Claude D. Pepper Older American's Independence Center, Divisions of Geriatrics and Gerontology and Metabolism, Endocrinology, and Diabetes, Washington University Medical Center, St. Louis, Missouri 63110
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ABSTRACT |
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Muscle atrophy (sarcopenia) in the elderly is associated with a reduced rate of muscle protein synthesis. The purpose of this study was to determine if weight-lifting exercise increases the rate of muscle protein synthesis in physically frail 76- to 92-yr-old women and men. Eight women and 4 men with mild to moderate physical frailty were enrolled in a 3-mo physical therapy program that was followed by 3 mo of supervised weight-lifting exercise. Supervised weight-lifting exercise was performed 3 days/wk at 65-100% of initial 1-repetition maximum on five upper and three lower body exercises. Compared with before resistance training, the in vivo incorporation rate of [13C]leucine into vastus lateralis muscle protein was increased after resistance training in women and men (P < 0.01), although it was unchanged in five 82 ± 2-yr-old control subjects studied two times in 3 mo. Maximum voluntary knee extensor muscle torque production increased in the supervised resistance exercise group. These findings suggest that muscle contractile protein synthetic pathways in physically frail 76- to 92-yr-old women and men respond and adapt to the increased contractile activity associated with progressive resistance exercise training.
sarcopenia; stable isotopes; mass spectrometry; physical activity
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INTRODUCTION |
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SARCOPENIA REFERS TO the undesirable loss of muscle mass that accompanies advancing age. It is associated with muscle weakness, increased fatigability, and a loss of independent function, all characteristics of physical frailty (1, 5, 7-11, 16, 17, 19, 21, 25-27, 31-33). The pathogenesis of sarcopenia is multifactorial, and the primary cause is unclear. Nevertheless, it appears that muscle contractile and mitochondrial protein synthesis rates are reduced with advancing age (1, 16, 19, 20, 25-27, 31, 32). The decrements in contractile and mitochondrial protein synthesis are associated with reduced muscle mass, muscle strength, and endurance capacity (1, 16, 19, 25-27, 31, 32). Therefore, an increase in the rate of muscle protein synthesis should result in an improvement in muscle strength and function and modulate the disability associated with physical frailty.
Progressive resistance exercise training (weight lifting) increased
muscle strength, gait velocity, and stair-climbing power in 70-yr-old
institutionalized physically frail women and men (8-10). Despite
this improvement in muscle performance and reduction in physical
frailty, the increase in muscle cross-sectional area was modest
(2.7%). This suggests that contractile proteins within the muscle
cells of physically frail elders have a reduced capacity to hypertrophy
in response to weight-lifting exercise training. This is contrary to
the observation that weight-lifting exercise increased the rate of
mixed-muscle protein synthesis in healthy 64- to 75-yr-old subjects to
a similar magnitude as it did in healthy 20- to 30-yr-old subjects
(31). Welle et al. (26) reported that 3 mo of progressive resistance
exercise training did not increase the rate of myofibrillar protein
synthesis in healthy, active 62- to 72-yr-old women and men. The
adaptability of muscle protein synthetic pathways to resistance
exercise training in
76-yr-old physically frail subjects has not been reported.
The purpose was to examine whether weight-lifting exercise training increases muscle protein synthesis rate and maximum voluntary muscle strength in physically frail elderly women and men. The results indicate that 3 mo of supervised resistance exercise training stimulates the in vivo rate of vastus lateralis muscle protein synthesis in physically frail 76- to 92-yr-old women and men.
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METHODS |
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Subjects. Seventeen sedentary 76- to
92-yr-old adults were screened by the Recruitment Core of the Claude
Pepper Older Americans Independence Center at Washington University
Medical School and enrolled in this study. Eight women and four men
were randomly assigned to the supervised exercise program, and four
women and one man were assigned to the home exercise program (control
group; Table 1). The study was approved by
the Human Studies Review Committee at Washington University School of
Medicine, and informed consent was obtained after the purpose and
procedures were explained to each volunteer.
