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Muscle metabolism during exercise in young

and older untrained and endurance-trained men
ANDREW
R. COGGAN,
AMIR M. ABDULJALIL,
SCOTT C. SWANSON,
MARGARET
S. EARLE,
JAMES W. FARRIS,
LISA A. MENDENHALL,
AND PIERRE-MARIE
ROBITAILLE
Exercise Physiology Laboratory, School of Health, Physical Education, and Recreation, and Departments
Radiology and Medical Biochemistry, The Ohio State University, Columbus, Ohio 43210
COGGAN,ANDREW R., AMIR M. ABDULJALIL, SCOTT C.
SWANSON,MARGARETS.EARLE,JAMES W. FARRIS,LISA A.
MENDENHALL,AND~IERRE-MARIEROBITAILLE.MUX~~
metabolism during exercise in young and older untrained and endurance-trained men. J. Appl. Physiol. 75(5): 2125-2133, 1993.To examine effects of aging and endurance training on human
muscle metabolism
during exercise, ‘lP magnetic resonance
spectroscopy was used to study the metabolic response to exercise in young (21-33 yr) and older (58-68 yr) untrained
and
endurance-trained
men (n = 6/group).
Subjects performed
graded plantar flexion exercise with the right leg, with metabolic responses measured using a ‘lP surface coil placed over
the lateral head of the gastrocnemius
muscle. Muscle biopsy
samples were also obtained for determination
of citrate synthase activity. Rate of increase in Pi-to-phosphocreatine
ratio
with increasing power output was greater (P < 0.01) in older
untrained
[0.058 k 0.022 (SD) W-l] and trained men (0.042 t
0.010 W-‘) than in young untrained
(0.038 t 0.017 W-l) and
trained men (0.024 k 0.010 W-l). Plantar flexor muscle crosssectional area and volume (determined using ‘H magnetic resonance imaging) were ll-12%
(P < 0.05) and 16-18% (P < 0.01)
smaller, respectively, in older men. When corrected for this
difference in muscle mass, age-related differences in metabolic
response to exercise were reduced by -50% but remained significant (P < 0.05). Citrate synthase activity was -20% lower
(P < 0.001) in older untrained
and trained men than in corresponding young groups and was inversely related to Pi-phosphocreatine
slope (r = -0.63, P < 0.001). Age-related
reductions in exercise capacity were associated with an altered muscle metabolic response to exercise, which appeared to be due to
smaller muscle mass and lower muscle respiratory capacity of
older subjects. Endurance
training
was associated with 60100% higher muscle citrate synthase activity and improved metabolic responses in young and older men but apparently could
not prevent an age-related decrement in these variables or an
age-related decrease in muscle mass.
aging; master athletes; muscle atrophy;
netic resonance spectroscopy; magnetic

citrate synthase; magresonance imaging

MUSCULARENDURANCE
in rats( 11,15)
and humans (10). In rats, this increase in muscle fatigability with age appears to be due, at least in part, to an
altered metabolic response to exercise (2, 11, 13, 15, 25).
Thus the muscles of older rats undergo greater depletion
of ATP, phosphocreatine (PCr), and glycogen and accumulate more lactate during electrical stimulation of the
motor nerve than the muscles of young rats (11,15). SimiAGINGREDUCES

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larly, the rate of muscle glycogen utilization during
treadmill running is greater in older rats than in young
rats (2). These differences between young and older rats
in the metabolic response to exercise appear to be largely
the result of an age-related decrease in skeletal muscle
mitochondrial respiratory capacity (1, 2).
Little is known about the effects of aging in humans on
the metabolic response of skeletal muscle to exercise. We
have found, however, that mitochondrial marker enzyme
activities are 15-30s lower in the muscles of healthy but
sedentary older (60-70 yr) subjects than in those of
young (20-30 yr) subjects (9). Similarly, others have reported that the capacity of human muscle to utilize O,,
measured in vitro using either whole muscle homogenates (26, 34) or isolated mitochondria (34), is 25-50%
lower in older subjects. It therefore seemspossible that,
as in rats, an age-related reduction in human muscle respiratory capacity could alter the metabolic response to
exercise and thus contribute to the reduction in muscular
endurance observed in older subjects (10). In keeping
with this hypothesis, McCully et al. (24) reported that
the rate of muscle PCr resynthesis after exercise is significantly reduced in older subjects. Others, however, found
no effect of aging on human muscle metabolism during or
after exercise (33). Thus, whether aging alters muscle
metabolic responses during exercise in humans remains
uncertain.
Reduced skeletal muscle respiratory capacity and altered metabolic responses during exercise in older rats or
humans may be due to a decrease in habitual physical
activity rather than the aging process per se. In support
of this hypothesis, young and older rats that have been
trained using an identical exercise program have similar
muscle mitochondrial respiratory capacities and use similar amounts of muscle glycogen during exercise (1,2). In
older men and women, we found that endurance exercise
training increases muscle mitochondrial marker enzyme
activities by ~50% (8), and Meredith et al. (26) demonstrated an even larger training-induced increase in in vitro muscle respiratory capacity. It is not known, however, whether endurance training of older humans can
prevent or ameliorate possible age-related alterations in
muscle metabolism during exercise.
