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Eur J Appl Physiol (1998) 77: 170175

Springer-Verlag 1998

ORIGINAL ARTICLE

Philip D. Chilibeck Aaron W. Calder Digby G. Sale Colin E. Webber

A comparison of strength and muscle mass increases during resistance training in young women

Accepted: 8 July 1997

Abstract Strength gains with resistance training are due to muscle hypertrophy and nervous system adaptations. The contribution of either factor may be related to the complexity of the exercise task used during training. The purpose of this investigation was to measure the degree to which muscle hypertrophy contributes to gains in strength during exercises of varying complexity. Nineteen young women resistance trained twice a week for 20 weeks, performing exercises designed to provide wholebody training. The lean mass of the trunk, legs and arms was measured by dual energy x-ray absorptiometry and compared to strength gains (measured as the 1-repetition maximum) in bench press, leg press and arm curl exercises, pre-, mid- (10 weeks) and post-training. No changes were found in a control group of ten women. For the exercise group, increases in bench press, leg press and arm curl strength were signicant from pre- to mid-, and from mid- to post-training (P < 0.05). In contrast, increases in the lean mass of the body segments used in these exercises followed a dierent pattern. Increases in the lean mass of the arms were signicant from pre- to mid-training, while increases in the lean mass of the trunk and legs were delayed and signicant from mid- to post-training only (P < 0.05). It is concluded that a more prolonged neural adaptation related to the more complex bench and leg press movements may have delayed hypertrophy in the trunk and legs. With the simpler arm curl exercise, early gains in

strength were accompanied by muscle hypertrophy and, presumably, a faster neural adaptation. Key words Strength Females Hypertrophy Neural adaptation

Introduction
It is well known that the strength of a muscle is proportional to its cross-sectional area (CSA; Sale et al. 1987). However, many resistance training studies have shown poor relationships between gains in strength and muscle hypertrophy. Rapid, early gains in strength are often accompanied by little or no hypertrophy (Wilmore 1974; Jones and Rutherford 1987; Cureton et al. 1988; Davies et al. 1988, Narici et al. 1989; Staron et al. 1989; Ishida et al. 1990). Early gains in strength may be due to adaptations within the nervous system such as increased motor neurone activation and motor unit synchronization (Sale 1988). Various measurement techniques have been employed to provide evidence that motor neurone activation is increased with resistance training. This evidence includes increases in integrated electromyographic activity (EMG. Moritani and deVries 1979; Hakkinen and Komi 1983; Haikinen et al. 1985; Higbie et al. 1996), reex potentiation (Sale et al. 1983a, 1983b) and maximal voluntary contraction (MVC) to maximal twitch torque ratio (Ishida et al. 1990). Motor unit synchronization has also been shown to be enhanced with resistance training, as measured by EMG (Milner-Brown et al. 1975). These neural adaptations appear to occur before muscle hypertrophy and may be necessary before hypertrophy is seen with resistance training (Sale 1988). Complex resistance exercises, such as those involving movement at more than one joint (i.e. the bench press or leg press), may involve a longer initial neural adaptation compared with simpler single-joint exercises, and this may result in delayed hypertrophy. Rutherford and Jones (1986) showed that with increasing complexity of

P.D. Chilibeck A.W. Calder D.G. Sale Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada, L8S 4K1 C.E. Webber Department of Nuclear Medicine, McMaster University, Hamilton, Ontario, Canada, L8S 4K1 P.D. Chilibeck (8) College of Physical Education, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, S7N 5C2

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exercise, learning and co-ordination become the main factors contributing to gains in weight lifting performance. This suggests that muscle hypertrophy plays a small role during the early enhancement of weight lifting performance during complex exercises. In analysing the results of a study designed to examine the eects of weight training on bone mass in young women (Chilibeck et al. 1996), and the relative eectiveness of whole- versus split-body weight training routines (Calder et al. 1994), we observed a striking dierence in the pattern of increases in strength and lean mass in response to training exercises representing complex (multi-joint) versus simple (single-joint) movements. Specically, the present report compares the hypertrophy and strength adaptations to bench press and leg press exercises, representing complex exercises, and the elbow exion curl exercise, representing simple exercises. It was found that hypertrophy was delayed in the musculature serving the complex exercises. It is suggested that the delayed hypertrophy response is the result of a longer neural adaptation phase necessitated by the complexity of the training exercises.