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Before enrollment, volunteers received a physical examination, including a medical history, cognitive function evaluation, physical performance/frailty evaluation, a blood chemistry profile, complete blood cell count, and urinalysis. Each volunteer's primary care physician authorized his or her participation in the exercise program. Physical frailty was objectively assessed using a physical performance test (e.g., stair climbing speed, walking speed, upper body strength, balance, lower back range of motion) and subjectively assessed by the participant's self-reported degree of difficulty with activities of daily living.
Volunteers were excluded if they were taking prescription
medications that might affect muscle amino acid metabolism
(-adrenergic blockers,
-agonists,
Ca2+ channel blockers,
corticosteroids) or if they had a metabolic (e.g., diabetes),
neuromuscular (Parkinson's disease, moderate to severe peripheral
neuropathy, sciatica), or any disorder that might affect muscle amino
acid metabolism, their ability to respond to resistance exercise, or
where exercise would be contraindicated (e.g., hypertension or coronary
artery disease).
Exercise program. All participants were transported by shuttle bus from their residence to the exercise and testing facilities in the Geriatrics and Gerontology Division at Washington University School of Medicine. Control subjects participated in testing and educational sessions and were prescribed a home exercise program that consisted of light muscle stretching and exercises focused on improving joint range of motion. One day per month, the control subjects were transported to the exercise facility where the group participated in a 1- to 1.5-h supervised stretching and flexibility exercise session. This session was used to direct and assist the control participants with the performance of the home exercises and to provide purposeful interaction between the control participants and the exercise training staff.
The supervised exercise participants attended controlled and prescribed exercise training sessions 3 days/wk. For the first 3 mo, all supervised exercise participants followed a stretching and flexibility physical therapy program similar to that of the home exercisers (control group). This supervised program was done 3 days/wk and was designed to improve range of motion and familiarize each participant with increased activity. This program was followed by 3 mo of supervised, closely monitored progressive resistance exercise training done 3 days/wk. One-repetition maximum (1-RM) voluntary muscle strength was determined in the supervised exercise participants (not controls) on each of eight different commercially available resistance exercise devices (Hoist Equipment) that included bench press, biceps curl, upright row, triceps extension, seated row, leg press, knee extension, and knee flexion. Abdominal muscle exercises and free-weight squats were incorporated into the later stages of the exercise program. An individualized resistance exercise program was designed for each participant based on a percentage of his or her 1-RM. The 1-RM measures were used to adjust the exercise intensity and to corroborate changes in muscle strength determined on a dynamometer. For safety, electrocardiogram and blood pressure were monitored during maximum voluntary strength testing and in some participants during the initial weeks of weight training. Initially, one to two sets of six to eight repetitions of each exercise were completed at 65-75% of 1-RM. This progressed to 3 sets of 8-12 repetitions done at 85-100% of initial 1-RM.
Maximum voluntary muscle strength assessment. Before and at the end of the supervised weight-lifting program, maximum voluntary isometric and isokinetic torque production (ft-lb. at 60°/s) of the knee extensor muscles was determined on a Cybex dynamometer (intermeasure coefficient of variation <10%). Maximal voluntary isometric force production was obtained at 45° of knee flexion. In the home exercise group, the same measures were made after 3 and 6 mo in the program.
Dietary control. For 3 days before initiating the resistance exercise program and for the final 3 days of resistance exercise, all participants consumed meat-free, controlled protein and energy meals supplied to them by the research kitchen on the General Clinical Research Center (GCRC). These meals were delivered to the control subjects or distributed to them in conjunction with other testing visits to the Pepper Center. Meat-free meals were employed to reduce the effects of dietary creatinine and 3-methylhistidine intake on 24-h urinary creatinine excretion measurements used to estimate whole body muscle mass (11, 13) and urinary 3-methylhistidine excretion measurements used as an indicator of myofibrillar proteolysis (14, 24, 28).
Before admission, a research dietitian surveyed each participant's
typical eating habits and designed a 3-day meal plan. The meals
provided 1.2-1.3 g
protein · kg1 · day
1,
125-165 kJ (30-40
kcal) · kg
1 · day
1,
18% of calories from protein, 49% of calories from carbohydrate, and
33% of calories from fat in 3 daily meals with small snacks. The
participants were instructed to eat no other food and to eat all food
provided. Small amounts not consumed were returned and weighed, and the
daily intake record was corrected. Intake was controlled to stabilize
body weight and control protein and energy intake to minimize their
effects on the measures of whole body and muscle protein metabolism.
