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ActaPhysiol2006,188,77–89
REVIEW
Atrophy and hypertrophy of skeletal muscles: structural
and functional aspects
O. Boonyarom1 and K. Inui2
1 Department ofPhysicalTherapy, Naresuan University, Phitsanulok, Thailand
2 Department ofPhysicalTherapy, Sapporo MedicalUniversity, Sapporo, Japan
Received20April2006, Abstract
revisionrequested6May2006, This review summarizes current information on structural and functional
finalrevisionreceived1July2006,
changes that occur during muscle atrophy and hypertrophy. Mostpublished
accepted2July2006
studies consider an increase in total mass of a muscle as hypertrophy,
Correspondence:O.Boonyarom,
whereas a decrease in total mass of a muscle is referred to as atrophy. In
DepartmentofPhysicalTherapy,
SchoolofHealthSciences, hypertrophy,therateofsynthesisismuchhigherthantherateofdegradation
SapporoMedicalUniversity,PO ofmusclecontractileproteins,leadingtoanincreaseinthesizeorvolumeof
Box060-8556,West17,South3, an organ due to enlargement of existing cells. When a muscle remains in
Chuo-ku,Sapporo,Japan.
disuse for a long period, the rate of degradation of contractile proteins
E-mail:[email protected]
becomes greater than the rate of replacement, resulting in muscle atrophy.
This defect may occur as a result of lack of nutrition, loss of nerve supply,
micro-gravity, ageing, systemic disease, prolonged immobilization or disuse.
An understanding of the specific modifications that occur during muscle
atrophyandhypertrophymayfacilitatethedevelopmentofnoveltechniques,
as well as new therapies for affected muscles.
Keywords atrophy, functional change, hypertrophy, structural change.
Atrophy and hypertrophy are two opposite conditions Moreover, it can result either from increased protein
that can be found in pathological or diseased muscles. production, decreased protein breakdown, or a combi-
Atrophy is characterized by a wasting or loss of the nationofbothoftheseaspectsofproteinturnover.The
musclemass(A1)andusuallyinvolvesadecreaseinthe processes that govern the extent of muscle atrophy are
sizeorcross-sectionalarea(CSA)(A2)ofanindividual basedonthemagnitudeoftheregulateddeclineinrate
myofibreoranumberofmyofibres(Grounds2002).In ofproteinsynthesis,increasedlevelofoxidativedamage
contrast, hypertrophy is an increase in muscle mass (A4), and subsequent unregulated protein degradation
(Russell etal. 2000) and CSA (Russell etal. 2000, (Hudson & Franklin 2002, Glass 2003). For example,
Grounds 2002), specifically due to an increase in the inhibitors of the proteosome block increases in protein
CSA of individual muscle fibres (Grounds 2002). As a breakdown normally seen in atrophy (Tawa etal.
result, the muscle strength (A3) and the bone mass 1997), the level of ubiquitinated conjugates increase
(Fluckey etal. 2002)are significantly affected. during atrophy (Lecker etal. 1999b) and genes that
To maintain homeostasis, the biological response of encode various components of the ubiquitin pathway
the human body generates a dynamic balance between increase during atrophy (Attaix etal. 2001, Gomes
syntheticanddegradativeprocesses(Mitch&Goldberg et al. 2001). An increase in muscle activity stimulates
1996, Lecker etal. 1999a, Hornberger & Esser 2004) the expression of a protein growth factor known as
for both atrophic and hypertrophic muscles. This insulin-like growth factor I (IGF-I). IGF-I has been
dynamic balance occurs in response to any stimuli shown to be sufficient to induce hypertrophy through
(Hoffman & Nader 2004), due to processes that eitherautocrineorparacrinemechanisms(DeVoletal.
promote muscle growth via increased protein content. 1990, Barton-Davis etal. 1999). IGF-I expression is
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increased during compensatory hypertrophy (De Vol clinical assessments for disuse muscle atrophy can be
etal.1990)causedexperimentallybyremovingseveral performed at the bedside, accompanied with the
muscles to force those remaining to take up the strength assessment by observing muscle movement,
resultant increase in load. muscle tone,muscle size andmuscle strength.
