Article

Age and sex affect human muscle fibre adaptations to heavy-resistance strength training

Department of Physical Therapy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
Experimental Physiology (Impact Factor: 2.67). 03/2006; 91(2):457-64. DOI: 10.1113/expphysiol.2005.032771
Source: PubMed
ABSTRACT
This study assessed age and sex effects on muscle fibre adaptations to heavy-resistance strength training (ST). Twenty-two young men and women (20-30 years old) and 18 older men and women (65-75 years old) completed 9 weeks of heavy-resistance knee extension exercises with the dominant leg 3 days week(-1); the non-dominant leg served as a within-subject, untrained control. Bilateral vastus lateralis muscle biopsies were obtained before and after ST for analysis of type I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type distribution. One-repetition maximum (1-RM) strength was also assessed before and after ST. ST resulted in increased CSA of type I, IIa and IIx muscle fibres in the trained leg of young men, type I and IIa fibres in young women, type IIa fibres in older men, and type IIx fibres in older women (all P<0.05). Analysis of fibre type distribution revealed a significant increase in the percentage of type I fibres (P<0.05) along with a decrease in type IIx fibres (P=0.054) after ST only in young women. There were no significant changes in muscle fibre CSA or fibre type distribution in the untrained leg for any group. All groups displayed significant increases in 1-RM (27-39%; all P<0.01). In summary, ST led to significant increases in 1-RM and type II fibre CSA in all groups; however, age and sex influence specific muscle fibre subtype responses to ST.

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Exp Physiol 91.2 pp 457–464 457
Experimental Physiology
Age and sex affect human muscle fibre adaptations
to heavy-resistance strength training
GregoryF.Martel
1,2
, Stephen M. Roth
2
,FrederickM.Ivey
2,3
, Jeffrey T. Lemmer
2,4
, Brian L. Tracy
2,5
,
Diane E. Hurlbut
2
, E. Jeffrey Metter
6
,BenF.Hurley
2
and Marc A. Rogers
2
1
Department of Physical Therapy, University of Maryland Eastern Shore, Princess Anne, MD, USA
2
Department of Kinesiology, University of Maryland, College Park, MD, USA
3
Division of Gerontology, University of Maryland School of Medicine, and the Baltimore VA GRECC, Baltimore, MD, USA
4
Department of Kinesiology, Michigan State University, East Lansing, MI, USA
5
Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA
6
Clinical Research Branch, National Institute on Ageing, Baltimore, MD, USA
This study assessed age and sex effects on muscle fibre adaptations to heavy-resistance strength
training (ST). Twenty-two young men and women (20–30 years old) and 18 older men and
women (65–75 years old) completed 9 weeks of heavy-resistance knee extension exercises with
the dominant leg 3 days week
1
; the non-dominant leg served as a within-subject, untrained
control. Bilateral vastus lateralis muscle biopsies were obtained before and after ST for analysis
of type I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type distribution. One-
repetition maximum (1-RM) strength was also assessed before and after ST. ST resulted in
increased CSA of type I, IIa and IIx muscle fibres in the trained leg of young men, type I and
IIa fibres in young women, type IIa fibres in older men, and type IIx fibres in older women (all
P < 0.05). Analysis of fibre type distribution revealed a significant increase in the percentage
of type I fibres (P < 0.05) along with a decrease in type IIx fibres (P = 0.054) after ST only in
young women. There were no significant changes in muscle fibre CSA or fibre type distribution
in the untrained leg for any group. All groups displayed significant increases in 1-RM (27–39%;
all P < 0.01). In summary, ST led to significant increases in 1-RM and type II fibre CSA in all
groups; however, age and sex influence specific muscle fibre subtype responses to ST.
(Received 15 November 2005; accepted after revision 22 December 2005; first published online 11 January 2005)
Corresponding author G. F. Martel: Department of Physical Therapy, University of Maryland Eastern Shore, Princess
Anne, MD 21853, USA. Email: gfmartel@mail.umes.edu
Age-related declines in muscle mass (sarcopenia) and
strength lead to an increased risk of falls and reduced
functional mobility (Campbell et al. 1989; Rantanen et al.
1999). Thus, strength training (ST) is an intervention
of choice for addressing these risks. Although study
of the effects of ST on older individuals initially
suggested that strength gains were primarily due to
neurological adaptations (Moritani & De Vries, 1980), it
is now understood that heavy-resistance ST can induce
hypertrophy of whole skeletal muscle (Tracy et al. 1999;
Ivey et al. 2000) as well as individual muscle fibres
(H
¨
akkinen et al. 1998; Hikida et al. 1998; Fiatarone-Singh
et al. 1999) in the elderly. In this regard, previous work has
shown that ST can induce relative hypertrophy of skeletal
muscle fibres in older individuals that is comparable to
that observed in youngerindividuals (H
¨
akkinen et al. 1998;
Hikida et al. 1998); however, these adaptations may take
longer in older individuals (Moritani & De Vries, 1980).
