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review

Wien Med Wochenschr


https://doi.org/10.1007/s10354-018-0618-2

Sarcopenia
Karsten Keller

Received: 7 November 2017 / Accepted: 19 January 2018


© Springer-Verlag GmbH Austria, ein Teil von Springer Nature 2018

Summary Sarcopenia is a very common, but fre- Sarkopenie


quently overlooked and undertreated geriatric syn-
drome comprising pronounced muscle mass and Zusammenfassung Die Sarkopenie ist ein häufiges
strength/performance loss. Estimated prevalence is und oft übersehenes geriatrisches Syndrom mit ei-
between 5 and 40% in the general population, ac- nem verstärkten Verlust von Muskelmasse und Mus-
companied by an exponential incline with increasing kelkraft/Leistung. Die geschätzte Prävalenz liegt bei
age. Sarcopenia is connected to atrophy and loss of 5–40 % in der Bevölkerung – mit einem altersbezo-
muscle fibers and motor units, affecting primarily the genen exponentiellen Anstieg. Einer Sarkopenie lie-
fast-twitch muscle fibers und their motor units. Fast- gen eine Atrophie und ein Verlust von Muskelfasern
twitch muscle fibers seem to be more prone to failure bzw. der motorischen Einheiten zugrunde. Sie betrifft
of function and loss over time. Main causes for the vorrangig die schnellen Typ-II-Muskelfasern und de-
development of sarcopenia are hormonal changes (re- ren motorische Einheiten. Schnelle Typ-II-Muskelfa-
duced release of testosterone, estrogen, and growth sern scheinen anfälliger für einen Funktionsverlust
hormone), nutritional deficiencies, chronic inflam- und einen Untergang der Muskelfasern zu sein. Wich-
mation, and particularly a decrease in physical ac- tige Ursachen einer Sarkopenie sind hormonelle Ver-
tivity due to sedentary lifestyle with advancing age. änderungen (abfallende Testosteron-, Östrogen- und
Treatment options for sarcopenia comprise an active Wachstumshormonspiegel), Mangelernährung, chro-
lifestyle with physical activity and exercise training, nische Entzündungsprozesse und insbesondere eine
modifications of nutritional intake, and pharmaco- reduzierte körperliche Aktivität aufgrund eines vor-
logical therapies. Strength training and an adequate wiegend bewegungsarmen Lebensstils. Behandlungs-
nutritional intake form the basis of successful sar- optionen umfassen einen aktiven Lebensstil mit viel
copenia treatment. körperlicher Bewegung und sportlicher Aktivität, An-
passung der Ernährung und ggf. auch eine pharma-
Keywords Sarcopenia · Muscle · Strength · Perfor- kologische Therapie. Krafttraining und eine adäquate
mance · Age Ernährung stellen die Grundlage eines erfolgreichen
Behandlungskonzepts einer Sarkopenie dar.

Schlüsselwörter Sarkopenie · Muskel · Kraft · Leis-


tungsfähigkeit · Alter

K. Keller, MD () Introduction


Centrum Thrombosis and Haemostasis, University Medical
Center Mainz, Johannes Gutenberg-University Mainz, Human muscle undergoes continual changes [1, 2].
Langenbeckstraße 1, 55131 Mainz, Germany Increasing age is attended by typical changes in hu-
Karsten.Keller@unimedizin-mainz.de man body composition [2–15]. In general, the aging
K. Keller, MD process leads to a decline in physical capacities [4,
Center for Cardiology, University Medical Center Mainz, 10, 14, 16, 17]. Important factors affecting the mus-
Johannes Gutenberg-University Mainz, Mainz, Germany culoskeletal system with growing age are the losses of

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muscle and bone mass, but additionally the reduction Age-related changes in skeletal muscle
of elastic capacities of the tissues (for example, ten-
dons) and the decrease of balance capacities [3–5, 7, The muscular system accounts for roughly 40% of the
14, 18–20]. total body mass and the cell mass of the human body
Particularly the loss of muscle mass resulting col- consists of approximately 60–75% muscle cells. Over-
laterally in strength decline is a key factor for the all, a quarter of the total protein synthesis is within the
reduction of physical capacities. Excessive muscle muscular system [21, 36]. While the muscle strength
mass and strength losses in the context of increas- ensures mobility and autonomy [11, 21, 23, 26, 36],
ing age, diseases, inflammation, and malnutrition are it is well established that the aging process is associ-
termed sarcopenia [6–10, 21–26]. Strength loss and ated with a significant decline in muscle mass, neu-
muscle atrophy are associated with limited mobility, romuscular function, and performance (strength and
falls, fractures, loss of autonomy, and increased mor- power; [16, 21, 37–39]). Strength declines were thereby
tality [27–32]. Falls, fall-related injuries, and the fear not only related to muscle mass reduction, but also to
of falls are common in older persons and the numbers a decrease of strength capacities per motor unit as
of falls and fall-related injuries increase exponentially a sign of a decline in muscle quality [21]. The aging
with advancing age [27–29, 31, 32]. Key factors in the process was accompanied by a reduction of the fat-
occurrence of falls are a decline in balance capacities, free muscle mass [16].
but, in particular, a low muscle strength level [11, 27, In most individuals, the peak of physical capacity
28, 32, 33]. Sarcopenia plays a main role in the de- and strength is observed in the third life decade [11,
velopment of frailty and functional impairment in old 14]. Although the changes in power and strength in
women and men [2, 9, 21–24, 34]; resulting disability the next two decades up to the 50th life year are small
could lead to nursing home institutionalization and [6, 14, 16], a decline in muscle strength could be de-
an increased number of hospitalizations of the older tected, beginning especially after reaching the 40th
persons [11, 21, 23, 26]. life year [12]. However, it seems uncertain whether
Thus, sarcopenia, with the losses of muscle mass this decline in muscle mass and muscle strength be-
and strength/performance, is an important factor in fore the 50th life year is strongly related to an age-
the development of functional impairment and dis- dependent loss of muscle mass and strength; it must
ability, with crucial life changes affecting patients’ rather be presumed that these losses of muscle mass
quality of life as well as patients’ morbidity and mor- and muscle strength are the results of changes in life
tality [7, 21–24, 35]. circumstances, with less sports activities, spending
more time with the family, and a higher workload in
Epidemiology a job with lower physical requirements during daily
life, summarized as a shift towards sedentary life style.
Studies have reported a wide range regarding the The largest changes in muscle mass and strength
prevalence of clinically relevant sarcopenia. Even regarding an age-dependent decline take place be-
conservative estimations suggest that sarcopenia af- tween the sixth and seventh life decades [4, 6, 14,
fects more than 50 million people today and will affect 16, 18, 20]. Although muscle mass and strength losses
more than 200 million people in the next 40 years [24]. with aging are a continuous process, muscle mass and
Actually, prevalence rates between 5 and 40% in the strength loss is accelerated in men and women after
general populations of western countries were re- the 50th life year [4, 6, 14]. While the loss of strength
ported [21, 23, 24, 34]. The prevalence increases in the sixth and seventh life decades comprise ap-
exponentially with inclining age [11, 21, 24]. While proximately 15% per decade, this decline exceed even
the prevalence ranges between 5 and 13% in the sev- 30% per decade after the 70th life year [14, 18]. Other
enth decade, it inclines to rates between 11 and 50% studies reported a 20 to 40% reduction of muscle mass
in individuals aged >80 years [24, 26]. In males, this comparing individuals 25 years of age and those who
age-dependent increase of sarcopenia was more pro- were aged 75 years; this decrease in muscle mass was
nounced in comparison to females. While the preva- accompanied by a doubling of fat mass replacing the
lence approximately doubled in women >80 years in muscle cells [37, 40, 41].
comparison to those aged <70 years (16% vs. 8.8%), The declines of muscle mass and strength with
the incline was substantially larger in males, with aging depend on health status, individual genetics,
an increase from 13.5% in individuals <70 years to physical activity with strength, power and muscle
29–40% in those >80 years [21, 23]. mass training, nutrition, as well as initial peak level of
Remarkably, sarcopenia is dependent on the so- muscle status in early adulthood [11, 14]. The rate of
cioeconomic status and the prevalence of sarcopenia muscle mass loss is not uniformly localized across all
was higher in people with low income [21]. muscles of the human body: weight-bearing muscles
of the lower limbs are particularly affected [42].
Even in highly trained individuals such as elite
power lifters, continuous age-dependent declines of
strength and power are observed [11, 14]. Although

