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Nosaka & Aoki: Repeated bout effect www.brjb.com.br
Brazilian Journal of Biomotricity, v. 5, n. 1, p. 5-15, 2011 (ISSN 1981-6324)
5
INVITED REVIEW
REPEATED BOUT EFFECT:
RESEARCH UPDATE AND FUTURE
PERSPECTIVE
Kazunori Nosaka
1
, Marcelo Saldanha Aoki
2
1
School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup,
WA, Australia
2
School of Arts, Sciences and Humanities, University of Sao Paulo, Sao Paulo, SP, Brazil
Corresponding author:
Kazunori Nosaka, PhD
School of Exercise, Biomedical and Health Sciences
Edith Cowan University
270 Joondalup Drive, Joondalup, WA 6027, Australia
E-mail: k.nosaka@ecu.edu.au
Telephone: (+61) 8 6304 5655
Fax: (+61) 8 6304 5036
Submitted for publication: Jan 2011
Accepted for publication: Jan 2011
ABSTRACT
NOSAKA, K.; AOKI, M. S. Repeated bout effect: research update and future perspective. Brazilian Journal of
Biomotricity, v. 5, n. 1, p. 5-15, 2011. Responses to the same exercise are never the same, which is
particularly so for eccentric exercise. Eccentric exercise results in muscle damage when performed by
individuals who are unaccustomed to the exercise. However, when the same exercise is performed again
within a certain period of time, it does not induce as sever muscle damage as that was induced previously. It
looks as if a bout of eccentric exercise induced protective adaptation in the process of recovering from
muscle damage. This adaptation is referred to as the repeated bout effect. The protective adaptation against
“maximal” eccentric contractions is induced by submaximal eccentric contractions, a small number of
eccentric contractions, eccentric contractions at short muscle lengths, or slow velocity eccentric contractions,
which induce less muscle damage, as well as low-intensity eccentric contractions that do not induce any
muscle damage, or isometric contractions at a long muscle length. The protective effect could last up to
several months, but the remaining length of the effect appears to be influenced by the magnitude of muscle
damage in the initial bout. It seems that adaptations of muscle fibers and/or connective tissue are
responsible for the repeated bout effect, although neural adaptations are not totally discarded, and the
underlying mechanisms need to be investigated further. It should be noted that the magnitude of muscle
damage can be attenuated by the use of the repeated bout effect more efficiently than any other prophylactic
interventions such as nutritional supplementations, and the effect should be considered when designing a
study.
Key Words: eccentric exercise, muscle damage, muscle adaptation, delayed onset muscle soreness,
muscle strength, recovery.
Nosaka & Aoki: Repeated bout effect www.brjb.com.br
Brazilian Journal of Biomotricity, v. 5, n. 1, p. 5-15, 2011 (ISSN 1981-6324)
6
INTRODUCTION
When the skin is exposed to strong ultraviolet for the first time or a long interval from the
previous exposure, sunburn is induced. However, if the skin was previously exposed to
ultraviolet that resulted in sunburn or suntan, severe sunburn is avoided for a period of
time during when another exposure to ultraviolet is encountered. This kind of adaptation is
also observed for the skeletal muscle when it is exposed to eccentric exercise in which
contracting muscles are lengthened (eccentric contractions). If muscles involving in an
exercise have been exposed to the same or similar eccentric contractions, severe muscle
damage is prevented in the next eccentric exercise that is performed within a certain
period of time after the previous damaging exercise. This adaptation, often referred to as
the repeated bout effect, is the topic of this review. There are some review articles that
explain the repeated bout effect (e.g. EBBELING & CLARKSON, 1989; CLARKSON et al.,
1992; MCHUGH et al., 1999; MCHUGH, 2003), but new important information has become
available in the last 5 years, which was not included in the previous review articles. This
review article mainly focuses on the studies of our group and provides overview of the
development of the repeated bout effect research.
What is the repeated bout effect?
We often experience muscle pain and weakness for several days after performing
unaccustomed exercise or exercise with higher intensity, longer duration or larger volume
than normal. Delayed onset muscle soreness (DOMS) and prolonged loss of muscle
function are typical symptoms of muscle damage that is induced by eccentric contractions
or isometric contractions at a long muscle length (NOSAKA, 2008). We also experience
that when the same or similar exercise is repeated within several weeks, even without any
exercises in between, less muscle pain or no pain is felt after exercise that previously
resulted in severe DOMS. This is a typical example of the “repeated bout effect”
(NOSAKA, 2008; NOSAKA, 2010).