The purpose of the present study, therefore, was to
determine the effects of aging and endurance training on

Copyright 0 1993 the American Physiological Society

2125

Whereas these men were competitive in local and correct for the possible effects of age-related muscle atroregional endurance competitions. 128 X 256 matrix.ducted 26 h after the subjects’ last meal and. Running distance. The Values are means -t SD.meter (Rayfield RAM-9200).Magnetic Resonance Facility. walking short distances). sports such as distance running or cycling. These latter measurements could not be performed in conjunction with the subsequent 31P-MRS exever.5-T instruswimming. To cyclist. six young (27 t 4 yr) trained men.col .8 X lo-mm 180 km cycling. Total resolution. most had not achieved phy on the metabolic response to exercise.. Muscle biopsy sam. h/wk 6 7+2 B&4 tions. Running and/or tween the femoral epicondyles and the calcaneus was cycling pace. 0.. and some participated in recre. 42 km running) after this study.2126 AGING AND HUMAN MUSCLE 1.6 X 0. was used to determine maximal 0. for the ing of two runners. km/wk 4 137+77 190+114 Cycling pace. the cross-secsuccesson a national level and would not be considered tional area and total volume of the plantar flexors were first determined using ‘H magnetic resonance imaging. was greater in the young athletes first determined by acquiring several sagittal images. None. subjects were studied at the hand.ercise. TR (repetition third in the Hawaii Ironman Triathlon (4 km swimming. driving. to be elite athletes. max. and six fold measurements (19). To ensure that 7j02max had &indeed been Subjects and preliminary testing. 224 h after their last training session. On the other Approximately 1 wk later. despite an increase in treadmill community publications and media. Preliminary testing included a medical history. m8x.g. tronic 0. All untrained subjects tial study served to minimize possible learning effects and also enabled quantification of the subjects’ heart performed normal daily activies (e.001) different from first test. at least two of the following criteria had to be cruited through advertisements placed with campus and met: a plateau in VO. we used 31Pmagnetic resonance spectroscopy (31P. km/wk 5 55+19 56+24 physical examination. cardiovascular abnormalities. After premaximal heart rate. km/h 4 33s 29+2* treadmill tests to volitional fatigue while blood pressure and a 1%lead electrocardiogram were monitored. human skeletal muscle metabolism during exercise. time) = 600 ms. how. uptake MRS) to examine the metabolic response of the plantar (VO 2.ally adjusted running test to fatigue to determine VO.In the young and older subjects. shopping. The young subjects performed only an individuflexor muscles during exercise in young and older un.). Subjects were rereached. whereas the second test. of excitations). however. Subjects first perolder (62 t 2 yr) trained men were enrolled in the study. liminary screening of health status (seebelow). was used to screen for young trained men.. or musculoDuration of training. The older subjects also underwent two graded Cycling distance. a respiratory exchange ratio >l. metabolic. None was taking prescription medicaTotal training volume. and CO.g. Training duration. however. and pace in young and older trained men METABOLISM DURING EXERCISE was approved by The Ohio State University Human Subjects Review Committee.5 km Imaging was performed with a GE Signa 1. and VO. six older (63 t 3 yr) untrained men. Young Older All subjects were normotensive nonsmokers who were n Trained Trained free of detectable cardiovascular. six young Body fat and fat-free mass were estimated from skin[25 t 2 (SD) yr] untrained men. using a Bruce protocol. whereas another older standard multislice multiecho sequence. km/h 5 1421 12+1* test. was defined METHODS as V0. than in the older athletes (Table 1). The mean of the two highest consecutive 30-s values for VO. mixing chamber. yr 6 12+6 12+5 skeletal disease. To using an individually adjusted walking or running protodo so. held a job requiring strenuous physical labor or properiment. Experiments were conmost continuously for Z-20 yr. both the young and older trained men had been training for and/or competing in endurance sports al. trained and endurance-trained men. This iniwhereas most of the older men were employed in or retired from professional careers. tennis). 40 km cycling. The distance beand the older trained men (Table 1). respectively). below) at the Exercise Physiology Laboratory. * Significantly (P < 0. had won the World Triathlon Championship (1. The study protocol Without moving the subject. 1. blood pressure. 10 km running) in his age ment and a quadrature detection body coil with use of a group -1 yr before being studied. and none participated in endurance the use of ferrous metal equipment. Endurance-trained speed and/or grade.. and elecity and metabolic responses during exercise. subjects were also recruited using the published results of or a heart rate within 10 beats/min of age-predicted local running and/or triathlon competitions. One of the older athletes. during plantar flexion exational sports or games (e.lO. Magnetic resonance experiments. Parameters athlete had finished fourth in the same event and placed were as follows: TE (echo time) = 20 ms. The subject was years of training and average weekly training volume did placed in the magnet in the supine posture with the right not differ significantly between the young trained men leg positioned in the center of the coil. and one trained men. 35-40 sequential transaxial TABLE . with both groups consist. formed the entire plantar flexion exercise protocol (see Most of the young men were university students. three duathletes/triathletes. and all subjects provided informed written consent. (ZO). uptake (vo2) was ples were also obtained from the lateral gastrocnemius measured every 30 s during exercise by use of an automuscle to examine the possible relationship between mated open-circuit system that incorporated a dry gas age-related changes in mitochondrial respiratory capac. squash. 2 NEX (no. analyzers (Applied Electrochemistry S3-A and Beckman LB-Z.rate. and a 75-g oral glucose tolerance Running pace. because the powerful magnetic field precluded longed walking. volume.