During the training program, the participants were given instructions
on appropriate nutrient and energy intake. During the exercise program,
the adequacy of each participant's dietary intake was monitored by
diet recall and, if necessary, adjusted by the research dietitian.
Body composition assessment. Fat-free mass (FFM) was determined using a Hologic QDR-1000/W whole body dual-energy X-ray absorptiometer (Hologic, Waltham, MA). Hologic enhanced whole body analysis software (version 5.71) was used to process the images and determine FFM. Whole body measures of leucine and protein metabolism are expressed per kilogram FFM.
Total body muscle mass was determined from three 24-h urinary creatinine excretion measures. The three daily measures were averaged, and total body muscle mass was calculated by assuming 1 g urinary creatinine excreted/day is equivalent to 20 kg muscle mass (11, 13). Urinary 3-methylhistidine concentration was determined in the three 24-h urine collections. These measures were averaged, and urine 3-methylhistidine excretion was expressed per millimolar creatinine excreted in 24 h.
Urinary creatinine and 3-methylhistidine concentration were determined
using a stable isotope dilution assay and gas chromatography-electron impact-quadrupole-mass spectrometry (Hewlett-Packard 5890 GC and 5970 mass selective detector, EI-GC-MS; unpublished observations). To a 1-ml
aliquot of each 24-h urine collection, 1.99 µmol of guanido-[13C]creatinine
and 540 nmol of
N-[13C]methylhistidine
(MassTrace, Woburn, MA) were added as internal standards. A small
amount (400 units) of urease (type III; Sigma-Aldrich, St. Louis, MO)
was added to remove urinary urea by conversion to ammonia and carbon
dioxide (23). The urease reaction was buffered with ~99%
CO2 gas injected into the sealed
reaction vial. The tertiary butyldimethylsilyl derivative
(N-methyl-N(tert-butyldimethylsilyl)-trifluoroacetamide + 1% tert-butyldimethylchlorosilane; Regis Chromatography,
Mortongrove, IL) of creatinine and 3-methylhistidine was formed (4, 18, 24). The samples were injected onto a DB-1 capillary column (J&W
Scientific, Folsom, CA), and methane was the carrier gas. The intensity
of the ions at mass-to-charge ratio
(m/z)
298 and 299 for creatinine and
m/z
238 and 239 for 3-methylhistidine was monitored and quantitated in a
single-sample injection onto the GC-MS.
Whole body and skeletal muscle leucine kinetics. Participants were admitted to the GCRC on the evening of the third day of the controlled meal plan. For the supervised exercise group, this occurred 3 h after the most recent exercise session, whereas the control participants were permitted to do their home stretching exercise program within 24 h of admission to the GCRC. In the supervised exercise group, the GCRC admissions for the measures of whole body and skeletal muscle leucine metabolism were done on the following two occasions: 1) at the conclusion of the 3-mo supervised stretching program and just before enrollment in the weight-training exercise program and 2) at the conclusion of 3 mo of supervised resistance exercise training. In the home exercise control subjects, these measures were made 1) at the conclusion of 3 mo of the home stretching exercise program and 2) 3 mo later, while they were still doing the home stretching exercise program.
Amino acid metabolism was determined before starting the resistance
exercise program and ~3 h after the final resistance exercise session. At 1800, a baseline intravenous blood sample was obtained, and
a primed (7.58 µmol/kg) 14-h constant intravenous infusion (7.58 µmol · kg1 · h
1)
of 1-[13C]leucine (99 atom%; MassTrace) was initiated. A controlled protein and calorie,
meat-free dinner meal was provided after all baseline samples were
obtained. The plasma leucine rate of appearance
(Ra; estimate of whole body
proteolytic rate), the rate of exhaled 13CO2
(estimate of whole body leucine oxidation rate), the nonoxidative leucine disposal rate (estimate of whole body protein synthesis rate),
and the fractional rate of mixed skeletal muscle protein synthesis were
determined in the overnight-fasted condition (1, 3, 12, 15, 17,
29-33). These determinations were made using blood, breath, and
muscle tissue samples obtained at the end of the 14-h infusion.