Muscle atrophy Changes in muscle atrophy
Thecausesofmuscleatrophyarefromseveralsources,
Muscle fibre CSA
such as neuromuscular diseases, immobilization and
denervated conditions. In addition, the muscle atrophy At the cellular level, there are some noticeable changes
may also take place, secondary to some devastating in the muscle cell including sarcomere dissolution and
injuries or common health problems (Kandarian & endothelial degradation (Oki et al. 1995). In addition,
Stevenson 2002, Jackman & Kandarian 2004),suchas there is a marked reduction in the number of mitoch-
spinal cord injury (SCI) (Shields 1995, Castro etal. ondrias (Rifenberick etal. 1973, Mujika & Padilla
1999), ageing and various systemic diseases (A5), 2001), accumulation of connective tissue (Oki etal.
respectively. Moreover, the condition may be exacer- 1995),eliminationofapoptoticmyonuclei(Smithetal.
batedbystarvation(Mitch&Goldberg1996,Jackman 2000), and a decrease in capillary density and signs of
& Kandarian 2004, Lecker etal. 2004), micro-gravity tortuosity(Hudson &Franklin 2003).
(A6), detraining (A7), reduction in neuromuscular Thegeneralappearanceindicatesanoticeablereduc-
activity(Fittsetal.2000),decreasedlevelsofhormones tion in the muscle fibre CSA when the muscle is in an
(A8),increasesinproteindegradation(A9),decreasesin atrophic condition (A18). Edgerton etal. (1995) have
protein synthesis (A10), decreases in protein content studied a tendency towards of muscle fibre atrophy in
(Jackman & Kandarian 2004), and various forms of threeastronautsusingtissuebiopsiesobtainedfromthe
reduced use (A11). vastus lateralis muscle. They found a significant reduc-
Among acute and critically ill patients, the onset of tioninthemusclefibreCSAaswellasamarkeddecrease
muscleatrophyisrapidandsevere,beginningwithin4h in the type IIb >type IIa>type I fibres, respectively,
of hospitalization (Kasper etal. 2002). In the first few after these astronauts spent 11days in a micro-gravity
weeks during hospitalization, the antigravity or the environmentinspace.Inaddition,Widricketal.(1999)
extensorgroupmuscleswillshowgreateratrophythan took tissue biopsies of the soleus muscle from four
non-antigravityorflexorgroupmuscles(Fittsetal.2000, astronauts on the 45th day before spaceflight (SF) and
Kasper etal. 2002). During extended periods of hospi- made a comparison with the samples taken from the
talization,aprolongedunusedlimbleadsnotonlytoan 17th day of SF. They found a similar reduction as
impairmentofthemusclefunction(A12),butalsotoa previously reported by Edgerton etal. (1995) in which
deleteriousalterationinthemusclemorphology(Bloom- the type IIa and the type I fibre CSA had declined by
field1997),manifestedinsymptomssuchasadecreasein 26% and 15%, respectively. Moreover, Kawashima
muscle mass (A13), a reduction of the muscle fibre etal.(2004)haveinvestigatedthephysiologicalCSAof
diameter(Widricketal.1997,Kasperetal.2002),anda thighadductormusclesof10healthysubjects(fivemen
reductionintheoverallnumberofmusclefibres(Kasper andfivewomen)andfoundanatrophicchangeinthese
etal. 2002). Moreover, this condition may also have a muscles following 20 days of bed rest. In this case,
negativeaffectonbonehealthbydecreasingbonemineral muscle wasting due to disuse can be restored to its
densityatthelumbarspine,femoralneckandcalcaneus original size after a 1month period of reambulation.
