Open Access Rambam Maimonides Medical Journal

TRANSLATIONAL GERONTOLOGY

Lifestyle and Sarcopenia—Etiology,

Prevention, and Treatment§
Oren Rom, M.Sc.1, Sharon Kaisari, B.Sc.1, Dror Aizenbud, D.M.D., M.Sc.1,2, and
Abraham Z. Reznick, Ph.D.1*
Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion–Israel Institute of
1

Technology, Haifa, Israel; and 2Orthodontic and Craniofacial Department, Rambam Health Care Campus,
Haifa, Israel

ABSTRACT
The term sarcopenia describes the loss of skeletal muscle mass, strength, and function in old age. As the
world population continues to grow older, more attention is given to the phenomena of sarcopenia and the
search for strategies of prevention and treatment. The progression of sarcopenia is affected by age-related
physiological and systemic changes in the body, including alterations in skeletal muscle tissue, hormonal
changes, increased inflammatory activities, and oxidative stress. Sarcopenia progression is also affected by
lifestyle factors which are far more controllable. These factors include various aspects of nutrition, physical
activity, exercise, alcohol intake, and tobacco use. Raising the public awareness regarding the impact of
these factors, as causes of sarcopenia and potential strategies of prevention and treatment, is of great
importance. In this review we aim to describe various lifestyle factors that affect the etiology, prevention,
and treatment of sarcopenia.
KEY WORDS: Alcohol intake, cigarette smoking, exercise, nutrition, physical activity, sarcopenia

§ Special Issue on Ageing. Guest Editor: Nir Barzilai

Abbreviations: BMI, body mass index; DEXA, dual energy X-ray absorptiometry; EAA, essential amino acid; ERK1/2,
extracellular signal-regulated kinase 1 and 2; EWGSOP, European Working Group on Sarcopenia in Older People; HMB,
β-hydroxy-β-methylbutyrate; IGF-1, insulin-like growth factor-1; MAFbx/atrogin-1, muscle atrophy F-box; MAPK,
mitogen-activated protein kinases; mTOR, mammalian target of rapamycin; MuRF1, muscle ring finger 1; MyHC, myosin
heavy chain; PRT, progressive resistance training; RDA, recommended dietary allowance.
Citation: Rom O, Kaisari S, Aizenbud D, Reznick AZ. Lifestyle and Sarcopenia—Etiology, Prevention, and Treatment.
RMMJ 2012;3 (4):e0024. doi:10.5041/RMMJ.10091
Copyright: © 2012 Rom O, et al. This is an open-access article. All its content, except where otherwise noted, is
distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Acknowledgements: This study was supported by grants from the Rappaport Institute, the Krol Foundation of
Barnegat N.J., the Myers-JDC-Brookdale Institute of Gerontology and Human Development, and ESHEL—the association
for planning and development of services for the aged in Israel.
Conflict of interest: No potential conflict of interest relevant to this article was reported.
* To whom correspondence should be addressed. E-mail: [email protected]
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 Lifestyle and Sarcopenia

INTRODUCTION From the third decade of life a shift in body

composition occurs. Between the ages of 30 and 60,
The term sarcopenia (in Greek, sarx for flesh and
the average adult is expected to gain approximately
penia for loss), first proposed by Irwin Rosenberg,
0.45 kg (1 lb) of fat and lose about 0.23 kg (0.5 lb) of
describes the age-related loss of skeletal muscle
muscle yearly.6 From the age of 60, loss of muscle
mass and strength.1 Sarcopenia is a common
mass is accelerated and is estimated at 2% annually.
impaired state of health with a high personal toll
Also, decline of muscle strength over the age of 60 is
and huge financial costs.2 However, sarcopenia has
estimated at 3% yearly. The result of these losses is a
no accepted clinical definition and no codes in the
decrease in total muscle cross-sectional area of
International Classification of Diseases 9th Revision
about 40% between 20 and 60 years of age.6 Loss of
(ICD-9).2 Therefore, the European Working Group
muscle mass accompanied by increase in fat mass
on Sarcopenia in Older People (EWGSOP), assem-
may lead to a body composition phenotype known
bled in 2009, developed definitions, diagnostic
as sarcopenic obesity. It was estimated that
criteria, categories, and stages in sarcopenia.2
approximately 30% of men and 10% of women over
According to the EWGSOP, sarcopenia is diagnosed
the age of 80 have sarcopenic obesity.6 In addition,
by the presence of low muscle mass along with low
aging is associated with alterations in skeletal
muscle function (strength or physical perform-
muscle tissue and low muscle quality. For instance,
ance).2 The EWGSOP suggested the following
skeletal muscle is infiltrated by fat and connective
categories to reflect the severity of sarcopenia: Pre-
tissue, the number and size of muscle fibers are
sarcopenia, characterized by low muscle mass with
decreased, there is a decrease in motor units,
no impact on muscle function; Sarcopenia,
disarrangements of myofilaments, accumulation of
characterized by low muscle mass plus low muscle
reactive oxidative species, and reduction in satellite
strength or low physical performance; and Severe
cell activity and number.7
sarcopenia, characterized by low muscle mass plus
low muscle strength and low physical performance.2
In order to develop strategies to prevent and
The EWGSOP also suggested using healthy young
treat sarcopenia, the risk factors and causes of
adults as reference populations, with cut-off points
sarcopenia must be identified. The progression of
at two standard deviations below the mean reference
sarcopenia is affected by age-related systemic
value for muscle mass, muscle strength, and
changes and by lifestyle habits.8 Age-related changes
physical performance. Recommended measurement
include reduction in anabolic hormones such as
techniques include dual energy X-ray
testosterone, estrogen, growth hormone, and
absorptiometry (DEXA) scan for muscle mass,
insulin-like growth factor-1 (IGF-1), increased
isometric hand grip test for muscle strength, and
inflammatory activity, and oxidative stress which
gait speed test for physical performance.2
contribute to muscle catabolism.7 Lifestyle habits
The prevalence of sarcopenia among people older have a major impact on sarcopenia as well. These
than 65 years has been estimated as high as 15%, factors include impaired nutrition, reduced physical
and 50% among people over the age of 80.3 As a activity, alcohol consumption, and cigarette
major public health problem, the health care cost of smoking.7–9 A scheme of the effects of these lifestyle
sarcopenia in the United States alone was estimated factors on skeletal muscle and the progression of
at 18.5 billion dollars in the year of 2000.3,4 This sarcopenia is presented (Figure 1). Genetic factors
estimation took into consideration the direct costs of may also affect the progression of sarcopenia.
sarcopenia, including hospital, out-patient, and Muscle mass and strength are multifactorial traits
home health care expenditures, and did not include that vary widely among individuals. The genetic
the indirect costs of sarcopenia such as loss of component of sarcopenia is complex and driven by
productivity.4 The world’s population over the age of many genes. Several genes have been identified that
60 is expected to triple from 600 million in 2000 to contribute to variation of skeletal muscle mass and
more than 2 billion by the year of 2050.5 Owing to strength, including the IGF-1 and vitamin D
this worldwide increase in life expectancy, the receptor genes.10 Since lifestyle factors are more
prevalence and cost of sarcopenia are likely to rise. controllable in comparison with age-related
Therefore, developing strategies to prevent and treat systemic changes and genetic factors, it is of great
sarcopenia are of great importance. importance to raise the public awareness regarding

