Journal of Gerontology:
2000, Vol. 55A, No. 11, M641–M648
MEDICAL SCIENCESCopyright 2000 by The Gerontological Society of America
Effects of Age, Gender, and Myostatin Genotype
on the Hypertrophic Response to Heavy
Resistance Strength Training
Frederick M. Ivey,
Stephen M. Roth,
Diane E. Hurlbut,
E. Jeffrey Metter,
Robert E. Ferrell,
Brian L. Tracy,
and Ben F. Hurley
Jeffrey T. Lemmer,
James L. Fozard,
Gregory F. Martel,
Eliot L. Siegel,
Jerome L. Fleg,
Department of Kinesiology, College of Health and Human Performance, University of Maryland College Park.
Division of Gerontology, University of Maryland, School of Medicine, Baltimore.
Department of Human Genetics, University of Pittsburgh, Pennsylvania.
Department of Kinesiology and Applied Physiology, University of Colorado, Boulder.
Jean Mayer USDA HNRC on Aging at Tufts University, Boston, Massachusetts.
Department of Physical Therapy, University of Maryland Eastern Shore, Princess Anne.
Department of Radiology, Baltimore VA Medical Center, Maryland.
National Institute on Aging, Gerontology Research Center, Baltimore, Maryland.
Florida Geriatric Research Program, Morton Plant Mease Health Care, Clearwater.
same relative training stimulus, it is unknown whether older individuals can increase their muscle mass as much as
young individuals and whether women can increase as much as men in response to strength training (ST). In addition,
little is known about whether the hypertrophic response to ST is affected by myostatin genotype, a candidate gene for
Because of the scarcity of data available from direct comparisons of age and gender groups using the
years), 12 older men (69
lateral quadriceps muscle volume measurements performed using magnetic resonance imaging (MRI) before and after
ST and detraining. Training consisted of knee extension exercises of the dominant leg three times per week for 9 weeks.
The contralateral limb was left untrained throughout the ST program. Following the unilateral training period, the sub-
jects underwent 31 weeks of detraining during which no regular exercise was performed. Myostatin genotype was deter-
mined in a subgroup of 32 subjects, of which five female subjects were carriers of a myostatin gene variant.
Eleven young men (25
3 years, range 21–29 years), 11 young women (26
3 years, range 65–75 years), and 11 older women (68
2 years, range 23–28
2 years, range 65–73 years) had bi-
older individuals. The gender effect remained after adjusting for baseline muscle volume. In addition, there was a signif-
icantly greater loss of absolute muscle volume after 31 weeks of detraining in men than in women (151
.05), but no significant difference between young and older individuals. Myostatin genotype did not explain
the hypertrophic response to ST when all 32 subjects were assessed. However, when only women were analyzed, those
with the less common myostatin allele exhibited a 68% larger increase in muscle volume in response to ST (
A significantly greater absolute increase in muscle volume was observed in men than in women (204
.01), but there was no significant difference in muscle volume response to ST between young and
13 vs 88
men increased their muscle volume about twice as much in response to ST as did women and experienced larger losses
in response to detraining than women. Young men
were the only group that maintained muscle volume adaptation after
31 weeks of detraining. Although myostatin genotype may not explain the observed gender difference in the hyper-
trophic response to ST, a role for myostatin genotype may be indicated in this regard for women, but future studies are
needed with larger subject numbers in each genotype group to confirm this observation.
Aging does not affect the muscle mass response to either ST or detraining, whereas gender does, as
(1) can adversely affect activities of daily living (2) and
health status in elderly persons (3). Loss of strength and
skeletal muscle mass have been identified as among the pri-
mary risk factors for falls and impaired mobility in the very
elderly population (2,3). Strength training (ST) has been
shown to be a safe (4) and effective (4–18) intervention for
counteracting these detrimental changes. Fiatarone and col-
leagues (8), for example, demonstrated that even in very el-
derly persons, significant gains in muscle size, strength, and
in body composition that occur with aging functional mobility could be achieved through ST. Other in-
vestigators have reported the effects of moderate to heavy re-
sistance ST on the lean, fat, and mineral components in vary-
ing population subgroups, including young (10,19,20) and
older (4–6,9,10,13,15,17,20–23) women and men. However,
because of the scarcity of data available from direct compar-
isons of age and gender groups, information is lacking on
how the capacity of older individuals to alter their muscle
mass with ST compares with that of young people, and
whether women adapt differently than men at a given age.