Furthermore, a large proportion of the muscle mass and
strength lost with ageing involves preferential reductions
in the number and cross-sectional area (CSA) of fast-
twitch (type II) muscle fibres (Lexell et al. 1988; Lexell
& Downham, 1992; Fiatarone-Singh et al. 1999; Trappe
et al. 2003). Thus, assessment of age and sex effects on
muscle fibre responses to heavy-resistance ST could aid in
the development of ST protocols that favourably recruit
type II muscle fibres (Fiatarone-Singh et al. 1999).
Previous investigations have examined the effects of ST
on skeletal muscle morphology in young men (Kraemer
et al. 1995; McCall et al. 1996), young women (Staron et al.
1989, 1994), older men (Brown et al. 1990; Hikida et al.
2000; Trappe et al. 2000) and older women (Charette et al.
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458 G. F. Martel and others
Exp Physiol 91.2 pp 457–464
1991; Taaffe et al. 1996) separately, and have attempted
to assess age (H
¨
akkinen et al. 1998, 2001; Hikida et al.
1998) or sex effects (Staron et al. 1994; Fiatarone-Singh
et al. 1999; Frontera et al. 2000; Trappe et al. 2000;
H
¨
akkinen et al. 2001; Bamman et al. 2003) on muscle
fibre responses to ST by including comparisons of men
with women, or younger with older individuals. However,
becausethesestudiesusedvarying ST intensities, durations
and volumes, it is difficult to draw consistent conclusions
regarding responses of specific muscle fibre subtypes to
ST in individuals of different age and/or sex. In both
previous studies that directly examined the effects of age
and sex on muscle fibre hypertrophic responses to ST
by comparing muscle samples obtained from men and
women of different ages before and after ST (H
¨
akkinen
et al. 2001; Kim et al. 2005b), the investigators did not
report inclusion of control muscle samples; thus, an impact
of factors such as non-study-related physical activity
(Lexell et al. 1985) or differences in genotype (Roth et al.
2003; Schrager et al. 2004) on muscle fibre adaptations
cannot be ruled out.
Other factors that may influence the interpretation of
morphological adaptation to ST involve methodology.
For example, current studies involving the effects
of ST on muscle fibre characteristics tend to use
immunocytochemistry to analyse subtle changes in
myosin heavy chain (MHC); however, much of our present
understanding regarding the effects of ST, age and sex
on muscle morphology is derived from studies that used
techniques involving myofibrillar ATPase activity (Lexell
et al. 1983, 1985, 1988; Staron et al. 1989; Brown et al. 1990;
Charette et al. 1991; Lexell & Downham, 1992; Kraemer
et al. 1995; McCall et al. 1996; Taaffe et al. 1996; H
¨
akkinen
et al. 1998, 2001; Hikida et al. 1998). Inaddition, Lexell et al.
(1983, 1985) reported that a single musclesample obtained
via needle biopsy, the technique most often used in studies
of muscle morphology, can provide a poor estimation of
whole muscle fibre type distribution and that sampling
error can be significantly reduced in biopsy samples by
obtaining larger samples (>450 fibres).
Another method of reducing the impact of muscle
sample variation on study findings involves the inclusion
of appropriately matched control muscle samples. In this
regard, Young et al. (1982) reported a strong correlation
between muscle fibre distributions in bilateral muscle
samples obtained from within the same individual,
but substantial variation exists when comparing muscle
samples obtained from separate individuals. Despite
this, the recruitment of separate control groups for
comparison purposes is a technique frequently employed
by investigators. Blomstrand et al. (1984) also examined
the issue of muscle sample variability involved with biopsy
techniques, reporting standard deviations for type I, IIa
and IIx fibre CSA in bilateral muscle samples that were
24–47% lower than repeat samples obtained from the
same biopsy site within these individuals. Similar to Lexell
et al. (1985), the authors emphasized the importance
of analysing all viable muscle fibres within a muscle
sample region and having the same investigator perform
all measurements within a study. Collectively, these studies
suggest that a superior method of controlling for inherent
muscle sample variability and the potential confounding
effects of age, sex, genotype and physical activity (Young
et al. 1982; Lexell et al. 1983, 1985; Blomstrand et al.
1984; Roth et al. 2003; Schrager et al. 2004) would be
to obtain experimental and control muscle samples from
within a group of subjects (bilateral samples) rather than
comparing samples obtained from two separate groups.
Although unilateral ST models have been used for years,
we are aware of only a single study that compared muscle
samples from strength-trained’ limbs to ‘untrained’ limbs
within the same group of individuals (Brown et al. 1990).