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 Lifestyle and Sarcopenia

Figure 1. Lifestyle factors affecting sarcopenia.

their influence on the progression of sarcopenia. The current recommended dietary allowance
This review aims to present the importance of (RDA) of protein is 0.8 g/kg/day.3 It has been
lifestyle factors as causes of sarcopenia and potential estimated that approximately 40% of people over
strategies for prevention and treatment of the age of 70 do not meet this RDA.3 Furthermore,
sarcopenia. nitrogen balance studies in aging populations have
indicated greater protein needs for the elderly (1.14
DIETARY FACTORS IN SARCOPENIA g/kg/day) relative to the young (0.8 g/kg/day).13
Thalacker-Mercer et al.14 assessed the effect of 1
Aging is associated with reduced appetite and low week of inadequate protein intake (0.5 g/kg/day)
food intake, which was previously termed the compared with adequate protein intake (1.2
“anorexia of ageing.”11 Several causes have been g/kg/day) on gene expression profiles in skeletal
suggested to explain this phenomenon. Anorexia of muscle of older adults. It was shown that inadequate
aging may be the result of early satiety owing to protein intake is associated with down-regulation of
decreased relaxation of the fundus, increased release transcripts associated with protein synthesis,
of cholecystokinin, and increased leptin levels.6,11 myosin formation, and proliferation of satellite cells.
Altered taste and smell, social changes, and
economic limitations may also lead to decreased Increased protein needs in the elderly might be
food intake.12 These may result in low nutrient explained by the phenomenon of “anabolic
intake, which is an important risk factor in the resistance,” a blunted response of muscle protein
development of sarcopenia. In particular, protein synthesis following ingestion of dietary protein in
intake has a major influence on skeletal muscle the elderly relative to the young.13,15 This
metabolism. Inadequate protein intake is one of the phenomenon is associated with reduction in IGF-1
major mechanisms underlying sarcopenia. levels in old age. IGF-1 activates the mammalian

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 Lifestyle and Sarcopenia

target of rapamycin (mTOR) which in turn regulates E3 ligases, muscle ring finger 1 (MuRF1) and muscle
muscle protein synthesis by initiating translation. atrophy F-box (MAFbx/atrogin-1) of the ubiquitin–
Thus, impairment in mTOR signaling leads to proteasome system.21 These E3 ligases mediate the
decreased capacity and efficiency of protein ubiquitination of muscle proteins and play an
synthesis.11 Previous studies have shown that the important role in myofibrillar protein breakdown.
elderly are less able efficiently to utilize amino acids Knock-out mice lacking these E3 ligases are
for muscle protein synthesis. For instance, Katsanos protected from muscle atrophy.21 C2C12 muscle cells
et al.16 examined the effect of essential amino acid treated with 5 mM leucine have demonstrated
(EAA) small bolus (6.7 g) on synthesis of muscle suppressed MAFbx/atrogin-1 and MuRF1 mRNA
proteins in the elderly compared with the young. It levels.22 Therefore, leucine supplementation to older
was found that protein synthetic response was adults may serve as a potential strategy to combat
diminished in the elderly relative to the young.13,16 the progression of sarcopenia. The dose–response of
However, Symons et al.17 examined muscle protein leucine supplementation is unknown, and future
synthesis in elderly compared with young subjects studies should focus on finding effective and safe
following ingestion of a 113-g serving of lean beef doses for the use of leucine as an anti-atrophic agent
(approximately 30 g of amino acids). They have in sarcopenia.18 In the meantime, older adults
shown that muscle synthesis rate was increased should be encouraged to consume a diet high in
equally in both the elderly and the young and EAAs, in particular leucine-rich food sources such as
concluded that aging does not impair the ability to beef, fish, and legumes.6
synthesize muscle protein after ingestion of protein-
Vitamin D has recently received recognition as
rich food. These studies demonstrate the importance
another potential intervention modality for
of the amount of protein ingested and its source in
sarcopenia.6 Recent findings have demonstrated
order to stimulate synthesis of muscle protein
that vitamin D plays an important role in skeletal
despite the observed anabolic resistance in the
muscle tissue by maintaining the function of type II
elderly. Also, the timing of protein intake by older
fibers, preserving muscle strength and preventing
adults may be critical to maintain muscle mass. It
falls.23 Vitamin D receptor knock-out mice are
was suggested that sufficient protein with each meal
characterized by growth retardation, muscle
should be encouraged more than an overall increase
impairment, and smaller diameters of muscle fiber
in daily protein intake.12 Nevertheless, optimal
than those of wild-type mice.24 Older adults are at
protein intake as a strategy to prevent and treat
increased risk of vitamin D insufficiency due to
sarcopenia needs to be further investigated in future
various factors. As people age, the skin’s ability to
studies.
synthesize vitamin D efficiently is reduced, and the
The EAA leucine plays an important role in kidney is less able to convert vitamin D to its active
regulating muscle metabolism and is known as an form; in addition, inadequate sunlight exposure
anti-atrophic agent. Leucine regulates translational which is essential for vitamin D synthesis and low
control of protein synthesis through activation of the consumption of dietary vitamin D are common
mTOR signaling pathway.15 Also, in-vivo and in- among the elderly.24–26 Indeed, the prevalence of
vitro studies have demonstrated the ability of vitamin D insufficiency in the elderly has been
leucine to attenuate skeletal muscle wasting by estimated at 78%.26 Clinical, in-vivo, and in-vitro
interaction with proteolytic pathways.18 Katsanos et studies have shown that vitamin D affects muscle
al.19 have shown that increasing the proportion of strength and function.26 For instance, Bischoff-
leucine in a mixture of EAA given to elderly subjects Ferrari et al.27 have shown that higher concentra-
can reverse the attenuated response of muscle tions of vitamin D are associated with better
protein synthesis. Flakoll et al.20 have found that 12 musculoskeletal function in the lower extremities
weeks of daily supplementation of leucine than lower vitamin D concentrations in people over
metabolite β-hydroxy-β-methylbutyrate (HMB) the age of 60. Also, Pfeifer et al.28 have
together with arginine and lysine can positively alter demonstrated that combined vitamin D (800
measurements of functionality, strength, fat-free IU/day) and calcium (1,000 mg/day) supplementa-
mass, and protein synthesis in elderly women. tion are superior to calcium alone in reducing the
Leucine supplementation to immobilized rats has number of falls and improving muscle function and
been shown to reduce muscle wasting via strength in community-dwelling older individuals.
minimizing gene expression of the muscle-specific On the cellular level, in-vitro studies have