The magnitude of muscle damage symptoms is significantly attenuated in the second bout
such that the extent of DOMS is less and recovery of muscle function (e.g. maximal
voluntary contraction strength) is faster following the second exercise bout compared with
the initial bout (EBBELING & CLARKSON, 1989; CLARKSON et al., 1992). It should be
noted that the magnitude of decrease in maximal voluntary contraction (MVC) strength
immediately after exercise is generally similar between bouts, but the recovery is facilitated
in the repeated bout effect (HIROSE et al., 2004; NOSAKA et al., 2005a; NOSAKA et al.,
2006). The repeated bout effect is also characterised by less swelling of muscle, smaller
increases in blood markers of muscle damage such as creatine kinase (CK) and
myoglobin (Mb), and less abnormalities detected in magnetic resonance and/or B-mode
ultrasound images following the second bout than the first bout (CLARKSON et al., 1992;
HIROSE et al., 2004; NOSAKA & CLARKSON, 1996). It has been shown that the repeated
bout effect could last 6-9 months, but does not last more than a year (NOSAKA et al.,
2001a). We tend to think that repeated stimuli for a certain period of time (i.e. training) are
necessary to induce muscle adaptations, but it is interesting that a single bout of exercise
can also provide such strong and long-lasting effects.
Initially, the repeated bout effect was referred to as the adaptation in which the magnitude
of muscle damage was attenuated when the same eccentric exercise was repeated
(BYRNES et al., 1985; CLARKSON et al., 1992); however, such adaptation is induced
even when the initial exercise bout is different from the subsequent exercise bouts. For
example, eccentric exercise that induces little or no muscle damage in the initial bout still
attenuates the magnitude of muscle damage in the subsequent maximal eccentric
exercise (LAVENDER & NOSAKA, 2008). Thus, it is better to define the repeated bout
Nosaka & Aoki: Repeated bout effect www.brjb.com.br
Brazilian Journal of Biomotricity, v. 5, n. 1, p. 5-15, 2011 (ISSN 1981-6324)
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effect as a phenomenon in which the magnitude of muscle damage is attenuated in a
subsequent exercise bout after performing a single bout of exercise.
Factors influencing the repeated bout effect
The magnitude of the muscle damage attenuation in the second exercise bout is
dependent on muscles, markers of muscle damage, the magnitude of muscle damage in
the initial bout, and the time elapsed from the initial exercise bout. Most of the studies that
have reported the repeated bout effect use the elbow flexors; however, others muscles
such as the knee extensors are also reported to present the repeated bout effect (e.g.
BYRNES et al., 1985; ESTON et al., 2000; KAMANDULIS et al., 2010; MIYAMA &
NOSAKA, 2007).
In the case of elbow flexors when maximal eccentric exercise is repeated, Chen et al.
(2007) reported that when the second maximal eccentric exercise bout was performed 2-3
weeks after the first maximal exercise bout, recovery of MVC strength at 5 days post-
exercise was enhanced by 80%, increases in plasma CK activity and Mb concentration
were completely abolished, and peak muscle soreness was reduced by 70%. In contrast,
when a submaximal eccentric contractions were performed for the initial bout (e.g. 40% of
MVC intensity), the recovery of MVC strength at 5 days post-exercise was enhanced by
11%, peak plasma CK activity were lowered by 50%, and peak muscle soreness was
attenuated by 20%, which were smaller than those shown when maximal eccentric
exercise was repeated. It appears that the greater the magnitude of muscle damage in the
initial exercise bout, the greater the protective effect demonstrated in the second exercise
bout. The magnitude of muscle damage is greater when the interval between bouts is
short (e.g. 2 weeks) compared with long (e.g. 6 months) (NOSAKA, 2009), and the
magnitude of the attenuation effect conferred by a single bout of maximal eccentric
exercise is reduced as the time between bouts increases (NOSAKA et al., 2005a;
NOSAKA et al., 2009).