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the decline in muscle strength in the athletes demon-


strated a more pronounced loss in females compared
to males, noticeable in a relatively lower strength level
in older female athletes compared to males (Fig. 2).
On the one hand, the main problem with strength
loss in women is the lower strength maximum in
younger age compared to men leading to a higher
risk for developing sarcopenia in females, although
similar relative levels of strength declines are evident
compared to men (smaller muscle strength reserve
to prevent sarcopenia; [44]). On the other hand, for
daily activities, the relative strength (strength related
to body weight) is of outstanding interest and this rel-
ative strength might be higher in women compared
to men, especially in older persons, probably due to
higher body weight driven by larger body fat levels in
Fig. 1 Development of powerlifting world records in several older men [45].
age categories of the International Powerlifting Federation Briefly summarizing the study results above, losses
IPF (record list 26 February 2017): We presented the weight
of muscle mass and strength can be decelerated and
classes up to 93 kg in men (blue line) and up to 63 kg in
women (red line; web page: http://www.powerlifting-ipf.com/ decreased by training and adequate nutrition, but
championships/records.html) might not be stopped at all. Also highly trained elite
athletes show comparable relative age-dependent de-
clines of muscle mass and strength in comparison to
the general population, but the implication on ev-
eryday activities is significantly less intense, because
the strength levels are far removed from the critical
limit influencing mobility and autonomy. Beside the
normal decline in muscle mass und strength with
aging, a pronounced decrease of these capacities is
found in sarcopenia [39].

Definition of sarcopenia

In 1989, Rosenberg et al. [46] first coined the term


sarcopenia for description of age-associated loss of
skeletal muscle mass [38, 39, 46]. Although there was
an accordance that sarcopenia is a condition charac-
terized by losses of muscle mass and strength [36], no
Fig. 2 Development of powerlifting world records in females universally accepted definition existed up to the year
(weight class up to 63 kg in women) in relation to males (weight 2009, caused by an absence of well-accepted stan-
class up to 93 kg) stratified by several age categories of the In- dardized methodology and diagnostic criteria to make
ternational Powerlifting Federation IPF (record list 26 February and clarify the diagnosis [38, 39].
2017): The world record load of males was equated with 100% In 2009, the International Working Group on Sar-
(Web page: http://www.powerlifting-ipf.com/championships/ copenia [35] provided a consensus definition: “Sar-
records.html)
copenia is the age-associated loss of skeletal muscle
mass and function. Sarcopenia is a complex syn-
the strength levels of these athletes are far above the drome that is associated with muscle mass loss alone
average in the general population and even older or in conjunction with increased fat mass. The causes
athletes show strength levels which are significantly of sarcopenia are multifactorial and can include dis-
higher compared to the normal citizens in their best use, changing endocrine function, chronic diseases,
age (third decade of life), these athletes also demon- inflammation, insulin resistance, and nutritional de-
strate similar age-dependent decreases of strength ficiencies. While cachexia may be a component of
and power to the general population; however, their sarcopenia, the two conditions are not the same” [35].
declining strength levels are fortunately far removed This definition was followed in 2010 by the current
from development of disability or frailty (Fig. 1; [11, European consensus definition of sarcopenia repre-
14]). sented by the European Working Group on Sarcopenia
Interestingly, studies reported a similar strength in older people [24]: “Sarcopenia is a syndrome char-
loss for women and men, with a tendency to higher acterized by progressive and generalised loss of skele-
absolute loss of strength in men [38, 43], whereby tal muscle mass and strength with a risk of adverse

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mass but also on strength and muscle performance


[24].

Severity categories of sarcopenia

According to the European Working Group on Sar-


copenia [24], sarcopenia is categorized into three
severity stages: the pre-sarcopenia stage comprises
muscle mass reduction alone, without strength or
performance declines. Contrary to this, the sarcope-
nia categories depend on muscle mass plus muscle
strength or muscle performance decreases, and se-
vere sarcopenia includes all three diagnosis criteria of
sarcopenia (Table 2; [24]).

Fig. 3 Pathomechanism of primary sarcopenia (modified Pathophysiology of sarcopenia


