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Quadriceps Muscle Energetics during Incremental Exercise in Children and Adults


Medicine & Science in Sports & Exercise: July 2010 - Volume 42 - Issue 7 - pp 1303-1313
doi: 10.1249/MSS.0b013e3181cabaeb
BASIC SCIENCES: Contrasting Perspectives

Purpose: This study tested the hypothesis that the muscle metabolic responses of 9- to 12-yr-old children and young adults during incremental quadriceps exercise are dependent on age and sex.

Methods: Fifteen boys, 18 girls, 8 men, and 8 women completed a quadriceps step-incremental test to exhaustion inside a magnetic resonance scanner for determination of the muscle metabolic responses using 31P-magnetic resonance spectroscopy. Quadriceps muscle mass was determined using magnetic resonance imaging scans enabling comparison of metabolic data at a normalized power output.

Results: The power output and the energetic state at the Pi/PCr and pH intracellular thresholds (IT) were independent of age and sex. The rate of change in Pi/PCr against power output after the ITPi/PCr (S2) was lower in boys (0.158 ± 0.089) and girls (0.257 ± 0.110) compared with men (0.401 ± 0.114, P < 0.001) and women (0.391 ± 0.133, P = 0.014), respectively, with sex differences present for children only (P = 0.003). Above the ITpH, S2 was more rapid in the men (−0.041 ± 0.022, P = 0.003) and girls (−0.030 ± 0.013, P = 0.011) compared with boys (−0.019 ± 0.007), with no differences between the girls and the women (−0.035 ± 0.015, P = 0.479). The increase in Pi/PCr at exhaustion was lower in boys (0.85 ± 0.38) than that in men (1.86 ± 0.65, P < 0.001) and in girls (1.78 ± 1.25) than that in women (4.97 ± 3.52, P = 0.003), with sex differences in both the child (P = 0.005) and the adult groups (P = 0.019).

Conclusions: During moderate-intensity exercise, muscle metabolism appears adult-like in 9- to 12-yr-old children, although both age- and sex-related differences in the "anaerobic" energy turnover are present during high-intensity exercise.

1Children's Health and Exercise Research Centre, School of Sport and Health Sciences, University of Exeter, Exeter, UNITED KINGDOM; 2Peninsula NIHR Clinical Research Facility, University of Exeter, Exeter, UNITED KINGDOM; and 3Cardiff School of Sport, University of Wales Institute, Cardiff, UNITED KINGDOM

Address for correspondence: Neil Armstrong, Ph.D., FACSM, Executive Suite, Northcote House, The Queen's Drive, University of Exeter, Exeter,EX4 4QJ, United Kingdom; E-mail:

Submitted for publication March 2009.

Accepted for publication November 2009.

Eriksson and Saltin (15) documented that at maximal cycling exercise, 16-yr-old boys had a 1.6- to 2-fold greater increase in muscle lactate and breakdown of muscle phosphocreatine (PCr) in the rectus femoris muscle compared with their 11-yr-old counterparts. In addition, the activity of the glycolytic rate-limiting enzyme phosphofructokinase was lower in 11-yr-old boys than that in adults. Although these data support the concept of an age-related development of anaerobic metabolism during childhood and adolescence, subsequent studies of glycolytic enzymatic activities have failed to corroborate Eriksson and Saltin's findings (9,20).

Given the ethical restrictions of using the biopsy technique with healthy minors, the noninvasive technique of 31P-magnetic resonance spectroscopy (31P-MRS) has become a useful tool for investigating developmental exercise metabolism under in vivo conditions. During incremental plantarflexion exercise, Zanconato et al. (48) reported a lower rise in inorganic phosphate (Pi)/PCr and a fall in pH in the calf muscle of 7- to 10-yr-old children compared with adults at exhaustion. This was attributable to a lower rate of change in Pi/PCr and pH against power output in children during exercise above the Pi/PCr and the pH intracellular thresholds (ITPi/PCr and ITpH), with no differences observed for sub-IT intensities (high and moderate intensity, respectively). Findings of a reduced "anaerobic" energy contribution were also reported in trained and untrained 12- to 15-yr-old boys compared with adult men during incremental quadriceps exercise (31). However, a more recent study found no significant differences in calf muscle Pi/PCr and pH between prepubertal and pubertal female swimmers after a 2-min bout of plantarflexion exercise at 140% maximal work capacity and concluded that "anaerobic" metabolism is maturity independent (36).