Protective effect conferred by “repeated exercises”
Muscle damage is less for trained individuals compared with untrained individuals. A study
(NEWTON et al., 2008) compared resistance-trained men who had trained for at least
three sessions per week incorporating exercises involving the elbow flexor musculature for
more than a year and untrained men who had not performed any resistance training for at
least one year for changes in muscle damage markers following eccentric exercise
consisting of 10 sets of 6 maximal isokinetic (90º
⋅
s
-1
) eccentric contractions of the elbow
flexors of one arm. The trained group showed significantly smaller changes in all markers
except for muscle soreness and faster recovery of MVC strength compared with the
untrained group such that the MVC strength of the trained group recovered to the baseline
by 3 days post-exercise, where the untrained group showed approximately 40% lower
strength than baseline. This suggests that resistance training makes muscles less
susceptible to eccentric exercise-induced muscle damage, probably due to accumulative
“repeated bout effect” from the training.
Chen et al. (2011) compared the four limb muscles; the elbow flexors (EF) and
extensors (EE), knee extensors (KE) and flexors (KF) for the changes in indirect markers
of muscle damage following maximal eccentric exercise. It was found that compared with
KF and KE, EF and EE showed significantly greater changes in all markers without
significant differences between EF and EE, and changes in all variables were significantly
greater for KF than KE. The results suggest that the two arm muscles are more
susceptible to muscle damage than leg muscles, but KF is more susceptible to muscle
damage than KE. The difference in the susceptibility to muscle damage seems to be
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associated with the use of muscles in daily activities. It may be that the use of muscles in
daily activities confers the protective effect, which is similar to the repeated bout effect.
Chen et al. (2009b) investigated whether four bouts of submaximal eccentric exercise
would confer similar protective effect to one bout maximal eccentric exercise. One group of
subjects performed 30 eccentric contractions with a load of 40% MVC every 2 weeks for
four times followed 2 weeks later by 30 maximal eccentric exercise of the elbow flexors of
the non-dominant arm. Other group of subjects performed two bouts of the maximal
eccentric exercise separated by two weeks. They found that repeating the submaximal
eccentric exercise conferred the same magnitude of protective effect as one bout of
maximal eccentric exercise.
Barroso et al. (2010) examined two velocity (60°·s
-1
, 180°·s
-1
) eccentric exercises
consisting of 30 maximal eccentric contractions of the elbow flexors for changes in indirect
markers of muscle damage following 3 exercise bouts that were performed every 2 weeks.
No significant differences between velocities were evident for changes in any variables
following exercise bouts; however, the changes were significantly smaller after the second
and third bouts than after the first bout without significant differences between the second
and third bouts. When 30 maximal eccentric contractions of the elbow flexors were
performed every 4 weeks for 4 times by untrained subjects, changes in muscle damage
markers following the second to fourth bouts became significantly smaller than those after
the first bout, without significant difference between the second and third bouts (CHEN et
al., 2009a). However, the decreases in MVC strength and range of motion immediately
after the fourth bout were significantly smaller than other bouts. It appears that the first
eccentric exercise bout confers the greatest adaptation, but further adaptation is induced
when the exercise is repeated more than three times. Thus, it seems that repeating
eccentric exercises consolidates the repeated bout effect; however, the greatest
adaptation is produced after the first bout.
Variation of the repeated bout effect
The typical “repeated bout effect” refers to the situation that the same eccentric exercise
bout is repeated; however, a similar or different type of exercise could induce the
“repeated bout effect.” For example, maximal isometric contractions at a long muscle
length (160°) but not at a short muscle length (90°) confer protective effect against
maximal eccentric exercise performed 2 weeks later (NOSAKA, 2009). This suggests that
not only eccentric contractions but also isometric contractions at a long muscle length
produce protective effect against muscle damage induced by eccentric contractions.
It has been reported that performing 2 or 6 maximal eccentric contractions attenuate the
magnitude of muscle damage following 24 maximal eccentric contractions performed 2
weeks later, and the magnitude of the attenuation effect conferred by the 6 contractions is
the same as that induced by 24 maximal eccentric contractions, but that by the 2
contractions is smaller (NOSAKA et al., 2001b). It should be noted that only a few
maximal eccentric contractions are still effective in attenuating muscle damage in
subsequent exercise consisting of a larger number of eccentric contractions.