according to [24, 62, 95])
The pathophysiology of sarcopenia is complex and
Table 1 Criteria for the diagnosis of sarcopenia according several different causes have been identified [24, 25].
to the European Working Group on Sarcopenia in older In the majority of cases, sarcopenia is observed in
people [24] older individuals, but it can also occur in younger
Diagnosis of sarcopenia is based on documentation of criterion 1 plus people [24, 51]. While in a few sarcopenia patients
criteria 2 or 3 a single responsible cause can be identified, in most
Criterion 1 Low muscle mass individuals no evident cause or a variety of different
Criterion 2 Low muscle strength reasons are detected (Fig. 3; [24]). Sarcopenia cor-
Criterion 3 Low physical performance relates significantly with body mass index (BMI; [52,
53]) and can be understood as a multifaceted geriatric
syndrome [24, 53, 54].
outcomes such as physical disability, poor quality of According to the recommendations of the Euro-
life and death” [24]. pean Working Group on Sarcopenia [24], differenti-
The criteria of the European Working Group on Sar- ation between primary and secondary sarcopenia is
copenia in older people [24] for the diagnosis of sar- advised [24]. Primary sarcopenia is equivalent to an
copenia are shown in Table 1. Therefore, the men- age-related pronounced muscle mass and strength/
tioned definition used both low muscle mass as well performance loss when no other causes can be iden-
as low muscle function (strength or performance) for tified [24]. In cases of secondary sarcopenia, one or
diagnosis of sarcopenia. Diagnostic approach for sar- more causes (beside age) are evident or can be de-
copenia is based on low muscle mass plus identifi- tected after diagnostic work-up [24]. Important causes
cation of low muscle strength or low physical perfor- of sarcopenia are summarized in Table 3. The differ-
mance [24]. entiation between primary and secondary sarcopenia
Although several studies have shown that the loss of is a key aspect regarding therapy planning, because
muscle mass is directly related to a decline in strength treatment of underlying secondary causes of sarcope-
capacities [4, 14, 47, 48], the reason for the different nia is of outstanding and central importance in the
criteria is that muscle strength does not depend sin- majority of diseases to prevent further losses of mus-
gularly on muscle mass, and the relationship between cle mass, strength, and performance, and to avoid
muscle strength and muscle mass is not linear [24, other secondary complications of the underlying ill-
48, 49]. In addition, Goodpaster et al. [43] demon- nesses, and might save patients’ lives [24]. Sarcope-
strated that strength reduction with aging was much nia could be a relevant part of other syndromes as-
more rapid than the loss of muscle mass, indicating sociated with prominent muscle wasting in consum-
a decline in muscle quality [43], and Newman et al. ing diseases like cancer, congestive heart failure, and
[50] highlighted that strength, but not muscle mass, rheumatoid diseases. Important syndromes comprise
was associated with mortality [50]. Therefore, the def- cachexia, frailty, and sarcopenic obesity [24, 55]. Sar-
inition of sarcopenia was based not only on muscle copenia is associated with patients’ BMI [52] and most
patients with cachexia are sarcopenic [24]. Frailty

Table 2 Severity status Category/stage of sarcopenia Muscle mass Muscle strength Performance
categories of sarcopenia
Pre-sarcopenia Reduced Not reduced Not reduced
according to the European
Working Group on Sarcope- Sarcopenia Reduced One of both reduced
nia in older people [24] Severe sarcopenia Reduced Both reduced

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Table 3 Sarcopenia categories modified according to 4. decrease in physical activity and sedentary lifestyle
the recommendation of the European Working Group on 5. inadequate nutrition
Sarcopenia [24] 6. other factors contributing to sarcopenia
Primary sarcopenia
Age-related sarcopenia No other causes could be identified except Loss of alpha motor neurons and degeneration of
age
muscle contractility
Secondary sarcopenia
Activity-related sarcopenia Limited mobility such as bed rest, immo- Sarcopenia with atrophy as well as apoptosis of mus-
bilization, athrogenic muscle inhibition cle fibers and decomposition of motor units is con-
after trauma/surgery, sedentary life-style,
deconditioning, or zero-gravity conditions nected with reduced strength capacities, decreased
Disease-related sarcopenia Association with advanced organ failure muscle metabolism, and increased risk of muscle
of heart, lung, liver, kidney and brain, damage [14, 21]. The atrophy of muscle fibers is
inflammatory and endocrine diseases, or disproportionately distributed, with a pronounced
malignancy atrophy rate of type IIa fast-twitch muscle fibers and
Nutrition-related sarcopenia Inadequate dietary intake of energy and/or their motor units [4, 6, 11, 14, 17, 21, 26, 35, 61–63].
protein, or malabsorption, gastrointestinal
disorders, anorexia, bulimia, medications
Fast-twitch muscle fibers seem to be more prone to
develop a function failure over time [6, 14, 22, 23,
63]. Studies showed a decreased proportion of fast-
overlaps with sarcopenia regarding the effects on the twitch muscle fibers compared to slow-twitch muscle
musculoskeletal system [24, 56]. fibers from proportions ranging around 60% in young
Sarcopenic obesity is a specific form of sarcopenia untrained men, declining to 30% in 80-year-old men
with loss of lean body mass including muscle mass, in the same muscle groups [11, 14].
whereas the fat mass is preserved or even increased Cellular pathomechanisms are based on a decrease
(absolute or relative increase of body fat; [24, 57]). Re- in the synthesis rate of muscle proteins, especially
markably, sarcopenic obesity is an independent pre- regarding the synthesis of myosin heavy chain pro-
dictor of survival [57, 58]. teins [8, 16, 17, 19, 21–23, 26]. The reduced pro-
tein content of the muscle cells is not merely due to
Pathomechanisms of sarcopenia a decline in protein synthesis, but rather the prod-
uct of an increased protein turnover with the rate
As mentioned above, sarcopenia is connected with of breakdown exceeding the rate of synthesis [8, 16,
losses of muscle mass, strength, and performance 17, 19, 23]. The numbers of mitochondrial oxida-
[6–10, 21–26, 59]. The decline in muscle mass is not tive enzymes also decline, resulting in reduced mi-
only caused by losses of the numbers of muscle fibers tochondrial protein synthesis and maximum oxygen
and motor units, but also by a decrease in muscle fiber uptake (VO2 max) [16, 17, 21, 26]. But beyond the
size and accompanied by reduced muscle quality (less lower number of mitochondrial proteins in older per-
strength production of each muscle fiber; [4, 14, 23, sons compared to younger individuals, the activity of
25, 26, 41]). Notably, if muscle fiber size falls below the proteins is markedly reduced, followed by a fall in
a critical minimal size, apoptosis begins [14]. Other oxidative capacities with reduced levels of adenosine
reasons for apoptosis of muscle cells are denervation tri-phosphate (ATP) provided as an energy source for
and loss of neurons [6, 14, 60]. The apoptotic muscle muscle contraction [11, 17]. Moreover, type II (fast-
fiber cells are replaced by fat cells and connective twitch) muscle fibers showed an uncoupling of the
tissue [8, 14, 20, 25]. The changes of muscle wasting signal for the release of calcium (Ca2+), resulting in
are not gender specific and the loss of muscle mass a reduced amount of calcium for the initiation of mus-
did not refer to special muscle groups, but to whole cle contraction and the movement, which is the main
body muscles [14]. Remarkably, the loss of explosive reason for a delayed Ca2+ peak concentration with de-
power caused by the aging process is more intense layed and decreased rapid force as well as power out-
compared to the loss of other strength capacities [4, put [17]. The Ca2+-ATPase of muscle cells has a slower
14]. turnover rate in aged muscle cells, accompanied by
Although the mechanisms of primary sarcopenia a higher risk of damage due to free radicals [17].
are not completely understood, promoting factors While the number of motor units declines with the
were identified (Fig. 3; [11, 14, 25]): aging process, the frequency of irregularity of muscle
1. loss of alpha motor neurons and degeneration of unit firing increases, which is causative not only of
muscle contractility a reduced number of activated muscle fibers but also
2. hormonal changes with decline in release of espe- of a decline in coordinated muscle action [10, 15, 21,
cially androgens and estrogens as well as growth 41, 64].
hormone (GH) Summarizing the mentioned factors, younger peo-
3. chronic inflammation with an increase in the syn- ple reach with the same training efforts more and
thesis and release of catabolic cytokines faster growth of muscle mass and strength, mainly due
to higher protein synthesis [14]. Especially explosive

