Sports Med 2004; 34 (12): 809-824

REVIEW ARTICLE 0112-1642/04/0012-0809/$31.00/0

 2004 Adis Data Information BV. All rights reserved.

Effects of Aging on Muscle Fibre

Type and Size
Michael R. Deschenes
Department of Kinesiology, The College of William & Mary and the Center for Excellence in
Aging and Geriatric Health, Williamsburg, Virginia, USA

Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 809
1. Muscle Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 810
1.1 Power . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 810
1.2 Strength . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 811
1.3 Muscular Endurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
2. Sarcopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
2.1 Whole Muscle and Fibre Size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
2.2 Fibre Type Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 814
3. Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 815
3.1 Denervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 815
3.2 Protein Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 816
3.3 Circulating Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 816
3.4 Autocrine Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 817
3.5 Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 818
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 819

Abstract Aging has been associated with a loss of muscle mass that is referred to as
‘sarcopenia’. This decrease in muscle tissue begins around the age of 50 years, but
becomes more dramatic beyond the 60th year of life. Loss of muscle mass among
the aged directly results in diminished muscle function. Decreased strength and
power contribute to the high incidence of accidental falls observed among the
elderly and can compromise quality of life. Moreover, sarcopenia has been linked
to several chronic afflictions that are common among the aged, including osteo-
porosis, insulin resistance and arthritis. Loss of muscle fibre number is the
principal cause of sarcopenia, although fibre atrophy – particularly among type II
fibres – is also involved. Several physiological mechanisms have been implicated
in the development of sarcopenia. Denervation results in the loss of motor units
and thus, muscle fibres. A decrease in the production of anabolic hormones such
as testosterone, growth hormone and insulin-like growth factor-1 impairs the
capacity of skeletal muscle to incorporate amino acids and synthesise proteins. An
increase in the release of catabolic agents, specifically interleukin-6, amplifies the
rate of muscle wasting among the elderly. Given the demographic trends evident
in most western societies, i.e. increased number of those considered aged, man-
810
agement interventions for sarcopenia must become a major goal of the healthcare
profession.
Demographic data indicate that the populations
of most western nations are growing older. In the
US, for example, it has been estimated that the
number of people considered to be aged (>60 years
old) will more than double between the years of
1990 and 2030.[1] By the year 2050, the average life
expectancy of Americans will climb to 84.3 and
79.7 years for women and men, respectively.[2] Con-
comitant with this ‘greying’ of western societies is
growing healthcare costs. Indeed, in the US it is
expected that government expenditures for health-
care among the aged will increase 6-fold by the year
2040.[3] Similarly, rapid increments in healthcare
costs have also been reported in the UK.[4]
Many of the healthcare costs attributed to aging
result from treatment of medical conditions that
have been associated with sarcopenia, or the age-re-
lated loss of skeletal muscle mass. Research has
consistently demonstrated a greater incidence of
osteoporosis,[5-7] insulin resistance,[8-10] obesity[11-14]
and arthritis[12,15,16] among those with sarcopenia.
Moreover, the strength decrement that is concomi-
tant with sarcopenia leaves older individuals more
susceptible to accidental falls and resultant inju-
ries.[17,18] Alone, the expense of treating hip frac-
tures is projected to increase from $US2 billion in
the year 2000 to approximately $US6 billion by
2040.[3]
Perhaps more important than the financial burden
associated with sarcopenia, is the detrimental effect
on quality of life that it imparts. Normal daily activi-
ties, not to mention recreational activities that add
joy to life, can be curtailed as a result of age-related
loss of muscle mass and strength.[19] For example,
20% of those who experience hip fractures will not
regain their ability to walk,[20] while the average
80-year-old no longer retains the capacity to rise
unassisted from a chair.[21] Even more striking are
recent data demonstrating that the degree of
sarcopenia evident among the aged serves as a sig-
nificant predictor of all-cause mortality.[22] Thus,
 2004 Adis Data Information BV. All rights reserved.
Deschenes
sarcopenia affects not only the quality, but also the
quantity of life among the aged. Given the severity
of the consequences of sarcopenia and the demo-
graphic trends observed among western societies, it
is imperative to gain a thorough understanding of
the effects of senescence on skeletal muscle, as well
as the aetiology of sarcopenia.