The. despite strong verbal encouragement.. This device consisted of a wooden foot pedal and a cable-and-pulley system arranged so that plantar flexion from 0’ (vertical) to 24” raised a weight 10 cm. 5 mM . carefully excluding all visible noncontractile tissue (i.AGING AND HUMAN MUSCLE METABOLISM images (10 mm thick. flexor digitorum long-us. Briefly.02% citrate-free bovine serum albumin (BSA). The three areas quantified were I) the lateral gastrocnemius. resonance spectra acquired of’ a young endurance-trained flexion exercise (3-27 min). The citrate formed was then measured fluorometri- DURING 2127 EXERCISE ATP CP 0 min __h__ihc?s*_ij_l 9 min 12 min @--++fi -A- 15 min 27 min 10 2 -6 -14 -22 -30 PPm FIG. and a wide strap was placed tightly over the waist and upper thighs to minimize horizontal or vertical movement. diet and exercise controls were again imposed as described above. 0. 1. Partially saturated 31P spectra were acquired during the last -60 s of each exercise stage with use of a 2-s TR. 0.5 mM EDTA. Data analyses.1. 1. Thereafter. The latter area included the soleus. ‘lP magnetic gastrocnemius muscle min) and during plantar phate. and the coil was tuned to 31P.4) containing 0. the power output was increased by 0. and (where present) plantaris but excluded the popliteus and peroneus longus and brevis. This second strap also served to keep the knee fully extended. as previously described (5-9). from right1 lateral man at rest (0 CP. blood vessels. 20 averages/ spectrum. NY). thereby maximizing involvement of the gastrocnemius muscle (31). Citrate synthase activity was measured by adding 2 ~1 of the diluted homogenate to 50 ~1 of assay reagent [50 mM tris(hydroxymethyl)aminomethane buffer. 5). and excess oxaloacetate was destroyed by adding 5 ~1 of 0. Once the magnetic field had been shimmed. tendons. 500 PM oxaloacetate. which was maintained for 3 min. a 2-kHz sweep width. and then stored at -8OOC until subsequently analyzed for citrate synthase activity (4) and protein content (2l).25% BSA] and incubating at room temperature (24 t O. ‘H magnetic resonance imaging scans were printed on film and digitized using a video analysis system. flexor hallucis longus. A 4cm-diam 31P-tuned surface coil was positioned directly under the lateral head of the subject’s right gastrocnemius muscle and secured to the leg with adhesive tape. For each image. 31P spectra were acquired at 25. CA). and a l-kilobyte block size. and a muscle biopsy sample was obtained from the lateral head of the right gastrocnemius muscle by use of a 5mm Bergstrom needle (Stille-Werner.75 W every 3 min until. The subject then began performing repeated plantar flexions at a rate of 3O/min (paced by a metronome) using a custom-built exercise device. fat). 400 PM acetyl-CoA. The initial power output was 0. creatine phos- tally using citrate lyase and malate dehydrogenase. thereby minimizing movement of the leg within the magnet.02% BSA. 1 mm interspacing) were then obtained covering this linear distance (total scan time -10 min). The subject was then repositioned within the magnet. The metabolic response to exercise was then studied using 31P-MRS. as previously described in detail (4. tibialis posterior. 2) the medial gastrocnemius. both fully relaxed (10-s TR) and partially saturated (2-s TR) 31P spectra were acquired before exercise. Jandel Scientific. Muscle biopsy.0) containing 0. The axis of rotation of the foot pedal was positioned at the ankle joint. Each cross-sectional area . nerves. Total exercise duration ranged from 12 to 30 min (4-10 stages). Corta Madera. Protein concentration of the homogenate was measured calorimetrically (21) using BSA as the protein standard. a 5.to lo-mg portion of each sample was homogenized in 50 vol of 20 mM sodium phosphate buffer (pH 7.86 MHz by use of a l-pulse sequence. pH 8. To correct for saturation effects. On a subsequent day.5 N NaOH and boiling for 5 min. This weight also served to return the pedal to O” after each movement. and 3) the remaining plantar flexor muscles of the posterior compartment. This system consisted of a light box and a video camera interfaced with a laboratory computer operating commercial software (JAVA. Representative spectra acquired from a young trained subject at rest and during exercise are shown in Fig.75 W. Ronkonkoma. An aliquot of this homogenate was then diluted further (20-fold) with 20 mM imidazole buffer (pH 7.muscle specimen was frozen in liquid N.8-mercaptoethanol. and 50% glycerol.e. connective tissue. The foot was secured to the pedal with a strap. the cross-sectional areas of three separate regions were determined by manually tracing the desired muscle area with a mouse-driven cursor. the subject was I) unable to maintain the cadence or 2) unable to move the foot pedal over the required range of motion. The reaction was stopped.I”C) for 1 h.