(Bloomfield 1997, Hasselgren 1999). Interestingly, the Consequently, the production of muscle force is pro-
durationofimmobilityhasbeenshowntobepositively portional to the number of days of disuse (A19). The
correlatedwiththedegreeofmuscleatrophy(A14). decrease in muscle fibre CSA due to the atrophic
The early signs of muscle atrophy found in these condition can affect not only the maximal force (A20)
patients are accompanied by general weakness (A15) and muscle power output, but also the locomotor
andfatigue(A16),especiallyinthelowerlimb(A17).In activity (Hudson & Franklin 2002). The degrees of
fact, these clinical signs may be caused either by the muscle weakness due to SF or bed rest (LeBlanc etal.
medicationorpathologicalconditionperse.Therefore, 1992, Fitts et al. 2000, Stein & Wade 2005) are
it is inappropriate to conclude the patient’s condition correlatedwiththeperiodofunloading(A21).
basedonlyonmuscletestingalone.Someotherclinical
assessments such as electrodiagnosis, computerized
Myonuclear number and domain size
muscle strength analysis and biochemical analyses are
essential for providing verification and further confir- Disappearanceofmyonuclearisoneofthepathological
mation of the status of the muscles in question. The signsofmuscleatrophy(A22).Studiesinanimalswhich
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have undergone SCI (Dupont-Versteegden etal. 1999, eter of the type I fibres was decreased, whereas that of
2000) or hindlimb immobilization (Smith et al. 2000) the type II fibres varied from 56% to 73%. However,
haveshownareductioninnuclearnumber.Inaddition, Booth (1982) found an absolute reduction in the
Machida&Booth(2004a)havereportedthatthissign number of the slow-twitch fibres, but no significant
canbecoincidentwiththedecreaseofmusclefibreCSA. changewasobservedintheabsolutenumberofthefast-
However,severalgroupsofinvestigatorshavesuggested twitch fibres in the cross-section of the soleus muscles
that the quantitative loss of myonuclei during muscle from limbs that had experienced immobilization for
atrophy is not always proportional to the decrease of 4weeks. This finding is consistent with the subsequent
muscle fibreCSA,buttoasmallermyonucleardomain reports from Edgerton etal. (1975) and Maier etal.
size(Allenet al.1996,1997,Smithetal.2000).Another (1976) which show a decrease in the proportion of
study carried out on patients following 2–4months of slow-twitchfibresoftheimmobilizedlimbs.Incontrast,
bedrestbyOhiraet al.(1999)hasalsoshownadistinct Cardenas etal. (1977) employed the similar immobi-
decreaseinmyonucleardomainsizewithoutanychange lized model and also reported no significant change in
in myonuclear number. Due to the difference in the the total number of muscle fibres of the soleus muscle.
musclefibretyperatios,thequestionregardingmyonu- These findings are supported by the results obtained
clearlossiswhetherspecificfibretypesaremoreorless from many studies which show no change in the
sensitive to myonuclear shifts in comparison with the number of fibres despite significant increase in the
others(Edgertonetal.2002).TheslowortypeImyosin muscle mass (A26).
heavychain-expressing(MHC-expressing)fibresinrats
contain a greater number of myonuclei per unit length
Muscle volumes
than the fast fibres (Allen etal. 1996). Several micro-
scopic studies in adult rats were able to induce an Akima etal. (2000) utilized a magnetic resonance
atrophic condition that demonstrated type I fibres also imaging (MRI) technique to measure the volume of
seem to lose more myonuclei than type II fibres (A23). knee extensor, knee flexor and plantar flexor muscles
Similarfindingswereobtainedinhumansubjectswhose before and after 2weeks of SF and found similar
leg muscles were inactive during SF or hindlimb reduction of 5.5–15.4%, 5.6–14.1% and 8.8–15.9%,
unloading (HU) (A24). These studies found a greater respectively.Inaddition,theynoticedthatthedegreeof
reduction in myonuclear number in type I MHC- atrophyinducedbythe2-weekSFwasgreaterthanthat
expressing fibres of the soleus muscle when compared inducedbythe20-daybedrest.TheMRIresultsofthe
withthetypeIIMHC-expressingfibresoftheplantaris SF crew members during 17 days of the mission also
muscle. However, a study of neonatal muscle fibres in shown a decrease in the muscle volume of 5–17% for
ratsunderthereducedweight-bearingconditionsshown most muscle groups, accompanied with a loss in the
similarreductionsinthefibresize,myonuclearnumber bone mineral content proportional to the lean body
and myonuclear domain size among all fibre types mass by approx. 3.4–3.5% (LeBlanc etal. 2000).