1. Muscle Function
1.1 Power
Aging is known to negatively impact each pa-
rameter of muscle function, i.e. power, strength and
endurance. A loss in muscle power, or ‘explosive
strength’ is first evident by the age of 40 years and
demonstrates a more rapid decline than that of
strength.[23,24] This adaptation to aging occurs in
both men and women,[23,25] has been detected in
muscles of both the upper and lower body,[24] and
has been confirmed by longitudinal, as well as cross-
sectional data.[23] This decrement in muscle power
contributes to the loss of short-term, or anaerobic,
muscle performance that has been documented
among the aged.[26,27] More importantly, the loss of
power noted among the aged directly relates to the
increased number of falls experienced by the elder-
ly[28] and can also hinder the performance of normal
daily activities such as stair climbing and the ability
to rise from a chair unassisted.[25]
Recent investigation has sought to elucidate the
mechanisms that explain the diminished power ca-
pacity in aged muscle. Ferretti et al.[29] demonstrated
that the loss of power displayed by the aged is only
partly accounted for by decreased muscle mass. In
analysing electromyographic (EMG) characteristics
of single motor units in young and senescent mus-
cles, Vaillancourt et al.[30] detected significant age-
related differences. Compared with young subjects,
there was a shift towards the slower firing 10Hz
motor units from the faster (40Hz) firing motor units
in the hand muscles of older subjects during maxi-
Sports Med 2004; 34 (12)
Effects and Causes of Sarcopenia
mal voluntary contraction. This indicates the pres-
ence of fewer fast-twitch motor units within aged
muscle. Of course, it is the fast-twitch motor units
that are responsible for the degree of power exerted
by muscle. These data are consistent with earlier
findings showing a selective denervation of fast-
twitch fibres within aged muscle that is concomitant
to a decrease in the number of myelinated neuronal
axons present in that muscle.[31]
In addition to changes in muscle mass and inner-
vation properties, other factors contribute to age-
related reductions in muscle power. For example,
when isolated single muscle fibres from aged and
younger adults were examined, it was determined
that maximal shortening velocity was significantly
less in aged fibres.[32] This suggests that the contrac-
tile apparatus itself within the fibre is altered with
aging, leading to decreased power output. Also of
interest is a recent report that the basic excitation-
contraction coupling mechanism within fibres is
impaired among the aged. Researchers found that
within fast-twitch fibres (those that determine mus-
cle power) the amount of calcium released from the
sarcoplasmic reticulum upon electrical stimulation
is attenuated in aged muscle.[33] Moreover, this re-
sult was attributed to a functional uncoupling of the
dihydropyridine receptors, acting as voltage sensors
in the T-tubules from the ryanodine receptors, i.e.
calcium channels of the sarcoplasmic reticulum. The
authors concluded that the uncoupling that had been
identified may be manifested in the reduced muscu-
lar power displayed by aged muscle.
1.2 Strength
Numerous studies have shown that strength (the
maximal amount of force exerted in a single at-
tempt) is diminished in senescent muscle.[34-41] This
is true in both men and women,[40-42] as well as in the
muscles of the lower and upper extremities.[42] Al-
though all forms of strength expression (concentric,
eccentric, isometric) are negatively impacted by se-
nescence,[43] eccentric strength appears to be more
resistant to the adverse effects of aging.[42,44,45]
Cross-sectional studies indicate that muscular
strength reaches its peak at about 30 years of age and
 2004 Adis Data Information BV. All rights reserved.
811
is well maintained through the 50th year of life.[46]
Although a decline in strength occurs between 50
and 60 years of age, a much more rapid rate of loss is
evident beyond the age of 60 years.[46,47] When
averaged beyond the fifth decade of life, these data
indicate that strength decreases at a pace of nearly
15% per decade.[43,46,48] Moreover, both men and
women exhibit the same rate of strength decrement
during aging.[43,49] Recent longitudinal investiga-
tions, however, have revealed a greater rate of age-
related strength reduction than what is apparent in
cross-sectional studies. For example, Frontera et
al.[50] detected decreases of 2.5% per year in the leg
strength of older men followed for a 12-year period.
Other longitudinal studies report strength reductions
approaching 5% per year in senescent muscle.[51-53]
Much of the strength deficit observed among the
aged can be explained by the loss of muscle mass
that occurs in a near parallel fashion with the loss of
strength.[54-57] Indeed, it has recently been estimated
that the process of sarcopenia accounts for more
than 90% of age-related strength diminution.[50] This
implies that, although minor, other factors contrib-
ute to strength decrements noted in aged muscle.
Several researchers have documented that the elder-
ly are capable of fully activating motor units during
maximal voluntary contraction, suggesting well
maintained central drive among the elderly.[58,59]
Other neural factors, however, may participate in
age-related strength reductions. Using EMG tech-
niques, Hakkinen et al.[60,61] noted a greater degree
of antagonist muscle coactivation in aged than in
young muscle during maximal effort knee exten-
sion. The authors concluded that this may help ex-
plain the attenuated force production observed
among their older subjects.