IVEY ET AL.
Evaluating the relative usefulness of ST as an intervention
for elderly persons of both genders has important implica-
tions because of the age-associated losses in strength and
muscle mass (18) and because of the relationship between
these losses and the health and well-being of older individu-
als (24). In addition, women may be more susceptible to the
adverse consequences and disabilities associated with decre-
ments in strength and muscle mass (25) because they typi-
cally live a longer time in infirmity than men (26).
Welle and colleagues (7) compared young and older men
and women after 3 months of ST using magnetic resonance
imaging (MRI) cross-sectional areas (CSA) of the elbow
flexors and the knee flexors and extensors, and concluded
that aging reduced the hypertrophic response of muscle.
However, the low number of subjects per group (
and relatively mild training stimulus may have prevented
this study from providing definitive conclusions concerning
age or gender responsiveness to ST. The effect of ST on
neuromuscular parameters in middle-aged and older men
and women was recently studied by Hakkinen and col-
leagues (27), but no between-group comparisons of muscle
mass changes were made. To our knowledge, no direct age
or gender comparisons have been reported for muscle vol-
ume response to the cessation of an ST stimulus (detraining).
Thus, given the need to better understand whether muscle
mass adaptations to ST and detraining are age- or gender-
dependent, the primary purpose of this study was to com-
pare muscle mass responses of young and older men and
women to the same relative ST and detraining protocols.
We hypothesized that there would be no age or gender
group differences in hypertrophic response to ST.
Mutations in the myostatin gene have been shown to have
a significant impact on muscle phenotype in mice (28) and
cattle (29,30), and myostatin protein levels have recently
been related to muscle mass in humans (31). We have previ-
ously noted sequence variations in the human myostatin
(growth and differentiation factor 8) gene (32). Although a
role for myostatin genotype in affecting muscle response to
ST was not indicated in that preliminary, cross-sectional in-
vestigation (32), a significant gender difference in the fre-
quency of a common myostatin variant was detected (unpub-
lished observations). Thus, a second aim of our investigation
was to assess the possible role of myostatin genotype on mus-
cle mass response to ST. Based on our preliminary work (32),
we hypothesized that myostatin genotype might explain any
observed gender differences in hypertrophic responses to ST.
4 or 5)
Eleven young men (20–30 years), 11 young women (20–30
years), 12 older men (65–75 years), and 11 older women (65–
75 years) volunteered to participate in this 9-week unilateral
ST program. Subjects were screened by a physician who per-
formed a medical history, physical examination, and maximal
graded exercise test. All subjects were nonsmokers, free of
significant cardiovascular, metabolic, or musculoskeletal dis-
orders. Only sedentary persons who had not exercised regu-
larly (more than once every 2 weeks) during the 6 months
prior to the study were allowed to participate. Prior to partici-
pation, the purpose and procedures of the study were ex-
plained in detail, and the subjects gave their written informed
consent to participate. The procedures used in this study were
approved by the human subjects institutional review boards of
the University of Maryland, College Park, the Baltimore Vet-
erans Affairs Medical Center, the Johns Hopkins Bayview
Medical Center in Baltimore, and the University of Pittsburgh.
Muscle Volume Measurement
The thighs of both legs were scanned via MRI before and
at least 48 hours after the last training session and after 31
weeks of detraining. A Picker Edge 1.5 Tesla MRI scanner
(Picker International, Cleveland, OH) was used to obtain a
series of axial slices, extending from the superior border of
the patella to the anterior superior iliac spine and encom-
passing the entire quadriceps femoris muscle group. The
images were produced using 9-mm thick (1-mm gap) T1-
weighted axial scans, with an echo time of 14 ms and a re-
laxation time of 700 ms. Subjects were instructed not to eat
or drink anything after midnight on the night before the
scans or perform any vigorous activity prior to the scans,
which were consistently performed between 8 and 10
The scan files were stored on magnetic disk for subsequent
analysis on a personal computer. The MRI scanner calibra-
tion was checked daily and adjusted if needed. MRI accu-
racy and precision of volume determination were assessed
by repeat scanning and analysis of a lean beef phantom with
dimensions approximating the knee extensor group. Repeat
MRI volume measurements on the beef phantom yielded a
0.12% difference between measurements.