(Ohiraetal.2001). Moreover, Henriksen et al. (1993) have reported an
increase in the interstitial fluid volume (IFV) during
muscleatrophy.TheysuggestedthattheincreasingIFV
Muscle fibre type
might be responsible for the loss of muscle mass and
Afterafewweeksofimmobilization,musclescomposed contractile proteins.
predominately of type I fibres assumed properties
characteristic of type II fibres (A25). Tischler etal.
Amounts of muscle protein and DNA
(1993) has demonstrated that the slow-twitch fibres of
the extensor muscles in young rats during SF-induced In atrophic muscles, the amount of the contractile
atrophy show a marked increase in susceptibility. proteins (A27), a-actin mRNA (Babij & Booth 1988),
Followinga5.4-daySF,theweightsofthegastrocnem- and cytochrome c mRNA (Morrison etal. 1987, Babij
ius, plantaris and soleus muscles, but not the tibialis &Booth1988)areenormouslyreduced.Bycomparing
anterior and extensor digitorum longus muscles, were per gram of the muscle mass, there is a decreased
decreasedby16%,24%,and38%respectively.Inrats, utilizationofb-hydroxybutyrate,palmitateandglucose,
the slow-twitch fibres of the antigravity and extensor and levels of high-energy phosphates decline (Booth
group muscles, such as the soleus and adductor longus 1977), as do levels of oxidative enzymes (Sasa etal.
muscles, were actually more affected by atrophic 2004) such as citrate synthase (Bebout etal. 1993),
conditions than the fast-twitch fibres and flexor group malate dehydrogenase (Rifenberick etal. 1973), and
muscles (Fitts et al. 2000). Kauhanen etal. (1998) phosphokinase (Carmeli etal. 1993). In rats, the first
utilized a free microvascular muscle flap technique for week of muscle wasting with HU is primarily caused
9months and found that the mean muscle fibre diam- by a decline in protein synthesis, whereas myofibril
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degradation does not reach its maximum until days IGF-Iisalsothoughttobeinvolvedintheactivation
9–15(Thomasonetal.1989).Moreover,theresponses of satellite cells (Barton-Davis etal. 1999, Machida &
ofthetissue-culturedmyofibrestoSFwerequitesimilar Booth 2004a), satellite cells are small mononucleate
to that reported for humans and animals in space muscle stem cells located between the sarcolemma and
(Vandenburgh etal. 1999). Thus, there is little alter- basal lamina of muscle fibres. Recently, the link
ation in muscle protein degradation rates (Stein & between satellite cell number and myofibre size has
Schluter 1997, Vandenburgh etal. 1999), or muscle beendemonstratedinbothuntrainedandhypertrophied
metabolic rates (Miu etal. 1990, Vandenburgh etal. human muscle fibres (Kadi & Thornell 2000). These
1999), and there is preferential loss of myofibrillar cells, when activated, are believed to proliferate and
proteins (A28). In the case of muscle fibres, the DNA differentiate into myoblasts, which then fuse with
fragmentationandnucleardestructionwouldeliminate existing fibres, thus providing new nuclei to maintain
someunneededmyonuclei,whileleavingtheremaining the ratio of DNA to protein for fibres undergoing
myonuclei and the fibre itself relatively unharmed hypertrophy.ThelinkbetweenIGF-I,satellitecells,and
(Edgerton etal. 2002). Evidence for DNA fragmenta- hypertrophy hasbeen showninstudieswherelocalised
tion and transformations in myonuclear morphology infusion of IGF-I into the tibialis anterior muscle of
indicative of apoptosis were observed in the muscle adult rats resulted in an increased total muscle protein
fibres of hindlimb suspended rats (Vandenburgh etal. and DNA content (Adams & McCue 1998). More
1989), denervated rats (Vandenburgh etal. 1990), as recently,Bammanetal.(2001)reporteda62%increase
wellasinimmobilizedrabbitmuscle(Smithetal.2000). in IGF-I mRNA concentration in human muscle 48 h
Muscledisuseisapathologicalconditionthataffects after a single boutof eccentric resistance typeexercise.