In attempting to determine factors other than
decreased muscle mass or neural factor modifica-
tions that may lead to strength decrements in the
aged, a host of studies have investigated the effects
of age on muscle quality or specific tension. Briefly,
specific tension is a relative expression of strength,
whereby force produced is a function of a given unit
of contracting muscle tissue. The data regarding
adaptations of specific tension to aging yield con-
Sports Med 2004; 34 (12)
812 Deschenes

Table I. Effects of aging on specific tension of skeletal muscle

Study Muscle Muscle size/mass Muscle Mode of contraction Sex Result
activation
Lynch et al.[42] Biceps/triceps Arm muscle mass Voluntary Concentric/eccentric F ND
Quad/ham Leg muscle mass Voluntary Concentric/eccentric F ↓
Biceps/triceps Arm muscle mass Voluntary Concentric/eccentric M ↓
Quad/ham Leg muscle mass Voluntary Concentric/eccentric M ↓
Lindle et al.[43] Quad/ham Leg muscle mass Voluntary Concentric/eccentric M/F ↓
Frontera et al.[54] Quad Whole body muscle mass Voluntary Concentric M/F ND
Biceps Whole body muscle mass Voluntary Concentric M/F ND
Kent-Braun & Ng[59] Ankle flexor Whole muscle CSA Voluntary Isometric M/F ND
Metter et al.[62] Biceps Whole muscle CSA Voluntary Isometric M ND
Quad Whole muscle CSA Voluntary Isometric M ND
Overend et al.[63] Quad/ham Whole muscle CSA Voluntary Isometric M ND
Quad/ham Whole muscle CSA Voluntary Concentric M ↓
Frontera et al.[65] Quad Whole muscle CSA Voluntary Concentric M/F ND
Frontera et al.[65] Single quad fibres Fibre CSA Calcium Isometric M/F ↓
stimulated
Hakkinen et al.[49] Quad Whole muscle CSA Voluntary Isometric M/F ND
Young et al.[40] Quad Whole muscle CSA Voluntary Isometric M ND
Quad Whole muscle CSA Voluntary Isometric F ↓
Larsson et al.[66] Single quad fibres Fibre CSA Calcium Isometric M ↓
stimulated
CSA = cross-sectional area; F = females; ham = hamstrings; M = males; ND = no difference; quad = quadriceps; ↓ indicates decrease in
specific tension of skeletal muscle.

flicting results. Many authors have reported that
specific tension is unaffected by age,[59,62,63] while
others have offered evidence that muscle quality is
compromised among the aged.[42,43,64] Moreover,
within even a single investigation it has been report-
ed that aging may, or may not, alter muscle quality
depending upon whether upper or lower extremities
are assessed, or whether men or women are being
examined.[42]
Much of the equivocal nature of the present liter-
ature can be explained by the array of methodologi-
cal approaches employed by researchers. Specific
tension can be quantified at the whole muscle level
or within isolated single fibres. Force can also be
related to unit of muscle mass or total muscle mass,
as well as whole muscle cross-sectional area or
average fibre cross-sectional area. Also, strength
can be measured in various ways, i.e. static versus
dynamic contractions, by differing isokinetic veloci-
ties, as well as during voluntary contraction or su-
perimposed electrical stimulation. Moreover, mus-
cles featuring different daily functions and fibre type
populations have been investigated. Table I presents
the results of some studies investigating the impact
of aging on muscle quality, along with the experi-
mental methodologies utilised.
Perhaps the most revealing data regarding the
influence of senescence on specific tension was
recently presented by Frontera et al.[65] In this study,
muscle quality was assessed as force produced rela-
tive to whole muscle cross-sectional area, as well as
tension generated by isolated single fibres when
normalised to that fibre’s cross-sectional area. These
data revealed no significant difference in whole
muscle specific tension between young and aged
subjects during maximal contraction of the quadri-
ceps. In contrast, when examined at the cellular
level, both slow- and fast-twitch fibres isolated from
the quadriceps of aged subjects demonstrated spe-
cific tension that was ~30% less than that observed
in fibres taken from the quadriceps of young sub-
jects. These findings confirm a deficit in the func-
tion of the contractile apparatus of aged myofibres
and provide the most compelling argument to date

 2004 Adis Data Information BV. All rights reserved. Sports Med 2004; 34 (12)
Effects and Causes of Sarcopenia
that aging, indeed, impairs the specific tension of
muscle tissue. This deficit could be related to a
decrease in the number of myosin cross-bridges
within aged muscle that has been postulated by
others.[67]
Several studies indicate that adaptation to
strength training among the aged is similar to that
detected among the young, if training protocols are
matched for intensity, volume and duration.[61,68-71]
Yet when comparing strength between highly
trained young and senior athletes, a decrement exists
even among those elderly who have trained regular-
ly throughout their adult lives.[72,73] It appears then,
that if performed throughout middle and old age,
strength training mitigates, but does not eliminate,
age-related strength loss. Thus, it appears that there
are factors inherent in the aging process that act to
inexorably decrease muscular strength.[74]
1.3 Muscular Endurance
Local muscular endurance is best described as
the capacity to resist muscular fatigue, particularly
when the resistance is submaximal. This parameter
of muscle fitness can be assessed during static or
dynamic contractions. In contrast to strength and
power, where the evidence overwhelmingly con-
firms a significant aging effect, the literature con-
cerning senescence-induced alterations in muscle
endurance is equivocal. Although some studies have
reported decreased muscle endurance among the
aged,[38,64,75,76] others have shown no difference in
the fatigability of aged and young muscle.[77-79] As
with muscle quality, much of the variability in the
findings concerning muscle endurance can be attrib-
uted to differences in methodologies. For example,
endurance can be assessed by quantifying the drop-
off in force production during a series of maximal
effort contractions, the duration which one can sus-
tain a relative (percentage of peak force) submax-
imal contraction or even the amount of time taken to
recover peak force production following prolonged
maximal effort. Moreover, muscle endurance can be
determined with protocols featuring voluntary acti-
vation of muscle or external electrical stimulation of
muscle.