However, although Brown et al. (1990) compared muscle
fibre responses to ST between trained and untrained arms,
the biceps brachii musculature of both arms may havebeen
indirectly involved in additional ST exercises, since the
authors reported hypertrophy of type I and type II fibres
in both arms. Furthermore, Brown et al. (1990) included
only older men, since examining the effects of age or sex
on muscle fibre responses to ST was not their objective.
Because a number of previous studies examined the
role of age or sex on muscle fibre hypertrophy after
various ST protocols via analysis of myofibrillar ATPase
activity, but without inclusion of within-subject control
samples, we attempted to replicate previous findings while
addressing these issues. Thus, the purpose of our study was
to compare bilateral skeletal muscle samples from trained
and untrained legs of young and older men and women
before and after completing an identical single-leg, heavy-
resistance ST protocol.
Methods
Subjects
The 13 young men, nine young women (young being 20–
30 years old), 11 older men and seven older women (older
being 65–75 years old) that participated in the study were
a subset of subjects from a larger study conducted in
our laboratory (Tracy et al. 1999; Lemmer et al. 2000;
Ivey et al. 2000). All aspects of this study complied with
the Declaration of Helsinki and were approved by the
Institutional Review Boards at the University of Maryland
College Park and at the Veterans Affairs and the Johns
Hopkins Bayview Medical Centers in Baltimore, MD, USA.
Following thorough written and verbal explanations of
all methods and procedures, subjects provided written
informed consent. All subjects were healthy non-smokers
who had not participated in regular exercise for at
least 6 months prior to the study. A medical history,
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Muscle fibre adaptations to strength training 459
maximal graded exercise test with measurement of oxygen
consumption, and physical examination were performed
by a physician on all older subjects to screen for
musculoskeletal and cardiovascular disease. Subjects were
excluded if there were any musculoskeletal problems
preventing them from successfully completing the ST
programme, if the exercise test provided evidence of
cardiovascular disease, or if they were taking medications
known to affect cardiovascular or metabolic function.
Dual energy X-ray absorptiometry was used to assess body
composition before and after the study using methods
previously described (Tracy et al. 1999); this, along with
weekly measurement of body mass, was used to assess
whether significant changes in physical activity or dietary
habits had occurred during the course of the study.
Strength testing
Strength testing of the quadriceps femoris muscle groups
was conducted in a unilateral manner on both legs before
and after the study as previously described (Lemmer et al.
2000). Briefly, following three familiarization sessions in
which the participants completed the training programme
protocol with little resistance, one-repetition (1-RM) and
five-repetition maximum (5-RM) tests were performed on
an air-powered leg extension machine that provided both
concentric and eccentric actions. The 1-RM resistance
was recorded as a measure of baseline muscular strength,
while the 5-RM was used as the initial resistance for
the ST programme. All strength tests were conducted by
the same investigator before and after the study, paying
special attention to consistency with seat adjustment,
body position, amount of stabilization, and level of vocal
encouragement.
ST programme
The unilateral ST programme, as previously described
(Tracy et al. 1999; Lemmer et al. 2000), was designed
to require near-maximal effort on all repetitions, while
maintaining a high training volume to optimize muscle
fibre hypertrophy. Briefly, the ST programme consisted
of five sets of unilateral leg extension exercise, performed
3daysweek
1
for 9 weeks. The dominant leg of each
individual was used as the training leg, while the non-
dominant leg served as the untrained, within-subject
control. All subjects completed each ST session under
the direct supervision of one of the investigators. For
each ST session, all subjects completed a 10 min warm-up
period consisting of light stationary cycling and stretching,
followed by a warm-up set consisting of five repetitions at
50% of the predetermined 1-RM resistance. The second
set consisted of five repetitions using a predetermined
5-RM resistance. If an individual was able to lift the
5-RM resistance more than five times, the resistance was
increased for the subsequent ST session. The third set
required subjects to lift the 5-RM resistance until failure.
The subjects then quickly pressed an air ‘release’ button
near their thumb (to gradually reduce the resistance) just
enough to perform one or two more repetitions without
interruption. This processwas repeated(usually one or two
slight reductions in resistance during the third set) until a
total of 10 repetitions could be completed. The fourth set
also required the subjects to perform as many repetitions
as possible at the 5-RM resistance, at which time they were
allowed to gradually reduce the resistance (as described
above) until a total of 15 repetitions were completed. The
fifth and final set followed the same procedure, except that
a total of 20 repetitions were completed. The number of
reductions in resistance required for the fourth and fifth
sets varied by individual, but ranged from roughly four
to seven. This training protocol required each individual
to perform 50 repetitions at near-maximal effort on every
repetition after the warm-up set. Rest periods of 30, 90,
150 and 180 s were allowed between each of the five sets,
respectively.