The scan files were imported into National Institute of
Health (NIH) Image version 1.61 (NIH, Bethesda, MD) for
analysis. For each axial slice, the CSA in centimeters squared
(cm ) of the quadriceps muscle group was manually outlined
as a region of interest. The quadriceps CSA was outlined in
every axial image from the superior border of the patella to a
point where the quadriceps muscle group is no longer reliably
distinguishable from the adductor and hip flexor groups. The
same number of slices proximal from the patella was mea-
sured for a particular subject, before and after training, to en-
sure within-subject measurement replication. The sartorius
muscle was not included in the CSA because it does not con-
tribute to knee extension. The same investigator, blinded to
both subject identification and training condition, performed
baseline and after training analysis. Repeat measurement by
the same investigator of 300 different cross sections from dif-
ferent areas of the muscle yielded an average coefficient of
variation of 0.78%. Intrareader variability of total quadriceps
volume assessed by repeat determination of the same set of ax-
ial scans on different days by the same investigator was 3.5%.
Muscle Volume Calculation
The CSA of each axial slice was multiplied by the dis-
tance between slices (1 cm) and summed across slices. This
value represents quadriceps muscle volume, expressed in
cubic centimeters (cm ).
The training program consisted of unilateral training of the
knee extensors of the dominant leg, three times per week, for
MUSCLE VOLUME RESPONSE TO STRENGTH TRAINING
approximately 9 weeks. Training was performed on a Keiser
K-300 air-powered knee extension machine (Keiser Sport/
Health Equipment, Fresno, CA) that allows the subject to
change the resistance easily, without interrupting the cadence
of the exercise. The untrained control leg was kept in a relaxed
position throughout the training program. This was accom-
plished by having the subject rest their leg in front of the pad
on the exercise machine and verified by constant investigator
observation during every training session for all subjects.
Prior to the regular training sessions, subjects underwent
three familiarization sessions during which they completed
a typical training sequence with little or no resistance. Sub-
jects performed a 3-minute warm-up on a bicycle ergome-
ter, followed by supervised stretching of the knee extensor
and flexor muscle groups. The training consisted of five sets
of knee extension exercise designed to include a combina-
tion of heavy resistance and high volume exercise. The first
set was considered a warm-up and consisted of 5 repetitions
at 50% of the 1-repetition maximum (1-RM) strength value.
The second set consisted of 5 repetitions at the current 5-RM
value. The 5-RM value was increased continually through-
out the training program to reflect increases in strength lev-
els. The third set consisted of 10 repetitions, with the first 4
or 5 repetitions at the current 5-RM value, in which the
resistance was lowered just enough to complete 1 or 2 more
repetitions before reaching muscular fatigue. This process
was repeated within the same exercise set and without
changing the cadence until a total of 10 repetitions were
completed. This same procedure was used in the fourth and
fifth sets, but the total number of repetitions was increased.
The fourth set consisted of 5 repetitions at the 5-RM resis-
tance, followed by 10 more repetitions for a total of 15 repe-
titions carried out in the same manner as described previ-
ously for the 10-repetition set. The fifth set consisted of 4 or
5 repetitions at the 5-RM resistance, followed by 15 more
repetitions for a total of 20 repetitions performed in the
same manner as the other sets. This procedure allowed sub-
jects to use near maximal effort on every repetition, while
maintaining a relatively high training volume. The second,
third, fourth, and fifth sets were preceded by rest periods
lasting 30, 90, 150, and 180 s, respectively.
Following completion of the unilateral ST program, sub-
jects were instructed to resume their normal lifestyle, but to
avoid any form of regular exercise for 31 weeks. During this
period, subjects were contacted monthly to ensure that they
did not participate in any form of regular exercise or make
any other lifestyle changes. Strength tests were performed at
the 15-week midpoint and again after 31 weeks of detrain-
ing. MRI scans were also taken at the end of the detraining
period. These results were compared with those obtained
before and after the unilateral training program. The com-
pliance rate for all aspects of the study was 85%.
