J Nutr Sci Vitaminol, 61, S125–S127, 2015

Role of Exercise and Nutrition in the Prevention of Sarcopenia

Yuhei Makanae1,2 and Satoshi Fujita2

1
Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, Kusatsu, Shiga, Japan
2
Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga, Japan

Summary The age-associated loss of skeletal muscle mass and strength (sarcopenia) has
been shown to increase the risk of injury due to falls and incidence of metabolic complica-
tions including insulin resistance and diabetes, which subsequently becomes a significant
factor to disability among the elderly population. Nutrient intake is the most important ana-
bolic stimulus for skeletal muscle. Specifically, the amino acid leucine and meal-induced insu-
lin both independently stimulate muscle protein synthesis. However, age-specific changes
in muscle anabolic responses to leucine become apparent when sub-maximal amounts of
amino acids are administered in older subjects. Furthermore, insulin resistance of muscle
protein metabolism with aging has been demonstrated in healthy non-diabetic older sub-
jects. Resistance exercise is another anabolic stimulus which increases myofibrillar muscle
protein synthesis in both young and older individuals. The increased muscle anabolism is
apparent within 2–3 h after a single bout of heavy resistance exercise and remains elevated
up to 2 d following the exercise. The mTOR signaling pathway in skeletal muscle is associ-
ated with an increased rate of muscle protein synthesis during the early recovery phase
following a bout of resistance exercise. Finally, recent evidence on the cumulative effect of
resistance exercise in combination with nutritional supplement on muscle protein metabo-
lism will be discussed to propose a possible preventative measure against sarcopenia.
Key Words muscle protein synthesis, amino acids, exercise, sarcopenia

Sarcopenia is the age-associated loss of skeletal mus-
cle mass and strength that develops slowly over decades
and becomes a significant factor for disability among the
elderly population. The mechanisms that trigger sarco-
penia have not been clarified yet, but they are likely to be
multifactorial, and they all appear to affect the balance
between muscle protein synthesis and breakdown rate,
which subsequently results in the loss of muscle mass.
This review will be focused on interventions to pre-
vent and/or ameliorate the age-associated changes in
muscle protein metabolism in relation to nutrient intake
and exercise, which have important implications in the
prevention of sarcopenia.
Muscle Anabolic Response to Amino Acids and
Protein
Nutrient intake, especially proteins and amino acids,
is the most important anabolic stimulus for skeletal
muscle. A previous study has indicated that the anabolic
action of amino acids on muscle proteins occurs mainly
because of essential amino acids (EAA) (1). Among
the essential amino acids, branched-chain amino acids
(BCAAs) are known to be most involved in the direct
stimulation of muscle protein synthesis. Specifically,
leucine is the most potent of the BCAAs. Intake of leu-
cine alone can activate several intracellular signaling
proteins involved in the initiation of mRNA transla-
tion, including the mammalian target of rapamycin
(mTOR), 70-kDa ribosomal protein S6 kinase (S6K1),
E-mail: safujita@fc.ritsumei.ac.jp
and eukaryotic initiation factor 4E binding protein-1
(4E-BP1)(2).
Recently, age-specific changes in muscle anabolic
response to EAA have been uncovered. One study has
demonstrated that older subjects had significantly less
muscle protein accretion than younger subjects follow-
ing the ingestion of a 7 g EAA supplement. The same
authors also reported that while both 26% (1.7 g leu-
cine in 7 g EAA) and 41% (2.8 g leucine in 7 g EAA)
leucine EAA ingestion increased muscle protein syn-
thesis in young men, only the 41% leucine EAA bolus
was effective in stimulating muscle protein synthesis
in elderly men (3). Although large amounts of EAA
(~15 g) exert similar effects in the elderly and young
individuals, these studies indicate that the age-related
differences in the muscle anabolic response becomes
apparent when sub-maximal amounts of amino acids
are administered. Huston et al. (2008) have investi-
gated over 2,000 older subjects, and demonstrated an
inverse relationship between loss of muscle mass over
a 3-y period and dietary protein intake after adjusting
for confounding variables including other dietary intake
and physical activities (Fig. 1) (4).
Insulin Resistance of Muscle Protein Synthesis
A mixture of amino acids with other nutrients, specif-
ically carbohydrates, has a profound impact on endoge-
nous hormone response and muscle metabolism. When
carbohydrates are added to the amino acid mixture,
muscle protein synthesis almost doubles in young sub-
jects, while the addition of carbohydrate does not induce