When comparing the effect of four different intensities (40%, 60%, 80% and 100%) of
initial eccentric exercise on the extent of muscle damage induced by subsequent maximal
eccentric exercise performed 2-3 weeks later, all submaximal intensity eccentric exercise
reduced the magnitude of muscle damage following the maximal eccentric exercise, but
the magnitude of repeated bout effect was significantly smaller for the 40% and 60%
compared with the 80% and 100% (CHEN et al., 2007). Lavender and Nosaka (2008)
found that an eccentric exercise with a light dumbbell that did not change any muscle
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damage markers provided some protection against a subsequent bout of a higher intensity
eccentric exercise with a heavier dumbbell performed 2 days later. It appears that such
effect could last 2 weeks (CHEN et al. under review).
It is known that fast velocity eccentric contractions induce greater muscle damage than
slow velocity eccentric contractions (CHAPMAN et al., 2008). Chapman et al. (2011)
examined whether the first bout of exercise consisting of slow velocity (30°·s
-1
) maximal
eccentric contractions would confer protection against a subsequent bout of exercise
consisting of fast velocity (210°·s
-1
) eccentric contractions. They found that a bout of slow
velocity eccentric contractions confer protection against muscle damage induced by fast
velocity eccentric contractions.
It is known that eccentric contractions at long muscle lengths induce greater muscle
damage than eccentric contractions at short muscle lengths. Nosaka et al. (2005b) found
that the eccentric exercise at the short muscle length (50-100°) produced a partial
protective effect against muscle damage induced by the eccentric exercise of the long
muscle length (130-180°, full extension: ∼180°) performed 2 weeks later. The magnitude of
protection varied among muscle damage markers, but this amounted to a “partial”
protection of around 50% for most of markers.
Applications of the repeated bout effect to minimise muscle damage
It is likely that large number of high intensity and fast velocity lengthening contractions at
long muscle lengths result in sever muscle damage. The magnitude of muscle damage
can be attenuated by eliminating a factor or factors exacerbating muscle damage; that is,
reducing the number of contractions, intensity, velocity, and muscle length during eccentric
exercise. If eccentric exercise is preceded by isometric contractions at a long muscle
length, small number of lengthening contractions, slow velocity lengthening contractions,
lengthening contractions at small muscle lengths, severe muscle damage can be avoided
(NOSAKA, 2009). A combination effect such as having small number and slow velocity
lengthening contractions has not been investigated, and warrants further study.
It is important to note that the initial eccentric exercise bout that does not necessarily
induce muscle damage still confer the repeated bout effect as mentioned above. For
example, a low-intensity eccentric exercise that does not result in any changes in muscle
damage markers can still attenuate the magnitude of muscle damage in the subsequent
more demanding eccentric exercise (LAVENDER & NOSAKA, 2008). It should be noted
that the magnitude of the attenuation in muscle damage conferred by such low-intensity
eccentric exercise (e.g. 50% reduction in the peak DOMS) is greater than that induced by
prophylactic interventions such as nutritional supplementation.
Because of the repeated bout effect, the recovery of muscle from eccentric exercise-
induced muscle damage is not retarded by additional eccentric exercise bouts performed
in early recovery days (CHEN & NOSAKA, 2006a; NOSAKA & CHEN, 2006b; NOSAKA &
NEWTON, 2002a; NOSAKA & NEWTON, 2002b). Chen and Nosaka (2006a) investigated
whether the second eccentric exercise performed 3 days after the initial bout would
exacerbate muscle damage and retard the recovery, and showed that the elbow flexors
could perform high-intensity eccentric exercise in the early stage of recovery from the
initial bout and the muscles were not damaged further by performing the subsequent bout.
They also reported in a separate study (CHEN & NOSAKA, 2006b) that recovery from
eccentric exercise was not retarded by the second bout of eccentric exercise consisting of
greater number of eccentric contractions (70 contractions) than the initial bout (30
contractions) separated by 3 days. These findings suggest that protective mechanisms are
taken place soon after the first exercise bout, and further muscle damage is prevented.