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power and strength within the first 0.2 sec of move- IGF-1 are implicated in the sarcopenia process [6, 11,
ments are reduced in older people. After the 65th life 16, 17, 20, 21].
year, explosive power and rapid strength productions The menopause is linked to reduced concentra-
to initiate and to perform fast movements decline in tions of circulating estradiol in women [14, 26, 62,
magnitude between 3.5 and 4.0% per year. In the life 71]. As part of the decrease in ovarian hormone pro-
period between the 20th and 75th life years, 50 to 70% duction, an impaired muscle performance during the
of fast-twitch muscle fibers are lost. Beside the mus- postmenopausal period was observed [26, 62, 72], but
cular changes, loss of elasticity of connective tissue, the transition is not only based on estradiol short-
age-related cell dehydration, and reduced balance ca- age, but also associated with a decline in GH, IGF-
pacities attribute to the negative effects of aging and 1 (thyroxine, progesterone), and dehydroepiandros-
might also be limiting regarding the capabilities to terone, as well as a chronic inflammatory state [72,
train unrestrictedly in older age [14]. 73]. However, the largest contributor to sarcopenia
in postmenopausal women is most likely the physical
Hormonal changes inactivity [72]. Nevertheless, it has been hypothesized
that estrogens might also play an important role in
Around the 50th life year, the change in hormonal sarcopenia, especially in older women [62], but the
status of human body accelerates in both sexes [14, effects of estrogens on muscle and its function are
37]. While in males andropause refers to a general- poorly understood [73, 74]. Study results about hor-
ized decline of male hormones, including testosterone mone replacement therapy are conflicting [73]. While
and dehydroepiandrosterone in middle-aged and ag- some of the studies reported a lower decline of muscle
ing men [14, 65], menopause in women with fall in mass in patients with estrogen replacement therapy
estrogen levels starts between the 45th and 55th life [71], others showed no effect [53] or no correlation
years [14, 26, 66]. of estrogen levels with muscle mass [74]. Nonethe-
The decline of anabolic hormones with growing less, some studies reported the presence of estrogen
age is a well-established factor in sarcopenia [6, 16, receptors on muscle tissue, especially on type II mus-
17, 20, 21, 26, 37]. Falls in the hormonal synthesis of cle fibers [72]. Additionally, satellite cells are targets
testosterone and estrogens lead to distinct changes of estradiol and testosterone [75]. Satellite cells pro-
in the human body [14, 26, 37], with, among other vide necessary precursors of skeletal muscle repair
things, decreased muscle mass and strength levels and growth [75]. They are affected by age and in-
[26]. Beside these hormones, others such as de- flammation, with a decrease in their total numbers
hydroepiandrosterone, GH, and insulin-like growth leading to limited capabilities for muscle repair and
factor-I (IGF-1) are also involved in this process [6, growth [75]. Estradiol might reduce the inflammatory
16, 17, 20, 21]. state and therefore stabilize the numbers of satellite
Testosterone is secreted by the Leydig cells in cells [75].
males and ovarian thecal cells in females [62]. It is Another important hormone for the maintenance
well known that higher testosterone levels are related of muscle and bone mass is GH [62]. GH exerts most
to increased muscle protein synthesis [21, 37, 53, of its anabolic actions through IGF-1, which is syn-
67, 68], but both hormone levels (testosterone and thesized in the liver for systemic release [62]. IGF-
adrenal androgens) decline with age [17, 21, 26, 40], 1 improves muscle function by causing an increased
accompanied by a decrease in muscle mass and mus- production of muscle satellite cells, but also by stim-
cle strength [20, 21, 26, 37, 40]. Testosterone levels ulating the production of contractile muscle proteins
decline gradually at a rate of approximately 1% per [62]. With increasing age, GH and IGF-1 levels decline,
year and bio-available testosterone by approximately whereby additionally, the amplitude and frequency of
2% per year in males after reaching the age of 30 life pulsatile GH release is also significantly lowered in
years [62, 69]. older persons compared to the young [62].
Normal testosterone levels are required for a range Beside the decreases in synthesis of anabolic hor-
of developmental and biological processes, includ- mones with the aging process [14, 20, 37], which lead
ing maintenance of muscle mass and strength [53, to a decline in anabolic hormone levels accompanied
70]. Skeletal muscle is a direct target tissue for an- by domination of catabolic effects on muscles and
abolic steroids [70]. While high levels are related to bones [14, 20, 37, 62], the release of anabolic hor-
muscle hypertrophy, low levels are epidemiologically mones as a direct reaction upon training stimulus de-
associated with muscle mass reduction, but also with creases in men after begin of andropause as well as
metabolic syndrome and diabetes, which on their own in women after begin of menopause. This is one of
could negatively influence the muscle function [70]. the main reasons why the adaptations upon training
Studies in men with sarcopenic obesity demon- stimulus accompanied by an increase of strength ca-
strated lower serum testosterone, dehydroepiandros- pacities in old people are distinctly smaller than in
terone, and IGF-1 levels in comparison to controls young or younger people [11, 14].
[21]. Testosterone, dehydroepiandrosterone, GH, and However, it is often the effect of pharmacological
treatments themselves that induce muscle mass loss