Methods
Twenty-nine young women with minimal strength training experience served as subjects. Nineteen women were assigned to a training group and the remaining ten comprised a control group. The groups did not dier signicantly in age, height, body mass or physical activity patterns. The mean (SD) age, height and body mass of the training group were 20.2 (0.8) years, 166.2 (5.4) cm and 60.8 (7.0) kg respectively. The corresponding values for the control group were 20.2 (0.4) years, 165.8 (6.5) cm and 61.9 (7.7) kg respectively. Subjects were fully informed of the procedures and signed a consent form before the start of the study, which carried the approval of the McMaster University Ethics Committee. Resistance training exercises were performed twice a week for 20 weeks. Subjects performed the complex (dened as movement at more than one joint) exercises of the bench press (transverse shoulder exion, combined with elbow extension) and leg press (combined hip and knee extension), and the simple (dened as movement at one joint) exercise of the arm ``curl'' (elbow exion). All exercises were performed bilaterally. Two additional upper body exercises, the ``lat'' pulldown (shoulder adduction and elbow exion) and triceps (elbow) extension, and two additional lower body exercises of knee extension and knee exion were also included to ensure overall muscle balance. The upper body exercises were performed for ve sets of 610 repetitions maximum (RM), while the lower body exercises were performed for ve sets of 1012 RM. The greater number of repetitions prescribed for the lower body exercises took into account our previous observations that for a given percentage of the 1 RM, more repetitions can be performed with lower body than with upper body exercises (Sale and MacDougall 1981; Sale et al. 1990b). Based on these observations, we estimated that training weights equivalent to 7590% 1 RM would result in sets of 610 RM in upper body exercises and 1012 RM in lower body exercises. Ten of the exercise-trained subjects performed all exercises on the same day, resulting in 2 training days per week, while nine of the exercise-trained subjects performed a ``split'' routine, such that upper body exercises were performed on Monday and Thursday and lower body exercises on Tuesday and Friday of each week. A comparison of the ``whole-'' versus ``splitbody'' routines was the subject of a separate study (Calder et al. 1994). Each exercise session was supervised and the resistance, sets, and repetitions entered into training logs. The resistance used in an

exercise was increased when the upper limit of the prescribed repetition range could be achieved with good exercise ``form''. Strength in the bench press, arm curl and leg press exercises was measured as the 1 RM; that is, the heaviest weight that could be lifted only once. A standard protocol was used (Sale 1991). The lean tissue mass of the arm, leg and trunk subregions, corresponding to body segments that are dominant during the arm curl, leg press and bench press, respectively, was measured with the aid of whole-body scans obtained by dual-energy X-ray absorptiometry (DEXA) on a Hologic 1000 W DPX densitometer (Waltham, Massachusetts 02154, USA). To obtain this measurement, the subjects lay in a supine position within specic markings upon the scan table and beside a soft tissue standard, while the densitometer scanned from head to toe. Analysis of the original scans involved the dening of specic subregions of the body by the operator. A ``compare'' feature, incorporated into the Hologic software (version 5.56), allows analysis of duplicate scans by comparison to the original scan made on a subject. This provides for the identical placement of regions of interest between two scans, making duplicate scans more reproducible. All scans were performed and analysed by the same technician. The precision (reproducibility) of lean tissue measurements by the DEXA machine used in the present study was determined previously in a group of 21 young women (Chilibeck et al. 1994). The coecients of variation (CVs) for subregions were 2.0%, 2.0% and 5.7% for the trunk, legs and arms, respectively. All measurements on the training group were performed pre-, mid- (after 10 weeks) and post-training, while measurements on the control group were performed only pre- and post-training. Pre- and post-training data were analysed by a two factor (group time) analysis of variance (ANOVA) with repeated measures on one factor (time, pre/post). Pre-, mid- and posttraining measures for the training group were analysed using a repeated measures ANOVA. Tukey post-hoc tests determined signicant dierences among mean values. Signicance was accepted at P < 0.05.