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 Lifestyle and Sarcopenia

demonstrated that vitamin D can stimulate PHYSICAL ACTIVITY, SEDENTARY

proliferation and differentiation of myoblasts. LIFESTYLE, AND SARCOPENIA
Signaling pathways involved in vitamin D-associated
Physical activity is defined as any movement
proliferation and differentiation of myoblasts
produced by the contraction of skeletal muscles that
include the mitogen-activated protein kinases
increases energy expenditure. Physical activity
(MAPK) pathways such as the extracellular signal-
includes daily activities such as standing up from a
regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and
chair and climbing stairs, as well as intentional
c-Jun NH2-terminal 1 and 2 MAPK (JNK1/2).26
movements for health benefits such as walking or
Nevertheless, the exact mechanisms of vitamin D
biking.31 Persons performing only baseline physical
action in skeletal muscle and how it promotes
activities such as standing, walking slowly, and
improvements in muscular performance are yet to
lifting light objects are considered inactive. Physical
be clear, and further studies are needed. The role of
activities added to these baseline activities produce
vitamin D in skeletal muscle and its ability to
substantial health benefits.31 Exercise is planned,
prevent muscular deterioration has been
structured, and repetitive physical activity
demonstrated at all research levels. Supplementa-
performed during leisure time for the purpose of
tion of vitamin D on the basis of measured low levels
maintaining or improving the components of
or in groups at high risk for deficiency appears as an
physical fitness, functioning, and health.31 Older
important strategy for the prevention and treatment
adults who are less physically active are more likely
of sarcopenia.6
to have lower skeletal muscle mass and strength and
Another main issue in the context of sarcopenia are at increased risk of developing sarcopenia.3
is weight management and body mass index (BMI).
As more attention is given to the prevention of Sedentary behavior refers to activities that do not
obesity, older people already at risk of sarcopenia substantially increase energy expenditure above the
may attempt to lose weight when weight stability is resting level. It includes sleeping, sitting, lying
more important to them. Older people with BMI down, and watching television.32 Sedentary lifestyle
within what is considered an ideal range for younger has been shown to be a major risk factor for chronic
individuals may be at nutritional risk and at risk of disease, frailty, and sarcopenia as well.33 Studies
sarcopenia.7 Weight loss attempts in older adults dealing with the effects of bed rest on skeletal
may lead to caloric insufficiency that can accelerate muscle demonstrate the impact of sedentary
the progression of sarcopenia.12 On the other hand, behavior on muscle mass and metabolism. Only 7
the issue of sarcopenic obesity must also be taken days of recumbency has been shown to result in
into consideration. Excess caloric intake that results rapid loss of muscle mass. More prolonged periods
in obesity may also accelerate sarcopenia.12 Obesity of bed rest have resulted in 30% reduction of muscle
is a BMI equal or greater than 30 kg/m2.29 volume, particularly in muscles of the lower limbs.34
Sarcopenic obesity is an alternate model of obesity Studies examining the effect of immobilization on
characterized by loss of muscle mass and increased skeletal muscle have shown a disruption in the
fat mass.30 Obese older adults have higher muscle balance between protein synthesis and breakdown
mass than non-obese; however, it was suggested in which muscle protein anabolism is reduced and
that muscle quality in obese individuals is poor due catabolism is increased.34 Studies conducted on
to increased intramuscular adipose tissue, leading to immobilized animals have demonstrated that the
muscle weakness, frailty, and disability.12 In damage caused to skeletal muscle is associated with
sarcopenic obese individuals, weight loss may be activation of various proteolytic systems which are
necessary but should be achieved in a way that further activated in muscles of old animals in
preserves lean tissue.7 This may be achievable comparison with young animals.35 For instance,
through inclusion of an exercise program focusing increased ubiquitination of myosin heavy chain
on resistance training which will be discussed later. (MyHC) protein was observed in muscles of old
Also, during calorie-restricted diets increased immobilized animals in comparison with young
protein intake is important to maintain muscle mass immobilized animals.35 Bar-Shai et al.36,37 have
especially in sarcopenic obesity.30 suggested that activation of extracellular hydrolytic