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[76]. For example, glucocorticoids are an effective riods [83]. Fast-twitch type II muscle fibers are more
treatment administered for inflammatory-based dis- prone to atrophy compared to type I muscle fibers
eases, but potent triggers of muscle loss [76]. [26, 85]. Therefore, one of the important challenges
of a healthy aging is preservation of an active lifestyle
Inflammation and increase of synthesis and release with reduced muscle mass loss and loss of strength of
of catabolic cytokines the aging body and avoidance of a sedentary lifestyle
[14, 21, 85]. Strength training is in this context the
Besides reduction of anabolic factors such as neu- most important tool to counteract this problem [4,
ral growth factors, GH, androgens, and estrogens, as 14, 21].
well as physical inactivity, an increase of catabolic fac-
tors such as inflammatory cytokines could also be an Nutrition
important cause of muscle mass and strength losses
[6, 21, 26, 63]. Studies highlighted that a (chronic) Although food intake declines with aging also in
systemic inflammatory status is involved in the de- healthy people of the general population, the role of
crease of skeletal muscle function [77, 78], and the physiologic anorexia in the development of sarcope-
aging process is accompanied by a higher inflamma- nia is not proven in large studies [21]. While in sick
tory activity in older people [79]. A growing body of older patients sarcopenia was related to malnutri-
evidence indicates an important role of proinflamma- tion with low protein, energy, and vitamin intakes,
tory and catabolic cytokines in sarcopenia [6, 21, 26, in healthy older people this association remains con-
35], comprising interleukin-1β (IL-1), tumor necrosis troversial [21, 36]. Anorexia as the reduced desire
factor(TNF)-α, and interleukin-6 (IL-6; [6, 21, 25, 26, to eat and loss of appetite could be age dependent,
63]). IL-1 and TNF are both factors supporting the re- based on anorexia nervosa or caused secondarily by
cruitment of T cells and development of specific im- underlying diseases [36]. Anorexia could result in
mune response against antigens [21, 79]. Both acti- sarcopenia as well as cachexia [36]. Nevertheless,
vate mutually their synthesis and stimulate IL-6 se- nutritional status is of outstanding importance for
cretion [21]. Although these cytokines show highest muscle maintenance and muscle growth, with a focus
levels in acute states of diseases like sepsis and are on protein and energy intake and vitamin D status
up-regulated in trauma or after surgery, they also play [35].
key roles in chronic diseases such as chronic inflam-
matory diseases, e.g., rheumatoid arthritis, and infec- Other factors contributing to sarcopenia
tions leading to loss of muscle cells and acceleration
of muscle protein breakdown contributing to sarcope- Other factors which are considered to be involved in
nia [9, 17, 20, 21, 25]. Since the development of sar- the sarcopenic process are genetic disposition [35, 42],
copenia is a longstanding process over many years or lung and cardiovascular diseases, and atherosclerosis
even over decades, small changes in the balance of [35, 42, 86, 87], partly driven by reduced physical ac-
muscle proteins might have a large effect when accu- tivity and cachexia due to these diseases [88, 89], but
mulating over this long duration [21]. The catabolic also based on perfusion reduction and nutritional de-
protein process is supported by insulin resistance [80] ficiency regarding the skeletal muscle [90]. While the
and loss of appetite with insufficient nutrient intake degree to which the human muscles’ composite phe-
[17]. notypes are heritable is widely explored, it seems that
Body fat seems to be involved in sarcopenia by in- there is no single genotype which is associated with
fluencing hormones and cytokines affecting muscle an accelerated sarcopenia development [42]. The cor-
mass [17]. Remarkably, the catabolic role of IL-6 is relation between sarcopenia and smoking seems to be
exacerbated in obese individuals [17] and in condi- weak [91], whereby studies have shown a lower BMI
tions like malignancy, rheumatoid arthritis, and aging; in smokers [21, 92, 93] and chronic obstructive pul-
lean body mass is reduced, whereas fat mass is, in the monary disease (COPD) patients [21, 94].
early stages, preserved or even relatively increased,
contributing to the phenomenon of sarcopenic obe- Methods to identify sarcopenia
sity [24].
According to the International Working Group on Sar-
Decrease of physical activity copenia Diagnosis [35], sarcopenia should be consid-
ered in all older individuals who presented with de-
Declined physical activity with the aging process is the clines in physical function, strength, or poor health
key factor in development of sarcopenia [17, 21, 26]. condition, but especially in patients who are bedrid-
It is well known that even short durations of physi- den, cannot independently rise from sitting in a chair,
cal inactivity as well as hospitalizations lead to mus- or showing a measured gait speed <1.0 m/s [35, 95,
cle atrophy [26, 32, 81–84]. The muscle atrophy was 96]. It has been confirmed that gait speed (over a 6-
approximately threefold higher in older compared to min course) is a predictor of adverse health events
younger individuals in the same immobilization pe- such as severe mobility limitation and mortality [1, 24,

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the capability of separation between fat and other soft


tissues of the body and, therefore, the gold standards
for estimating muscle mass in sarcopenia research;
however, high costs and the radiation exposure in CT
limit their use for routine clinical assessment. DEXA is
an alternative radiation method to examine the body
and assess fat, bone, and muscle tissue [8, 20, 21,
24–26, 34, 38, 39, 41].
Bio-impedance analysis (BIA) is another method to
estimate the volume of fat and lean body mass. Re-
sults of BIA correlate under standard conditions with
MRI results [24, 25, 80].
Anthropometric measurements are easy to measure
and the first choice for a practical approach in am-
bulatory settings like nursing homes. Considerations
regarding muscle mass are based on the assessment
Fig. 4 Modified algorithm for diagnostic assessment for sar- of mid-upper arm circumference and triceps skin fold
copenia of the European Working Group on Sarcopenia in thickness with calculation of the corresponding mid-
Older People [24] arm muscle area. Studies confirmed that the circum-
ference of the calf muscle correlates positively with the
25]. Additionally, for patients who are ambulatory and muscle mass. While some studies related a calf mus-
can arise from chair, gait speed should be assessed cle circumference <31 cm to disability [24, 25], oth-
over a 4-meter distance. Those patients with abnor- ers reported 34 cm in men and 33 cm in women as
mal findings in the basis tests should undergo further the best cut-offs to predict sarcopenia [98]. Indeed,
examinations such as body composition assessment this method is widely used, but not recommended as
using dual energy x-ray absorptiometry (DEXA; [35, a standard method and age-related changes in com-
96]). position of the lower leg, with increased fat deposits
Diagnosis of sarcopenia should be based on a com- and loss of skin elasticity, could lead to misclassifica-
posite of low whole body or an appendicular skeletal tion in older persons [24].
muscle mass and poor physical function. In patients Another important measurable parameter to assess
with poor functional capacities (most easily identi- sarcopenia is muscle strength. Although the relevance
fied by using a gait speed <1.0 m/s), sarcopenia can of muscle strength decline in lower limbs is higher
be diagnosed when the lean mass is smaller than the for gait and physical function, handgrip strength has
20th percentile of values for healthy young adults. been widely used to assess muscle strength in older
Currently, recommended cut-off values for sarcope- patients. Handgrip strength measurements correlate
nia are an appendicular skeletal muscle mass/height2 well with sarcopenia assessment. Low costs and sim-
of ≤7.23 kg/m2 in men and ≤5.67 kg/m2 in women [35, ple use make strength testing one of the useful meth-
96, 97]. ods for clinical practice [24, 25, 81, 96, 99]. Inter-
In contrast, as mentioned above in the definition estingly, studies revealed that the measured isometric
section for sarcopenia, diagnosis according to the Eu- hand grip strength relates strongly with lower extrem-
ropean Working Group on Sarcopenia in Older People ity muscle power, especially knee extension torque,
[24] is based on the criteria shown in Table 1. The but also calf cross-sectional muscle area. Additionally,
proposed algorithm for diagnostic assessment for sar- poor handgrip strength is associated with disability for
copenia of the European Working Group on Sarcope- activities of daily living [24, 26].
nia in Older People [24] is similar to the diagnostic Another approach for sarcopenic testing is the peak
approach of the International Working Group on Sar- expiratory flow (PEF), determined by the strength of
copenia Diagnosis [35], but not congruent (Fig. 4). To respiratory muscles. PEF is a simple and widely acces-
identify sarcopenia in individuals, the amount of mus- sible technique to measure muscle force, but study
cle loss and decline of muscle function and strength data about PEF for identification of sarcopenia are
could be assessed. Therefore, measurable variables very limited and require caution in patients with lung
are muscle mass, strength, and physical performance diseases [24, 100].
[24, 39]. Additionally, physical performance could be as-
There were several approaches to measure the de- sessed by a wide range of functional tests like the
cline of these parameters. In studies, imaging tech- Short Physical Performance Battery, timed get-up-
niques were used to estimate muscle mass includ- and-go test, and the stair climb power test [1, 24, 25,
ing computed tomography (CT), magnetic resonance 95, 101, 102].
imaging (MRI), ultrasound, and dual energy X-ray ab- For most of the tests’ age-related cut-off levels with
sorptiometry (DEXA; [20, 21, 24, 25, 34, 38, 39, 62, 71, cut-off points at two standard deviations below the
95]). CT and MRI are precise imaging methods with mean reference value of young healthy adults were de-