Genomic DNA was prepared from ethylenediamine-tet-
raacetic acid anticoagulated whole blood or from cheek
swabs using standard methods (33). Subjects were genotyped
for a human myostatin exon 2 variant that is predicted to re-
sult in a lysine to arginine amino acid substitution (Lys 153
Arg) in the myostatin protein, as we reported previously (32).
Using the difference between the muscle volume change
in the trained leg and the volume change in the untrained leg
as the dependent variable, a two-factor (age and gender)
ANOVA (ANOVA) was performed to determine the pres-
ence or absence of age and gender effects. A separate
ANOVA was done using the change values from before and
after detraining to determine whether age or gender influ-
enced the response to cessation of training. The extent to
which baseline levels of muscle mass influenced the out-
comes of these comparisons was assessed by using the vol-
ume of the trained leg before training as a covariate.
Tukey’s analysis was used to identify specific differences
between the mean values shown in
simple effects tests were used when appropriate. Following
this primary analysis, 32 subjects were grouped by genotype
(with and without the arginine variant) for subsequent anal-
ysis of the role of myostatin genotype in muscle mass re-
sponse to ST, with baseline muscle volume used as a covari-
ate. Because all subjects with the arginine allele were
women, a subanalysis of myostatin genotype group effects
was performed for female subjects. Values are presented as
standard error. A two-tailed
quired for statistical significance.
Table 2. Within-cell
.05 was re-
At baseline, the men in both age groups were signifi-
cantly taller and heavier with lower percent body fat and
greater nonosseous fat-free mass (FFM) than the women
.05). There were no significant differences in age
between men and women within the young or older age
groups. Body mass, percent body fat, and total body
nonosseous FFM did not change significantly as a result of
training, except in the young and older men, who displayed
a small but significant increase in body mass after training
.05; Table 1).
Muscle volume increased significantly in the trained leg
of all four groups (
.01; Table 2). Although there was
not a significant change in muscle volume in the untrained
leg in either the young or older women, the small change
seen in the untrained limbs of both the young and older men
was significant (
Using the difference in change values between the trained
and untrained limbs as the dependent variable, age and gen-
der comparisons were made on the muscle volume re-
sponses to training
The presence of a significant age by
gender interaction with respect to muscle volume gain was
indicative of a greater disparity in the response between
young gender groups than between the older gender groups
.05; Figure 1). Tests of simple effects comparing age
groups within genders, and gender groups within ages, are
IVEY ET AL.
illustrated in Figure 1. There was not a significant differ-
ence in the muscle volume response between ages in either
gender group. However, there was a significant difference
in the muscle volume response to training between genders
in the young age group (
.01), and a difference that ap-
proached significance (
.057) between genders in the
older age group (Figure 1). When values were pooled across
genders, there was a nearly identical gain in muscle volume
between young and older subject groups (Figure 2). How-
ever, there was a significant difference of 104 cm
the pooled men’s and women’s groups observed in the mus-
cle volume response to ST, with men achieving greater
gains than the women in absolute terms (
The gender effect remained after covarying for baseline
muscle volume (
.01), indicating that the effect was not
a function of smaller baseline volumes in women.
Figure 3 shows the effects of age and gender on the mus-
cle volume response to 31 weeks of detraining. Again, the
difference in muscle volume loss between pooled age
groups (7 cm
) was not significant, whereas the mean differ-
ence in muscle volume loss between men and women (63
cm) was significant (
.01; Figure 3). Young men were
the only group to have retained a significant portion of their
ST-induced gain in muscle volume after 31 weeks of de-
.01; Figure 1). There was no significant inter-
action in the muscle volume response to detraining.
.01, Figure 2).
Based on these results, the role of myostatin genotype
was assessed in several of these subjects (
and 14 women). The less common myostatin allele was ob-
served in only five female subjects. When all subjects (men
and women) were grouped according to myostatin geno-
type, muscle volume response to ST or detraining was not
significantly different between genotype groups. When only
32; 18 men
women were compared, no significant differences in muscle
volume characteristics were noted between genotype groups
(Table 3). However, a trend was noted for a genotype effect
on the muscle volume response to ST, such that women het-
erozygous for the rare allele exhibited a 68% higher in-
crease in trained leg muscle volume with ST than women
without the variant (
.056; Table 3). This trend was
maintained when baseline muscle volume was covaried in
the analysis (
.067). Although limited, these data indi-
cate a possible role for myostatin genotype in muscle vol-
ume response to ST.
