Dietary strategies to promote muscle protein anabolism in the elderly

Aging is associated with the loss of lean muscle mass, termed sarcopenia. Food
intake and in particular the ingestion of protein or amino acids has been shown
to be a powerful stimulus to promote net muscle protein anabolism. However this
anabolic response following a meal-like protein bolus seems to be blunted in
the elderly as compared to young adults. It has been speculated that this
blunted protein synthetic response to meal ingestion prevents net muscle
protein accretion throughout the day, leading to the structural loss of
skeletal muscle tissue over the years. An important factor that has been
suggested to contribute to the blunted anabolic response to meal ingestion in
the elderly is an impaired and/or delayed protein digestion. It is evident that
the quantity, as well as the quality of the ingested protein, i.e. its
digestibility and its amino acid composition, strongly modulate protein
metabolism. Besides nutrition, exercise has been shown to be a powerful
stimulus to promote net muscle protein anabolism and/or muscle tissue
remodeling. The nutrition effect on muscle protein synthesis is relatively
transient and acts on a global whole body level rather than on a specific
skeletal muscle level. Physical activity stimulates a longer-term adaptive
response, which may stimulate muscle protein synthesis for up to 48 h. So
providing nutrition after physical activity creates a large positive net muscle
protein balance, and leads to an increase in muscle mass. However the available
data in humans is scarce whether a period of physical activity prior to a
meal-like protein intake, an increase in protein intake, or an improved quality
of the protein bolus can overcome the blunted anabolic response in the elderly.

The first aim of this proposal is to investigate the post-prandial muscle
protein synthesis rates in young and elderly men in response to a meal-like
protein bolus after a period of rest or physical activity (study A). The rest
trial (REST) will act as a proof-of-principle study to examine the blunted
protein synthetic response in the elderly, and as a control trial in comparison
with the exercise trial (EXC) to establish the surplus value of physical
activity prior to protein intake on muscle protein synthesis.
The second aim of this proposal is to determine the surplus value of an
increased quantity of the ingested protein bolus (study B). Large amounts of
protein (40 and 60 g) will be compared to a meal-like amount of protein (20 g)
as a means to maximize plasma amino acid availability and/or to stimulate
muscle protein anabolism.
The third aim of this proposal is to study the differences in quality of the
ingested protein bolus (study C). Instead of significantly increasing the
quantity of the protein bolus, we will also apply a more practical approach to
augment skeletal muscle protein synthesis rates; modifying the digestibility or
amino acid composition of a meal-like protein bolus. With the concept of slow
and fast digestible proteins in mind, we will compare a meal-like bolus of
*slow* intact protein to a meal-like bolus of its *fast* hydrolysate and to a
meal-like bolus of *fast* intact protein. Furthermore, we will compare a
meal-like bolus of intact protein with or without the addition of a small
amount of the amino acid leucine.

Previous studies have contributed significantly to our current knowledge on the
post-prandial muscle protein synthesis response, but due their methodology,
were unable to mimic the normal physiological process of protein intake,
digestion and the muscle protein synthetic response following on it. Only with
the use of an intrinsically labeled protein source will we be able to clearly
mimic the normal physiological process of meal ingestion and measure the rate
of protein digestion. We have produced an intrinsically labeled protein and
used it successfully in a recent human intervention study (MEC 06-3-064).
Furthermore will we combine the use of these intrinsically labeled milk
proteins with a labeled amino acid infusion protocol as previously described in
MEC 02-060, MEC 03-090, MEC 05-028 and MEC 06-3-064. This offers us a powerful
tool and a unique method to quantify the in vivo response of protein intake on
skeletal muscle protein synthesis rates.

Study A: Moderate physical exercise versus rest prior to protein intake
Study B: Protein intake differing in quantity
Study C: Protein intake differing in quality

The risks involved in participating in this experiment are minimal. Insertion
of the catheters in a vein is comparable to a normal blood drawn and the only
risk is of a small local hematoma. This is the same for the muscle biopsy. The
incision made for obtaining the muscle biopsy will be done by an experienced
physician and will heal completely. The labeled amino acids tracers applied in
this experiment are not radioactive and are completely safe. De test beverages
are made from normal nutritional ingredients and for this reason do not form
any health risks. The exercise protocol exists of cycling and resistance-type
exercise on a low to moderate intensity which may lead to some muscle soreness
in the upper legs the next day.

• General screening 3 h (all the subjects in all three studies A, B, C)
• Additional screening 1 h (only for the subjects in study A)
• Trial day 8 h (all the subjects in all three studies A, B, C)


All subjects of study A will visit the University for a total time of 12 h. All
subjects of studies B and C will visit the University for a total time of 11 h.