consequently. data for the young and older untrained and trained men are presented separately as means t SD. however. cm2/W. Percent body fat.001.the effect of training were statistically significant (P < vided that ATP and H+ are constant (3). 2). was significantly higher metabolic stress (3.. Despite a similar age differential. The volume of each imaged subjects. regardless of training status.50 t 0. the calcaneus and especially the popliteal space. muscle volume (W/l). PCr.89 t 0. Total plantar flexor trained men were somewhat smaller (32 and 22% for l/ muscle volume (in liters) was calculated by summation of min and ml min-’ kg-‘. l/W.001) in the older untrained men than in the young unware (GE) to give relative concentrations of ATP (cu. the trained was measured three to eight times. These analyses were performed with power output expressed in absolute terms (W) and relative to muscle cross-sectional area (W/ cm2).68 t measure because both the numerator and denominator 0. This is most likely training may slow the fall in maximal heart rate with due to an inadequate signal-to-noise ratio in the 31P age (28). 3. consistent with their roughly four-decade and y peaks).2128 AGING HUMAN MUSCLE m 0. no significant interaction effects were observed. howlated by measuring the PCr-P. 1.recent longitudinal data. regardless of age.e.interaction between the effects of aging and the effects of ments.5 t 8.& trained men.62 in the older of this ratio reflect changes in bioenergetic status. signal before Fourier transformation.3 t 6. Intracellular pH was calcu. this ratio remains an accurate gross measure of young trained men (54.only 20 beats/min less (P < 0. Significance was untrained men (0. Because P. Peak areas were Maximal heart rate was ~40 beats/min lower (P < integrated by a blinded technician using commercial soft0. and peak plantar flexor power (%peak power). and as such we have used this ratio ences in muscle cross-sectional area were greater near while recognizing its shortcomings.liters per minute or in milliliters per minute per kiloculated assuming that each such nonimaged segment had gram.05) than terpreted in terms of thermodynamically significant reac. and Changes in Pi/PCr under equilibrium conditions have 5.20 training were obtained for a number of variables. 22) (Fig.(48. indicating that the effects of aging were generally similar in the untrained and the trained men.25 - m I n I R 0. we chose it as a more sensitive ity (in mol h-l kg muscle protein-‘) averaged 3./PCr with increasing power output (i. Physical characteristics of the subjects are shown in Table 2. As a result of this lower body fat content. Although Pi/ATP and (P < 0. Howliters). 0.99 in the young trained men.e. being higher in the older than in the young men but lower in the trained than in the untrained subjects. AlPCr/ATP are more directly relevant from a thermodythough based on a relatively small number of subjects.those in the young untrained men (56. furthermore. pH decreased during Maximal plantar flexor cross-sectional areas in the older exercise../PCr is unitless. endurance training on VO 2maxwas not statistically signifiA ~-HZ line broadening was applied to the “lP-MRS cant (P = 0. although changes in Pi/PCr cannot be easily in.5 ’ . whereas P.00 ’ 0.5 cm2). untrained men. however.05. respectively). The than in the young untrained men. and Pi.9 cm2) were ll-12% smaller (P < 0. 3.75 - 1 0.5 t 4. The rate of increase in the Pi/PCr ratio with in. The P values reported here therefore refer to these significant main effects./PCr may be less thermodyMuscle citrate synthase activity. whether expressed in volume of muscle between the imaged segments was cal.01) than that of the young creasing power output was used as an indicator of muscle trained men and. respectively). Neveruntrained men (49.0 Power ’ 4. The effect of age and been theoretically linked to changes in free ADP. 10 mm). with an average coeffisubjects weighed significantly less than the untrained cient of variation of ~2%. but this apparent the volume of the imaged and nonimaged muscle seg. respectively.09 t 0.01) than that in the young untrained men (1. Physical characteristics.44 in the older trained men.0 cm2) and older trained men theless. chemical shift difference ever.62 t 0. It is uncertain. namic perspective.05 and P < 0. Pi/PCr slope) was calculated by regression analysis (solid line) and was used as an index of muscle metabolic stress.5 t 6.52 in the young untrained men. 1.5 . Data were analyzed using two-way quently.5 cm2) and tions. maximal heart rate of the older trained men was (30). Relationship of Pi/PCr to power output for subject whose data are shown in Fig. on the other hand.021 n : R=0.50 0 -. Thus. Initial linear rate of increase in P. Citrate synthase activnamically appropriate. ConseStatistical analyses. albeit only near fatigue (see RESULTS).099+0.0 (W) RESULTS 2. and %peak power-‘.05) than that in the older untrained men.14). pro. muscle segment was calculated by multiplying the crossvo 2max was -45% lower in the older untrained men sectional area by the image thickness (i. 7. FIG.96 2 AND *x n n 