To our knowledge, this study is the first to show that age
does not attenuate the hypertrophic response to ST, when
comparing young and older individuals in the same study
using the same relative training stimulus. ST-induced mus-
cle volume changes in the older subjects were not signifi-
cantly different than in the young subjects, thus supporting
our original hypothesis that aging skeletal muscle retains
the capacity to fully adapt to an ST stimulus. However, the
finding that young men experience significantly greater in-
creases in muscle volume than young women in response to
ST did not support our hypothesis and conflicts with find-
ings of previous investigations (10,14,19,34). Our findings
that men lose significantly greater muscle volume during
detraining than women and that the detraining response is
not significantly different between age groups are also
unique. Finally, although myostatin genotype did not ex-
plain the significant gender difference noted in muscle vol-
ume response to ST, a possible genotype effect on muscle
volume response to ST was indicated in the female subjects.
The finding in the present study that age does not attenu-
ate the hypertrophic response to ST conflicts with the con-
Table 1. Physical Characteristics Before and After 9 Weeks of ST
Young Men (
11)Young Women (
11) Older Men (
12)Older Women (
Before AfterBeforeAfter BeforeAfterBefore After
Percent body fat
62.3 ? 3
30.8 ? 2
43 ? 2
28.3 ? 2
53.8 ? 1
38.8 ? 2
39.1 ? 1
23.2 ? 2
62.7 ? 3
31.1 ? 1
43.1 ? 2
28.3 ? 1
54.2 ? 1
38.1 ? 2
39.6 ? 1
Notes: Values are means ? SE. Before ? before strength training (ST); After ? after ST; FFM ? fat-free mass.
†Significantly different than before training.
Table 2. MRI Muscle Volume (cm3) Measurements Before and After Strength Training and Detraining
Trained LegControl Leg
Before TrainingAfter TrainingAfter DetrainingBefore Training After TrainingAfter Detraining
2297 ? 170
1435 ? 82
1753 ? 44
1125 ? 53
2574 ? 174†
1525 ? 85†
1955 ? 43†
1260 ? 65†
2416 ? 175†
1467 ? 54
1774 ? 43
1162 ? 57
2287 ? 161
1453 ? 78
1757 ? 43
1141 ? 53
2326 ? 165†
1458 ? 79
1791 ? 41†
1158 ? 51
2331 ? 169†
1482 ? 88
1754 ? 40
1154 ? 48
Notes: Values are means ? SE. MRI ? magnetic resonance imaging.
†Significantly different than before training.
MUSCLE VOLUME RESPONSE TO STRENGTH TRAINING
clusion of Welle and colleagues (7). Using single MRI cross
sections, they observed a relatively attenuated hypertrophic
response in elderly persons, based upon a diminished re-
sponse of the elbow flexors and knee flexors in older com-
pared with young subjects after 3 months of ST. However,
Welle and colleagues (7) reported that the knee flexor mus-
cle CSA increased only 1% and the knee extensor CSA only
6% after 3 months of ST in the older group. In comparison,
older subjects in the current study had mean relative in-
creases of between 11% and 12% in the volume of the knee
extensor group after only 9 weeks of ST. This difference
suggests that the training stimulus provided by Welle and
colleagues (7) was less intense than that in the present
study. The training protocol in the present study was de-
signed to optimize both strength and muscle mass gains in
all groups, by requiring subjects to exert a near maximal ef-
fort on every repetition, while maintaining a high volume
protocol (50 repetitions per session) for the quadriceps mus-
cle group. In addition, the differences between Welle and
colleagues (7) and the current study may have been en-
hanced by using volume measurements of the entire trained
musculature, which, to date, have not been utilized in the
context of evaluating age and gender responsiveness to ST
or detraining. The use of volume measurements is supported
by unpublished data from our lab, which show that the
change in a single mid-thigh slice across a training period
explains only 50% of the variance in volume change. How-
ever, the measurement of the change in every other slice
from the knee to the hip explained over 98% of the variance
in muscle volume change in the same subjects.