It is therefore unclear whether the muscle metabolic responses in young people during exercise are age and/or maturity dependent. However, such findings may be related to methodological concerns. The heterogeneity in calf muscle size between prepubertal and more mature children or adults may result in a disproportionate sampling of the gastrocnemius and soleus muscle compartments between groups, such that the soleus represents a greater portion of the 31P-MRS signal in the smaller subjects (36). It is documented that the soleus (∼80%-90% type I) and the gastrocnemius (∼50% type I and type II) muscles have markedly different fiber-type composition (24). Given the metabolic differences that exist between muscles of different fiber-type composition (34), it is plausible that previous 31P-MRS studies interrogating the calf muscle may have been biased to a lower accumulation of Pi, breakdown of PCr, and fall in pH in the child muscle. Secondly, interpretation of the muscle metabolic responses during exercise requires quantification of the recruited muscle mass to normalize power output (19). However, this has yet to be suitably addressed in 31P-MRS studies with young people, with previous studies making no attempt to normalize for muscle mass (31), using body mass as a proxy (48), or exercising each subject relative to their maximal voluntary contraction (36).

It has been documented that 10- to 11-yr-old girls exhibit slower oxygen uptake (V˙O2) kinetics and a greater V˙O2 slow component amplitude during heavy cycling exercise compared with boys (17). Because the kinetics of V˙O2 is a determinant of the muscle O2 deficit (PCr splitting and anaerobic glycolysis) and approximately 90% of the magnitude of the V˙O2 slow component is reflected in the muscle PCr response (40), one may hypothesize a greater breakdown of muscle PCr and fall in pH during high-intensity exercise in girls than boys. However, the issue of sexual dimorphism in the child's muscle phosphate and pH responses during exercise has yet to be investigated.

The purpose of the present study was to determine whether the quadriceps muscle phosphate and the pH responses during incremental exercise to exhaustion in children and adults are dependent on age and sex. The quadriceps muscle was selected for 31P-MRS interrogation to avoid concerns with using the calf muscle. This was achieved using a 6-cm surface coil, which sampled metabolic changes to a depth of approximately 3 cm over the rectus femoris muscle that displays a similar muscle fiber-type composition to the vastus muscles (24). In addition, magnetic resonance (MR) imaging scans were used to quantify muscle mass to enable power output measures obtained during exercise to be normalized using allometric modeling procedures. It was hypothesized that 1) children would be characterized by a lower anaerobic energy contribution during moderate- and high-intensity exercise, with sex differences appearing during high-intensity exercise, and 2) the metabolic IT will occur at a higher power output normalized for muscle mass in children compared with adults with no sex differences.

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Thirty-three children (15 boys and 18 girls) and 16 adults (8 men and 8 women) volunteered to take part in the current study. After a written and verbal explanation of the study's aims, risks, and procedures, all subjects and the children's parent(s)/guardian(s) provided informed consent to take part in the project, which was approved by the institutional ethics committee. We do not have a detailed analysis of the habitual physical activity patterns of the subjects in the current study, although none were involved in a formalized training program. The adults were low to moderately active, participating in one to three sessions of moderate type activity per week (i.e., cycling, running, soccer, trampoline classes, etc.), whereas the children participated in school PE lessons and local sports clubs. Both cross-sectional and longitudinal studies examining the physical activity patterns of over 1000 children from the same catchment area are available, however, showing both boys and girls to have low levels of habitual physical activity (1,2,4).

Subjects' body mass was measured using a calibrated balance beam scale (Avery, Birmingham, UK), with stature and seated height determined using a stadiometer (Holtain, Crymych, Dyfed, UK). To provide an estimation of the boys' and girls' stage of maturation, sex-specific regression algorithms were used to determine an "offset" score from the age at peak height velocity (APHV) using anthropometric measurements (33).

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Step-incremental test to exhaustion.

Each subject completed a quadriceps step-incremental test to exhaustion inside the MR scanner for determination of the muscle metabolic and pH responses during exercise. After a 2-min baseline measurement period and starting with an initial basket load of 5 N, an incremental test was undertaken whereby the basket load was increased in "steps" of 5 N·min−1 until subject exhaustion occurred. This was typically 8-12 min for the children and 12-17 min for the adults. During the test, two experienced investigators were present to provide strong verbal encouragement and to reinforce compliance with the exercise protocol. A maximal effort was accepted when, in addition to signs of extreme discomfort, the subject was unable to remain compliant with the exercise protocol either due to an inability to maintain the required exercise cadence or a truncation of the exercise movement distance.