 2004 Adis Data Information BV. All rights reserved.
813
Among those studies that have identified age-
related decreases in muscular endurance, there is
evidence that the mechanisms involved in muscle
failure are age dependent. Within aged muscle, fati-
gability is largely explained by failure in central
drive, i.e. neural factors.[80] In young muscle, how-
ever, muscle fatigue is ascribed to peripheral factors,
i.e. metabolite accumulation and/or substrate deple-
tion.[81] Gonzalez and Delbono[82] have recently sup-
ported the findings of previous in vivo studies with
data collected from isolated single muscle fibres
taken from aged and young muscle. In summarising
their results, these authors concluded that the greater
fatigability observed among aged whole muscles
were not due to differences in the contractile appara-
tus itself of senescent fibres. This, then, supports the
assertion that central fatigue is more pronounced
among older neuromuscular systems, and when evi-
dent, accounts for age-related decrements in muscu-
lar endurance.
The assessment of the effects of aging on muscu-
lar endurance, as well as the mechanisms involved,
has important practical implications. Recall that
high rates of morbidity and mortality have been
linked to falls among older adults. It is significant
that a recent investigation has demonstrated that
impaired muscular endurance contributes to the in-
cidence of falls among the elderly.[83]
2. Sarcopenia
2.1 Whole Muscle and Fibre Size
It has been found that total muscle mass, as well
as whole muscle size peaks at about the age of 24
years.[84] Similar to strength, muscle mass is well
maintained throughout the fifth decade as only a
modest (10%) decrease in whole muscle size occurs
between 24 and 50 years of age.[84] But between 50
and 80 years of age an additional diminution of 30%
occurs so that between the ages of 24 and 80 years a
total decrease of 40% in muscle size is apparent.[84]
This decrease in whole muscle size is mirrored by a
loss of fibre number.[85] Indeed, while only a 5%
decrement in fibre number is evident between 24
and 50 years of age, the fibre count within whole
Sports Med 2004; 34 (12)
814
muscles declines by 35% between 52 and 77 years
of age.[86] This translates to an annual 1% decrease
in whole muscle cross-sectional area beyond the
fifth decade of life. More recent research using
sophisticated technology such as magnetic reso-
nance imaging,[59] computer tomography[65] and ul-
trasonic scanning[49] have identified decrements in
whole muscle size occurring at an annual rate of
0.5–0.8% beyond 50 years of age. However, those
figures, drawn from cross-sectional analysis, i.e.
muscles from individuals of different ages, may
underestimate the rate of sarcopenia. A recent longi-
tudinal study examining the same aged men over a
12-year period indicated that, as determined by
computerised tomography, whole muscle sarcope-
nia occurs at a rate of 1.4% per year.[50]
Although a decline in fibre number principally
explains the loss of muscle mass that takes place
during aging, atrophy at the fibre level has also been
implicated.[51,72,84,87,88] Unlike loss of fibre number,
which occurs equally among fast- and slow-twitch
fibres,[51,72,84,88] the cellular atrophy associated with
senescence is fibre-type specific. In quantifying fi-
bre size in older and younger human muscle, Lexell
et al.[84] found that type II (fast-twitch) fibres exper-
ienced a 26% loss in cross-sectional area, while the
size of type I fibres (slow-twitch) did not differ
between 20- and 80-year-old individuals. Even
among subtypes of type II fibres it appears that
aging elicits preferential atrophy. Coggan et al.[89]
reported that compared with muscle samples of
young men, type IIA fibres displayed a 13% reduc-
tion in size while type IIB fibres were 22% smaller
in aged men. In the same study, it was demonstrated
that muscle fibres from aged women exhibited 24%
and 30% atrophy in IIA and IIB fibres, respectively.
In another aging study,[51] the atrophy of type IIA
fibres (14%) was again less than that of IIB fibres
(25%). A caveat is warranted here; it is now under-
stood that type IIB fibres actually express the IIx
myosin heavy chain isoform.[90]
This selective atrophy among fibre types is relat-
ed to changes in the genetic regulation of muscle.
Recent molecular biological approaches have re-
vealed a decrease in myosin mRNA content ex-
 2004 Adis Data Information BV. All rights reserved.
Deschenes
tracted from aged, compared with young muscle.