In contrast to our finding of a gender difference in the mus-
cle mass change with ST, Cureton and colleagues (19) ob-
served no differences between young men and women for ab-
solute or relative increases in elbow flexor CSA (measured
by computed tomography [CT]) with ST. However, training
volume was again described by the authors to be lower than
in the present study. O’Hagan and colleagues (10), also used
CT-measured elbow flexor CSA to observe no differences
between young men and women for the relative or absolute
hypertrophic response to heavy resistance ST. Staron and col-
leagues (34) found no significant hypertrophy of muscle fi-
bers in either young men or women after 8 weeks of quadri-
ceps ST, but there was no direct measurement of whole
muscle hypertrophy. Moreover, McCartney and colleagues
(14) observed no gender differences in muscle hypertrophy
after the first 10 months of moderate ST in older men and
women, but when an additional training period was intro-
duced, there was a trend toward a greater absolute change in
CSA for men compared with women. The important method-
ological distinction between these previous studies and the
present investigation is that these studies did not assess the
volume of the entire trained musculature as a means of mak-
ing the gender comparisons. We reported previously from our
investigation on the muscle quality changes in the older men
Figure 1. Individual group comparisons of muscle volume responses to strength training and detraining. There was no significant difference in
the training responses between ages in either gender group or in the detraining responses between ages in either gender group. *Significantly dif-
ferent from young women (training and detraining response; p ? .01). †Significantly different from older women (detraining response; p ? .05).
Values for each group represent the difference between the mean change in the trained leg and the mean change in the untrained leg.
IVEY ET AL.
and women in this study that absolute changes in muscle vol-
ume were greater in men compared with women, when the
volume of the entire trained musculature is assessed (35). An-
other limitation related to comparing the results of these stud-
ies with the present investigation is the focus on different
muscle groups, which may vary in their response to ST. Fur-
thermore, as in most training studies, it was impossible, based
on a reading of the papers alone, to evaluate the level of su-
pervision present during each of the training sessions, thus
leaving unanswered the issue of whether the ST stimulus was
consistently applied between groups.
To our knowledge, no direct comparisons of age and gender
groups have been reported during the period after ST has been
discontinued (detraining), but some information is available
on how skeletal muscle responds to detraining. Narici and col-
leagues (36) studied four male subjects (23–34 years) during
40 days of detraining following a 60-day unilateral ST pro-
gram. Upper-leg muscle CSA increased by 9% in the trained
leg during the 60 days of training. During detraining, muscle
CSA was observed to be lost at the same rate at which it was
gained, based upon MRI images taken at 20-day intervals. In
contrast, Staron and colleagues (20) studied six college-aged
women who had participated in a 20-week lower-limb ST pro-
gram during 30–32 weeks of detraining and found that some
adaptations, specifically fiber area and maximal dynamic
strength, were retained for up to 32 weeks of detraining.
Our detraining results show the presence of a gender effect,
but no age effect, in the quadriceps muscle volume lost in the
trained leg during 31 weeks of detraining. This may have been
predictable based upon the nature of the findings during the
training phase. An unexpected observation, however, was that
except for the young males, who maintained some of their
adaptation even 31 weeks after the cessation of the training
stimulus (Figure 2), all of the age and gender groups showed
no significant differences with baseline levels of muscle vol-
ume after the 31-week detraining period. Although Staron and
colleagues (20) reported that fiber diameter changes were re-
tained 30 weeks after the onset of detraining in young women,
our study is the first to show that it is possible for young men
to maintain some of the whole muscle volume changes 31
weeks after the ST stimulus has ended. This conclusion seems
to conflict with Narici and colleagues (36), who suggested that
young men lose all of their adaptation after 60 days of detrain-
ing. However, Narici and colleagues (36) studied their sub-
jects for only 40 days of detraining and thus had to speculate
based on the rate of muscle mass lost.
The young men in the present study may have been the
only group to retain any of their muscle mass increase for
31 weeks of detraining because they were also the highest
responders to ST in absolute terms (Figure 2). Therefore,
one possible interpretation of these results is that some
threshold of adaptation must be achieved in order for mus-
cle mass gains to be preserved for this long. However, the
possibility that the young men may have stayed relatively
more active during the detraining period than the other
groups cannot be ruled out.