To determine whether the child-adult differences in time to exhaustion had an influence on the peak power output and muscle metabolic responses during exercise, five adults (three men, two women), aged 24-28 yr, completed on separate days and in a randomized order an incremental test to exhaustion at two different "step" increments of 5 and 10 N·min−1. The protocol was successful in obtaining a test duration (5 N: 13.9 ± 1.3 vs 10 N: 7.5 ± 0.4 min, P < 0.001), which is similar to the observed child-adult differences in the time to exhaustion (see Results section). No significant differences were noted for the quadriceps peak power output, the muscle phosphate and pH responses at exhaustion, or the IT metabolic parameters (Table 1), suggesting that the child-adult difference in the time to exhaustion is unlikely to be a confounding factor in the current study.

Exercise was performed on a single-legged nonmagnetic quadriceps ergometer while lying prone inside an MR scanner. The right foot was fastened to a padded foot brace, which was connected to the ergometer load basket using a rope and pulley system. This provided resistance against which continuous concentric and eccentric quadriceps contractions could be performed inside the MR scanner over a distance of approximately 0.22 m. The quadriceps exercise was performed at a cadence set in unison with the magnetic pulse sequence (40 repetitions per minute). Alignment of the quadriceps muscle contractions with the pulse sequence was guided using a projected image of a vertical moving cursor set to the frequency of 40 pulses per minute. The subjects were required to follow the cursor using a second vertical cursor under voluntary control of the subject. To prevent displacement of the quadriceps volume of interest relative to the surface coil and to minimize adjacent muscles contributing to the exercise task, nylon straps were fastened over the subject's legs, hips, and lower back. Power output (W) was calculated continuously during the exercise test as previously detailed (5). All subjects were well habituated to exercising on the ergometer.

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31P-MRS measurement and quantification.

A 1.5-T whole-body MR scanner (Philips Gyroscan Intera, The Netherlands) was used to monitor the changes in quadriceps muscle energetics. A 6-cm 31P transmit/receive surface coil was fastened securely to the scanner bed, above which the subject's right quadriceps muscle was positioned midway between the hip and the knee joints. Gradient echo images were initially acquired to ensure the quadriceps muscle was positioned correctly relative to the coil. Tuning and matching of the coil were performed to maximize energy transfer between the coil and the muscle. An automatic shimming protocol using the 1H signal was undertaken within a volume that defined the quadriceps muscle to optimize the homogeneity of the local magnetic field. 31P spectra were obtained every 1.5 s, with a spectral width of 1500 Hz and 512 data points. Phase cycling using 20 phase cycles was used, and 20 measurements were performed, leading to spectra acquired every 30 s. T1 correction factors were determined during the rest phase using a pulse interval of 20 s and applied to all peak intensities.

The 31P spectra areas were quantified using a nonlinear least squares peak fitting software package (jMRUI Software, version 2.0, using the AMARES fitting algorithm (44). Spectral areas were fitted assuming prior knowledge of the following peaks: Pi, phosphodiester, PCr, α-ATP (two peaks, amplitude ratio 1:1), γ-ATP (two peaks, amplitude ratio 1:1), and β-ATP (three peaks, amplitude ratio 1:2:1). Because data documenting the resting quadriceps muscle ATP content during growth and maturation for boys and girls are unavailable, it was deemed inappropriate to apply a fixed resting muscle ATP concentration in the present study to calculate absolute phosphate concentrations. Rather, in accord with previously published pediatric studies (6,36,48), the Pi/PCr ratio was used to reflect the aerobic-anaerobic energy status of the muscle. A muscle with a greater aerobic energy transfer requires a lower change in Pi/PCr for a given increase in power output as a lower modulation in cellular PCr is required to match the rate of ATP synthesis to ATP demand (10,45). Intracellular pH was determined using the chemical shift of the Pi spectral peak relative to the PCr peak (35).

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Normalization of power output.