Results
For the training group, strength (1 RM) increased signicantly throughout the entire program, from pre- to mid- (10 weeks) training and from mid- to post- (20 weeks) training, for the arm curl (Fig. 1a), bench press (Fig. 2a), and leg press (Fig. 3a) exercises. Unlike strength, the lean mass of the body segments increased only during specic time points. Gains in lean mass during the rst 10 weeks of training were signicant in the arms only (Fig. 1b). Gains in trunk and legs lean mass were signicant from mid- to post-training (Figs. 2b and 3b), while mid- to post-training gains in arms lean mass were smaller and not signicant (Fig. 1b). Percent changes in strength and lean mass measures are shown in Table 1. With the precision (CVs) of the DEXA measurements, our sample size of 19 in the training group was adequate to demonstrate the above treatment eects with an a level of 0.05 and a power of 0.9 (Chilibeck et al. 1994). In general, gains in lean mass correlated poorly with gains in strength. Signicant correlations were found for gains in legs lean mass versus gains in leg press strength mid- to post-training (r = 0.51, P < 0.05) and gains in trunk lean mass versus gains in bench press strength pre- to post-training (r = 0.50, P < 0.05). There were no signicant changes for any lean mass or strength measures in the control group.

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Fig. 1 A Changes in arm curl strength, and B arms lean mass throughout 20 weeks of training. Error bars indicate standard deviations. (1 RM 1-Repetition maximum, pre pre-training, mid mid-training, post post-training). * Signicantly dierent from pretraining value (P < 0.05); ** signicantly dierent from mid-training value (P < 0.05)

Fig. 2 A Changes in bench press strength, and B trunk lean mass throughout 20 weeks of training. Error bars indicate standard deviations. * Signicantly dierent from pre-training value (P < 0.05); ** signicantly dierent from mid-training value (P < 0.05)

Discussion
It has been suggested that adaptations within the nervous system, rather than muscle hypertrophy, account for increases in strength during the rst few weeks of resistance training (Sale 1988). In the present study, this seems to be true with regard to the bench and leg press exercises; since the majority of strength gains were accomplished during the rst half (10 weeks) of the training period, without signicant hypertrophy, as estimated by changes in lean mass of the trunk and legs. In contrast, with the arm curl exercise, gains in lean mass of the arms occurred relatively early, with signicant changes occurring only during the rst half of the training program. The dierences between the leg and bench press versus the arm curl exercise with respect to the pattern of changes in lean mass may be related to their level of complexity. Rutherford and Jones (1986) suggested that with a more complex exercise, learning and coordination play a dominant role early in training. This may delay hypertrophy of the muscle groups used in these exercises. They state that with complex exercises (such as the leg and bench press) that involve movement at more than one joint, xator muscles used in support of the

prime movers may have to increase in strength or improve their ability to activate and co-ordinate contractions. This results in strength improvements before signicant hypertrophy of the prime movers occurs (Rutherford and Jones 1986). This is consistent with the present results where hypertrophy appeared to be delayed in the trunk and leg regions while bench and leg press strength increased early. A review of training studies using either simple singlejoint or complex multi-joint exercises, outlined below, supports our nding that muscle hypertrophy occurs earlier when simpler exercises are performed. In females who trained with simple single-joint exercises, hypertrophy occurred early whether leg or upper body exercises were performed. Quadriceps CSA, as measured by ultrasound (Young et al. 1983) or magnetic resonance imaging (MRI; Higbie et al. 1996) increased by 5.06.6% following 510 weeks of unilateral knee extension training, and upper arm CSA, as measured by computerized tomography (CT), increased by 5.47.9% following 616 weeks of elbow exor or extensor training (Cureton et al. 1988; Davies et al. 1988). Similar degrees of early hypertrophy have been observed in males following training with single-joint exercises: Quadriceps CSA, as measured by MRI (Narici et al. 1989) or CT (Jones and Rutherford 1987), increased by

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Fig. 3 A Changes in leg press strength, and B legs lean mass throughout 20 weeks of training. Error bars indicate standard deviations. * Signicantly dierent from pre-training value (P < 0.05); ** signicantly dierent from mid-training value (P < 0.05)