Myostatin is a muscle growth inhibitor (28), high levels of
which have been associated with muscle wasting in HIV-
infected humans (31). Further, inactivating mutations in the
myostatin gene in mice (28) and cattle (29,30) result in a hy-
Figure 2. Age and gender comparisons of muscle volume responses to strength training. There was a significantly greater increase in muscle
volume in men than in women (*p ? .05), but no significant difference between age groups. Values for each group represent the difference be-
tween the mean change in the trained leg and the mean change in the untrained leg.
MUSCLE VOLUME RESPONSE TO STRENGTH TRAINING
permuscular phenotype. Despite this background, and consis-
tent with our group’s earlier work (32), a common Lys 153
Arg polymorphism in the human myostatin gene did not ap-
pear to explain the gender differences noted in muscle vol-
ume response to ST in these subjects. However, when the
myostatin Lys 153 Arg polymorphism’s role in muscle vol-
ume response to ST was explored in women only, a trend was
noted, indicating a possible role for the myostatin Arg allele
in explaining muscle volume response to ST. This interesting,
yet limited, finding suggests the need for further work in this
area. The results of the present investigation and other data
from our laboratory may also indicate a gender difference in
the frequency of the myostatin Lys 153 Arg variation. In the
present study, the Arg allele was observed only in female
subjects, and we have also noted a significant difference in
the frequency of the Arg allele in a larger, yet still unbal-
anced, sample (9 of 26 women vs 15 of 127 men carried this
allele; chi-squared, p ? .01; unpublished observations).
Figure 3. Age and gender comparisons of muscle volume responses to detraining. There was a significantly greater loss in muscle volume in
men than in women (*p ? .05), but no significant difference between age groups. Values for each group represent the difference between the
mean change in the trained leg and the mean change in the untrained leg.
Table 3. Muscle Volume Characteristics Before and After ST and After Detraining for Female Subjects Grouped by the Lys 153 Arg
Polymorphism in the Human Myostatin Gene
A/A Genotype (n ? 9)A/G Genotype (n ? 5)
Trained leg muscle volume before ST (cm3)
Muscle volume increase with ST (cm3)
Change in trained leg volume minus change in control leg volume (cm3)
Detraining-induced loss of muscle volume (cm3)
1224.7 ? 107.6
109.0 ? 15.4
98.23 ? 13.0
89.8 ? 16.5
1320.4 ? 125.9
183.3 ? 39.2*
133.4 ? 41.5
91.9 ? 39.5
Notes: Data are means ? SE. ST ? strength training.
*p ? .056 versus A/A myostatin gene variant; p ? .067 when baseline muscle volume was covaried in the analysis.
M648 Download full-text
IVEY ET AL.
In summary, aging does not appear to attenuate the hy-
pertrophic response to ST as was reported previously. How-
ever, gender does influence responsiveness to ST, as the
men in the present study had muscle mass gains that were
approximately twice as great as women when expressed in
absolute terms. There is no information available from this
or other studies to determine potential mechanisms for these
findings, although differences in hormonal responses to
training should be addressed in future studies. The observa-
tion of a gender effect and the lack of an age effect on the
muscle mass response to detraining also represent new find-
ings. The role of the Lys 153 Arg polymorphism in the hu-
man myostatin gene on muscle volume response to ST re-
mains unclear and needs further investigation, particularly
in a larger sample size of women.
The authors thank Dr. Moriel NessAiver for his technical assistance with
MRI scans, Elizabeth Lawrence for her technical assistance with myostatin
genotyping, Dorothy O’Donnell for her help with the recruitment of subjects,
Dan Barlow for his assistance in data analysis, Mary Lott for her overall con-
tribution to the project, and the subjects who made this investigation possible.
This study was supported by a research contract from the National Insti-
tutes of Health, National Institute on Aging (NIA; Grant AG42148). Dr.
Ivey was supported by NIA Grant T3200219. S.M. Roth was supported by
NIA Grant AG-00268.
Address correspondence to Ben Hurley, PhD, Department of Kinesiol-
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Received June 23, 1999
Accepted February 9, 2000
Decision Editor: William B. Ershler, MD