S125
S126 Makanae Y and Fujita S
Fig. 1. Changes in lean body mass in elderly subjects
with different dietary protein intakes. Changes in lean
body mass over a 3-y period for people with different
dietary protein intakes: Q1 (0.7 g/kg/d) and Q5 (1.1 g/
kg/d). Data represent the mean6standard error (SE);
* p,0.05 vs. Q5. Adapted from Houston et al., 2008
(4).
any additional anabolic response in older subjects. Insu-
lin is a potent muscle anabolic agent. However, insulin
resistance of muscle protein metabolism with aging
appears to be responsible for the blunted response to
mixed supplements. The existence of insulin resistance
of muscle protein metabolism with aging, independent
of glucose tolerance, has been demonstrated in healthy,
non-diabetic elderly subjects. This blunted response of
muscle anabolism to insulin is associated with the reduc-
tion in endothelium-dependent vasodilation and blood
flow (5). Interestingly, this insulin resistance of muscle
protein metabolism in the elderly can be reversed by
aerobic exercise through improved endothelial function,
insulin-induced vasodilation, and intracellular insulin
signaling (6).
Resistance Exercise and Muscle Protein Metabolism
Resistance exercise is another potent muscle anabolic
stimulus. The muscle protein synthesis increases within
2–3 h after a single bout of resistance exercise (7) and
remains higher for up to 24 h in trained individuals and
up to 48 h in untrained subjects (8).
The upregulation of mRNA translation to protein is
an important regulation for the acute increase in exer-
cise-induced muscle protein synthesis (9) (Fig. 2).
The mammalian target of rapamycin complex 1
(mTORC1), consists of mTOR, mLST8, regulatory associ-
ated protein of mTOR (Raptor), DEP domain-containing
mTOR-interacting protein (DEPTOR) and proline-rich
Akt substrate of 40 kDa (PRAS40), which is a key regu-
lator of translation initiation and protein synthesis. Pre-
vious studies have demonstrated that resistance exercise
activates mTORC1 and muscle protein synthesis (10),
while rapamycin, an mTORC1 inhibitor, suppressed
muscle protein synthesis and subsequent skeletal muscle
hypertrophy in an animal model. Furthermore, a recent
human study has shown that the ingestion of rapamy-
cin eliminated the increase in muscle protein synthesis
in response to resistance exercise in young males (11).
These results indicate that the activation of mTORC1
is a critical regulator for muscle protein synthesis and
Fig. 2. mTOR signaling pathway in skeletal muscle.
Filled circles indicate inhibitory proteins and open cir-
cles indicate stimulatory proteins. Adapted from Drum-
mond et al., 2009 (11).
subsequent skeletal muscle hypertrophy in response to
resistance exercise. The activated mTORC1 phosphory-
lates its downstream signaling protein, p70 ribosomal
protein S6 kinase (p70S6K) and eukaryotic initiation
factor 4E binding protein 1 (4E-BP1). The phosphoryla-
tion of p70S6K, a serine/threonine kinase, contributes
to enhance mRNA translation and subsequent muscle
protein synthesis. A previous study has shown that
the phosphorylation of p70S6K correlated with the
increase in muscle mass following 14 wk’ resistance
training in human subjects. Furthermore, phosphory-
lation of 4E-BP1 induces its dissociation from eIF4E,
leading to increased mRNA translation initiation. Taken
together, resistance exercise activates mTORC1 and its
downstream signaling pathway, increasing the muscle
protein synthesis. This anabolic response is critical in
long-term training-induced skeletal muscle hypertrophy.
Resistance Exercise in Combination with Nutrient
Intake
The provision of essential amino acids with or
without carbohydrates following resistance exercise
increases the rate of muscle protein synthesis (12).
Studies have shown that the ingestion of whole proteins
such as whey or casein following an acute bout of resis-
tance exercise augments muscle protein synthesis (13).
Furthermore, we have previously reported that inges-
tion of an essential amino acid and carbohydrate (EAA-
1CHO) mixture 1 h prior to a bout of resistance exercise
did not further increase muscle protein synthesis dur-
ing post-exercise recovery compared with performing
resistance exercise in the fasted state (14). In contrast,
an enhanced stimulation of muscle protein synthesis
was observed when the same EAA1CHO mixture was
ingested 1 h after a bout of resistance exercise, indicat-
 Exercise and Nutrition in Aging
Fig. 3. Effect of timing of amino acid supplementation
on muscle protein synthesis when combined with resis-
tance exercise. Mixed muscle protein synthesis assessed
by the stable isotope tracer method at baseline (Base-
line), 3 h after a bout of resistance exercise in a fasted
state (EX), amino acid ingestion 1 h prior to exercise
(Pre-EX), and amino acid ingestion 1 h after exercise
(Post-Ex). Data represent the mean6SE; * p,0.05 vs.
Baseline, # p,0.05 vs. other groups. Adapted from
Fujita et al., 2009 (4) and Dryer et al., 2008 (12).
ing more efficient muscle protein synthesis during the
early recovery phase when the supplement was given
post-exercise as compared to when administered before
exercise (12) (Fig. 3).
Conclusions
More evidence is accumulating that support the role
of nutritional intake, especially proteins and amino
acids, in stimulating muscle protein anabolism regard-
less of age. Aging is also associated with a reduced
anabolic response to an amino acid and carbohydrate
mixture, as well as amino acids themselves when
administered in a small quantity. Accumulating evi-
dence also indicates the role of resistance exercise in
stimulating muscle protein synthesis and in preventing
sarcopenia. Recent evidence supports the cumulative
effect of resistance exercise in combination with amino
acids/proteins to further facilitate muscle hypertrophy.
Further studies are warranted to clarify the optimal vol-
ume and intensity of exercise as well as the amount of
amino acids and/or proteins specific to populations with
different health, nutrition status, and physical activity
levels in order to effectively prevent the progression of
sarcopenia.
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