher in sprinter than in sedentary groups. Sprinters performed significantly better than marathon runners only in the 10 s capacity and power. Bodybuilders and sedentary subjects had similar results in the 90 s capacity test. Mean performance values per kilogram of body weight in sedentary females reached about 60% of sedentary males while marathon runners, physical education students and sprinter females reached about 80% of the male performances for the three indicators. When expressed per kilogram of fat-free mass, females reached a higher proportion of the male values for all performances. These results indicate that: a) there are differences for the power and capacity measured in predominantly anaerobic tests between athletes from different disciplines and sedentary individuals, and b) gender differences exist for these anaerobic performance indicators, but they appear attenuated in trained subjects.
Phenotypes of various glycolytic enzymes were determined in muscle biopsies. The results suggest that genetic effects on maximal enzyme activities may be associated with regulatory elements of the appropriate genes.
The time courses of changes in parvalbumin (PA) content, isometric twitch tension, and half-relaxation time (1/2 RT) were studied in rabbit tibialis anterior muscle following chronic 10 Hz nerve stimulation of 1-21 days. Up to 5 days stimulation had no effect on PA content, but it induced a slight (10-15%) increase in the 1/2 RT. This change occurred together with the previously observed 50% decrease in Ca2+-uptake by the SR (Leberer et al. 1987). While prolonged stimulation produced no further decrease in the Ca2+-uptake by the SR, PA content declined after 5 days of stimulation. The reduction in PA content was accompanied by a progressive lengthening of the 1/2 RT. However, the increase in 1/2 RT was particularly pronounced after PA had fallen below 50% of its normal value. A 90% reduction in PA coincided with a 60% increase in the 1/2 RT. By this time the staircase phenomenon, normally observed in fast-twitch muscle, was completely abolished. Although the changes in PA content and 1/2 RT were not linearly related, these results suggest that PA plays an important role in the relaxation process of mammalian fast-twitch muscle.
Tibialis anterior (TA) muscle of mouse, rat, guinea pig, and rabbit was indirectly stimulated for 10 h/day at 10 Hz up to 28 days. Changes in the activity levels of hexokinase (HK), phosphofructokinase (PFK), glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), creatine kinase (CK), citrate synthase (CS), malate dehydrogenase (MDH), 3-hydroxyacyl-CoA dehydrogenase (HADH), and beta-hydroxybutyrate dehydrogenase (HBDH) were compared. Although the direction of changes in the enzyme activity pattern was in accordance with previous findings on rabbit TA, the magnitude of the responses varied markedly between the mammals under study. Mouse TA was almost unaffected. A major effect of chronic stimulation in rat, guinea pig and rabbit was an increase in enzyme activities of aerobic-oxidative metabolism. According to intrinsic differences of the muscles under study, the increases varied among the species and appeared to be inversely related to the basal levels of these enzymes in the unstimulated muscles. Conversely, glycolytic enzyme activities (PFK, GAPDH, LDH) markedly decreased in rat, guinea pig, and rabbit, and were only slightly reduced in mouse. Changes in HK and HBDH activities displayed the largest variations in the induced change between species. These results indicate species-specific patterns of metabolic adaptation to increased contractile activity.