58.5% following 912 weeks of unilateral knee exion training, and upper arm CSA, as measured by CT (Cureton et al. 1988; Brown et al. 1990) or MRI (McCall et al. 1996), increased 7.917.4% following 1216 weeks of elbow exion or extension training. In contrast to the above training studies employing simpler exercises, training programs using complex exercises have resulted in little or no muscle hypertrophy early in training. Females who trained using the mainly multi-joint exercises of squats and leg press had signicant changes in lower extremity strength by 816 weeks, but no change in thigh girth or CSA (Cureton et al. 1988; Staron et al. 1989). Studies of males who trained using mainly squat or leg press exercises have, similarly,
Table 1 Percent increases in strength and lean mass measures with training Arm curl strength Arms lean mass Bench press strength Trunk lean mass Leg press strength Legs lean mass

resulted in signicant gains in strength, but little hypertrophy after 716 weeks of training when quadriceps CSA was measured by ultrasound (Dons et al. 1979) or CT (Cureton et al. 1988; Brown et al. 1990), or when muscle bre size was measured from biopsy samples (Hakkinen and Komi 1983). Thus, it seems that muscle hypertrophy is delayed when complex exercises are used for training. This may be due to a more prolonged neural adaptation compared to simpler exercises. Similar to our ndings, most of the above training studies have demonstrated poor correlations between muscle mass and strength gains, even for simpler exercises. This suggests that neural mechanisms always play a role in strength gains early in training. A longer neural adaptation when training with complex exercises may involve several aspects of the nervous system. Changes in maximal muscle activation levels with training may occur at dierent rates with complex versus simple exercises. During simple exercises, motor unit activation, as determined by the interpolated-twitch technique, is close to 100% in the untrained state (Vandervoort and McComas 1986; Brown et al. 1990; Sale et al. 1992) and changes little with training (Brown et al. 1990; Sale et al. 1992). Determination of motor unit activation during complex exercises would be technically dicult, but it is possible that when compared to simple exercises, activation is not as complete and an increase in this parameter would require longer training periods. Longer training periods for full activation may be required because of higher motor unit numbers and innervation ratios (muscle bres per motor unit) in the muscle groups involved in complex exercises. The muscle groups used in the complex leg press exercise (vastus lateralis and gastrocnemius) have a larger number of motor units and a higher innervation ratio compared to those used in the simple arm curl exercise (biceps brachii, Feinstein et al. 1955; Galea et al. 1991). To our knowledge there are no data on the muscle groups used in the bench press exercise. If training with complex exercises involves a longer period before full neural activation is realized, then any eects that neurotrophic factors may have on muscle characteristics (i.e. hypertrophy, Markelonis and Oh 1979; Thesle et al. 1990) may be delayed. The results of the present study only allow speculation on the possible causes of delayed hypertrophy when training with complex exercises. Further research is required
Pre- to mid-training (010 weeks) 50.5%* 7.5%* 22.3%* 0.5% 12.6%* 1.4% Mid- to post-training (1020 weeks) 15.0%* 2.3% 8.4%* 2.7%* 7.5%* 2.0%*

* Percent increase is signicant (P<0.05)

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before conclusions can be drawn as to the characteristics of neural adaptations and their eect on rates of muscle hypertrophy with dierent exercise training regimens. One limitation to the present study was the use of other exercises that trained the same musculature as the bench press, leg press and arm curl. These additional exercises were used in a study of the eects of wholeversus split-body weight training routines (Calder et al. 1994). The ``lat'' pulldown exercise involves the elbow exors and the sternal portion of the pectoralis major, so it involves muscles used in both the arm curl and bench press. Its inclusion, therefore, is likely to have had a similar eect on both the arm curl and bench press exercises, minimally eecting the comparison between these two exercises. The addition of knee extension and knee exion exercises may have had an eect on the musculature trained by the leg press exercise. It could be argued that the leg press involves the musculature both above and below the knee, which was measured as the total leg lean tissue mass in the present study, whereas the knee curl and extension involved only the musculature above the knee. If the knee extension and curl exercises did have a substantial eect on the total leg lean tissue measures, this indicates that even with simple exercises, hypertrophy is more dicult to achieve in leg versus upper body muscles. This is consistent with data showing that bodybuilders and powerlifters exceed untrained subjects to a greater extent in upper rather than lower limb strength and muscle size (Sale and MacDougall 1984). The lesser responsiveness of the legs to training may reect their greater initial state of training because of their role in posture and locomotion. It could be argued that our strength measures of 1 RM do not represent real strength measures such as those obtained isometrically or isokinetically. However, this measure is justied in that increases in strength are not only specic to the muscles involved in training, but also to the movement patterns used during training (Sale and MacDougall 1981). We have shown previously that muscle hypertrophy occurs in response to weight training with no corresponding increases in isometric MVC or twitch torque (Sale et al. 1992). Others have also shown that muscle hypertrophy occurs without increased strength when measured in a type of muscle action not used in training (Higbie et al. 1996). These specic training responses add further to the neural hypothesis of training adaptations with respect to movement patterns. If we had used male subjects (as opposed to the females used in the present study) with a greater potential for hypertrophy, dierent patterns of muscle mass gains in response to a similar weight training program may have been observed. A female population was used in the present study because, in addition to muscle mass measures, we were interested in determining the eectiveness of the weight training program on bone mass (Chilibeck et al. 1996), as this has been recommended as a measure protecting against the development of osteoporosis in this population (Chilibeck et al. 1995). With