More noteworthy was the decrease with respect to
specific myosin isoforms. After normalising to
young muscle values, senescent fibres displayed a
decrement in IIa mRNA, a greater decrease in IIx
transcript, but no alteration in type I mRNA con-
tent.[91]
The concept of ‘nuclear domains’ within muscle
fibres was initially proposed by Hall and Ralston.[92]
The premise of this concept is that each nucleus
within the fibre is responsible for the maintenance of
a given area of cytoplasm within the fibre. Research
has shown that during hypertrophy, nuclei are added
to the fibre so that the cytoplasm to nuclei ratio
remains constant; presumably new nuclear domains
have been added to the enlarged fibre.[93,94] Similar-
ly, during unloading-induced fibre atrophy there is a
decrease in the number of nuclei within the fibre,
such that again the nucleo-cytoplasmic relationship
is maintained.[95,96] Recent research suggests that the
atrophy detected among aged fibres is also reflected
by a decreased number of myonuclei, thus the size
of nuclear domains remains constant.[97] These data
suggest that as with other causes of atrophy, the
decreased cross-sectional areas noted in senescent
fibres results from a reduction in nuclear domain
number, not size.
2.2 Fibre Type Composition
Although early research had indicated that there
was a selective loss of type II fibres during aging,[98]
Lexell et al.’s landmark investigations[84-86] proved
this not to be the case. Using whole muscle cross-
sectional slices obtained from autopsy cases ranging
from 15 to 83 years old, these investigators painstak-
ingly classified each fibre within the vastus lateralis.
Previous investigation had assessed fibre type com-
position within small biopsy samples taken from
that same muscle. Lexell et al.’s data revealed that
although a loss of fibre number occurs with aging,
this decrement is equally apparent among type I and
II fibres. These findings have been confirmed by
subsequent analysis of upper body muscles.[88] On
the whole then, the evidence indicates that aging
does not affect the relative proportion of type I to
Sports Med 2004; 34 (12)
Effects and Causes of Sarcopenia
type II fibres within muscle. However, while aging
does not alter overall fibre type composition within
a muscle, is does impact the distribution of those
fibres within the muscle. Histochemical staining of
whole muscle sections revealed that unlike young
muscle, where different fibre types are interspersed
and present a ‘mosaic’ appearance, individual fibre
types are clustered together in older muscle, result-
ing in a ‘patchy’ appearance.[99]
Clearly, the evidence that aging fails to alter fibre
type composition within a muscle is convincing. Yet
it must be noted that these conclusions are derived
from data gathered using standard histochemical
staining of muscle cross-sections. More recently, gel
electrophoretic techniques have been used to deter-
mine myosin isoform expression within single mus-
cle fibres. Using these sensitive and sophisticated
techniques, it has been established that aging in-
creases the proportion of ‘hybrid’ fibres within mus-
cle.[100,101] These ‘hybrid’ fibres co-express more
than one myosin heavy chain isoform, as opposed to
‘pure’ fibres that express a single isoform. This co-
expression typically does not change histochemical
staining properties to the extent that the classifica-
tion of the fibre as type I, IIA or IIB would be
affected since one isoform is usually predomi-
nant.[102,103] As might be expected, however, the co-
expression of two or more myosin isoforms affects
contractile characteristics.[104,105]
3. Mechanisms
3.1 Denervation
EMG recordings taken during muscle contraction
demonstrate a decrease in the number of motor units
present in aged, relative to young, muscle.[106,107]
The authors of one study estimated that senescence
resulted in a 25% reduction in the number of func-
tional motor units.[108] Concomitant with the de-
crease in the number of motor units identified in
aged muscle is an increase in the size of the remain-
ing motor units.[109] That is, each motor neuron
innervating senescent muscle is associated with a
greater number of muscle fibres. Several authors
have attributed these findings to an age-related
 2004 Adis Data Information BV. All rights reserved.
815
denervation of muscle.[99,106-108] These investigators
reason that the normal cycling of denervation-rein-
nervation that is evident in younger muscle is im-
paired in aged muscle. Consequently, there is a net
effect of denervation affecting skeletal muscle of the
elderly, which significantly contributes not only to
the loss of motor units, but also to the loss of muscle
fibres that mainly accounts for sarcopenia.[84] In the
few direct studies that are available, microscopic
observations suggest that there are fewer motor neu-
rons in the ventral horn of aged spinal cords.[110,111]
Presumably, there are also fewer numbers of alpha
motor neurons innervating the skeletal muscle of
aged individuals. In addition to the loss of fibres,
Lexell et al.[85,86] have postulated that this denerva-
tion explains the ‘clustering’ of fibres of the same
type that is noted in aged muscle (see section 2.2).
Interestingly, a recent investigation reports that the
decreased specific tension noted in aged rat muscle
can at least be partly ascribed to denervation.[112]
Anatomical evidence of age-related denervation
is found not only within the spinal cord, but also
within the peripheral nervous system. In examining
the neuromuscular junctions of aged and young
muscle, markers of degeneration are apparent. For
example, Cardasis and LaFontaine[113] have
presented evidence that axonal withdrawal is preva-
lent at aged, but not young, neuromuscular junc-
tions. Moreover, the expression of neural cell adhe-
sion molecule (NCAM) is known to increase at the
neuromuscular junction following denervation of
young adult muscle.[114,115] NCAM concentrations
are also elevated at the neuromuscular junctions of
aged, compared with young, animals.[116-118] Again,
these data provide compelling evidence of an age-
related denervation of muscle.