Muscle sampling and analyses
Bilateral muscle samples were obtained from the vastus
lateralis muscles approximately 1 week prior to baseline
strength testing and within 24–48 h after completing
ST using a percutaneous needle biopsy technique with
suction (Evans et al. 1982). The initial sampling site was
superior to the proximal border of the patella by 14 cm
for women and 16 cm for men, and at the mid-line
of the quadriceps. All muscle biopsies were performed
by the same investigator through an incision 2.5 mm
proximal and lateral to the original biopsy scar, with
the needle inserted as closely as possible to the site of
the original biopsy. Also, all biopsies were taken from
approximately the same depth for each subject by using
markings engraved on the outside of the biopsy needle.
Although this method led to samples being obtained
from different muscle depths for individuals with different
muscle thicknesses, this technique allowed us to control
for the effect muscle depth on fibre type distribution
within each subject (i.e. for comparisons between time
points and control versus trained leg). After dissecting the
muscle samples of all visible blood, adipose and connective
tissue, the muscle samples were orientated in embedding
medium (OCT; Miles Laboratories, Naperville, IL, USA),
frozen in isopentane cooled to the temperature of liquid
nitrogen, and stored at 80
C. Frozen muscle samples
were subsequently orientated in a cross-sectional fashion
onto a microtome cryostat (IEC Microtome, International
Equipment Co.), cut into 12 μm thick sections at 20
C,
and analysed histochemically to classify fibres as type I, IIa,
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Table 1. Physical characteristics of the subjects before and after ST
Young men Young women Older men Older women
(n = 13) (n = 9) (n = 11) (n = 7)
Age (years) 25 ± 126± 0.4 69 ± 168± 1
Height (cm) 178 ± 3 167 ± 2 174 ± 2 161 ± 2
Body mass (kg)
Before 82 ± 5
62 ± 480± 2
68 ± 3
After 83 ± 562± 481± 268± 3
Body fat (%)
Before 24 ± 2
31 ± 2 30 ± 2 39 ± 2
After 23 ± 231± 229± 138± 2
˙
V
O
2
max
(ml kg
1
min
1
)43± 1†§ 33 ± 2 24 ± 220± 1
Significantly different from young and older women (P < 0.05); significantly different from older
men and women (P < 0.05); significantly different from older women (P < 0.05); and § significantly
different from young women (P < 0.05).
IIc and IIx using the method of Brooke & Kaiser (1970).
Owing to the extremely low occurrence of type IIc fibres in
the samples, they were not included in the final statistical
analyses. All samples obtained from a particular subject
werestainedin the same batchto avoidinterassayvariation.
Estimates of fibre type distribution were calculated using
all viable muscle fibres from contiguous regions of the
samples, resulting in an average of 774 ± 35 fibres being
included per sample.
Muscle fibreCSA was determined bydownloading video
images of the tissue cross-sections at ×100 magnification
from a light microscope interfaced with a video recorder.
The CSA of approximately 75 type I, IIa and IIx fibres
in artifact-free, contiguous regions of the sample were
measured before and after ST using a computer program
(Scion Image, Frederick, MD, USA). The same investigator
analysed all of the muscle samples (distribution and CSA)
in duplicate, in a blind fashion. Intra-individual test–retest
reliability showed a correlation of 0.99 (P < 0.001) for
muscle fibre CSA measured on different days.
Data analysis
All data are expressed as means ± s.e.m. Unpaired t tests
were used to examine group differences in descriptive
variables. Analyses of variance (ANOVA) with repeated
measures were used for assessing group differences and
the effect of ST on muscle fibre distribution and CSA.
The independent variables for the ANOVA included time
(before versus after ST), leg (trained versus control)
and group (young men, young women, older men and
older women); thus a 2 × 2 × 4 factorial design was
used for each fibre type. Since there were significant
group differences at baseline for muscle fibre CSA
(e.g. differences in baseline type IIa CSA between young
men and young women), factorial analyses of covariance
(ANCOVA) with repeated measures were performed using
the same independent variables mentioned above. When
significant time-by-group (4 separate groups; age and
gender groups were not pooled) interactions were present,
Tuke y post hoc procedures were used for identifying
the specific differences. Logistic regression was used to
verify the lack of individual cases present that could
skew group means. All statistical analyses were conducted
using statistical software (SPSS, Inc.; Chicago, IL, USA).
Statistical significance was set at P 0.05 for all tests.
Results
Physical characteristics and muscle strength
The body fat percentages and maximal oxygen uptake
(
˙
V
O
2
max
) values of the subjects in this study are indicative of
relatively sedentary individuals (Table 1). Despite baseline
group differences in body mass and body fat percentage,
there were no significant changes in either variable for
any group after ST, indicating that physical activity levels
and dietary intake during the ST programme were not
significantly altered. As reported previously (Lemmer et al.
2000), there were significant increases in 1-RM strength in
both the trained and untrained legs for all groupsfollowing
ST, with significantly larger increases occurring in the
trained leg versus the untrained leg for all groups (increases
of 31, 39, 27 and 29% in the trained legs of young men,
young women, older men and older women, respectively;
all P < 0.001).