In blood samples taken before and at 30-min intervals during the last
2.5 h of the overnight
[13C]leucine infusion
(0600-0800), plasma -ketoisocaproic acid (KIC) was isolated and
chemically derivatized, and
-[13C]KIC abundance
was determined using EI-GC-MS (22, 28). The plasma
[13C]KIC enrichment
(mole %excess) at equilibrium was used to calculate the rate of whole
body protein breakdown (1, 3, 12, 17, 25-27, 29-33) and was
used as an indication of the precursor pool 13C enrichment for the calculation
of the fractional rate of muscle protein synthesis (12, 17,
25-33). Exhaled breath samples were collected in 20-ml evacuated
tubes (Becton-Dickinson, East Rutherford, NJ) before and at the end of
the [13C]leucine
infusion (0800). These breath samples were analyzed for
13CO2
enrichment (atom %excess) using EI-GC-MS (12, 29, 32, 33).
Fifteen-minute measures of CO2
production and O2 consumption (ml/min) were made before starting the infusion and at 0700 using an
open circuit indirect calorimeter (DeltaTrac Metabolic Monitor; Sensormedics, Fullerton, CA). These measures were used to determine the
rate of whole body leucine oxidation (15, 28).
To assess the in vivo rate of incorporation of leucine into mixed
muscle protein, muscle
[13C]leucine
enrichment was measured using gas chromatography-combustion-isotope ratio mass spectrometry (1, 12, 29-33) in two muscle samples (~10-20 mg wet wt) removed from the vastus lateralis. One sample was removed ~1.5-2 h after the
[13C]leucine infusion
began, and a second sample was removed from the contralateral vastus
lateralis at the end of the infusion (0800). Whole body and skeletal
muscle protein kinetics were calculated as described previously (1, 12,
15-17, 25-33). The absolute rate of muscle protein synthesis
(mg protein synthesized · kg muscle
mass1 · h
1)
was calculated using the fractional synthesis rate (%/h) of vastus
lateralis muscle protein and by assuming 19% of total body muscle mass
is protein. This was expressed per whole body muscle mass to normalize
for the difference in muscle mass between men and women.
Statistics. Data are expressed as means ± SE. Baseline measurements were subtracted from final measures (end supervised exercise or home exercise period), and the difference was compared among the three groups using one-way ANOVA. When a significant interaction was identified (P < 0.05), a Student-Newman-Keuls post hoc analysis was used to determine which baseline-to-final changes differed. Baseline measures were compared with final measures using a paired t-test with Bonferroni correction for multiple comparisons.
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RESULTS |
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Whole body muscle mass was unchanged (from baseline to final) in the
home exercise group (0.0 ± 0.5 kg). The exercise-induced increments
in whole body muscle mass were greater in the women (1.0 ± 0.6 kg)
and men (2.2 ± 0.2 kg) in the supervised exercise group than in the
home exercise group (P < 0.05; Table
2). Small increments in FFM were noted in
the supervised exercise group of women but not in the supervised
exercise group of men.
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The maximum voluntary isometric torque production for the knee extensor
muscles of the women in supervised exercise increased more than in the
home exercise group (P < 0.05; Table
3). Maximum voluntary isokinetic force
production at 60°/s for the knee extensor muscles of the men in the
supervised exercise group increased more than in the home exercise
control group (P < 0.05). The
determination of 1-RM on the leg press, knee extension, leg flexor, and
seated rowing exercises increased in the supervised exercise group of women by 35 ± 7, 39 ± 4, 16 ± 7, and 12 ± 4%,
respectively. In the men, 1-RM on these exercises increased 27 ± 4, 42 ± 24, 6 ± 6, and 18 ± 4%, respectively.
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The resistance exercise-induced increase in total body muscle mass was
accompanied by greater increments in the fractional and absolute rates
of vastus lateralis muscle protein synthesis in the women and men
enrolled in the supervised exercise program (Fig.