0.0 ’ ’ .difference in age. total plantar flexor muscle volume in the older (age X training) analyses of variance. differed with age and with training status. Significant main effects for age and 0. These values are almost identical to those obever..20 t 0. Y=0. corresponding slopes have units of W-l. 6.13 liter) was 18% lower (P < defined as P 5 0. in the present studies. For comparison purposes. ’ METABOLISM DURING EXERCISE SULTS). Differences in VO 2maxbetween the young and older the shape of a truncated cone (27). (27) using computed tol l l l . with the exception of maximal heart rate (see RE. Age-related differbioenergetic status. differences between groups in these these cross-sectional observations are consistent with ratios did not achieve statistical significance when ana. whether equilibrium conditions were achieved Plantar flexor muscle cross-sectional area and volume. spectra.tained previously by Rice et al. suggesting that endurance lyzed as a function of power ouput. The older men were significantly shorter and had a lower fat-free mass than the younger men.

6620. was measured at rest and during plantar flexion exercise during the initial experiment performed at the Exercise Physiology Laboratory.33 52. averaging 7.1 22.001 P < 0. Fig. The Pi/PCr slope (in W-‘) was inversely related to muscle cross-sectional area (r = -0. 7. P < 0. Resting VO. kg Body fat. 2-way (age X training) analysis of variance. Subject characteristics Untrained Trained Young Height.5-tl.03 in the older trained men. kg VO DURING Age Effect Older Young Older 177-t9 77.4k9. was -20% lower (P < 0.ut during exercise. % Fat-free mass.001) in older untrained and trained men than in young untrained and trained men. B and C). Responsesduringplantar flexion exercise.) are presented for the first 4 exercise stages.2k5. 4). 5. 50). (AVO. Fig. with plantar flexor volume averaging 0.6 t 1. although Pi/PCr increased more slowly in athletes than in nonathletes regardless of age.0 57.6k5.13 liter in the older trained men compared with 1.SD for 6 subjs/group in ml/min.63 (P < 0. During exercise. cm Weight.12 t 0. A similar difference existed between the young and older trained men.0 P < 0. 0.001 P < 0.1t6. Similar results were obtained when power output was expressed relative to peak plantar flexor power (Fig. especially in the trained men.9 64.15 t 0.01) than in older untrained mography. and 7.0 15. Thus the mean Pi/PCr slope during exercise differed significantly with age (P < 0.9 7.06.5-tl. 5A). When power output was expressed relative to muscle cross-sectional area or muscle volume to correct for the reduced muscle mass of the older men. maximal 0.0* 14.001) to the Pi/PCr slope (expressed in W-l). the latter correlation coefficient increased to r = -0. ii0 2 max. the P..62kO. P < 0. respectively. At rest. When power output was expressed relative to muscle cross-sectional area or volume.8 199+9 2.05 t 0. indicating that the reduced muscle volume of the older men was not simply due to their smaller stature. P < 0. P < 0. these differences were not statistically significant because of large intersubject variability and/or the small number of subjects in each group.9 at fatigue (Fig.001) in the older untrained and older trained men than in the corresponding young groups (Table 3).1 t 0. 3.001 P values refer to significant main effects bY men.4 54. beatslmin l l Val ues are means -t SD for 6 subjs/group.4k9.03. Fig. Peak plantar flexor power averaged 4.. This difference is probably partially due to the lower fat-free mass of the older subjects.7 11.001 P < 0.8 W in the young trained men.4k5. DISCUSSION Numerous studies have demonstrated that the reduction in exercise capacity that accompanies aging is asso- . Resting muscle pH did not differ with age or with training status..3 170s 74.7 W in the older untrained men. 3A).5 179k5 70. * Significantly lower (P < 0.064).05). Although muscle pH tended to decrease earlier but to a lesser extent in the older subjects. P < 0. similar results were obtained when power output was expressed relative to peak plantar flexor power (Fig.001. as assessedusing 31P-MRS (22). differences between the young and older subjects in the metabolic response to exercise were reduced by -50% but remained significant (P < 0.6k4. At any given power outp.Ok2.02 t 0. and 0. 0.19kO. uptake. VO. 6.6 t 0.05). m aximal heart rate.9 W in the older trained men and was inversely correlated (r = -0.2k4.86 t 0.14-t0.02 in the older untrained men.04 in the young trained men.2k4. Data for increase in VO. Muscle pH did not change during the initial stages of exercise but then decreased to -6. the increase in whole body VO.7 169&6* P < 0.26 29.001 I’ < 0. however.0 W in the young untrained men. 3.10 t 0. P < 0. and 4.05.51. however.AGING TABLE AND HUMAN MUSCLE METABOLISM 2129 EXERCISE 2.02 in the young untrained men.07 t 0.001 P < 0. Resting %2 and increase in L%I~above resting during one-leggedplantar flexion exercise TABLE Ai’02 Stage 1 Stage 2701~25 205+21* 44+15 30+18 79+17 63+24 113221 96+35 147+27 128k46 277219 223+20* 34+20 34+18 75222 71+22 115k25 108k30 176~~51 143+37 Resting Untrained Young Older Trained Young Older VO.01. B and C). 