Each subject's quadriceps muscle mass was determined using MR imaging scans (1.5 T; Philips Gyroscan Intera). In the supine position, two repeat scan sequences, each consisting of 50 transverse plane images, were obtained from the right leg using a multislice turbo-spin-echo sequence (repetition time = 1830 ms, echo time = 15 ms, field of view = 80 mm, matrix = 2562). Slice thickness was 5 mm, and slice separation was 5 mm. Starting from the medial epicondyle and terminating at the head of the femur, the quadriceps muscles' anatomical cross-sectional area of each slice was determined by manually tracing around the relevant compartments. Quadriceps muscle volume was calculated using the sum of each anatomical cross-sectional area multiplied by 10 mm (5 mm slice thickness + 5 mm slice gap) and converted to mass assuming a muscle density of 1.043. The same investigator performed all muscle mass quantification procedures with an intraobserver typical error of 0.04 kg (∼5% coefficient of variation).

Log-linear allometric regression models were constructed to normalize the absolute power output measurements (peak power and power output at the IT) for quadriceps muscle mass. An interaction variable did not make a significant contribution to the model for all power output measures (P > 0.100), indicating that the scaling factor was appropriate for both children and adults. Power function ratios (Y/Xb) were determined to normalize the power output variables (Y) for quadriceps muscle mass (X), where b is the scaling factor (46). The bivariate relationship between log-transformed power output and muscle mass for the peak power output and power output at the ITs are presented in Figure 1.

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Step-incremental test analyses.

Resting Pi/PCr and pH responses were determined using the mean of the four 31P-MRS spectra obtained during the 2-min rest period before exercise. Peak power and changes in the muscle metabolites (Pi/PCr, PCr, and Pi) and pH were recorded at exhaustion. Using separate plots of Pi/PCr and pH versus power output, each subject's ITPi/PCr and ITpH were identified by two independent observers. The ITPi/PCr and the ITpH were defined as the power output at which a sudden and sustained breakpoint in Pi/PCr and pH from an initial slow phase occurred (32). To facilitate identification of the ITPi/PCr, the raw Pi/PCr values were log-transformed before analysis. No IT was recorded if one or both observers failed to identify an IT. When an IT was identified, separate single linear regression functions were used to quantify the rate of change in the slope preceding (S1) and after (S2) the ITPi/PCr, but only S2 for the ITpH.

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Statistical analyses.

As several outcome variables (peak power and Pi, PCr, and Pi/PCr at exhaustion) were not normally distributed, these variables were log-transformed before analyses. The mean differences in the descriptive characteristics and the muscle metabolic responses were examined using a 2 × 2 ANOVA. Follow-up means comparisons between groups were performed using independent t-tests using the false discovery rate procedure to determine an adjusted significance threshold (14). On the basis of an alpha level of 0.05 and a total of 72 means comparisons, an adjusted significance level of P = 0.032 was identified for the follow-up means comparisons. The relationship between the maturity "offset" score and the measures of muscle metabolism in children were analyzed using linear regression. All results are presented as mean ± SD. Rejection of the null hypothesis was accepted at an alpha level of 0.05.

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Table 2 displays the descriptive characteristics for the subjects in the current study. The boys (−2.7 ± 0.9 yr, range = −1.3 to −4.1) had a significantly higher "offset" score from the APHV than the girls (−1.3 ± 0.8, range = 0.2 to −2.5, P < 0.001) and were considered to range between early to midpuberty.

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Step-incremental test responses at rest and exhaustion.

An example profile of the dynamic changes in Pi/PCr, pH, PCr, and Pi against power output for a typical child and an adult subject is displayed in Figure 2. Table 3 presents the subjects' exercise performance and muscle metabolic and pH responses during an incremental test to exhaustion.

Resting Pi/PCr was significantly higher in the boys than men (0.17 ± 0.06 vs 0.12 ± 0.02, P = 0.020) and girls than women (0.17 ± 0.06 vs 0.12 ± 0.02, P = 0.013) but similar between the sexes for children (P = 0.964) and adults (P = 0.491). For resting pH, no differences were observed between boys and men (7.08 ± 0.04 vs 7.07 ± 0.02, P = 0.552), but girls had a significantly higher resting pH than women (7.09 ± 0.04 vs 7.05 ± 0.03, P = 0.011). No sex differences were present within the child (P = 0.638) or adult (P = 0.048) groups for pH at rest.