1). The fractional and absolute rates of
muscle protein synthesis were unchanged in the home exercise control
group. The baseline rate of mixed muscle protein synthesis was
identical in all three groups (0.050-0.056%/h or 96-106 mg
protein · kg muscle
mass1 · h
1)
but was elevated compared with rates determined previously in 60- to
72-yr-old men and women (1, 12, 16, 19, 25, 31).
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Despite the large increase in the fractional rate of vastus lateralis
muscle protein synthesis in the supervised exercise groups, the rate of
whole body protein synthesis only tended to increase after resistance
training (93 ± 3 to 96 ± 4 µmol · kg FFM1 · h
1;
P > 0.05; Fig.
2). The rates of whole body protein
breakdown (plasma leucine Ra)
and leucine oxidation were similar among the three groups and were not
altered after 3 mo of resistance training or 3 mo of home stretching
exercise (Fig. 2).
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Twenty-four-hour urinary 3-methylhistidine excretion (µM) is
expressed per millimolar urinary creatinine excretion to normalize for
gender differences in whole body muscle mass (Fig.
3). There was a trend toward a greater
increase (P > 0.05) in urinary
3-methylhistidine excretion in the women (0.7 ± 0.3 µM/mM) and
men (0.8 ± 0.3 µM/mM) in the supervised exercise group than in
the home exercise control group (0.1 ± 0.1 µM/mM).
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DISCUSSION |
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These findings indicate that 3 mo of supervised progressive weight-lifting exercise stimulates the in vivo rate of vastus lateralis (mixed) muscle protein synthesis and increases maximum voluntary knee extensor muscle torque production in physically frail 76- to 92-yr-old women and men. This suggests that skeletal muscle contractile proteins in 76- to 92-yr-old physically frail elders retain the ability to increase the rate of muscle protein synthesis in response to progressive weight-lifting exercise training. This adaptation should also involve an increase in the rate of myofibrillar protein turnover, as suggested by the slight increase in 3-methylhistidine excreted in the urine per kilogram muscle mass. Over the 3-mo exercise period, small increments in myofibrillar proteolysis would be expected, because if the increased rate of muscle protein synthesis was not counterbalanced by an increased rate of myofibrillar proteolysis, then muscle protein mass would have increased much more than the 1-2 kg observed in the supervised exercise groups. Unfortunately, the small increments in myofibrillar protein breakdown may not be easily detected using 24-h urinary 3-methylhistidine excretion, even when meat-free meals are consumed for 3 days and complete 24-h urine voids are obtained (11, 14, 25-27, 31). Although controversial, the mild increase in urinary 3-methylhistidine excretion may not be an adequate indicator of the rate of myofibrillar proteolysis (11, 14, 25-27, 31), especially in the individual muscle (vastus lateralis) in which the rate of muscle protein synthesis was determined. It has been suggested that 24-h urinary 3-methylhistidine is excreted in proportion to the quantity of muscle mass (11). In the present study, the small increase in 3-methylhistidine excretion may simply reflect the 1- to 2-kg increase in muscle mass observed in the supervised exercise groups.
Two weeks of weight-lifting exercise have been reported to increase the in vivo rate of vastus lateralis muscle protein synthesis in healthy 60- to 72-yr-old men and women (31). After 16 wk of progressive resistance exercise training, maximum voluntary knee extensor muscle strength was increased 12-22%, and the rate of mixed muscle protein synthesis measured in the fed condition was increased 48% in 64- to 75-yr-old men (32). The current findings extend these observations to an older more physically frail group of women and men. The findings indicate that skeletal muscle proteins maintain the ability to adapt to increased contractile demand even in 76- to 92-yr-old physically frail women and men.
Welle et al. (26) reported that the in vivo rate of vastus lateralis myofibrillar protein synthesis was not increased in 62- to 72-yr-old men and women at the end of a 3-mo progressive resistance exercise training program. The most plausible reason for the discrepancy between the findings of Welle et al. (26) and our findings is that the exercise intensity for the quadriceps muscle group was greater in our study. Our supervised exercise participants performed three sets of two to three different exercises for the quadriceps muscle group 3 days/wk for 3 mo. Welle et al. (26) used only three sets of one exercise for the quadriceps (knee extension), performed 3 days/wk for 3 mo.