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Underlying mechanisms of the repeated bout effect
The mechanisms underlying the repeated bout effect are yet to be elucidated; however,
neural, mechanical, and cellular adaptations are thought to be associated with the
repeated bout effect (MCHUGH et al., 1999; MCHUGH, 2003). The neural adaptations
include more efficient recruitment of motor units, increased synchrony of motor unit firing,
better distribution of the workload among fibres, improved usage of synergist muscles, and
increased slow-twitch fibre recruitment. Nosaka et al. (2002) reported that the second bout
of eccentric exercise in which the elbow flexors were forcibly stretched while being
stimulated by electrical stimulation resulted in smaller changes in muscle damage markers
compared with the initial bout of the same exercise performed 2 weeks before. Aldayel et
al. (2009) compared the first and second exercise bouts consisting of electrically evoked
isometric contractions separated by 2 weeks for muscle damage profile. The knee
extensors of one leg were stimulated by biphasic rectangular pulses (75 Hz, 400 µs, on-off
ratio 5-15 s) at the knee joint angle of 100° (0°: full extension) to induce 40 isometric
contractions. MVC decreased by 26% immediately and 1 h after both bouts, but the
recovery was faster after the second bout (100% at 96 h) compared with the first bout
(81% at 96 h). Development of muscle soreness and tenderness, and increases in plasma
CK activity were smaller after the second than the first bout. These results suggest limited
central regulations for the repeated bout effect.
Black and McCully (2008) compared the repeated bout effect on muscle damage between
voluntary and electrically stimulated eccentric exercise (80 eccentric contractions) of the
knee extensors. For both electrical voluntary and electrical stimulation conditions, two
bouts were separated by 7 weeks. A repeated bout effect was observed in the changes in
T2 relaxation time, MVC strength, and muscle soreness in both conditions similarly. They
concluded that the repeated bout effect was not related to changes in muscle recruitment
and was potentially related to structural changes within the muscles. Kamandulis et al.
(2010) also reported that a single eccentric exercise bout was not sufficient to change the
neural drive, and stated that repeated bout effect would reside primarily within the muscle
not at the neural level. Muthalib et al. (under review) found that muscle activation,
oxygenation and hemodynamics during eccentric exercise were not different between the
first and second eccentric exercise bouts, suggesting that neural and metabolic factors are
not the main mechanisms to explain the repeated bout effect.
In contrast, Howatson and van Someren (2007) reported the presence of a carry over
effect from one arm to the other such that changes in MVC strength, serum CK activity,
and muscle soreness were attenuated when a second bout of eccentric exercise of the
elbow flexors was performed by the contralateral arm 2 weeks later. Newton et al. (under
review) compared changes in markers of muscle damage between right and left arms
following maximal eccentric exercise of the elbow flexors separated by 4 weeks with the
order of testing between arms randomised. No significant group differences between arms
were evident for any of the criterion measures, but the recovery of MVC strength was
significantly faster, and increases in upper arm circumference and plasma CK activity were
significantly smaller after the second bout compared with the first bout, although the
magnitude of the difference between bouts was smaller when compared with the
magnitude of the repeated bout effect shown in the same arm. These results suggest that
the neural adaptation partially play a role in the repeated bout effect.
The repeated bout effect may be attributed more to mechanical adaptations (e.g.
increases in passive or dynamic muscle stiffness, remodelling of intermediate filament
system, increased intramuscular connective tissue) and/or cellular adaptations (e.g.
longitudinal addition of sarcomeres, adaptation in inflammatory response, adaptation to
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maintain excitation-contraction coupling, strengthened plasma membrane, increased
protein synthesis, increased stress proteins, removal of stress-susceptible fibers)
(NOSAKA, 2010). Proske and Morgan (2001) suggested that increases in sarcomere
number in series were associated with the repeated bout effect. This theory is indirectly
supported by a shift of optimum angle toward a longer muscle length probably caused by
increases in sarcomere number in series. However, it has been shown that the repeated
bout effect is induced without a shift of optimum angle (CHEN et al., 2007). It does not
appear that the repeated bout effect is explained by the increases in sarcomere number in
series.
Koh and Brooks (2001) explained that upregulation of cytoskeletal proteins (desmin, talin,
vinculin, dystrophin) and/or free radical scavenging pathways might be related to the
repeated bout effect. McArdle et al. (2004) postulated that activation of the
haemoxygenease-1 (HO-1) gene resulting from increased reactive oxygen and nitrogen
species generation was related to the repeated bout effect. It has been reported that
“remodelling” of cytoskeleton and/or endomysium could occur after a bout of eccentric
exercise (BARASHI et al., 2002; YU et al., 2004).