Sarcopenia K
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fined to differentiate between sarcopenia and a (still) pendent of age [14, 62]. The improvements in muscle
healthy reference [24, 26, 39, 52, 74]. strength can mostly be achieved with little efforts such
as a minimum of at least one resistance training ses-
Treatment sion per week [62]. Strength training is therefore a key
factor for preparation of the human body regarding
The underlying causes of sarcopenia guide the pri- stressors and loads [14].
mary treatment strategy [24]. Although the treatment Cross-sectional studies demonstrated that the type
strategies to reduce muscle mass, strength, and per- of sport/training has a very strong impact on the ex-
formance losses are principally equal between pri- tent of muscle mass loss with aging [38]. While swim-
mary and secondary sarcopenia, for secondary sar- ming and running were less effective to prevent the
copenia the treatment of the underlying illnesses is of muscle mass and strength losses, targeted long-du-
outstanding importance [24, 36]. rations of strength and power training were able to
In addition, the treatment should orientate toward counteract the problem [38, 62].
the sarcopenia severity stages to determine the inten- Physical activities in youth as well as adulthood
sity of the physical activity and training [24]. Women lead commonly to an all-life high in muscle mass and
are in general weaker than males, but showed similar capacities of muscle strength in the third life decade
gait speeds [103]. This has to be kept in mind during [12, 14]. From this peak on, the muscle mass starts
training planning. to decline due to physiological katabolic processes
Treatment options for sarcopenia comprise physi- triggered by age and other factors [14]. Driven by the
cal training, modifications of nutritional intake, and very different base levels in peak muscle performance,
pharmacological treatment [25]. muscle mass, and strength losses, affect the people
inter-individually in different intensity (smaller or
Physical training stronger and earlier or later in their lives) [4, 14],
but the performance losses in middle age seem to
Epidemiological studies as well as prospective co- be mainly due to the sedentary lifestyle, rather than
hort studies impressively highlighted the importance biological aging [112]. “Newcomers” to sports of older
of regular exercise and physical activity for disease age demonstrate that even these previous non-ath-
prevention and particularly for disease treatment letes can achieve high levels of performance through
[104–106]. Most adult subjects move and exercise regular training [112]. A well-trained 80-year-old man
on their own two feet only for less than 30 min daily could provide at least comparable strength capabili-
[104] and it is well known that sedentary lifestyle ties to an untrained 60-year-old man [4, 14].
is one of the causative factors of sarcopenia [71]. In studies, strength training led to an improvement
A large body of evidence supports the positive ef- of maximal power and strength, with 9 to 113% in
fects of sports and exercise; therefore, it is surprising 60 to 96-year-old men [3, 4, 14]. Highest improve-
that this “panacea” is still underutilized [62, 104]. It ments were obtained in leg muscles. The effects of
should be implemented in daily life in general, but strength improvements were observed especially for
especially, it should also be incorporated in therapy the first 6 months of training. While at the begin-
strategies for hospitalized patients and individuals in ning of strength training the incline of strength ca-
residential homes and other health care facilities [104, pabilities are mainly attributed to better activation of
107]. For example, Landi et al. [87] showed that 1 h of motor units, during the later course muscle hyper-
leisure physical activity per day reduced the risk for trophy plays more and more the dominant role in
sarcopenia by 60% in nursing home inhabitants [87]. raised strength capabilities [4, 14]. However, for hy-
Contrarily, especially older people have most likely pertrophic processes an appropriate training impulse,
to be placed in bed because of illnesses, trauma, loss adequate nutrition, intake of fluids, and sufficient re-
of balance, or diminished functional capacities [108], covery phases are necessary [14].
leading to additional muscle mass loss in already The effect of muscle training on the muscle system
low muscle mass levels (reserves) compromising for is preserved up to oldest age. Although sports and
sarcopenia. physical activity including muscle training could not
While the beneficial effect of resistance training is wholly prevent the physiological katabolic processes
well established to reverse losses of strength even in of muscle loss with aging, the training could reduce
the very old, the extent to which life-long activity pat- and slow down the losses of muscle mass, strength,
terns and training could prevent age-related declines and performance [4, 14]. Examples are senior ath-
in strength capacities has not been prospectively ex- letes, who impress with strong performances in power
amined [38, 109, 110]. Nevertheless, physical activity lifting and weight lifting (Fig. 1; [14]).
and especially strength training is one important tool Although senior athletes train with progressive
to counteract the problem [4, 14, 21, 25, 111]. strength training programs and they could reach and
Training of the muscular system is feasible in ev- preserve high muscle mass and strength levels, they
ery age [4, 8, 14, 21, 62, 111]. Adaptations in the are nevertheless exposed to losses of muscle mass and
muscular system develop quickly and are widely inde- performance with aging. One central factor in this