Time to exhaustion and absolute peak power were both significantly lower in the boys and girls compared with the men and women, respectively (P < 0.01). Within the adult group, men had a significantly higher time to exhaustion (P < 0.001) and absolute peak power (P = 0.004) than women. No sex differences were present in children for absolute peak power (P = 0.373) or time to exhaustion (P = 0.649). The log-linear allometric model revealed a significant relationship between absolute peak power and quadriceps muscle mass (R2 = 0.605, P < 0.001, b = 0.52, CI = 0.27-0.77). When absolute peak power was normalized for quadriceps muscle mass using the power function ratio (W·kg−0.52), no age- or sex-related differences were observed for the children or adult groups (P > 0.500).

The increase in muscle Pi and decrease in muscle PCr from baseline levels during exercise were found to be dependent on age and sex (Table 3). Exercise resulted in a marked increase in muscle Pi/PCr from rest, attaining significantly higher levels in men compared with boys (P < 0.001) and women compared with girls (P = 0.003) at exhaustion. Within the child group, girls had a significantly higher Pi/PCr at exhaustion compared with boys (P = 0.005), and in adults, women had a significantly higher Pi/PCr at exhaustion compared with men (P = 0.019). At exhaustion, the change in pH from rest was comparable between the girls and the women (P = 0.820) and between the boys and the men (P = 0.049). No sex differences in end-exercise pH were found in the child (P = 0.105) or adult (P = 0.886) muscle.

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Muscle IT.

An ITPi/PCr was identified for all subjects, while an ITpH was located in 13 boys (87%), 13 girls (72%), 7 men (88%), and 7 women (88%). For the subjects who displayed both an ITPi/PCr and an ITpH, the transition points occurred at a similar power output (10.6 ± 3.5 vs 10.5 ± 3.2 W) and were highly correlated (R2 = 0.86, P < 0.001). The ITPi/PCr and the ITpH parameters of muscle metabolism are presented in Table 4.

The absolute power output at the ITPi/PCr was significantly higher in men compared with boys (P < 0.001), women compared with girls (P = 0.006), and men compared with women (P < 0.001). No sex difference in the absolute power output at the ITPi/PCr was present in the child group (P = 0.639). The log-linear allometric model identified a significant linear relationship between power output at the ITPi/PCr and quadriceps muscle mass (R2 = 0.687, P < 0.001, b = 0.71, CI = 0.47-0.95). Using the derived power function ratio to normalize power output at the ITPi/PCr for muscle mass (W·kg−0.71), no age- or sex-related differences were identified between the children and the adults (P > 0.100). The increase in Pi/PCr at the ITPi/PCr was comparable between the boys and the men (P = 0.529), between the girls and the women (P = 0.963), and between the boys and the girls (P = 0.074). Women had a significantly higher Pi/PCr at the ITPi/PCr compared with men (P = 0.026). No age- or sex-related differences were found for the ITPi/PCr expressed as a percentage of peak power (P > 0.069). The slope parameters describing the relationship between Pi/PCr against normalized power output before (S1) and after (S2) the ITPi/PCr are shown in Figure 3. S1 was not significantly different between the boys and the men (0.090 ± 0.029 vs 0.119 ± 0.036, P = 0.047), between the girls and the women (0.117 ± 0.033 vs 0.143 ± 0.035, P = 0.088), and between the men and the women (P = 0.199). However, S1 was significantly higher in the girls compared with boys (P = 0.016). Above the ITPi/PC, S2 was significantly smaller in boys compared with men (0.158 ± 0.059 vs 0.401 ± 0.114, P < 0.001) and in girls compared with women (0.257 ± 0.110 vs 0.391 ± 0.133, P = 0.014). S2 was significantly lower in boys than girls (P = 0.003) but was similar between the men and the women (P = 0.878).

The absolute power output at the ITpH was significantly lower in boys than that in men (P < 0.001), in girls than that in women (P = 0.005), and in women than that in men (P = 0.005). The ITpH absolute power was similar between boys and girls (P = 1.000). The allometric log-linear model revealed a significant relationship between absolute power output at the ITpH and quadriceps muscle mass (R2 = 0.747, P < 0.001, b = 0.57, CI = 0.35-0.80). After normalization of power for muscle mass using the computed power function ratio (W·kg−0.57), the ITpH occurred at a similar relative power output between the children and the adult groups (P > 0.300). Likewise, ITpH expressed as a percentage of peak power demonstrated no sex- or age-related differences (P > 0.150). The change in pH from rest at the ITpH was independent of age and sex (P > 0.400). The slope parameter (S2) describing the relationship between pH and normalized power output after the ITpH is illustrated in Figure 4. S2 was significantly lower in the men (−0.041 ± 0.022, P = 0.003) and girls (−0.030 ± 0.013, P = 0.011) when compared with the boys (−0.019 ± 0.007). No age- or sex-related differences were found for S2 when the women (−0.035 ± 0.015) were compared with the girls (P = 0.479) or the men (P = 0.523), respectively.