It is also possible that muscle-tendon behaviour and fascicle length changes during
maximal eccentric contractions are modified in the repeated bouts. If muscle fibers are
lengthened less during eccentric contractions, less muscle damage may be induced. It
might be that an initial eccentric exercise makes the muscle length changes in the
subsequent exercise smaller, and reduced muscle strain during eccentric contractions.
Further studies are necessary to delineate the mechanisms underlying the repeated bout
effect.
Significance of the repeated bout effect
Regardless of the underlying mechanisms, the repeated bout effect should be used
effectively to attenuate the magnitude of muscle damage when it is necessary. As shown
in above, performing a light eccentric exercise or maximal isometric contractions at a long
muscle length attenuates the magnitude of muscle damage and enhances the recovery
following a higher intensity eccentric exercise. Peak muscle soreness is reduced 50% by
performing a low-intensity eccentric exercise that does not induce any indications of
muscle damage 2 weeks before maximal eccentric exercise (CHEN et al. under review).
Therefore, if it is necessary to minimize potential muscle damage in exercise to be
performed, it is advisable to perform a light eccentric exercise prior to the damaging
exercise within two weeks, preferably within a week. When introducing eccentric exercise
to individuals, it is better to start with eccentric contractions with very light load. Further
studies are necessary to investigate how muscle damage is avoided completely, whether
such strategy is beneficial for the outcomes of eccentric training.
It is also important to consider the repeated bout effect when designing a study. For
example, if a treatment condition and control condition are compared to examine the effect
of an intervention on muscle damage using a crossover design, the same muscle should
not be used for the conditions. If a limb-to-limb comparison model such that one of the
limbs (e.g. right arm) is used for a treatment condition, and other limb (e.g. left arm) is
used for a control condition, the repeated bout effect can be minimized, if the order of the
conditions is counterbalanced amongst the subjects. However, it should be noted that
minor “repeated bout effect” is still evident for this model (NEWTON et al. under review).
Perspective for future research
Definitely, more research is necessary to elucidate the mechanisms of the repeated bout
effect. It may be that there are several mechanisms involve in the repeated bout effect,
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and the main mechanism is different among different kinds of the repeated bout effect; the
repeated bout effect induced by maximal eccentric exercise; the repeated bout effect
induced by submaximal eccentric exercise, and the repeated bout effect induced by non-
damaging exercise. It is also possible that different mechanisms are responsible for
different aspects of the repeated bout effect; faster recovery of muscle function, reduction
of DOMS, and smaller or no increases in muscle proteins (e.g. CK, Mb) in the blood.
For the practical application of the repeated bout effect, it should be investigated further
whether this adaptation is similar between muscles, between genders, between trained
and untrained individuals, and between young and old individuals. It is interesting that
isometric contractions or low-intensity eccentric contractions provide the protective effect
against maximal eccentric contractions; however, it should be investigated further whether
repeating the non-damaging exercise several times confers greater protective effect than a
single bout. It is possible to minimize the magnitude of muscle damage using the repeated
bout effect; however, it is not known whether this strategy is beneficial for maximizing
muscle strength and size gain in training. If muscle damage is required to induce
resistance training adaptations, minimizing the repeated bout effect is necessary. It is not
known how the repeated bout effect can be eliminated. Better understanding of the
repeated bout effect is necessary to clarify the mechanisms of the exercise-induced
muscle damage, which have not been fully elucidated yet. Muscle damage and repeated
bout effect research should be continued, although the topic is not new.
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AUTHORS BIOGRAPHY
Name: Kazunori Nosaka
Employment: Professor of School of Exercise, Biomedical and Health
Sciences at Edith Cowan University, located in Joondalup, Western Australia,
Australia.
Degree: PhD
Research interests: Exercise-induced muscle damage, Neuromuscular
fatigue, Eccentric exercise, Resistance training, Exercise and Health.
Email: k.nosaka@ecu.edu.au
Name: Marcelo Saldanha Aoki
Employment: Assistant Professor of School of Arts, Sciences and
Humanities at University of São Paulo, located in São Paulo, São Paulo,
Brazil.
Degree: PhD
Research interests: Muscle plasticity, Sports nutrition, Training monitoring,
Resistance exercise.
Email: saldanha.caf@usp.br