Other minor differences in study design and exercise protocol exist between these two reports. They have been clearly described and are unlikely to account for the different findings (26). For example, our participants are fed a small meal at the start of the [13C]leucine infusion, whereas Welle et al. (25-27) determined myofibrillar protein synthesis after a prolonged 12-h fast plus 5-h infusion. In our studies, it is possible that increased circulating concentrations of insulin and substrates might have affected muscle amino acid balance, however, only during the initial few hours of the infusion when insulin was elevated. This represents only a small portion of the 14-h tracer infusion study because plasma insulin concentrations had returned to baseline even before the 12- to 14-h time period when the second muscle sample was obtained. Although controversial, our approach is supported by the fact that most in vivo human tracer studies report that insulin reduces the rate of human muscle proteolysis more than it increases the rate of muscle protein synthesis (2, 5, 20). Finally, if we had delayed the determination of the rate of muscle protein synthesis until the day after the final exercise session, we may not have observed an exercise training-induced increase in muscle protein synthesis rate. However, prior evidence suggests that acute exercise-induced increments in muscle protein synthesis rate persist for up to 48 h after exercise (6, 31).
Fiatarone et al. (8-10) reported that weight-lifting exercise training increased maximum voluntary thigh muscle strength in institutionalized physically frail men and women, but the increase in thigh muscle cross-sectional area was much smaller than the increase in strength. This suggests that the large increase in muscle strength represented primarily a neurological adaptation to weight training, whereas there was a very small metabolic (muscle protein accretion, hypertrophy) adaptation to resistance exercise in the frail elderly. The present findings confirm that vastus lateralis muscle protein synthesis responds favorably to 3 mo of supervised weight-training exercise in 76- to 92-yr-old physically frail women and men. The increase in muscle strength that accompanies the weight-lifting exercise in frail elders is a result of both improved neurological (motor unit) recruitment patterns and an increase in the rate of synthesis of muscle proteins. Maintaining the progressive resistance training program over a longer period of time (>3 mo) would presumably further increase muscle mass and improve physical function in frail elders.
Based on previous reports, we anticipated that the baseline rates of
mixed muscle protein synthesis in these physically frail 76-yr-old
men and women would be equivalent to or less than the 60- to 75-yr-old
men and women previously studied (1, 12, 19, 25-27, 31). We found
that the baseline rates of mixed muscle protein synthesis were the same
in all three groups but greater than previously observed in 60- to
75-yr-old men and women (31). The most likely explanation is that the
home and supervised stretching exercise program that was done by all
participants for 3 mo before the baseline determination of vastus
lateralis muscle protein synthesis was of sufficient intensity to
elevate the rate of mixed protein synthesis in the physically inactive
vastus lateralis muscles of frail elders. It is possible that physical
frailty and very old age is associated with an increase in the rate of muscle protein synthesis, perhaps as a protective response to prevent
against accelerated muscle protein wasting. It is also possible that
the mixed muscle proteins isolated from the vastus lateralis muscle
samples obtained from 76- to 92-yr-old men and women contained a
protein (e.g., sarcoplasmic, mitochondrial, enzymatic) with a very high
rate of synthesis. If these or other proteins have synthetic rates that
are faster than contractile proteins and they were present in the
muscle sample before hydrolysis and quantitation of
[13C]leucine
abundance, then they will confound the measure of "mixed" muscle
protein synthesis rate. It is also possible that the use of plasma
-[13C]KIC (rather
than muscle tissue free
[13C]leucine) as a
surrogate measure for the enrichment of the true in vivo precursor pool
for vastus lateralis muscle protein synthesis in physically frail
elders was inappropriate (1, 16, 19). However, in the current study,
this measure would be confounded because the
[13C]leucine infused
during the initial study was still present in vastus lateralis muscle
proteins during the final study (3 mo later). For this reason and so
that we can compare our current findings with previous studies, we have
used the plasma
-[13C]KIC abundance
to calculate the in vivo rates of vastus lateralis mixed muscle protein
synthesis. Also, all of our participants were of similar age;
therefore, it would be unlikely that the tissue
[13C]leucine abundance
would have differed much between the groups (1, 16, 19). In fact, the
muscle tissue
[13C]leucine abundance
would be predicted to be lower than the plasma
-[13C]KIC
abundance, and this would proportionally increase the calculated rate
of vastus lateralis mixed muscle protein synthesis. It is likely that a
combination of the above factors explains the greater-than-anticipated baseline rate of mixed muscle protein synthesis observed in these frail elders.