K Sarcopenia
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context is the decrease of fast-twitch motor units with is used as prophylaxis for falls, which are on their
aging [4, 14, 21]. After the 50th life year, the reduc- own problematic events accompanied by trauma,
tion of fast twitch type II muscle fibers motor units fractures, immobilization, and fear of recurrent falls
exceeds 10% per decade and, therefore, the trainabil- leading to reduced mobility and declined self-confi-
ity of explosive power and fast strength capabilities dence [4, 14, 32, 114].
declines in parallel with aging [14, 62]. Training of Besides the positive effects on the muscular sys-
strength and power focusing on fast-twitch muscle tem, physical activity and sport has benefits on bone,
fibers could prevent a larger loss of muscle function immune, endocrine, and cardiovascular systems [14,
[14, 111], whereas physical inactivity accelerates the 79]. Strength training leads additionally to an increase
processes with aging [4, 14, 21]. Although the number of bone mass [5, 115, 116]. The effects on cardiovas-
of muscle fibers decreases, muscle fiber hypertrophy cular system are better control and lowering of blood
caused by strength training programs can compensate pressure (mean decrease of 4.5 mm Hg in systolic and
muscle mass loss in part [21] and with increased phys- 3.8 mm Hg in diastolic blood pressure; [117]). This is
ical activity, a process of re-innervation has also been equivalent to a relative decrease of 3 to 4% of blood
recognized [14]. Improvements in explosive power pressure at rest and may be important in older indi-
and fast strength capabilities could be achieved by viduals with the comorbidity of arterial hypertension
continued challenging strength and power training [117]. In addition, sport activities have neuroprotec-
with appropriate training impulses. To reach this aim, tive effects [118]. Senior athletes of older age suffer
training programs have to focus on training of explo- less often from tiredness, cognitive deficits, feelings
sive power and fast strength training regarding effects of tension, confusion, anger, sleeping disorders, and
in fast-twitch muscle fibers (if individual’s health sta- depression [3, 14, 60, 118]. They showed an increased
tus and musculoskeletal system allows it). In older performance and vigor [14].
age, slow-twitch fibers as well as fast-twitch fibers
are trainable [4, 14, 62]. Strength training programs Nutrition
with high loads cause also in higher age an increased
fast-twitch muscle fiber hypertrophy [14, 62]. Stud- Beside the sedentary lifestyle, insufficient diet is an
ies with elite weight lifters showed that a continued important possible causative factor for sarcopenia
high-intensity strength training with focus on train- [62, 71]. From approximately the age of 70 years, in
ing of explosive power and fast strength capabilities both genders a slight decrease in body weight of 250 g
could reduce the decline in the number of fast-twitch per life year in median was reported [119]. A growing
muscle fibers and number of motor units [14]. body of evidence confirms that adequate nutrition
Remarkably, periods of limited mobilization or im- is necessary for prevention of functional downturns
mobilization both had a larger impact on neuronal [119, 120]. Inadequate nutrition with macronutrients
motor function and strength loss in the old subjects and micronutrients is almost driven by nutritional
compared to the young, and the capabilities to retrain deficiencies or malnutrition [62, 119]. Older subjects
the loss of muscle mass and muscle strength are lim- have more often acute and chronic comorbidities
ited in the older persons [113]. and are distinctly more frequently affected by func-
Explosive power and fast strength capabilities are tional downturns due to malnutrition compared to
important for fast reaction movements and preven- younger individuals [119]. The pathomechanism of
tion of falls [4, 14]. Strength training in older persons this anorexia of old age is complex and multifactorial,
and comprises visceral, hormonal, neurological, phar-
macological, inflammatory, and psychological factors
[42, 119]. Firstly, advancing age results in a change in
appetite with reduced feelings of hunger. Secondly,
older persons showed a decline of balancing capa-
bilities to compensate periods of reduced nutrition
such as acute disease phases compared to the young.
Thirdly, increasing age is accompanied by a decline
of both the sense of taste and the sense of smell.
Further factors interacting with those mentioned are
the catabolic effect due to the decrease of hormone
stimulation (especially reduction of testosterone and
GH) and persistent inflammation [119].
The decline in body weight of the older people is
not linear, but often occurs stepwise, driven by trigger
events such as hospitalizations for acute diseases [113,
119]. It is connected with a pronounced muscle mass
Fig. 5 Vicious circle consisting of malnutrition, functional loss in comparison to the younger subjects, mostly
deficits, sarcopenia, and frailty (modified according to [119])

Sarcopenia K
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due to both lower physical activity and inadequate [62]. It is well established that vitamin D plays a key
nutrition (Fig. 5; [119]). role in bone and muscle metabolism [62, 125]. In
Regarding the prevention of malnutrition and its older individuals with low vitamin D levels, proximal
results, concrete objectives for nutritional intake have muscle weaknesses were observed, resulting in diffi-
to be specified and patients’ compliance has to be culties in rising from a chair and stair climbing [62].
checked. Nutritional programs start with the evalua- Vitamin D deficiencies in the older persons should be
tion of the actual nutritional situation and the estima- treated [62, 119].
tion of the individual calorie requirement [119].
In the view of pending sarcopenia, especially the Pharmacological therapy
protein intake is of outstanding interest [62, 119].
Studies highlighted that a higher protein intake is as- Potential medical treatments of sarcopenia are not ev-
sociated with reduced muscle mass loss [62, 121]. An idence based [24, 62], and may be treatments for in-
adequate nutritional intake is a modifiable factor for dividual and selected cases, but not for all sarcopenic
sarcopenia [62, 120, 121] and the basis of a successful patients [85]. A large body of evidence demonstrated
treatment of sarcopenia [25, 62]. In order to ensure that medical substitution of androgenic hormones like
this adequate intake, the individual caloric and pro- testosterone leads to increase of muscle mass and
tein demand should be calculated [25]. It should be muscle strength [25, 67, 68, 70, 125–128]. While the
considered that people who take part in physical ac- use of anabolic androgenic steroids such as the syn-
tivities and in rehabilitation programs have a higher thetic derivates of testosterone is forbidden in sports
demand regarding the protein intake [25]. Studies and banned from training and competition as dop-
suggest a stimulation of muscle protein synthesis by ing [125, 126, 128, 129], it is well known that their
protein-rich nutrition [25, 122]. use is connected with a boost of muscle mass [62,
The currently recommended protein intake for 129, 130]. Testosterone has potent anabolic effects
adults comprises 0.8 g/kg (body weight) per day [62, on the musculoskeletal system, comprising an incline
119, 121, 122]. One important problem with this rec- in lean body mass, a dose-related hypertrophy of the
ommended protein intake (especially for the older muscle fibers, and a significant increase in muscle
individuals) is an insufficient stimulating effect re- strength [70, 129]. Especially athletes with required
garding the muscle protein synthesis [62, 121]. In the speed, strength, and power revealed benefits regard-
older persons, higher protein intakes are necessary ing their sport performance by the illegal use of testos-
to stimulate the muscle protein synthesis comparably terone derivates, despite the risk of side effects [62,
to younger individuals [123, 124]. Therefore, experts 126–130]. One important side effect in the older men
recommend a higher daily protein intake of 1.1 g/kg is the increase of prostate gland size and the risk for
(body weight) per day, if no renal insufficiency or prostate cancer due to testosterone supplementation
other contraindications are present [42, 85, 119, 122]. [62]. The reported side effect regarding an elevated
In order to receive an optimal stimulation of the risk for prostate cancer in combination with other
muscle protein synthesis, a balanced distribution of potential side effects such as allergic reactions, fluid
the proteins on the three main meals should be im- retention, gynecomastia, polycythemia, sleep apnea,
plemented [119]. In addition, snacks between the loss of appetite, nausea, depression, or mood changes
meals could support the supply of macronutrients limits its usefulness in the treatment of sarcopenia [62]
and micronutrients [119]. and authors saw also no clear indication for androgen
Moreover, creatine is a natural ingredient of food. therapy use in the older persons to counter sarcopenia
The main source is from meat products and the av- [25].
erage daily intake is approximately 1 g/day. It plays After menopause, circulating estradiol showed re-
is important role in muscle protein metabolism. As duced concentrations and during the postmenopausal
a result of creatine supplementation, muscle phos- period the muscle performance appears to be im-
phocreatine levels increase, connected with decreased paired [62]. Out of the temporal context it was hypoth-
muscle relaxation time, an incline in the performance esized that estrogens might play a role in sarcopenia
of high-intensity exercises, and enhancement of mus- [42, 62]. However, the effect of hormone replacement
cle protein synthesis, lean skeletal muscle mass and therapy in women remains controversial [42, 62, 73].
strength capabilities [62]. Although several studies Although hormone replacement therapies with estro-
have confirmed a positive effect of creatine supple- gens in older women might decrease muscle mass loss
mentation on muscle strength and power in younger [62, 71, 72], estrogen replacement therapy has only
men, only a few studies have provided data about modest benefits for muscle composition and perfor-
the effect in old individuals with controversial results. mance [62]. Estrogen replacement therapy combined
Creatine supplementation was connected with the with resistance training might enhance lower extrem-
side effect of acute nephritis and its use is currently ity strength, but the evidence is weak [62]. As hor-
not recommended for the therapy of sarcopenia [62]. mone replacement therapy revealed some important
Another important factor is vitamin D [62, 119, side effects, such as an elevated risk for breast cancer,
125]. Vitamin D levels decline with increasing age