2 Stage 3 Stage 4 Values-are m$ans -t.001 2 max l/min ml min-’ kg-’ HR max. These results are in keeping with prior observations indicating that maximal exercise capacity is inversely related to muscle metabolic stress during submaximal exercise. Training Effect. above resting was not significantly different among the four groups (Table 3).01) and with training status (P < 0.10 t 0.03 t 0.05 P < 0.9 t 0. 30). Fig.324.38 66.48.05 P < 0. muscle volume (r = -0. output in the older untrained men than in the young untrained men. The subjects were subsequently studied at the Magnetic Resonance Facility. Again.1k5. Pi/PCr averaged 0.4 189&6 3. Although Pi/PCr tended to be higher in the older subjects.10 liters in the young trained men. Relationship between metabolic responsesand skeletal muscle characteristics.01 3.49 47. and muscle citrate synthase activity (r = -0.7 65. Differences in muscle volume between young and older subjects were only slightly reduced (to 12-13%.04.05) when the data were expressed relative to height or tibia1 length (data not shown). * Significantly higher (P < 0.55./PCr ratio rose more rapidly with increasing power 3. HR. A similar age-related difference in muscle volume was observed in the trained subjects. this difference did not achieve statistical significance (P = 0.03 in the four groups. which were completed by all subjs.70.3k4.7 155t9 4. 7.05.06 t 0.9 16825 61.

was chosen in part because it facilitated noninvasive assessment of muscle metabolism using 31PMRS. at any given absolute power output.11. young untrained men. because exercise efficiency (as indicated by the relationship between VO.040 it 0 PcO.05 PcO. It is unlikely that the absolute rate of ATP hydrolysis was higher in the older men. and power output during plantar flexion exercise) did not differ with age. as measured by peak power output.13. Consistent with previous studies of aged rats (2. Thus a greater demand for ATP per unit of muscle tissue probably contributed to the altered metabolic response of the older subjects during exercise. Muscle pH also tended to decrease at a lower power output in the older subjects.13. The purpose of the present study was to determine whether aging also affects muscle metabolism during exercise in humans and. however. suggest that decreases in Vo2max and alterations in skeletal muscle metabolism contribute to the deterioration in exercise capacity with aging (2. although this latter difference was not statistically significant.05 0. we found that aging apparently altered the metabolic response to exercise in humans. Changes in Pi and PCr concentrations during exercise reflect the balance between the rate of ATP hydrolysis and the rate of ATP resynthesis. a slower rate of ATP production. The physiological importance of this greater disturbance to energetic homeostasis during exercise is demonstrated by the significant correlation between the Pi/PCr slope and the exercise capacity of the plantar flexor muscles.060 h raining: PcO.20 Training: g 0.05 PcO. Standard deviations (typically -0.020 CL 2 0. muscle volume (C).25).10 pH units) have been omitted for clarity.000 Age: : Q Y 1 Power (W) FIG. 30). although at rest Pi/PCr did not differ significantly between the young and older men.11. Martin et al. 7. older trained men. one-legged plantar flexion. older untrained men. or a combination of these factors. Indeed. i. 4.05 PcO. Studies of rats. In . young trained men. l&25).. Thus the altered metabolic response of the older subjects could theoretically be due to a faster rate of ATP utilization.15. to ascertain whether this effect could be prevented or ameliorated by endurance exercise training. the rate of ATP hydrolysis per gram of muscle was probably higher in the older men because of their smaller muscle mass. However. Significant main effects analysis of variance regardless of whether power output was expressed cross-sectional area (B). ciated with a decrease in VO 2max resulting from a decline in central cardiac function (cf. during exercise Pi/PCr increased more rapidly with increments in power output in the older subjects.2130 AGING AND HUMAN MUSCLE METABOLISM DURING EXERCISE A Age: 0. H.05-0. The exercise model that we used. or peak power (D). 6 s 0.01 L Young Untrained Old Untrained Young Trained Old Trained Young Untrained Old Untrained Young Trained Old Trained 0.01 g 0. Intramuscular pH during plantar flexion exercise in the 4 subject groups: l .001 0 v) Young Untrained Old Untrained Young Trained Old Trained FIG. Thus. however. 0. 0. This model was also chosen. because the metabolic response to exercise with a small muscle mass would be less likely to be influenced by the age-related decline in maximal cardiac output. if so.002 Q sw z 6 0. X Mean Pi/PCr slopes during exercise.e.05 PcO.000 L-- Young Untrained for age and training in absolute terms Old Untrained Young Trained Old Trained status were indicated by (A) or relati ve to muscle (23) demonstrated that maximal calf muscle blood flow is unaffected by aging in healthy men.060 Age: Training: h 3 2 PcO.01 Age: Training: PcO.