the short duration of training (20 weeks) used in the present study, however, the use of female subjects might not have had a limiting eect on the amount of hypertrophy possible. In a recent study we demonstrated that the absolute hypertrophy that occurs in response to a training program of this duration is similar in female and male individuals (O'Hagan et al. 1995). Longer durations of strength training may be necessary before sex dierences, with respect to hypertrophy, are observed. Therefore, the use of female, as opposed to male subjects, in the short-duration program of the present study, may not have aected the amount of hypertrophy observed. A second factor that may have limited the amount of hypertrophy possible was the training volume used. It is recognized that resistance training programs, with exercises performed three to four times per week (as opposed to the twice per week training of the present study), are optimal for producing muscle hypertrophy. However, we have shown previously that the training volume used in the present study produces a substantial muscle hypertrophy (Sale et al. 1990a). This training volume therefore seems to be adequate for studying the rates of muscle hypertrophy that occur with strength training. In summary, our results indicate that training with complex exercises (bench and leg press) causes delayed muscle hypertrophy when compared to a less complex exercise (arm curl). This may be due to a prolonged neural adaptation when training with complex exercises.
Acknowledgements Chris Gordon, John Moroz, and Douglas Oleksuik provided technical assistance. The study was supported by Sport Canada and the Natural Sciences and Engineering Research Council of Canada.

References
Brown AB, McCartney N, Sale DG (1990) Positive adaptations to weight-lifting training in the elderly. J Appl Physiol 69:1725 1733 Calder AW, Chilibeck PD, Webber CE, Sale DG (1994) Comparison of whole and split weight training routines in young women. Can J Appl Physiol 19:185199 Chilibeck P, Calder A, Sale DG, Webber C (1994) Reproducibility of dual-energy x-ray absorptiometry. Can Assoc Radiol J 45:297302 Chilibeck PD, Sale DG, Webber CE (1995) Exercise and bone mineral density. Sports Med 19:103122 Chilibeck PD, Calder A, Sale DG, Webber CE (1996) Twenty weeks of weight training increases lean tissue mass but not bone mineral mass or density in healthy, active young women. Can J Physiol Pharmacol 74:11801185 Cureton KJ, Collins MA, Hill DW, McElhannon FM (1988) Muscle hypertrophy in men and women. Med Sci Sports Exerc 20:338344 Davies J, Parker DF, Rutherford OM, Jones DA (1988) Changes in strength and cross sectional area of the elbow exors as a result of isometric strength training. Eur J Appl Physiol 57:667670 Dons B, Booerup K, Cone-Petersen F, Hancke S (1979) The eect of weight-lifting exercise related to muscle bre composition and muscle cross-section area in humans. Eur J Appl Physiol 40:95106