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Maturity and parameters of muscle metabolism.

The relationships between the predicted "offset" score from the APHV and the 31P-MRS measures are presented in Table 5. The muscle Pi/PCr and pH values at exhaustion and the slope parameters (S1 and S2) spanning the ITPi/PCr and the ITpH were all significantly associated with the maturity "offset" score in girls. However, in the boys only the change in Pi/PCr at the ITPi/PCr and the ITpH S2 displayed a significant relationship with maturity, which was positive rather than the negative relationship observed in girls. The association between Pi/PCr and pH at exhaustion and the "offset" from the APHV are illustrated in Figure 5.

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This study examined the muscle phosphate and pH responses in 9- to 12-yr-old children and young adults during incremental quadriceps exercise to exhaustion. The main findings are as follows: 1) the normalized power output and the cellular energetic state at the metabolic ITs were similar in children and adults and between sexes; 2) during quadriceps exercise above the ITPi/PCr, adults displayed a greater Pi/PCr S2 compared with children, which was also the case for the females compared with the males in the child group only. However, at exhaustion, both age- and sex-related differences in Pi/PCr were noted; 3) during quadriceps exercise above the ITpH, the change in pH against normalized power output was lower in the boys compared with the men and the girls, although no differences were present between the girls and the women; and 4) muscle pH at exhaustion was independent of age and sex. These results therefore demonstrate an age- and sex-related modulation of muscle metabolism during quadriceps exercise above but not below the IT (high and moderate intensity exercise, respectively), such that the "anaerobic" energy contribution for a given increase in normalized power output, is higher in adults than that in 9- to 12-yr-old children and in females compared with males.

All children and adults followed a comprehensive habituation to the quadriceps ergometer and test protocol, which has been shown to result in good reliability for peak power over three repeat exercise tests to exhaustion (5). In addition, the majority of muscle metabolic parameters used in the present study (IT and pH at exhaustion) show good to excellent reliability in children (5) and are comparable with adult data (32,38). However, the Pi/PCr exhaustion and the S2 variables have poor within-subject reliability, which may mask the detection of experimental differences between mean scores. However, despite the presence of large SD scores for the Pi/PCr variables in the current study, we have demonstrated significant age- and sex-related differences in the muscle Pi/PCr dynamics, which strongly support a modulation of phosphate energy metabolism in young people.

In accord with previous 31P-MRS studies using an incremental protocol (32,38,48), an IT was observed for muscle Pi/PCr and pH in the child and adult response profiles, and the ITs were temporally correlated. The accelerated rise in Pi/PCr at the IT represents an imbalance between the ability of oxidative phosphorylation to satisfy the rate of ATP turnover within the myocyte, thus requiring a greater fall in muscle PCr to buffer cellular ATP. In contrast, pH reflects the overall H+ balance within the myocyte, with the IT becoming evident when the production of H+ via anaerobic glycolysis exceeds cellular buffering and removal mechanisms (41). Although the data in the current study cannot identify the mechanism(s) underlying the coupling of the metabolic IT, this inflection point occurs at a similar power output to the blood lactate threshold (29), which is typically quantified as a parameter of aerobic fitness during whole-body exercise testing. Adult studies have also shown the IT to occur at a higher power output (classical rightward shift) after exercise training (25) and to positively correlate with the activity of the mitochondrial enzyme citrate synthase (11). Thus, the ITs are considered to provide an assessment of the oxidative functioning of the muscle.

The comparable IT in the current study therefore support the notion that the muscles' oxidative function is comparable between children and adults and between sexes. This conclusion is consistent with a recent study showing the recovery kinetics of muscle PCr after moderate-intensity quadriceps exercise, which is routinely used as a valid marker of the muscles' oxidative capacity, to be strikingly similar between 9- and 10-yr-old children and young adults (6). Although in conflict with data showing children and adolescents to have a higher activity of aerobic enzyme activities than adults (9,20), these 31P-MRS-derived in vivo measures of the muscles' oxidative function are adult-like in 9- to 10-yr-old children during moderate exercise.