Muscle fibre type distribution
Analysis of muscle fibre type distribution in both legs of
all four groups at baseline indicated no significant group
differences (Table 2). ANOVA with repeated measures
(including all groups) indicated a significant time-by-
group interaction (P < 0.05), so we performed a post hoc
analysis to examine the source of the interaction. We
observed no significant changes in fibre type distribution
for young men, older men or older women; however, there
was a significant increase in the percentage of type I fibres
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Muscle fibre adaptations to strength training 461
Table 2. Muscle fibre type distribution (%) before and after ST
Young men Young women Older men Older women
(n = 13) (n = 9) (n = 11) (n = 7)
Before After Before After Before After Before After
Trained leg
Type I 48 ± 544± 340± 351± 6
50 ± 448± 347± 649± 5
Type IIa 30 ± 434± 231± 330± 326± 232± 528± 229± 3
Type IIx 22 ± 422± 429± 319± 5
24 ± 420± 325± 622± 5
Untrained leg
Type I 40 ± 343± 447± 346± 347± 443± 344± 443± 5
Type IIa 31 ± 334± 532± 331± 229± 429± 226± 323± 3
Type IIx 29 ± 323± 421± 423± 324± 528± 330± 534± 5
Significantly different after ST (P 0.054).
Table 3. Muscle fibre CSA (μm
2
) before and after ST
Young men Young women Older men Older women
(n = 13) (n = 9) (n = 11) (n = 7)
Before After Before After Before After Before After
Trained leg
Type I 3306 ± 248 3917 ± 278 2485 ± 150 2977 ± 207 3680 ± 234
3919 ± 243 3422 ± 388 3664 ± 346
Type IIa 3484 ± 251
4202 ± 335 2203 ± 169 2622 ± 151 3061 ± 176
3804 ± 212 2281 ± 314 2598 ± 158
Type IIx 2652 ± 254
3744 ± 321 1491 ± 276 1806 ± 147 2902 ± 250
3631 ± 511 1295 ± 224 1929 ± 262
Untrained leg
Type I 3611 ± 288 3733 ± 209 2819 ± 264 2569 ± 199 3727 ± 245
3851 ± 345 2950 ± 392 3071 ± 448
Type IIa 3734 ± 368
3536 ± 198 2583 ± 271 2306 ± 336 3436 ± 213
3265 ± 304 1910 ± 192 2183 ± 208
Type IIx 3142 ± 337
3075 ± 213 1988 ± 466 1858 ± 411 2908 ± 170
2747 ± 216 1190 ± 195 1395 ± 255
Significantly greater than young and older women (P < 0.05); significantly greater than young women (P < 0.05); significantly
greater than before ST (all P < 0.05). None of the differences in the untrained leg from before to after were significant.
(40–51%; P < 0.05) along with a decrease in type IIx fibres
(29–19%; P = 0.054) in the trained leg of young women.
There were no significant group differences or changes in
fibre type distribution in muscle samples obtained from
the untrained leg for any group.
Muscle fibre CSA
Analysis of muscle fibre CSA for all four groups at
baseline indicated significant group differences in both
the trained and untrained legs for all three fibre types
(Table 3). The older men had significantly larger type I,
IIa and IIx muscle fibres than young and older women
(all P < 0.01), while young men had significantly larger
type IIa and type IIx muscle fibres than both young and
older women (all P < 0.05). Although the young men had
larger type I muscle fibres than young women (P < 0.05),
there was no significant difference in type I muscle fibre
CSA between young men and older women.
The factorial ANCOVA indicated significant effects of
ST on muscle fibre CSA, and significant leg and group
interactions for all three fibre types (all P < 0.05). Post
hoc analysis for the leg interactions for each fibre type
revealed significant changes in muscle fibre CSA in the
trained leg, but no significant changes in muscle fibre
CSA in the untrained leg. These findings verify that the
increases in muscle fibre CSA that were observed in the
trained leg were significantly larger than any variation in
the untrained leg. With regard to the significant group
interactions, post hoc analysis revealed significant increases
in type I fibre CSA in both young men and young women
(19 and 20%, respectively; both P < 0.05), whereas there
were no significant increases for older men (6%) or older
women (7%). For type IIa muscle fibre CSA, there were
significant increases in young men, young women and
older men (21, 19 and 24%, respectively; all P < 0.05),
with no significant changes occurring in the trained leg
of older women (14%). Finally, there were significant
increases in type IIx fibre CSA in young men and older
women (41 and 49%, respectively; both P < 0.05), with no
significant changes occurring in the trained leg of young
women (21%) or older men (25%).