175 Feinstein B, Lindegard B, Nyman E, Wohlfart G (1955) Morphologic studies of motor units in normal human muscles. Acta Anat (Basel) 23:127142 Galea V, De Bruin H, Cavasin R, McComas AJ (1991) The numbers and relative sizes of motor units estimated by computer. Muscle Nerve 14:11231130 Hakkinen K, Komi P (1983) Electromyographic changes during strength training and detraining. Med Sci Sports Exerc 15:455 460 Hakkinen K, Allen M, Komi PV (1985) Changes in isometric force and relaxation-time, electromyographic and muscle bre characteristics of human skeletal muscle during strength training and detraining. Acta Physiol Scand 125:573585 Higbie EJ, Cureton KJ, Warren GL, Prior BM (1996) Eects of concentric and eccentric training on muscle strength, crosssectional area, and neural activation. J Appl Physiol 81:2173 2181 Ishida K, Moritani T, Itoh K (1990) Changes in voluntary and electrically induced contractions during strength training and detraining. Eur J Appl Physiol 60:244248 Jones DA, Rutherford OM (1987) Human muscle strength training: the eects of three dierent regimes and the nature of the resultant changes. J Physiol (Lond) 391:111 Markelonis GJ, Oh TH (1979) A sciatic nerve protein has a trophic eect on development and maintenance of skeletal muscle cells in culture. Proc Natl Acad Sci 76:24702474 McCall GE, Byrnes WC, Dickinson A, Pattany PM, Fleck SJ (1996) Muscle bre hypertrophy, hyperplasia, and capillary density in college men after resistance training. J Appl Physiol 81:20042012 Milner-Brown HS, Stein RB, Lee RG (1975) Synchronization of human motor units: possible roles of exercise and supraspinal reexes. Electroencephalog Clin Neurophysiol 38:245254 Moritani T, DeVries HA (1979) Neural factors versus hypertrophy in the time course of muscle strength gain. Am J Phys Med 58:115130 Narici MV, Roi GS, Landoni L, Minetti AE, Cerretelli P (1989) Changes in force, cross-sectional area and neural activation during strength training and detraining of the human quadriceps. Eur J Appl Physiol 59:310319 O'Hagan FT, Sale DG, MacDougall JD, Garner SH (1995) Responses to resistance training in young women and men. Int J Sports Med 16:314321 Rutherford OM, Jones DA (1986) The role of learning and coordination in strength training. Eur J Appl Physiol 55:100105 Sale DG (1988) Neural adaptation to resistance training. Med Sci Sports Exerc Suppl 20:S135S145 Sale DG (1991) Testing strength and power. In: MacDougall JD, Wenger HA, Green HJ (eds) Physiological testing of the elite athlete. Human Kinetics, Champaign, Illinois pp 21106 Sale DG, MacDougall D (1981) Specicity in strength training: a review for the coach and athlete. Can J Appl Sports Sci 6:8792 Sale DG, MacDougall JD (1984) Isokinetic strength in weighttrainers. Eur J Appl Physiol 53:128132 Sale DG, Upton ARM, McComas AJ, MacDougall JD (1983a) Neuromuscular function in weight-trainers. Exp Neurol 82:521531 Sale DG, MacDougall JD, Upton ARM, McComas AJ (1983b) Eect of strength training upon motoneuron excitability in man. Med Sci Sports Exerc 15:5762 Sale DG, MacDougall JD, Alway SE, Sutton JR (1987) Voluntary strength and muscle characteristics in untrained men and women and bodybuilders. J Appl Physiol 62:17861793 Sale DG, Jacobs I, MacDougall JD, Garner S (1990a) Comparison of two regimens of concurrent strength and endurance training. Med Sci Sports Exerc 22:348356 Sale DG, MacDougall JD, Jacobs I, Garner SH (1990b) Interaction between concurrent strength and endurance training. J Appl Physiol 68:260270 Sale DG, Martin JE, Moroz DE (1992) Hypertrophy without increased isometric strength after weight training. Eur J Appl Physiol 64:5155 Staron RS, Malicky ES, Leonardi MJ, Falkel JE, Hagerman FC, Dudley GA (1989) Muscle hypertrophy and fast bre type conversions in heavy resistance-trained women. Eur J Appl Physiol 60:7179 Thesle S, Molgo J, Tagerud S (1990) Trophic interrelations at the neuromuscular junction as revealed by the use of botulinum neurotoxins. J Physiol (Paris) 84:167173 Vandervoort AA, McComas AJ (1986) Contractile changes in opposing muscles of the human ankle joint with aging. J Appl Physiol 61:361367 Wilmore JH (1974) Alterations in strength, body composition and anthropometric measurements consequent to a 10-week weight training program. Med Sci Sports Exerc 6:133138 Young A, Stokes M, Round JM, Edwards RHT (1983) The eect of high-resistance training on the strength and cross-sectional area of the human quadriceps. Eur J Clin Invest 13:411413

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