The mechanism(s) of the denervation occurring
during senescence has yet to be fully elucidated. Yet
an investigation recently conducted by Guillet et
al.[119] does provide interesting insight. Ciliary
neurotrophic factor (CNTF) has been identified as
an important molecule in the survival of motor neu-
rons.[120,121] Moreover, research has proved that rela-
tive to young motor neurons, CNTF production is
attenuated in aged peripheral nerves.[119] In the ex-
Sports Med 2004; 34 (12)
816
periment of Guillet and coworkers,[119] a strong cor-
relation was established between the decline of
CNTF expression and muscle strength measured
among aged rats. Remarkably, when aged rats were
administered CNTF, the strength of isolated soleus
muscles increased more than 2-fold. These data
confirm the importance of preventing the loss of
motor neurons in treating the decline in muscle
function associated with aging.
3.2 Protein Metabolism
The denervation that occurs with aging appears
to begin in earnest at 60 years old. Indeed, the
number of motor units within muscle remains con-
stant between 10 and 60 years of age.[122] The onset
of denervation is well matched with the sharp de-
cline in muscle mass that also occurs after the sixth
decade of one’s life.[99] Yet there is a moderate
decline in muscle mass between the ages of 50 and
60 years.[84] There are data to support that this early
phase of sarcopenia is related to changes in muscle
protein metabolism.[123] This senescence-induced
decrement in muscle protein, however, is not associ-
ated with an acceleration of protein degradation.[123]
Rather, it is a decrease in the rate of protein synthe-
sis that has been demonstrated among the aged that
accounts for slower overall rates of muscle protein
turnover.[124-126] In comparing young (23 years),
middle-aged (52 years) and elderly (77 years) sub-
jects, it was ascertained that mixed, as well as myo-
sin fractional, rates of protein synthesis declined
significantly by ~50 years of age and continued to
decrease into old age.[124] More recently, the slowed
rate of protein synthesis detected in aged muscle has
been coupled to diminished mRNA transcript con-
tent for myosin heavy chain, indicating a genetic
basis for impaired protein production.[91,127]
The decreased protein synthesis evident in aged
muscle may also be related to bioenergetic perturba-
tions. Since protein assembly requires the utilisation
of large amounts of energy, adequate adenosine
triphosphate (ATP) availability is essential to this
process. The vast majority of ATP production with-
in muscle occurs through oxidative phosphorylation
pathways located within mitochondria. It has been
 2004 Adis Data Information BV. All rights reserved.
Deschenes
determined that aging not only decreases mitochon-
drial density and aerobic enzyme activity within
muscle,[128-131] but also that a significant degree of
oxidative damage is apparent in the mitochondrial
DNA of aged muscle.[132] As further evidence that
senescence hinders mitochondrial ATP yield even at
the molecular level, Welle et al.[133] have recently
reported that the content of mRNA transcripts for a
number of essential mitochondrial proteins is lower
in aged muscle than in young muscle. In that study,
it was also found that mitochondrial DNA is reduced
by ~40% in aged muscle.
The net effect of age-related disturbances in pro-
tein metabolism is that aged individuals display
reduced muscle : body mass ratios. This is of con-
cern because as this ratio declines, the percentage of
body fat increases, resulting in ‘sarcopenic-obesity’,
which has greater negative health consequences
than sarcopenia alone.[134] Yet it is encouraging to
note that resistance training amplifies muscle prote-
in synthesis in the aged to the same degree as is
demonstrated in younger adults.[135,136]
3.3 Circulating Hormones
A convincing body of literature indicates that
aging alters circulating concentrations of anabolic,
or muscle building, hormones.[137-139] These data
reveal that aged men experience reductions in both
total testosterone and unbound or ‘free’ testosterone
levels. Significantly, the diminution is more pro-
nounced for the unbound fraction, which, of course,
is the biologically active form of this potent steroid
hormone.[140] A recent study reported that between
the ages of 20 and 80 years, total testosterone de-
creased by 35% while unbound testosterone was
reduced by 50%.[141] It is noteworthy, however, that
although aging is associated with decrements in
testosterone, blood-borne concentrations in healthy
aged men remain within normal limits, albeit at the
lower end of this range.[140] Thus, there is some
debate as to the appropriateness of using the term
‘hypogonadal’ to describe the condition of healthy
aged men.