During exercise above the IT (i.e., high-intensity exercise), Pi/PCr S2 was significantly lower in the boys and girls compared with the men and women, respectively, indicating that a reduced anaerobic contribution (lower PCr breakdown) was required to satisfy the rate of ATP turnover within the myocyte. This was also the case for boys compared with girls. Interestingly, pH S2 was only significantly lower in the boys compared with both the men and the girls, indicating a lower perturbation to the cellular H+ balance for a given increase in normalized power output during high-intensity quadriceps exercise. Given the strong linear relationship that exists between muscle H+ and lactate accumulation during intense exercise (39), this may indicate that glycolytic flux was lower in the boys compared with the men and girls during supra IT intensities.

That age- and sex-related differences in glycolytic flux are responsible for the pH changes during high-intensity incremental exercise must, however, be interpreted in the light that cellular H+ is influenced by buffering and efflux mechanisms. For example, the men and the girls were characterized by greater splitting of muscle PCr during high-intensity exercise compared with the boys, which will result in a greater consumption of cellular H+ through the creatine kinase reaction (39). It has recently been suggested that the production of lactate in the muscle and its subsequent rate of efflux from the muscle to blood are similar between boys and men (8). The bulk removal of lactate from muscle to blood occurs under the presence of an H+ ion via the monocarboxylate cotransporter-the main mechanism for cellular H+ efflux (26). This may imply that cellular H+ efflux is similar between children and adults. Using the reasonable assumption of a greater PCr-related buffering of cellular H+ in men, the less rapid pH S2 in the boys may reflect differences in ATP flux through anaerobic glycolysis during high-intensity exercise. A recent study by Ratel et al. (37), however, found 11- to 12-yr-old boys to have a 2.8-fold higher H+ efflux rate during the recovery from 3 min of forearm exercise compared with adult men. Extrapolation of this finding to the current study is however questionable, as glycolytic ATP production rapidly falls to baseline (13) and the creatine kinase reaction favors PCr resynthesis during recovery.

It is interesting to consider the results in the current study with previous research showing no child-adult differences in the O2 cost of exercise during a cycling ramp test to exhaustion under normoxic and hypoxic conditions (42). Because children were characterized by a lower anaerobic ATP turnover compared with adults, this may infer a reduced ATP cost of contraction in children during high-intensity exercise in the current study. However, this interpretation is difficult to reconcile with data showing children to have a higher O2 cost of cycling during constant work-rate exercise above and below the lactate threshold (49). Moreover, caution is required when extrapolating data from cycling studies to the quadriceps exercise conducted in the current study because the O2 cost of exercise has been reported to be approximately 30% greater in the latter (28). However, given the possibility that child-adult differences in the ATP cost of muscle contraction may exist during incremental type exercise, specifically during high-intensity exercise, future studies should aim to estimate the total ATP cost of contraction possibly by measuring O2 consumption during the experimental protocol.

The main finding in the present study is that the age- and sex-related differences in muscle metabolism are dependent on the intensity of the exercise, with the IT representing a boundary that differentiates the child-adult and the male-female responses. These findings are strikingly similar to the 31P-MRS study conducted by Zanconato et al. (48) and may shed some light into discrepancies within the extant literature. Specifically, there is conflict within the literature as to whether the kinetics of V˙O2 at exercise onset are age dependent (16,18) or age independent (21,42). However, given the context of the present study's findings, this conclusion may be overly simplistic, as the intensity of an imposed exercise bout should be considered. Indeed, it is pertinent to note that there is conflicting evidence concerning age-related differences in the V˙O2 kinetic response during moderate exercise (3), whereas during heavy-intensity exercise, an age-related slowing of the V˙O2 kinetic response is consistently found (16,47). Furthermore, there is recent evidence showing that the kinetics of muscle PCr at exercise onset, which has been shown to mirror the kinetics of V˙O2 in children (7), is adult-like in 9- to 10-yr-old children (6). Unfortunately, we are unaware of any study examining the muscle phosphate kinetics at the onset of high-intensity exercise in young people. Nonetheless, the findings in the current article raise an important question: what is(are) the mechanism(s) underlying this exercise-intensity dependence?