Discussion
Despite the utilization of an identical ST protocol in the
present study by young and older men and women, ST
led to significant increases in type I muscle fibre CSA only
in young men and young women. In addition, there were
non-significant increases after ST for type IIx fibre CSA
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462 G. F. Martel and others
Exp Physiol 91.2 pp 457–464
in young women (21%) and older men (25%) that were
50% smaller than the significant increases observed in
young men (41%) and older women (49%). Because these
differences in fibre hypertrophy occurred in the trained
leg with no significant changes in the untrained leg, our
results indicate that there are age and sex effects on muscle
fibre responses to ST, and that these dissimilarities are not
due to methodological variation, differences in physical
activity status or genotype, or differences in ST intensity,
volume or duration.
The findings of the present study regarding significant
sex effects on hypertrophic responses of skeletal muscle
to resistance exercise are supported by recent work
involving ST in men and women (Ivey et al. 2000;
H
¨
akkinen et al. 2001; Bamman et al. 2003; Kim et al.
2005a,b). For example, Kim et al. (2005a,b)reported
significant differences between men and women after
resistance exercise for the expression of myostatin (an
inhibitor of skeletal muscle hypertrophy), as well as
cyclin D1, myogenic gene (MyoD), tissue binding protein,
and muscle-specific insulin-like growth factor I, all of
which play an important role in muscle fibre hypertrophy
and/or regeneration. Although not assessed in the present
study, we hypothesize that sex-related hypertrophic
dissimilarities are related to underlying differences in the
expression of these factors (Kim et al. 2005a,b).
Our finding of a lack of increase in type I CSA in
older men and women is also supported by previous
work indicating blunted hypertrophic responses of muscle
fibres to ST in older individuals (Moritani & De Vries,
1980; Charette et al. 1991; Fiatarone-Singh et al. 1999;
H
¨
akkinen et al. 2001). For example, Charette et al. (1991)
observed increases in type II fibre CSA after 12 weeks of
ST in older women, but no increase for type I fibres.
Fiatarone-Singh et al. (1999) and H
¨
akkinen et al. (2001)
also reported no significant increases for type I fibre CSA
in older individuals after 10 weeks and 6 months of ST,
respectively, despite increases in type II fibre CSA. Itshould
also be noted that the findings of Fiatarone-Singh et al.
(1999) were a result of analysis of both myofibrillar ATPase
activity and immunocytochemistry. Furthermore, Hikida
et al. (1998) reported similar increases in type I CSA in
young and older men after ST, but the older men in their
study trained for 16 weeks, compared to only 8 weeks
for young men. Finally, Kim et al. (2005a,b) recently
reported significant differences between young and older
individuals for the expression of myostatin, myogenin,
MyoD, myogenic regulatory factor (myf-5) and muscle-
specific insulin-like growth factor I, indicating blunted
skeletal muscle responses in older men and women.
In addition to the underlying cellular mechanisms for
age and sex differences in muscle hypertrophy described
above, we propose that active older individuals who
have undergone age-related muscle changes (i.e. motor
unit remodelling, age-related loss of type II fibre number
and/or CSA) begin to rely more heavily on type I fibres
during everyday activities due to the normal pattern
of muscle fibre recruitment, thus inducing type I fibre
hypertrophy. Therefore, even ST programmes of high
intensity could require longer duration to induce further
improvements in type I fibre CSA and/or metabolic
capacity in older individuals.
In the present study, we observed significant
hypertrophy of type IIa and IIx fibres in young men,
type IIa fibres in young women and older men, and
type IIx fibres in older women after ST. Despite these
differences in group responses, the present study indicates
that young and older men and women can experience
type II muscle fibre hypertrophy in a relativelyshort period
of time (ranging from 19 to 49% depending on group
and fibre subtype). This is noteworthy, and may have
important clinical implications for addressing the effects
of sarcopenia, since a number of research groups (Lexell
et al. 1988; Lexell & Downham, 1992; Fiatarone-Singh et al.
1999; Trappe et al. 2003) have reported that most muscle
loss due to ageing is attributed to reductions in the number
and size of type II muscle fibres. Thus, ST programmes
requiring relatively high levels of resistance may be most
effective for recruiting type II fibres, helping to address the
problems associated with sarcopenia-related conditions.
In the only other study to our knowledge that has
directly comparedmuscle morphology in men and women
of different age groups before and after ST, H
¨
akkinen et al.
(2001) reported no significant baseline group differences
in muscle fibre type distribution, and no significant
changes in distribution as a result of 6 months of ST. These
findings are consistent with those of the present study,
but are in contrast to previous work reporting significant
alterations in type II muscle fibre subtype distributions
after ST, usually a decrease in the percentage of type IIx
fibres and an increase in IIa or IIab fibres (Staron et al.
1989, 1994; Kraemer et al. 1995; H
¨
akkinen et al. 1998;
Hikida et al. 1998, 2000). For example, Hikida et al.
(1998) observed a significant reduction in the percentage
of type IIx fibres for older men (9%) along with a
significant increase in the percentage of type IIa fibres
(4%) following 16 weeks of ST. In addition, H
¨
akkinen
et al. (1998) previously reported significant decreases in
the percentage of type IIx fibres for young and older men
(9% for both groups) and an increase in the percentage
of type IIab fibres (4%) in young men after 10 weeks of ST.