K Sarcopenia
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the primary therapy for sarcopenia is, at this time, not more than 200 million people in the next 40 years
recommended [62, 126–128]. [24]. Sarcopenia represents a major cause of disability,
GH is a required hormone for muscle and bone falls, morbidity, mortality, and inclined health costs in
maintenance and most of its anabolic effects are me- the older individuals [35, 38, 85, 136–141]. Sarcopenia
diated by IGF-1 [62]. GH stimulates protein synthe- is associated with a 2- to 3.6-fold risk of functional
sis and increases muscle mass, muscle strength, and impairment and disability in older sarcopenic men
interacts with sex hormones regarding an incline in and a 3- to 4.1-fold risk in women [38, 39]. Muscu-
their anabolic effect [125, 128]; thus, the use of GH lar strength is inversely and independently related to
was also banned in sports as doping [128]. Although death [50, 141–143].
it was hypothesized that GH in combination with re- The relevance of sarcopenic muscle mass, function,
sistance training might have a synergistic effect re- and strength loss for older individuals’ capabilities to
garding muscle function in older people, results were cope with the demands of their daily life is obvious
disappointing and the effect barely exceeded the effect [39]. Additionally, in hospitalized patients, sarcopenia
of exercise training alone [62]. In addition, GH sup- is attributed to an elevated risk of complications such
plementation is accompanied by a high incidence of as venous thromboembolism events (VTE), infections,
side effects comprising fluid retention, joint swelling, pressure ulcers, poor quality of life, loss of auton-
joint pain, gynecomastia, orthostatic hypotension, in- omy and institutionalization [138, 144]. While stud-
creased risk of diabetes, and carpal tunnel syndrome ies revealed a strong relation between age and VTE
[62, 125]. Summarizing the current stand of evidence, [145–151], Di Nisio et al. [144] reported that obesity,
GH supplementation for treatment of sarcopenia is previous VTE events, but also poor strength capabil-
not encouraging and not recommended [62]. ities were independent predictors of new VTE events
The administration of angiotensin converting en- [144]. Other factors that have to be considered as risk
zyme (ACE) inhibitors in studies resulted in increased factors for the development of VTE with increasing age
muscle strength and improved muscle function in are immobility and loss of muscle strength, hormone
older persons [25, 62, 125]. Observational studies replacement therapy, hemostasis factors, genetic risk,
have demonstrated that the long-term use of ACE endothelial dysfunction, varicosis, and comorbidities
inhibitors was associated with a lower decrease in such as heart failure, stroke, diabetes mellitus, and
muscle strength and walking speed in older hyper- COPD [152].
tensive people [62, 125]. Studies underlined that BMI and sarcopenia are correlated, as mentioned
cardiac diseases lead to calcium leak in skeletal mus- above [52, 53]. Study results emphasize that under-
cles, suggesting an important link between heart and weight individuals have a poorer prognosis in terms
skeletal muscle [125]. Further evidence is required of several acute illnesses [153, 154].
before recommending the use of ACE inhibitors to The burden of sarcopenia on the health care system
treat primarily sarcopenia, but ACE inhibitors therapy becomes visible when looking at the estimations of
might be preferred in hypertensive patients with ad- the health care costs: In the United States of America,
ditional pending or diagnosed sarcopenia instead of the health care expense for sarcopenia was estimated
other antihypertensive drugs [62]. at 18.4 billion $ in the year 2001 [35, 39]. A major
Some new pharmacological treatments such as challenge in prevention of sarcopenia-induced frailty
bimagrumab [131], but also established treatments of is the implementation of anabolic stimuli, sufficient
other diseases like allopurinol [132] or statin drugs physical activity, and adequate nutrition in the daily
[133], revealed promising results in sarcopenia, but life of the aging general population [109, 155].
these drugs are also not recommended at this time. In conclusion, sarcopenia is a very common, but
frequently overlooked and undertreated geriatric syn-
Relevance of sarcopenia and conclusions drome [35, 125].
Funding This study was supported by the German Federal
Changing demographics have led to a growing impor- Ministry of Education and Research (BMBF 01EO1003 and
tance to understand and prevent modifiable risk fac- BMBF 01EO1503). The author is responsible for the contents
tors for disability and loss of independence with in- of this publication.
creasing age [42]. The remarkable gain of the last four
Conflict of interest K. Keller declares that he has no compet-
decades in life expectancy in western Europe, the USA,
ing interests.
Canada, Australia, New Zealand, and Japan extends
almost linearly without deceleration [134]. In paral-
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