Despite the increased rate of mixed muscle protein synthesis induced by the supervised exercise program, the fasting rate of nonoxidative leucine disposal determined in the whole body (a reflection of protein synthesis in all body proteins) and the whole body rate of leucine oxidation and the Ra of leucine into the plasma compartment (a reflection of proteolysis in all body proteins) were not increased after supervised exercise. Welle et al. (26) have reported that the fasting rates of whole body proteolysis and nonoxidative leucine disposal were increased ~10% in 22- to 31-yr-old women and men after 3 mo of resistance training, but they were not increased after training in 62- to 72-yr-old women and men. We have reported no increase in fasting whole body leucine kinetic rates after resistance exercise training in young and older men and women (31). This probably reflects the fact that muscle protein synthesis represents only 20-25% of the whole body protein synthesis rate in young healthy subjects and slightly less in the elderly subjects (1, 12, 16, 17, 19, 31). The contractile muscle protein synthesis and breakdown rates are slow (relative to other body proteins) and comprise a small portion of the average turnover rate of all the body proteins. Our finding also supports the notion that advancing age alters the rate of turnover of specific body proteins differently (1, 5, 16, 19, 20, 31).
We found that the fasting whole body leucine kinetic parameters in
physically frail 76- to 92-yr-old men and women (when expressed per kg
FFM) were identical to healthy 20- to 30-yr-old and 62- to 74-yr-old
adults previously studied (12, 31, 33). This implies that, after an
overnight fast, the overall turnover of body proteins is maintained
remarkably constant with advancing age but that specific protein pools
in the aging body (muscle, liver, visceral organs) undergo substantial
changes in protein quantity and quality. This finding is in agreement
with Welle et al. (25-27) but contradictory to that of Balagopal
et al. (1) who reported that 52 ± 1- and 77 ± 2-yr-old women and men have lower rates of whole body leucine flux and
nonoxidative leucine disposal than 23 ± 1-yr-old men and women. In
this report (1), the young men and women had an inordinately high rate
of whole body leucine flux (150 ± 7 µmol · kg
FFM1 · h
1)
and nonoxidative leucine disposal (112 ± 5 µmol · kg
FFM
1 · h
1)
and a low FFM (45 ± 4 kg; 16.5 kg/m2). Previously (12, 31, 33),
we studied healthy 23- to 32-yr-old men and women with higher FFMs
(52-59 kg; 17.3-17.7
kg/m2) and reported lower whole
body leucine kinetic rates after an overnight fast (129-130 and
96-100 µmol · kg
FFM
1 · h
1).
Taken together, it appears plausible that the discrepancy between whole
body protein kinetic rates expressed per kilogram FFM in the current
and previous studies may be due to differences in the amount of lean
tissue in the young controls used as the comparison group for the older
subjects in previous studies (1, 12, 19, 25-27, 31, 33).
In summary, supervised progressive resistance exercise training increased the in vivo rate of vastus lateralis muscle protein synthesis and the maximum voluntary knee extensor muscle torque production capabilities in 76- to 92-yr-old physically frail women and men. Supervised weight-lifting exercise was well tolerated by these older women and men. As in healthy 60- to 73-yr-old men and women, muscle protein synthetic pathways maintain the ability to be activated by the increased contractile activity associated with progressive resistance exercise training.
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ACKNOWLEDGEMENTS |
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We thank the study participants for hard work and cooperation. The Washington University Claude D. Pepper Older American's Independence Center (OAIC) exercise technicians provided excellent support and expertise.
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FOOTNOTES |
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This work was supported by National Institutes of Health awards AG-13629 (OAIC), DK-49393 (K. E. Yarasheski), RR-00954, and RR-00036 (General Clinical Research Center).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: K. E. Yarasheski, Metabolism Division, Box 8127, Washington Univ. School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110 (E-mail: key{at}imgate.wustl.edu).
Received 30 December 1998; accepted in final form 18 March 1999.
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