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 Lifestyle and Sarcopenia

and proteolytic systems differ in muscles of old already after a few hours of an acute bout of
animals compared to young animals during exercise.43 The molecular mechanism of resistance
immobilization. A different activation pattern of training in which synthesis of muscle protein is
nuclear factor kB (NF-kB) in muscle atrophy was increased includes the MAPK and mTOR signaling
observed in which the canonic activation pathway of pathways. Following resistance training exercise,
NF-kB was more prominent in muscles from old phosphorylation of ERK1/2 MAPK is increased and
animals compared to young ones. Also, the mTOR is activated, leading to activation of
involvement of growth hormone in muscular downstream translation initiation factors and thus
damage and atrophy during limb immobilization resulting in increased muscle protein synthesis.43
was demonstrated by Carmeli et al.38 It was shown Numerous studies have demonstrated the effective-
that administration of growth hormone to old rats ness of resistance training in improving muscle
significantly reduced muscle weight loss and mass and strength in the elderly. For instance,
atrophy, protein oxidation, and fiber disorientation Frontera et al.44 have shown that a 12-week strength
caused by immobilization. training program of 3 days a week in older adults
resulted in increased muscle strength, muscle
Since low physical activity and sedentary lifestyle
hypertrophy, and myofibrillar protein turnover.
are main causes of sarcopenia, exercise is a primary
Moreover, improvements in muscle strength in
strategy in the prevention and treatment of
older adults have been shown to be achieved with as
sarcopenia. Both aerobic training and resistance
little as one resistance training session per week.3
training can improve the rate of decline in muscle
Taaffe et al.45 have shown that a resistance training
mass and strength with age.3 Aerobic training, in
program of only 1 day per week in older adults
which large groups of muscle move for a prolonged
improves muscle strength in a similar manner to a
period of time, is less likely to contribute to muscle
resistance training program of 3 days per week.
hypertrophy; however, it can increase the cross-
sectional area of muscle fibers, mitochondrial Progressive resistance training (PRT), in which
volume, and enzyme activity. Also, aerobic exercise the load is systematically increased as the person is
can reduce intramuscular fat and improve muscle able to work against a heavier load, is the most
functionality.3 Interestingly, several studies have commonly used resistance therapy in older
demonstrated the anabolic effects of aerobic people.3,42 It has been shown to produce large
training. Robinson et al.39 have shown that 6 weeks increases in muscle strength, physical function, and
of aerobic training in older adults resulted in lean body mass.3,42 According to the guidelines for
increased long-term synthesis of muscle protein and physical activity in older adults by the American
DNA in comparison with young sedentary subjects. College of Sports Medicine and American Heart
Pasini et al.40 have examined the effect of aerobic Association,46 in order to maintain or increase
treadmill exercise on muscle anabolic pathways in muscular strength and endurance, resistance train-
young versus old rats. They have found that aerobic ing sessions at a minimum of two non-consecutive
training ameliorated aging-associated impairments days per week should be performed. A progressive
in muscle anabolic pathways, affecting the insulin weight training program is recommended to include
and mTOR signaling pathways.38 In addition, 8–10 exercises for the major muscle groups using a
Timmerman et al.41 have reported that aerobic resistance that allows 10–15 repetitions for each
training in older adults improves nutrient delivery exercise.46 Mayer et al.47 recommended that PRT
to muscle, thus inducing an increased anabolic effect programs aiming to reduce sarcopenia should
of nutrient intake. consist of three training units per week. Exercises
should include 8–12 repetitions per muscle group in
In comparison to aerobic training, resistance
60%–80% of the one-repetition maximum.
training has a greater effect on increasing muscle
mass and strength and attenuates the development Healthy aging adults should be entirely capable
of sarcopenia.3 Resistance training is a form of of safe participation in PRT programs.48 Moreover,
exercise in which muscle contracts against an resistance training appears to be safe to perform
external load. Equipment commonly used to even in participants with multiple co-morbidities.3
perform resistance training includes free weights, However, among aged individuals with existing
exercise machines, body weight, and elastic bands.42 morbidities, careful risk stratification is necessary to
Resistance training increases muscle mass through ensure safety during resistance training.48 Familiar-
direct stimulation of muscle protein synthesis ization to the resistance training program, including

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 Lifestyle and Sarcopenia

a period of low-intensity training, is important for 70-year-old adults undergoing a resistance training
novice trainees, especially for the elderly. Following program in a randomized control study. Compared
this familiarization period older adults may benefit with the placebo group, the HMB-supplemented
from a more gradual increase in training intensity to group presented increased gain of fat-free mass and
accommodate improvements in strength and muscle loss of body fat. Older adults who are reluctant to
hypertrophy.48 use nutritional supplementation may benefit from
the consumption of EAAs from food products. Milk-
To summarize, an inactive and sedentary lifestyle
based proteins are an effective protein source for
is the main factor in the loss of muscle mass and
stimulating synthesis of muscle protein and
strength of old age. Exercise programs focusing on
promoting gains in muscle mass.50 Bovine milk
PRT combined with aerobic training are of great
contains a relatively high proportion of leucine.
importance in the prevention and treatment of
Also, milk contains both whey and casein proteins,
sarcopenia.
which have different absorption rates. Whey protein
has been hypothesized to promote rapid muscle
INTERACTIONS BETWEEN NUTRITION
protein synthesis, while casein promotes sustained
AND EXERCISE
synthesis of muscle protein.50 The timing of EAA-
Although PRT is a promising strategy for countering rich protein consumption relative to the resistance
sarcopenia, the cellular anabolic response to training bout may also play an important role in the
resistance training is blunted in older adults anabolic response. Resistance training induces
compared to the young.13 This may be the result of increased blood-flow and utilization of amino acids
greater susceptibility to load-induced myofiber for muscle protein synthesis. Therefore, milk-based
damage, attenuated regenerative capacity, and proteins should be consumed in close proximity to
limited myofiber plasticity in response to resistance the resistance training session.50 Also, the elderly, in
training in the elderly.48 Adequate dietary intake comparison to the young, may require a greater
may promote muscle anabolism and overcome the amount of protein to achieve an anabolic response
blunted cellular response in older adults to resistance training. Yang et al.53 have reported
participating in various exercise programs, that muscle protein synthesis in older adults is
particularly resistance training. increased with ingestion of 40 g of whey protein,
whereas in younger adults post-exercise rates of
First, adequate energy intake in elderly during
muscle protein synthesis are saturated with only 20
resistance training program is extremely important.
g of protein.
Singh et al.49 have demonstrated that increased
caloric intake can improve muscle strength and The creatine/phospho-creatine energy system is
growth in elderly who consumed less than the RDA used to sustain adenosine triphosphate (ATP) levels
for energy intake. They found that older adults during times of high energy demand as in resistance
participating in resistance training and taking a 360 training bouts.54 Previous studies have reported an
calories nutritional supplement increased their age-associated reduction in skeletal muscle
muscle strength and type II muscle fiber area creatine/phospho-creatine.54 Rawson et al.54
significantly when compared with older adults reviewed the effect of creatine supplementation on
taking part in resistance training alone. skeletal muscle of the elderly. They have reported
that supplementation of creatine in older adults, in
Second, increased protein intake may improve combination with resistance training, increases lean
the anabolic response to resistance training in the body mass, enhances fatigue resistance, increases
elderly. It appears that EAAs and in particular muscle strength, and improves performance of
leucine play the predominant role in promoting a activities of daily living to a greater extent than
positive muscle protein balance.50 Kim et al.51 have resistance training alone. Although reported to be a
examined the effect of exercise with or without safe dietary supplement, the safety of creatine
supplementation of a leucine-rich EAA mixture on supplementation and its long-term benefits to the
muscle mass and strength in 155 elderly sarcopenic elderly population need to be further investigated
women. They have found that the greatest increase before including it as a recommended strategy for
in muscle mass and strength was in the exercise plus the prevention and treatment of sarcopenia.54
EAA supplementation group. Vukovich et al.52 have
investigated whether the leucine metabolite HMB, In summary, to maximize the benefits of exercise
administered at a dose of 3 g a day, would benefit in older adults as a method to combat sarcopenia