.* 0 0. 34) [but not all (14)] prior investigations have found that muscle respiratory capacity is reduced in older subjects.. Peak plantar flexor power was also higher in the young trained men. * . and older trained men (0). muscle volume (C). Relationship between citrate synthase activity of lateral gastrocnemius muscle and Pi/PCr slope during plantar flexion exercise in young untrained men (o). . E.080 -& A 0 0 .OOl 0.o.060 o g 0. the latter adapation to endurance training has not been previously demonstrated in older humans. significant differences remained between the young and older subjects. Little attention has been directed. in addition to studying young and older sedentary individuals. o *. young trained men (m). . Although expected on the basis of studies of young individuals.000 ’ - ’ 2 - 4 ’ * 6 ’ .000 MUSCLE METABOLISM B DURING 0 0 r .98. O. because maximal voluntary torque per unit of muscle cross-sectional area or volume did not differ with age (12). 0.99. Factors in addition to a reduction in contractile tissue must therefore have contributed to the altered metabolic response and reduced exercise capacity of the older men. *.000 0 a.*. n n 0 * . inasmuch as citrate synthase activity was 13 and 25% lower in the older untrained and older trained men than in the corresponding young groups. toward the effect of this decline in muscle mass on metabolic responses and performance during dynamic exercise requiring submaximal force production. The benefits of endurance training are emphasized by the fact that.000 ’ 2 Citrate - ’ .001. As expected.000 3. 26). EXERCISE 2131 R--0. * . these correlations were almost perfect (r = -0.001 - R--0. we also studied young and older men who were training vigorously for endurance competitions. *. or peak power (U).63 P<O. *. P < 0.P. * . 0 . in absolute terms. 4 synthase keeping with this hypothesis. *. muscle respiratory capacity was roughly twofold higher and the Pi/PCr slope was substantially lower in the young trained men than in young untrained men. 0 AND H UMAN -r‘ s $ -0 g I+-0.55 PKO. One likely factor is muscle mitochondrial respiratory capacity.000 ‘I 2 Citrate - ’ 4 synthase - ’ 6 activity * ’ 8 (mol/h/kg) .AGING 0. *.55 P<O. P < 0.02 and r = 0. R. cf. This also appeared to be true in the present subjects. Therefore. Alterations in muscle mass and muscle respiratory capacity (and therefore in exercise metabolism) with advancing age could be due to a reduction in habitual physical activity rather than aging per se. 2).001 and r = 0. 26. the Pi/PCr slope and peak plantar flexor power of the older trained men were similar to . respectively) when variability was reduced by using group mean data instead of individual data in the calculations. Muscle respiratory capacity and peak plantar flexor power were also higher and the Pi/PCr slope was also lower in the older trained men than in the older untrained men. differences in the Pi/PCr slope between the young and older subjects were significantly reduced when corrected for differences in plantar flexor muscle cross-sectional area or volume. . This is unlikely to have been due to a greater amount of noncontractile (i. respectively). however. ’ IO 6 a. FIG. unpublished observations). ’ 10 (mol/h/kg) ity with aging plays a major role in the altered muscle metabolism and impaired exercise performance of older animals (1. An age-related reduction in muscle mass has long been recognized as an important factor in the decrease in muscular strength that occurs with aging (cf. older untrained men (0). The present results suggest. Alway and A.63. A significant inverse relationship was observed whether power output was expressed in absolute terms (A) or relative to muscle crosssectional area (B).020 * . cL 0. P < 0.001.66.ooo’l 10 - 0 0 * * ’ 4 2 0 * ’ 6 * ’ 8 * ’ 10 h ‘L C -2 1 0 0. 3. This was also true in the present subjects. g - V g 0. 0 0 z 8 0 *. 16). provided that the training stimulus is adequate (8.e. . 0 0 n n 0 I -.002 0. fat or connective) tissue in the muscles of the older subjects.63 P<O.Ol o •I 4. * 0.003 W-0.0 8 * . Indeed. . inasmuch as both the Pi/PCr slope and peak power output were significantly correlated with muscle citrate synthase activity (r = -0. P < 0.OOl 0 2 a 0. 0 . 5. Coggan. 18). 8 ’ 3 L 1. 2 0. Studies of rats have demonstrated that a decline in muscle respiratory capac- ’ 6 activity - ’ 8 . The mitochondrial content of muscle is an important determinant of the metabolic response to exercise (6. - 0 *. 060 p .01 0 0 ’. that a decrease in muscle mass with aging also plays a very important role in the reduced exercise capacity observed under these conditions. * * 0 0 0 s 0. The higher muscle respiratory capacity in the older trained men is consistent with prior studies demonstrating that older subjects can adapt to endurance exercise training with an increase in muscle respiratory capacity.000 2. and several (9. Histochemical analysis of selected biopsy samples also revealed no differences in noncontractile tissue between the young and older men (S. Although expressing power ouput relative to muscle cross-sectional area or volume reduced the effect of age on the Pi/PCr slope. Furthermore the present results suggest that this increase in muscle respiratory capacity reduces muscle metabolic stress during submaximal exercise.080 0 D- z Y l . though.