notonlythebiochemicalandcellularlevels,butalsothe
locomotive behaviour level. In addition, some of the
Changes in muscle hypertrophy
structural changes associated with muscle disuse atro-
phy are pathological and prolonged recovery periods
Muscle fibre CSA
are often required before full muscle and locomotion
performance is re-established (Hudson & Franklin Myofibre CSA increases during overload-induced
2002). The studies in frogs (St-Pierre etal. 2000, hypertrophyofamuscle.Radialenlargementofmuscle
Hudson & Franklin 2002), and some hibernating fibres after resistance training or external loading
mammals such as bears (Harlow etal. 2001) and rats confers to the muscle a greater potential for maximal
(Booth&Seider1979)haveshownthatdisusedmuscles forceproduction.Duringload-inducedmyofibrehyper-
actually require a long period time (3–4months) of trophythereisanincreasedaccumulationofcontractile
recovery to re-establish their strength and locomotor and non-contractile muscle proteins, and the synthesis
performance. and degradation rates of these proteins are critical for
determining their net quantity (Goldspink 1991). Pro-
teinsynthesisanddegradationrateshavebeenshownto
Muscle hypertrophy
be altered in hypertrophying muscle (Goldberg 1969,
Hypertrophyofamuscleisamultidimensionalprocess Laurent et al.1978).
involving several factors such as growth factors (GFs) Overload-induced hypertrophy is a complex event,
(Adams & Haddad 1996, Semsaria etal. 1999), IGFs buttheresearchinthisareasupportsatwo-stagemodel
(A29), clenbuterol (Argiles et al. 2001), anabolic ster- ofmuscleadaptationtooverload:(1)duringregulation
oids(Beineretal.1999,Argilesetal.2001),hormones at the onset of hypertrophy, muscle protein synthesis
(A30), the immune system (Shephard & Shek 1998), increases during overload-induced muscle hypertrophy
and satellite cells (A31). For example, in a study in both humans and animals (A33). Wong & Booth
investigating IGF-I peptide levels in human muscle (1990) found that the major mediator of increased
following10weeksofstrengthtraininginoldmenand myofibril protein synthesis in the rat gastrocnemius
women(aged72–98years),itwasshownthattherewas muscle after acute isotonic resistance exercise was not
a c. 500% increase in the levels of IGF-I within the RNA abundance, but most likely increased RNA
musclefibresofthesesubjectsafterthetrainingperiod, activity (g protein per lg RNA); and (2) during regu-
asdeterminedusingimmunohistochemistry(Singhetal. lation at later stages of hypertrophy, myofibrillar
1999).Thisdemonstratesthatthepeptidelevelsinolder protein mRNA levels increase later from overload-
muscles may adapt over the longer-term to exercise induced enlargement in most hypertrophy models.