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 Lifestyle and Sarcopenia

progression, adequate dietary intake is of great that acute intraperitoneal administration of alcohol
importance. This includes sufficient caloric intake impairs the IGF-1 signaling pathway in skeletal
and consumption of EAA-rich protein sources that muscle of rats, a key regulator of muscle anabolism.
would promote muscle anabolism, especially in Vary et al.60 reported that acute intraperitoneal and
older persons taking part in resistance training oral administration of alcohol increased the
programs. expression of muscle-specific E3 ligases MuRF1 and
MAFbx/atrogin-1 in skeletal muscles of rats.
ALCOHOL CONSUMPTION AND However, this up-regulation was not associated with
SKELETAL MUSCLE increased long-term rates of muscle proteolysis.
Therefore, it has been concluded that the loss of
Alcohol misusers frequently suffer from low muscle
muscle mass in response to chronic alcohol abuse
mass and strength, muscle pain, cramps, difficulties
results primarily from reduced synthesis of muscle
in gait, and falls.55 This phenomenon is known as
proteins and not increased degradation.60
alcoholic myopathy.55 Acute alcoholic myopathy
occurs after severe alcoholic binges in malnourished Alcohol abuse appears to affect skeletal muscle
alcoholics. It is a rare condition characterized by severely, promoting its damage and wasting. The
painful muscles, myoglobinuria, raised serum crea- above in-vivo studies indicate that alcohol-induced
tine kinase activities, and often renal impairment.55 muscle damage may be the result of impaired
However, chronic alcoholic myopathy is a common synthesis of muscle protein rather than increased
complication of alcoholism affecting approximately muscle catabolism. Although alcohol consumption is
50% of alcohol misusers.55 Chronic alcoholic myop- not known as a direct cause of sarcopenia, studies
athy is not associated with nutritional, vitamin, or demonstrating the adverse effects of alcohol on
mineral deficiencies or alcoholic liver disease, and it skeletal muscle suggest that chronic alcohol
is reversible within 6–12 months of abstinence.55 consumption may promote loss of muscle mass and
Chronic alcoholic myopathy is characterized by strength in old age. Therefore, it is proposed that
selective atrophy of type II muscle fibers, leading to high alcohol intake is a lifestyle habit that may
reduction of muscle mass by up to 30%.55 promote sarcopenia. Reducing alcohol consumption
may serve as a strategy for the prevention of
Previous studies attempted to explain the
sarcopenia.
molecular mechanisms of alcohol-induced skeletal
muscle damage. Tiernan and Ward56 administered CIGARETTE SMOKING AND SARCOPENIA
ethanol acutely to rats and investigated its effects on
whole-body and muscle protein synthesis. They have Cigarette smoking is associated with poor lifestyle
found that ethanol decreased whole-body and habits, such as low levels of physical activity and
muscle protein synthesis by 41% and 75%, impaired nutrition.8 However, smoking itself is
respectively. Reilly et al.57 studied the effects of another lifestyle habit that has been found to be
ethanol on skeletal muscle protein synthesis and associated with sarcopenia in previous studies.8
protease activities in rats. Compared with pair-fed Castillo et al.61 examined sarcopenia risk factors in
controls, significant reductions in skeletal muscle 1,700 community-dwelling men and women aged
protein, RNA, and DNA contents were found after 55–98 years. They have found that men and women
24 hours of ethanol administration. Fractional rate who were current smokers were more likely to have
of muscle protein synthesis was reduced, though sarcopenia. Szulc et al.62 investigated risk factors for
protease activities were not significantly affected by sarcopenia in a large cohort of 845 men aged 45–85
ethanol, indicating that alcohol-induced muscle years. They have reported that smokers had lower
damage is associated with impaired synthesis of relative appendicular skeletal muscle mass than did
muscle protein and is not promoted by increased subjects who never smoked and that men with
activation of proteolytic systems.55 Lang et al.58 have sarcopenia smoked significantly more. In addition,
shown that rats on a 14-week alcohol-containing diet Lee et al.63 studied the association between
presented an alcoholic myopathy phenotype sarcopenia and lifestyle factors in 4,000
confirmed by reduced skeletal muscle mass. Their community-dwelling Chinese elderly over 65 years
findings also indicated that chronic alcohol of age. Similarly, they have found that cigarette
consumption impairs translation initiation in smoking is associated with low appendicular skeletal
muscle by altering activities of several eukaryotic muscle mass. All of the above studies concluded that
initiation factors. Later, Lang et al.59 have shown tobacco smoking is a risk factor for sarcopenia.61–63