As further evidence that aging affects the anabol-
ic milieu, the normal circadian variation in testoster-
Sports Med 2004; 34 (12)
Effects and Causes of Sarcopenia
one levels noted in young men has been found to be
blunted, although not eliminated, in senescent
males.[142-144] The physiological basis of these age-
related changes in serum levels of testosterone have
yet to be fully identified, but a multitude of mecha-
nisms may be involved. Indeed, research has shown
that aging imparts disturbances throughout the hy-
pothalamic-pituitary-gonadal axis. For example, it
has been found that the testes’ Leydig cells (that
produce testosterone) are less responsive to the
luteinising hormone (LH), which is released by the
pituitary gland to stimulate the secretion of testoster-
one into the bloodstream.[145,146] Moreover, the re-
lease patterns of LH differ between young and aged
men. Specifically, the amplitude of the pulsatile
release of LH is attenuated among the aged, even
though the frequency of these pulses remains con-
stant throughout life.[141,147] Finally, it appears that
that the hypothalamus (that regulates the release of
LH from the pituitary gland) may secrete less gona-
dotropic releasing hormone to the pituitary among
aged men, thereby contributing to the limited release
of LH by that endocrine gland.[147] In addition to
these disturbances within the multi-gland secretory
pathway of testosterone, it has been postulated that
aging decreases the sensitivity of target tissues, in-
cluding muscle, to this androgenic-anabolic hor-
mone.[148] Regardless of its aetiology, evidence con-
firms that the decreased availability of testosterone
noted among aged men contributes to sarcope-
nia.[138] Also, it appears that testosterone replace-
ment therapy in aged men is effective in gaining
muscle mass and strength,[149-151] although the po-
tential for adverse effects with prolonged use has yet
to be thoroughly identified.[138,148,152]
Another potent endogenous anabolic hormone is
growth hormone (GH); indeed this peptide released
by the pituitary gland is probably the primary blood-
borne muscle-building agent in women.[153] As with
testosterone, circulating levels of GH progressively
decline during the aging process.[154,155] Between the
ages of 20 and 70 years, GH values are reduced by
roughly 50% in men and women.[156,157] It is impor-
tant to note that this change in GH secretion has
 2004 Adis Data Information BV. All rights reserved.
817
been linked to the loss of muscle mass observed in
the elderly.[158,159]
Although it interacts with many target tissues, it
is now understood that GH mediates its effects on
muscle by regulating the synthesis of insulin-like
growth factor-1 (IGF-1).[160] In view of this relation-
ship, aging has been associated with decreased cir-
culating IGF-1 levels.[161] In examining the relation-
ship between blood-borne IGF-1 levels and the per-
formance of a number of functional tasks in aged
women, Cappola et al.[162] found that those individu-
als with the lowest IGF-1 values were also those
exhibiting the lowest strength, walking speed and
mobility. However, these results may be sex specific
since an earlier study failed to reveal significant
correlations between IGF-1 and strength or walking
speed among elderly men.[163]
As with testosterone, attempts to stimulate
strength and muscle gains in the aged through GH
administration have recently been carried out. In
reviewing the published data gathered from test
trials on GH therapy, both Rosen[164] and Welle[159]
concluded that the present evidence did not justify
the use of GH therapy in treating sarcopenia. It
appears that the efficacy of this procedure in en-
hancing muscle mass and strength is equivocal,
while serious adverse health effects may develop.
In contrast to the decline in the major muscle-
building hormones documented among the elderly,
research shows that circulating cortisol levels are
unaffected by senescence.[137,139,165,166] This is en-
couraging since cortisol is the primary catabolic, or
muscle wasting, agent in the human endocrine envi-
ronment.
3.4 Autocrine Factors
Recall that in section 2.1 the nuclear domain
concept of muscle fibre size was described. In brief,
it has been noted that during myofibre hypertrophy,
as well as atrophy, the nuclear to cytoplasmic ratio
remains unaltered. Thus, during hypertrophy, nuclei
are added to the fibre while cellular atrophy is
accompanied by a loss of myonuclei. The source of
these nuclei are ‘satellite cells’ that are myogenic
precursors located between the sarcolemma and the
Sports Med 2004; 34 (12)
818
basal lamina of the fibre.[167] Upon stimulation,
these satellite cells undergo proliferation and the
resultant sister nuclei are included into the cyto-
plasm of the muscle fibre.[168]
There is evidence that aging not only decreases
the number of satellite cells present in muscle,[169]
but that the proliferative capacity of aged satellite
cells is limited compared with those residing in
young adult muscle.[170,171] These findings suggest
that age-related alterations in the number and apti-
tude of satellite cells contribute to sarcopenia.
More recent investigation has determined that the
interaction of IGF-1 with satellite cells acts to trig-
ger the proliferation of satellite cells.[170,172] Moreo-
ver, evidence indicates that it is not blood-borne
IGF-1 (initially secreted by the liver) that stimulates
satellite cell mitosis. Rather it is a specific isoform
of IGF-1 that is actually synthesised locally within
muscle tissue that regulates satellite cell activity in
vivo.[173] This powerful mitogen has been termed
‘mechanogrowth factor’ (MGF) and is produced in
response to injury and/or mechanical loading of
skeletal muscle.[168,174,175] It has recently been re-
vealed that not only does aging lead to decreased
baseline values of MGF mRNA,[176] but that in
response to mechanical overload, aged muscle dem-
onstrates significantly lower expression of MGF
than similarly overloaded young muscle.[177,178]
Those same authors also documented that overload-
Table II. Physiological mechanisms involved in sarcopenia
Mechanism
Denervation
Decreased density and function of mitochondria
Decreased mRNA transcript content
Decreased circulating testosterone
Decreased circulating growth hormone
Decreased circulating IGF-1
Decreased number of satellite cells
Decreased proliferation of satellite cells
Decreased autocrine synthesis of MGF
Inflammation, increased production of IL-6 Increased rate of muscle protein degradation
ATP = adenosine triphosphate; IGF-1 = insulin-like growth factor-1; IL-6 = interleukin-6; MGF = mechanogrowth factor; mRNA = messenger
RNA.