training. Indeed, the results of longitudinal strength Skeletal a-actin mRNA has been shown to increase
trainingstudieshaveconfirmedthatthemusclesofeven between 3 and 6days of chronic stretch overload
very elderly people are able to exhibit a hypertrophy (Carson et al. 1996). The increased mRNA template
response to resistance exercise(A32). can be achieved by increasing the transcription rate of
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ActaPhysiol2006,188,77–89 OBoonyaromandKInui Atrophyandhypertrophyofskeletalmuscles
the given gene and/or the addition of a satellite cell & Rosenthal (2002) have investigated these fibre
derived nuclei. Kadi etal. (2004) have demonstrated transmutations in two mouse gracilis muscles, in
that the high plasticity of satellite cells in response to responsetoexpressionofamuscle-specificIGF-Itrans-
training, providing new insights into the long-term gene (mIGF-I) or to chronic exercise. The gracilis
effectsoftrainingfollowedbydetraining.Thisresearch anterior muscle shown decreased type I and type IIa/x
has shownthat moderate changes in the size of muscle MHC-positivefibres,withanincreaseintypeIIbMHC-
fibres can be achieved without the addition of new positive fibres, although the trend was not statistically
myonuclei, which indicates that existing myonuclei are significant. Exercise, rather than the expression of the
abletosupportacertainlevelofmusclefibrehypertro- myosin light chain/mIGF-I transgene appears to be the
phy. Hypertrophying muscles appear to be sensitive to determinant of fibre type changes in this muscle, since
both loading conditions and the muscle fibre’s micro- only muscles from the wild-type-exercise and IGF-
environment, both of which govern the degree of exercise have shown a significant increase in type IIb
enlargement that the muscle fibre has achieved. Inte- MHC-positivefibres.Thegracilisposteriormusclealso
grins are proteins which connect the extracellular has shown a slight decrease in the number of type I
matrixtothecytoskeletonbyspanningthesarcolemma. MHC-positive fibres with a trend toward a greater
These integrins play a role as receptors, so that numberoftypeIIa/xMHC-positivefibresatthecostof
alterations in cell shape are a result of mechanical type IIb fibres. The preferential increase in type IIa/x
signalswhichhavebeenshowntoaltergeneexpression overtypeIIb-positivefibresinthismusclecomparewith
in the nucleus, and integrin receptors may play a the gracilis anterior muscle likely reflects the specific
prominent role in this pathway (Schwartz & Ingber activity patterns and loading of these muscles. These
1994). resultsindicatedthattheproportionoffibrephenotype
Skeletal muscle fibres have a remarkable ability to is predominantly influenced by exercise in both the
alter their phenotype in response to environmental single and themultiple-innervated muscle.
stimuliorperturbations.Anexampleofthiscapacityfor
adaptive change, or plasticity, is the cell hypertrophy
Muscle volume
that occurs after resistance training. There is a general
consensusthatresistancetrainingcauseshypertrophyof A pronounced adaptive response to high-intensity or
all muscle fibre types, with fast fibres often showing a weight bearing exercise interventions is muscle hyper-
somewhat greater response than slow fibres (A34). In trophy. The increased mass of active muscle groups is
addition, McCall etal. (1996) have reported that the achieved by an increase in the volume of individual
pattern of hypertrophy differed between the type I and myofibres (Green etal. 1999). The enlarged myofibre
II fibres. In the type I population, the hypertrophy can only expand with the insertion of new nuclei,
occurred in the medium size fibres, whereas the entire because a constant ratio of nuclei to cytoplasmic
range of fibres underwent hypertrophy in the type II volume is maintained throughout all hypertrophic
population.Finally,thedistributionoftypeIIfibreswas responses (McCall etal. 1998, Barton-Davis etal.
much wider than that of type I fibres, both before and 1999). Thus,hypertrophy isdependenton the prolifer-
after training. Other studies in human muscle fibres ative activation of satellite cells and their myogenic
have reported that the CSA of vastus lateralis muscle differentiation (Seale & Rudnicki 2000) before fusion
fibrescontainingtypeI,IIaorIIa/IIxMHCincreasedby withtheexistingmyofibre(Garryetal.2000).Another
anaverageof 30%after 36resistancetrainingsessions study observed in 60 healthy men (aged 18–35years)
(Widricketal.2002).Thesedataareconsistentwiththe treatedwithgradeddosesoftestosteroneareassociated
resistance training-induced increases in slow- and fast- withconcentration-dependentincreasesinCSAofboth
fibreCSAreportedinthehistochemicalliterature(A35). typeIandtypeIImusclefibresandmyonuclearnumber.
They concluded that the testosterone-induced increase
in muscle volume can be attributed to muscle fibre
Muscle fibre type
hypertrophy (Sinha-Hikimet al.2002).