Although our analysis of muscle fibre type distribution
revealed no significant main effects of ST for any group,
there was a significant time-by-group interaction; post hoc
analysis revealed significant changes only in the fibre type
distribution of young women. Despite our observation of
a reduction in the percentage of type IIx fibres after ST in
young women being consistent with previous literature,
our observance of an increase in type I fibre percentage
is not. We believe that this increase in type I fibres after
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2006 The Authors. Journal compilation
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2006 The Physiological Society
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Exp Physiol 91.2 pp 457–464
Muscle fibre adaptations to strength training 463
ST in young women may be due to our collapsing of fibre
types into only four major categories for reporting, similar
to previous investigators (Kraemer et al. 1995; H
¨
akkinen
et al. 1998, 2001); however, this method may not allow for
the detection of subtle changes in other fibre subtypes. For
example, the work of Staron et al. (1989, 1994) involved
assessment of six muscle fibre subtypes (I, Ic, IIc, IIa, IIab
and IIx) for their muscle fibre distributions. Thus, we
recommend that future studies examining muscle fibre
type distribution continue to use methods that allow for
examination of all six detectable muscle fibre subtypes to
avoid the limitations presented by assessing only type I,
IIc, IIa and IIx fibres.
As can be seen, the available literature regarding the
effects of ST on muscle morphology is quite extensive, with
research groups using an array of laboratory techniques
and ST protocols to assess changes in muscle fibre
characteristics. Although the present study, as well as
others (H
¨
akkinen et al. 2001; Bamman et al. 2003; Kim
et al. 2005a,b), indicate inherent differences in how muscle
fibres of young and older men and women respond to ST,
the potential impact of ST protocols of varying frequency,
duration, intensity and volume on muscle fibre responses
cannot be ignored, since these factors may affect the
degree and rate of response. For example, the present
study examined vastus lateralis muscle fibre responses to
a rather short, but very intense ST protocol (150 near-
maximal lifts per week for 9 weeks) in young and older
men and women. In addition, our ST protocol involved
only a single ST exercise, seated leg extensions. On the
contrary, H
¨
akkinen et al. (2001) examined vastus lateralis
muscle samples obtained from middle-aged and older men
and women after performing multiset combinations of
heavy resistance and explosive leg extension and leg press
exercises; also, these subjects trained only twice weekly for
6 months with a gradually increasing load (from 50% 1-
RM to 80% 1-RM by the end of the study). Thus, it seems
logical to assume that some of the differences between our
findings and those of previous investigators could be partly
due to the use of such a vast array of ST programmes.
In summary, our study indicates the presence of
significant age and sex effects on muscle fibre hypertrophic
responses to ST, since older individuals appear to develop
hypertrophy of type I muscle fibres more slowly than
young individuals, while young men appear to have greater
hypertrophic capacity than young women as well as older
men and women. By evaluating bilateral muscle biopsy
samples from young and older men and women before and
after completion of the same ST protocol, the impact of
confounding factors such as differences in ST frequency,
intensity and duration, as well as biological and genetic
variation on our data were minimized. Furthermore, when
comparing our findings to recent work in this area, it
appears that age- and sex-related differences in muscle
hypertrophy may be due to varying expression of cellular
components known to impact muscle fibre hypertrophy.
However, despite potential age and sex differences, young
and older men and women appear to display type II fibre
hypertrophy after heavy-resistance ST. Thus, we strongly
encourage the use of heavy-resistance ST to help reduce
risks associated with sarcopenia.
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Acknowledgements
We thank Dr Barbara Albert, MD, for the medical screening
of our subjects, Dorothy O’Donnell for her help with subject
recruitment, and Kevin Cross, Joe Gillespie, Ken Lytle, Mary
E. Lott, Lindsay Mulinazzi, Dan Oetken and Autumn Powell
for their assistance with training the subjects. We also thank
Dr Colleen Farmer and the staff at the University of Maryland
Wellness Research Laboratory for their support, and all
subjects who volunteered for this study. We thank Drs Thomas
Castonguay and Charles Dotson for their assistance with data
analysis, and Drs Carol Hamelink and Robert Eskay for their
technical expertise and use of equipment in the Neurochemistry
Section of the Clinical Sciences Laboratory within the National
Institute of Alcohol Abuse and Alcoholism. The National
Institute of Ageing provided financial support for the completion
of all aspects of this study through contract #1-AG-4–2148.There
were no conflicts of interest associated with this study.