 2004 Adis Data Information BV. All rights reserved.
Deschenes
induced hypertrophy was ameliorated in aged mus-
cle leading to speculation that sarcopenia may be a
consequence of decreased MGF availability and
thus, diminished satellite cell activity. This premise
has been supported by studies where MGF expres-
sion in aged muscle was amplified by injecting an
MGF expression vector into muscle[179] or by exam-
ining transgenic mice that overexpress the MGF
gene.[180] In both experiments, sarcopenia was effec-
tively prevented in aged muscle and strength was
found to be no different than that observed in young
muscle. Although preliminary, these results have
been so well received that experts have recently
suggested that MGF therapy may be a uniquely
effective method of preventing or treating
sarcopenia.[181]
3.5 Inflammation
A potential mechanism of sarcopenia that has
received much recent attention is the inflammatory
response. Several conditions that commonly occur
with aging (particularly rheumatoid arthritis) are
associated with a chronic manifestation of the im-
mune system’s inflammatory response. The inflam-
matory response results in the release of cytokines
that trigger muscle wasting effects. Interleukin (IL)-
1 and tumour necrosis factor-α (TNFα) modulate
the production of both anabolic and catabolic hor-
Effect References
Apoptosis of muscle fibres, re-innervation of 99,106,107,110,111
surviving fibres
Decreased ATP production, reduced muscle 74,89,128,130,188
protein synthesis
Decreased mitochondrial proteins, decreased 91,127,133
myofibrillar proteins
Decreased muscle protein accretion 137,140,142
Decreased muscle protein accretion 154,155,157
Increased rate of muscle protein degradation 159,161
Decreased muscle fibre size 169
Decreased capacity for repair from normal 170,171
‘wear and tear’ muscle damage
Decreased proliferative capacity of satellite cells 174,175
182,183
Sports Med 2004; 34 (12)
Effects and Causes of Sarcopenia
mones in such a way that a negative nitrogen bal-
ance (indicative of protein breakdown) is incurred.
Although few studies have directly investigated the
effects of aging on the release of IL-1 and TNFα, the
little data that are currently available indicate that
aging, per se, is not associated with elevated levels
of those cytokines.[182] In contrast, it has been found
that the leucocytes of older individuals show greater
release of IL-6, resulting in increased circulating
concentrations of that inflammatory agent.[182,183] In
other research, it has been demonstrated that IL-6
has potent catabolic effects[184,185] and its elevation
among the aged has recently been suggested to play
a role in sarcopenia.[186] In addition to its direct
impact on muscle metabolism, IL-6 may also have a
more general influence by contributing to the an-
orexia routinely noted among the aged. The lack of
protein consumption consequent to this anorexia is
considered to be an important causative factor of
sarcopenia.[187] Although preliminary at this point,
results from the few studies completed suggest that
the chronic, low-grade inflammation that is coupled
with numerous senescence-related medical condi-
tions may, in fact, be a significant mediator of
sarcopenia. Putative mechanisms involved in age-
related muscle wasting are presented in table II.
4. Conclusions
Senescence is associated with a decrement in
muscle fibre number along with a reduction in the
size of type II, but not type I fibres. The relative
percentages of different fibre types appears to be
unaffected by age. Muscle mass is well maintained
through the fifth decade of life and shows a moder-
ate decline between 50 and 60 years of age, followed
by a more accelerated rate of loss beyond 60 years of
age. As would be expected, the age-related decrease
in muscle tissue results in impaired muscle function.
Most problematic, however, may be the loss of
muscle power since this component of muscle func-
tion is closely linked to the incidence of accidental
falls experienced by the elderly. Such falls typically
lead to fractured bones and/or confinement to bed
rest, which can result in further health complica-
tions.
 2004 Adis Data Information BV. All rights reserved.
819
Several physiological mechanisms (denervation,
reduced protein turnover, altered endocrine/
autocrine function) have been implicated in the aeti-
ology of sarcopenia. However, a more complete
understanding of the causes of sarcopenia is re-
quired in order to design interventions to prevent, or
at least temper, the onset of sarcopenia and to devel-
op effective treatment strategies for those who have
already been affected by this serious health condi-
tion.
Acknowledgements
The author is supported by the National Institute on Aging
(AG 1744C) and the Borgenicht Program for Aging Studies
and Exercise Science. No potential conflict of interest exists.
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Correspondence and offprints: Dr Michael R. Deschenes,
Department of Kinesiology, The College of William & Ma-
ry, Williamsburg, VA 23187-8795, USA.
E-mail: mrdesc@wm.edu
Sports Med 2004; 34 (12)