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 Lifestyle and Sarcopenia

Several studies attempted to explain the cellular model of cigarette smoke-induced skeletal
mechanism by which cigarette smoking promotes muscle catabolism.9 In this model, components of
muscle catabolism and accelerates the progression cigarette smoke may reach skeletal muscle of
of sarcopenia. The effects of cigarette smoking on smokers, leading to increased oxidative stress and
skeletal muscle structure and metabolism were activation of signaling pathways which trigger up-
demonstrated in clinical, in-vivo, and in-vitro regulation of muscle-specific E3 ubiquitin ligases. As
studies. Montes de Oca et al.64 explored the effects a result, degradation of skeletal muscle protein is
of smoking on skeletal muscle by studying biopsies increased and the progression of sarcopenia in
of the vastus lateralis muscle from smokers and elderly smokers may be accelerated.9
healthy control subjects. They have found structural
and metabolic damage in skeletal muscle of
CONCLUSION
smokers, including decreased cross-sectional area of
type I muscle fibers, and a similar trend in type IIa Lifestyle habits regarding nutrition, physical
fibers of smokers. Petersen et al.65 studied the effect activity, exercise, alcohol consumption, and tobacco
of smoking on protein metabolism in skeletal use have a substantial impact on the progression of
muscle of smokers and non-smokers about the age sarcopenia and the ability to prevent and treat the
of 60. They have found that the fractional synthesis loss of muscle mass and function in old age. As life
rate of muscle was significantly lower in smokers expectancy is increasing worldwide, the prevalence
compared with non-smokers. Also, smokers and costs of sarcopenia are expected to rise. In order
presented greater expression of the muscle-specific to treat and delay sarcopenia, the choices we make
E3 ligase MAFbx/atrogin-1 and the muscle growth in our lifestyle habits must be taken into considera-
inhibitor myostatin. Therefore, Petersen et al.65 tion. In contrast to physiological and systemic
concluded that smoking may increase the risk of changes that occur in our body as we age and
sarcopenia by impairing muscle protein synthesis accelerate the progression of sarcopenia, lifestyle
and up-regulating genes associated with impaired factors are far more controllable. Therefore, raising
muscle maintenance. Chronic exposure of animals the public awareness regarding the importance of
to cigarette smoke also resulted in muscular lifestyle habits on the status of skeletal muscle in old
damage.66–68 Mice exposed to cigarette smoke daily age is of great importance in the management of
for 16 weeks presented a reduction in body and sarcopenia.
gastrocnemius muscle mass and up-regulation of
MAFbx/atrogin-1 and MuRF1 in sampled skeletal
REFERENCES
muscles.66 In addition, 6 months of cigarette smoke
exposure to mice resulted in a 20% reduction of 1. Rosenberg IH. Sarcopenia: origins and clinical
force at high-stimulation frequencies.67 Barreiro et relevance. J Nutr 1997;127:990–1.
al.68 have also demonstrated that 6 months of
2. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al.
cigarette smoke exposure to mice led to reduction in Sarcopenia: European consensus on definition and
body weight gain and increased oxidative stress in diagnosis: Report of the European Working Group on
gastrocnemius muscle. In an attempt to understand Sarcopenia in Older People. Age Ageing 2010;
better the molecular mechanism of cigarette smoke- 39:412–23. Full Text
induced muscle catabolism, we have studied the
3. Burton LA, Sumukadas D. Optimal management of
effects of cigarette smoke exposure on C2 myotubes
sarcopenia. Clin Interv Aging 2010;7:217–28.
from an in-vitro skeletal muscle cell line. We have
found that exposure of C2 myotubes to cigarette 4. Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R.
smoke caused a decrease in diameter of myotubes, The healthcare costs of sarcopenia in the United
degradation of the main contractile proteins, MyHC States. J Am Geriatr Soc 2004;52:80–5. Full Text
and actin, and up-regulation of MAFbx/atrogin-1 5. Loenneke JP, Pujol TJ. Sarcopenia: an emphasis on
and MuRF1. These catabolic processes were occlusion training and dietary protein. Hippokratia
mediated by increased intracellular oxidative stress 2011;15:132–7.
and activation of p38 MAPK. Pretreatment with the 6. Waters DL, Baumgartner RN, Garry PJ, Vellas B.
antioxidant N-acetyl-cystein (NAC) and inhibition of Advantages of dietary, exercise-related, and
p38 MAPK prevented cigarette smoke-induced therapeutic interventions to prevent and treat
catabolism in C2 myotubes. Based on the above sarcopenia in adult patients: an update. Clin Interv
studies and our recent findings, we have suggested a Aging 2010;7:259–70. Full Text