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    • "Yet, other studies focusing on quadriceps muscles are of mixed consensus with some reporting greater increases in younger (Raue et al. 2009, Greig et al. 2011), and others equal (Ivey et al. 2000, H€ akkinen et al. 2001, Mayhew et al. 2009). At the level of fibre CSA, the available data generally show younger subjects exhibit greater increases in type I fibre CSA (Kosek et al. 2006, Martel et al. 2006, Mero et al. 2013) with increases in type II CSA also being greater (Kosek et al. 2006, Raue et al. 2009, Mero et al. 2013) or equal (Hakkinen et al. 1998, Martel et al. 2006, Mayhew et al. 2009). These discrepancies are likely to arise from variances in training regimes, nutritional support and analytical techniques. "
    [Show abstract] [Hide abstract] ABSTRACT: Skeletal muscles comprise a substantial portion of whole body mass, and are integral for locomotion and metabolic health. Increasing age is associated with declines in both muscle mass and function (e.g. strength-related performance, power) with declines in muscle function quantitatively outweighing those in muscle volume. The mechanisms behind these declines are multi-faceted involving both intrinsic age-related metabolic dysregulation and environmental influences such as nutritional and physical activity. Ageing is associated with a degree of "anabolic resistance" to these key environmental inputs, which likely accelerates the intrinsic processes driving ageing. On this basis, strategies to sensitize and/or promote anabolic responses to nutrition and physical activity are likely to be imperative in alleviating the progression and trajectory of sarcopenia. Both resistance and aerobic type exercises are likely to confer functional and health benefits in older age, and a clutch of research suggests that enhancement of anabolic responsiveness to exercise and/or nutrition may be achieved by optimizing modifications of muscle-loading paradigms (workload, volume, blood flow restriction) or nutritional support (e.g. EAA/ leucine) patterns. Nonetheless, more work is needed in which a more holistic view in ageing studies is taken into account. This should include improved characterization of older study recruits i.e. physical activity/nutritional behaviours, to limit confounding variables influencing whether findings are attributable to age, or other environmental influences. Nonetheless, on balance, ageing is associated with declines in muscle mass and function and a partially related decline in aerobic capacity. There is also good evidence that metabolic flexibility is impaired in older age. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Acta Physiologica
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    • "Histological studies also indicated that age-related changes in fiber type composition may affect muscle strength negatively (Korhonen et al., 2006; Martel et al., 2006). In our study, we observed significantly higher Pi/ATP ratios in the late-middle-age group indicating reduced type II fiber fraction (Madhu et al., 1996 ). "
    [Show abstract] [Hide abstract] ABSTRACT: During aging declining maximum force capacity with more or less unchanged fatigability is observed with the underlying mechanisms still not fully understood. Therefore, we compared morphology and function of skeletal muscles between different age groups. Changes in high-energy phosphate turnover (PCr, Pi and pH) and muscle functional MRI (mfMRI) parameters, including proton transverse relaxation time (T2), diffusion (D) and vascular volume fraction (f), were investigated in moderately exercised low back muscles of young and late-middle-aged healthy subjects with (31)P-MR spectroscopy, T2- and diffusion-weighted MRI at 3T. In addition, T1-weighted MRI data were acquired to determine muscle cross-sectional areas (CSA) and to assess fat infiltration into muscle tissue. Except for pH, both age groups showed similar load-induced MR changes and rates of perceived exertion (RPE), which indicates comparable behavior of muscle activation at moderate loads. Changes of mfMRI parameters were significantly associated with RPE in both cohorts. Age-related differences were observed, with lower pH and higher Pi/ATP ratios as well as lower D and f values in the late-middle-aged subjects. These findings are ascribed to age-related changes of fiber type composition, fiber size and vascularity. Interestingly, post exercise f was negatively associated with fat infiltration with the latter being significantly higher in late-middle-aged subjects. CSA of low back muscles remained unchanged, while CSA of inner back muscle as well as mean T2 at rest were associated with maximum force capacity. Overall, applying the proposed MR approach provides evidence of age-related changes in several muscle tissue characteristics and gives new insights into the physiological processes that take place during aging. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Mar 2015 · Experimental Gerontology
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    • "Thus, the 8-week duration of RW activity applied at 16–17 months of age in this study may not have delivered a strong enough metabolic or biomechanical stimulus for MHC isoform modulation or myohypertrophy . A number of studies indicate that the hypertrophic response of muscle may be blunted with aging (Degens and Alway 2003; Martel et al. 2006). It may also be the case that the same duration of activity applied at an earlier age could promote persistent myohypertrophy throughout older age, as suggested by studies of testosterone injections at early middle age in mice (Egner et al. 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle-aged male Sprague Dawley rats (16-17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage-matched without running wheel access (RW-). The 9 RW+ rats averaged 83 m/day (range: 8-163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross-sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1α, P = 0.03), increased autophagy (36% increase in LC3B-II/-I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low-volume voluntary running wheel activity is associated with decreases in many long-chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW- rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle-age promote extensive metabolic remodeling of skeletal muscle. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    Full-text · Article · Feb 2015
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