The effects of transgenic or exercise-induced hypertro-
phy on shifts in muscle fibre type were investigated by
Protein synthesis
scoringthepercentageoftypeI,typeIIbandtypeIIa/x
MHC-positive fibres in gracilis anterior and gracilis Muscle hypertrophy is a condition characterized by
posterior muscles. Minimal fibre type changes have increasingproteinaccumulationinthestimulatedmus-
been observed previously in the myosin light chain/ clecells.Itisduetoanimbalanceturnoverratebetween
mIGF-I transgenic mice (Musaro et al. 2001), whereas increased protein synthesis and the lesser protein
significant fibre type changes have been observed with breakdown (Hornberger & Esser 2004). It is known
voluntaryexercise(Allenetal.2001).Inaddition,Paul that a period of resistance training enhances protein
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synthesisinhumanmuscles(A36).Theenhancementof replacement,resultinginadefectcalledmuscleatrophy.
proteinsynthesismightbemediatedbypre-translational Muscle atrophy may occur from lack of nutrition, loss
(alteration in the abundance of mRNA), translational of nerve supply, micro-gravity, ageing, systemic dis-
(alteration in protein synthesis per unit of mRNA), or eases, as well as from prolonged immobilization or
post-translational(transformationoftheproteinsuchas disuse. Examination of the muscle fibre may reveal a
phosphorylation) events (Booth et al. 1998, Tipton & shrinking of diameter and strength, in addition to a
Wolfe 1998). It is suggested that changes in the fundamentalalterationofthetypesofremainingmuscle
translational efficiency are responsible for the early fibres. Antigravity muscles that frequently contract to
stages of protein synthesis enhancement (Laurent etal. supportthebodytypicallyhavealargenumberofslow
1978). During the later stages of protein synthesis fibres (type I), which appear to change more rapidly
enhancement, it appears that pre-translational events than fast fibres (type II) during prolonged periods of
become critical (abundance of mRNA) (Adams 1998). unloading. This process is often quite rapid, as one
In this respect, adult muscle fibres are multinucleated completecycleiscompletedeveryfewweeks.Detailsof
cellswhereeachmyonucleuscontrolstheproductionof thestructuralandfunctionalchangesthatoccurduring
mRNA and protein synthesis over a finite volume of atrophy and hypertrophy muscles, as well as mechan-
cytoplasm, a concept known as the DNA unit or istic explanations for how these changes occur, are
myonuclear domain (Cheek 1985, Hall & Ralston lacking. Basic questions that must be addressed in this
1989). There is evidence showing that a stimulation of fieldfollowlogicallyfromthematerialpresentedherein.
myofibres with low-frequency, high-intensity intermit- Whataretheproteinsthatarealteredwithinatrophied
tentcurrentsproducesahypertrophicchange,resulting and hypertrophied muscles? Are the signalling proteins
in a 45–80% increase in total protein synthesis essential to the mechanisms regulating muscle atrophy
(Vandenburgh etal. 1989) and 15–30% decrease in and hypertrophy? Does the muscle respond differently
total protein degradation (Vandenburgh etal. 1990). tovaryingcausesofatrophyandhypertrophy?Doesthe
The increase in translational capacity is indicated by age of the fibres have an influence on the atrophy and
increasednumbersofribosomeswhichleadstoprotein hypertrophy process affecting the properties of the
expression and protein synthesis, respectively (Nader muscular tissue? These are the types of questions that
etal.2002).Thenewlysynthesizedcontractileproteins must ultimately be answered to develop rational ther-
arelikelytobeincorporatedintotheexistingmyofibrils. apy and rehabilitation strategies to be able to provide
However, there is a limit to the growth of myofibrils. effective treatmentto affected muscles.
After reaching this particular threshold limit, each
myofibrilcaninitiateaseparationprocess.Alltogether,
Conflict of interest
itis generally accepted thatmuscle hypertrophy results
primarily from the growth of individual muscle cells There are noconflicts ofinterest.
rather thanincreasing thenumberof muscle fibres.
The authors gratefully acknowledge the help of Dr Niwat
Taepavarapruk,DepartmentofPhysiology,FacultyofMedical
Conclusion Science,NaresuanUniversity,forhisinsightfulcomments,and
SompiyaSomthavil,DepartmentofPhysicalTherapy,Faculty
Musclecanbecharacterizedbytwoterms,hypertrophy of Allied Health Sciences, Naresuan University, for helpful
andatrophy,dependingonwhetherthereisanincrease preparationofthemanuscript.
in the total mass of a muscle or a decrease in the total
mass of a muscle, respectively. In almost all cases,
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