Rambam Maimonides Medical Journal 9 October 2012  Volume 3  Issue 4  e0024

 Lifestyle and Sarcopenia

7. Visvanathan R, Chapman I. Preventing sarcopaenia 20. Flakoll P, Sharp R, Baier S, Levenhagen D, Carr C,
in older people. Maturitas 2010;66:383–8. Full Text Nissen S. Effect of beta-hydroxy-beta-methyl-
butyrate, arginine, and lysine supplementation on
8. Rom O, Kaisari S, Aizenbud D, Reznick AZ.
strength, functionality, body composition, and
Identification of possible cigarette smoke
protein metabolism in elderly women. Nutrition
constituents responsible for muscle catabolism. J
2004;20:445–51. Full Text
Muscle Res Cell Motil 2012;33:199–208. Full Text
21. Baptista IL, Leal ML, Artioli GG, et al. Leucine
9. Rom O, Kaisari S, Aizenbud D, Reznick AZ.
attenuates skeletal muscle wasting via inhibition of
Sarcopenia and smoking: a possible cellular model of
ubiquitin ligases. Muscle Nerve 2010;41:800–8. Full
cigarette smoke effects on muscle protein breakdown.
Text
Ann NY Acad Sci 2012;1259:47–53. Full Text
22. Herningtyas EH, Okimura Y, Handayaningsih AE, et
10. Tan LJ, Liu SL, Lei SF, Papasian CJ, Deng HW.
al. Branched-chain amino acids and arginine
Molecular genetic studies of gene identification for
suppress MaFbx/atrogin-1 mRNA expression via
sarcopenia. Hum Genet 2012;131:1–31. Full Text
mTOR pathway in C2C12 cell line. Biochim Biophys
11. Chapman IM, MacIntosh CG, Morley JE, Horowitz Acta 2008;1780:1115–20.
M. The anorexia of ageing. Biogerontology 2002;3:
23. Montero-Odasso M, Duque G. Vitamin D in the aging
67–71. Full Text
musculoskeletal system: an authentic strength
12. Buford TW, Anton SD, Judge AR, et al. Models of preserving hormone. Mol Aspects Med 2005;26:203–
accelerated sarcopenia: critical pieces for solving the 19. Full Text
puzzle of age-related muscle atrophy. Ageing Res Rev
24. Ceglia L. Vitamin D and its role in skeletal muscle.
2010;9:369–83. Full Text
Curr Opin Clin Nutr Metab Care 2009;12:628–33.
13. Kim JS, Wilson JM, Lee SR. Dietary implications on Full Text
mechanisms of sarcopenia: roles of protein, amino
25. Hamilton B. Vitamin D and human skeletal muscle.
acids and antioxidants. J Nutr Biochem 2010;21:1–
Scand J Med Sci Sports 2010;20:182–90.
13. Full Text
26. Dirks-Naylor AJ, Lennon-Edwards S. The effects of
14. Thalacker-Mercer AE, Fleet JC, Craig BA, Carnell NS,
vitamin D on skeletal muscle function and cellular
Campbell WW. Inadequate protein intake affects
signaling. J Steroid Biochem Mol Biol 2011;125:159–
skeletal muscle transcript profiles in older humans.
68. Full Text
Am J Clin Nutr 2007;85:1344–52.
27. Bischoff-Ferrari HA, Dietrich T, Orav EJ, et al.
15. Breen L, Phillips SM. Skeletal muscle protein
Higher 25-hydroxyvitamin D concentrations are
metabolism in the elderly: interventions to counteract
associated with better lower-extremity function in
the 'anabolic resistance' of ageing. Nutr Metab (Lond)
both active and inactive persons aged > or = 60 y. Am
2011;8:68. Full Text
J Clin Nutr 2004;80:752–8.
16. Katsanos CS, Kobayashi H, Sheffield-Moore M,
28. Pfeifer M, Begerow B, Minne HW, Suppan K,
Aarsland A, Wolfe RR. Aging is associated with
Fahrleitner-Pammer A, Dobnig H. Effects of a long-
diminished accretion of muscle proteins after the
term vitamin D and calcium supplementation on falls
ingestion of a small bolus of essential amino acids.
and parameters of muscle function in community-
Am J Clin Nutr 2005;82:1065–73.
dwelling older individuals. Osteoporos Int 2009;20:
17. Symons TB, Schutzler SE, Cocke TL, Chinkes DL, 315–22. Full Text
Wolfe RR, Paddon-Jones D. Aging does not impair
29. Benton MJ, Whyte MD, Dyal BW. Sarcopenic obesity:
the anabolic response to a protein-rich meal. Am J
strategies for management. Am J Nurs 2011;111:38–
Clin Nutr 2007;86:451–6.
44. Full Text
18. Nicastro H, Artioli GG, Costa Ados S, et al. An
30. Li Z, Heber D. Sarcopenic obesity in the elderly and
overview of the therapeutic effects of leucine
strategies for weight management. Nutr Rev
supplementation on skeletal muscle under atrophic
2012;70:57–64. Full Text
conditions. Amino Acids 2011;40:287–300. Full Text
31. Freiberger E, Sieber C, Pfeifer K. Physical activity,
19. Katsanos CS, Kobayashi H, Sheffield-Moore M,
exercise, and sarcopenia—future challenges. Wien
Aarsland A, Wolfe RR. A high proportion of leucine is
Med Wochenschr 2011;161:416–25. Full Text
required for optimal stimulation of the rate of muscle
protein synthesis by essential amino acids in the 32. Pate RR, O'Neill JR, Lobelo F. The evolving definition
elderly. Am J Physiol Endocrinol Metab of "sedentary". Exerc Sport Sci Rev 2008;36:173–8.
2006;291:E381–7. Full Text Full Text