During quadriceps exercise above 50% of peak power, muscle Pi is higher and muscle PCr and pH are lower while breathing hypoxic compared with normoxic and hyperoxic air (22). One possible explanation is that children are characterized by a reduced magnitude of the fall in intracellular PO2 during incremental exercise, thus requiring a lower perturbation of the cellular energetic state compared with adults (and between sexes) to satisfy the rate of ATP turnover within the muscle. Indeed, sparse data show an approximately 30% decrease in mass-specific blood flow (and presumably O2 delivery) to the vastus lateralis muscle in boys between the ages of 12 and 16 yr during submaximal and maximal cycling exercise (27), which is consistent with the hypothesis that children are able to maintain a high cellular PO2 during high-intensity exercise.

The age- and sex-related muscle metabolic differences observed in the current article are similar to the muscle phosphate and pH profiles in muscles with distinct fiber-type profiles. Mizuno et al. (34) found during incremental forearm exercise a lower increase in Pi/PCr and fall in pH to be associated with a higher expression of type I muscle fibers. Interestingly, a review of the literature supports an age-related decline in the percentage of type I muscle fibers in men but not women, between the ages of approximately 10 and 40 yr (23). It is known, at least in adults, that during moderate-intensity exercise type I muscle fibers are preferentially recruited, and both type I and type II fibers are recruited during higher exercise intensities (30). It is therefore plausible that during high-intensity exercise, children are able to achieve the required power output with a reduced requirement to recruit higher-order type II muscle fibers, possibly because of their greater proportion of oxidative type I muscle fibers. Indeed, the attenuated accumulation of the fatigue inducing metabolites (H+, Pi) during high-intensity exercise in children is indirectly consistent with this proposal.

Finally, it is important to consider the role muscle pH may play in inhibiting the maximal rate of muscle ATP synthesis during high-intensity exercise through the creatine kinase reaction (12). A recent study has shown that a fall in quadriceps muscle pH by 0.2 units reduces the maximum rate of oxidative ATP synthesis by approximately 20% (43). Consequently, the children's ability to keep muscle pH high may have enabled a greater rate of oxidative ATP flux to be maintained, thereby reducing the requirement for substrate level phosphorylation during exercise above the metabolic IT.

A commonly held notion within the pediatric literature is that anaerobic metabolism during high-intensity/exhaustive exercise is maturity dependent. In the current study, we found significant relationships between indices of anaerobic metabolism and maturity, as indicated using an "offset" score from the APHV. Interestingly, this was only consistently the case for the girls who were on average 1.4 yr closer to the APHV than the boys (−1.3 vs −2.7 yr, respectively). Against the maturity "offset" score in girls, significant negative correlations were observed for pH S2 and pH at exhaustion and positive associations for Pi/PCr S2 and Pi/PCr at exhaustion. The negative relationships for pH at exhaustion and pH S2 are interesting because these variables were independent of age in the current study. This suggests that although the more mature girls display pH dynamics that are akin to women, the pH response is likely to be attenuated in peripubertal girls. The lack of significant relationships between the Pi/PCr and pH values at exhaustion and for S2 with indices of metabolism and maturity in the current article for the boys may be a consequence of their age range (9-12 yr) not spanning the APHV, which was the case for the girls. That is, the boys were prepubertal or early pubertal in the current study.

In conclusion, this study has demonstrated that age- and sex-related differences in muscle metabolism between 9- and 12-yr-old children and adults during incremental quadriceps exercise are dependent on the intensity of the imposed exercise bout. Specifically, the metabolic ITs, indices of the muscles' oxidative capacity, are strikingly similar between children and adults and between sexes. In contrast, during high-intensity exercise above the ITs, age- and sex-related differences in the muscle phosphate and pH responses were revealed, with a lower accumulation of Pi/PCr and fall in pH for a given increase in normalized power output evident in children compared with adults. This greater "anaerobic" component was also observed in girls compared with boys during high-intensity exercise, which may be attributable to their more advanced level of maturation between the ages of 9 and 12 yr. The mechanisms accounting for these age- and sex-related differences in muscle energetics are largely unknown but may reside in altered muscle oxygenation and/or muscle fiber-type recruitment patterns during high-intensity exercise.

This project was funded by the Darlington Trust.

The authors thank the children and the staff of Wynstream primary school for commitment and participation in this project and Dr. Craig Williams for his constructive comments. The technical expertise and support of David Childs was much appreciated.

The results of the present study do not constitute endorsement by the American College of Sports Medicine.

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