Rambam Maimonides Medical Journal 10 October 2012  Volume 3  Issue 4  e0024

 Lifestyle and Sarcopenia

33. Chastin SF, Ferriolli E, Stephens NA, Fearon KC, 44. Frontera WR, Meredith CN, O'Reilly KP, Knuttgen
Greig C. Relationship between sedentary behaviour, HG, Evans WJ. Strength conditioning in older men:
physical activity, muscle quality and body compo- skeletal muscle hypertrophy and improved function.
sition in healthy older adults. Age Ageing 2012;41: J Appl Physiol 1988;64:1038–44.
111–4. Full Text
45. Taaffe DR, Duret C, Wheeler S, Marcus R. Once-
34. Narici MV, de Boer MD. Disuse of the musculo- weekly resistance exercise improves muscle strength
skeletal system in space and on earth. Eur J Appl and neuromuscular performance in older adults. J
Physiol 2011;111:403–20. Full Text Am Geriatr Soc 1999;47:1208–14.
35. Bar-Shai M, Carmeli E, Ljubuncic P, Reznick AZ. 46. Nelson ME, Rejeski WJ, Blair SN, et al. Physical
Exercise and immobilization in aging animals: the activity and public health in older adults:
involvement of oxidative stress and NF-kappaB recommendation from the American College of
activation. Free Radic Biol Med 2008;44:202–14. Sports Medicine and the American Heart Association.
Full Text Circulation 2007;116:1094–105. Full Text
36. Bar-Shai M, Carmeli E, Reznick AZ. The role of NF- 47. Mayer F, Scharhag-Rosenberger F, Carlsohn A,
kappa B in protein breakdown in immobilization, Cassel M, Müller S, Scharhag J. The intensity and
aging, and exercise: from basic processes to promo- effects of strength training in the elderly. Dtsch
tion of health. Ann NY Acad Sci 2005;1057: 431–47. Arztebl Int 2011;108:359–64.
Full Text
48. Peterson MD, Gordon PM. Resistance exercise for the
37. Bar-Shai M, Carmeli E, Coleman R, et al. The effect of aging adult: clinical implications and prescription
hindlimb immobilization on acid phosphatase, guidelines. Am J Med 2011;124:194–8. Full Text
metalloproteinases and nuclear factor-kappaB in
muscles of young and old rats. Mech Ageing Dev 49. Singh MA, Ding W, Manfredi TJ, et al. Insulin-like
2005;126:289–97. Full Text growth factor I in skeletal muscle after weight-lifting
exercise in frail elders. Am J Physiol 1999;277:E135–
38. Carmeli E, Hochberg Z, Livne E, et al. Effect of 43.
growth hormone on gastrocnemius muscle of aged
rats after immobilization: biochemistry and morph- 50. Forbes SC, Little JP, Candow DG. Exercise and
ology. J Appl Physiol 1993;75:1529–35. nutritional interventions for improving aging muscle
health. Endocrine 2012;42:29–38. Full Text
39. Robinson MM, Turner SM, Hellerstein MK, Hamilton
KL, Miller BF. Long-term synthesis rates of skeletal 51. Kim HK, Suzuki T, Saito K, et al. Effects of exercise
muscle DNA and protein are higher during aerobic and amino acid supplementation on body compo-
training in older humans than in sedentary young sition and physical function in community-dwelling
subjects but are not altered by protein supplemen- elderly Japanese sarcopenic women: a randomized
tation. FASEB J 2011;25:3240–9. Full Text controlled trial. J Am Geriatr Soc 2012;60:16–23.
Full Text
40. Pasini E, Le Douairon Lahaye S, Flati V, et al. Effects
of treadmill exercise and training frequency on 52. Vukovich MD, Stubbs NB, Bohlken RM. Body
anabolic signaling pathways in the skeletal muscle of composition in 70-year-old adults responds to dietary
aged rats. Exp Gerontol 2012;47:23–8. Full Text beta-hydroxy-beta-methylbutyrate similarly to that of
young adults. J Nutr 2001;131:2049–52.
41. Timmerman KL, Dhanani S, Glynn EL, et al. A
moderate acute increase in physical activity enhances 53. Yang Y, Breen L, Burd NA, et al. Resistance exercise
nutritive flow and the muscle protein anabolic enhances myolibrillar protein synthesis with graded
response to mixed nutrient intake in older adults. Am intakes of whey protein in older men. Br J Nutr
J Clin Nutr 2012;95:1403–12. Full Text 2012;7:1–9. Full Text
42. Mangione KK, Miller AH, Naughton IV. Review: 54. Rawson ES, Venezia AC. Use of creatine in the elderly
improving physical function and performance with and evidence for effects on cognitive function in
progressive resistance strength training in older young and old. Amino Acids 2011;40:1349–62. Full
adults. Phys Ther 2010;90:1711–5. Full Text Text
43. Fry CS, Drummond MJ, Glynn EL, et al. Aging 55. Preedy VR, Adachi J, Ueno Y, et al. Alcoholic skeletal
impairs contraction-induced human skeletal muscle muscle myopathy: definitions, features, contribution
mTORC1 signaling and protein synthesis. Skelet of neuropathy, impact and diagnosis. Eur J Neurol
Muscle 2011;1:11. Full Text 2001;8:677–87. Full Text

Rambam Maimonides Medical Journal 11 October 2012  Volume 3  Issue 4  e0024

 Lifestyle and Sarcopenia

56. Tiernan JM, Ward LC. Acute effects of ethanol on skeletal muscle mass in men: the MINOS study. Am J
protein synthesis in the rat. Alcohol Alcohol Clin Nutr 2004;80:496–503.
1986;21:171–9.
63. Lee JS, Auyeung TW, Kwok T, Lau EM, Leung PC,
57. Reilly ME, Mantle D, Richardson PJ, et al. Studies on Woo J. Associated factors and health impact of
the time-course of ethanol's acute effects on skeletal sarcopenia in older Chinese men and women: a cross-
muscle protein synthesis: comparison with acute sectional study. Gerontology 2007;53:404–10. Full
changes in proteolytic activity. Alcohol Clin Exp Res Text
1997;21:792–8. Full Text
64. Montes de Oca M, Loeb E, Torres SH, De Sanctis J,
58. Lang CH, Wu D, Frost RA, Jefferson LS, Kimball SR, Hernández N, Tálamo C. Peripheral muscle altera-
Vary TC. Inhibition of muscle protein synthesis by tions in non-COPD smokers. Chest 2008;133:13–18.
alcohol is associated with modulation of eIF2B and Full Text
eIF4E. Am J Physiol 1999;277:E268–76.
65. Petersen AM, Magkos F, Atherton P, et al. Smoking
59. Lang CH, Pruznak AM, Deshpande N, Palopoli MM, impairs muscle protein synthesis and increases the
Frost RA, Vary TC. Alcohol intoxication impairs expression of myostatin and MAFbx in muscle. Am J
phosphorylation of S6K1 and S6 in skeletal muscle Physiol Endocrinol Metab 2007;293:E843–8. Full
independently of ethanol metabolism. Alcohol Clin Text
Exp Res 2004;28:1758–67. Full Text
66. Tang K, Wagner PD, Breen EC. TNF-alpha-mediated
60. Vary TC, Frost RA, Lang CH. Acute alcohol reduction in PGC-1alpha may impair skeletal muscle
intoxication increases atrogin-1 and MuRF1 mRNA function after cigarette smoke exposure. J Cell
without increasing proteolysis in skeletal muscle. Am Physiol 2010;222:320–7. Full Text
J Physiol Regul Integr Comp Physiol 2008;294:
67. Rinaldi M, Maes K, De Vleeschauwer S, et al. Long-
R1777–89. Full Text
term nose-only cigarette smoke exposure induces
61. Castillo EM, Goodman-Gruen D, Kritz-Silverstein D, emphysema and mild skeletal muscle dysfinction in
Morton DJ, Wingard DL, Barrett-Connor E. mice. Dis Model Mech 2012;5:333–41. Full Text
Sarcopenia in elderly men and women: the Rancho
68. Barreiro E, Del Puerto-Nevado L, Puig-Vilanova E, et
Bernardo study. Am J Prev Med 2003;25:226–31.
al. Cigarette smoke-induced oxidative stress in
Full Text
skeletal muscles of mice. Respir Physiol Neurobiol
62. Szulc P, Duboeuf F, Marchand F, Delmas PD. 2012;182:9–17. Full Text
Hormonal and lifestyle determinants of appendicular

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