J. KING. Address for reprint requests: A. LOWRY. S. compared with young untrained men. 4. FARRAR. Physiol. M. 47: B71-B76. in the present study we used 31P-MRS to study muscle metabolic responses during exercise in young and older untrained and endurance-trained men. Mechanical 10. this appears to have been due to the fact that plantar flexor muscle cross-sectional area and volume were 11 and 16% smaller in the older trained men than in the young trained men. DURING EXERCISE older untrained men demonstrated greater muscle metabolic stress during exercise. Physiol. S. AND S. J.-M. E. THOMAS. The latter possibility is consistent with animal studies demonstrating that mitochondrial respiratory capacity adapts equally in young and older muscles exposed to the same absolute training stimulus (1). Physiol. Coggan. The latter was true even though total duration of training and training volume were similar in the two groups of athletes. the present group of young trained men more closely resembles the group of competitive young runners we studied previously who had muscle mitochondrial enzyme activities 14-23% higher than those of the older runners (7). 2. SPINA. 0.. 73: 1873-1880. 0. whereas the young athletes of the present study trained and competed at higher absolute intensities than the older athletes. 45: 2915-2920. AND J. G.. M. P. S. such that their metabolic response and exercise performance were equal to or even slightly better than those of untrained men -40 yr younger. Tim Kirby. 1988. HINTZ. Ageing changes in mammalian skeletal muscle. Effects of detraining on enzymes of energy metabolism in individual human muscle fibers. A. A. 0. AND J. These findings seemingly conflict with our previous report that mitochondrial marker enzyme activities are actually higher in older athletes than in young athletes with whom they are matched on the basis of absolute training volume (7). Skeletal muscle adaptations to endurance training in 60-70 year old men and women. M. 126: 107-114. P. R. Shriners Burns Institute. 12. TX 77550. In part. properties of young and elderly muscle. S. 64: 259265. MCCULLY. CARTEE. R. M.. LEIGH. 11. using anthropometry. R. Metabolism Unit. DAVIES. Physiol. Med.. BIER. M. Galveston. AND 0. BROWN. In this regard. A. 244 (Cell Physiol. Effect of aging and/or endurance training on muscle strength and volume in men (Abstract). B. Stand. J. 1992. W. 1988. R. D. 68: 1896-1901. 13. A. 13): C276-C287. IVY. M. Appl. the Pi/ PCr slope still differed between the young and older trained men. KING. ALWAY. This was apparently due to both their smaller muscle mass and their lower muscle respiratory capacity. Metabolite changes in aged muscle during stimulation. 264 (Endocrinol. 1986. R. P. 1983. 1984. COGGAN. To summarize. J. HOLLOSZY. R. A. F.. M. muscle respiratory capacity. We found that. J. Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. E. REFERENCES 1. KOHRT. 0. 0. W. Even when power output was expressed relative to muscle cross-sectional area or volume. J. J. Metabolic control principles and ‘lP NMR. Alternatively. I? FARRAR. M. COGGAN. 72: 1780-1786. P. R. HOLLOSZY. Am. SPINA. M. Acta Med. Despite this compensatory effect of endurance training. J. C. EARLE. and exercise performance still differed between young and older trained men. SWANSON. The authors thank Drs. H.. HOLLOSZY. CHI. AND S.to 69-yr-old) endurance athletes compared with younger (17. 39: 183-186. J. Appl. A. 15. Appl. 1993. ROGERS. Similarly. KIRWAN. However. Exercise training induces glycogen sparing during exercise by old rats. Saltin (29) reported that muscle citrate synthase and .. J. ROGERS. the Pi/PCr slope was higher and peak plantar flexor power was lower in the older athletes than in the young athletes. therefore suggest that the decrease in muscle mass with aging is due to factors other than or in addition to simple inactivity and that endurance exercise training does not entirely prevent this age-associated loss of muscle tissue. Federation Proc. however. Suppl. COGGAN. BARGES. AND J. and Richard Strauss for assistance with various aspects of the study. Gerontol. AND R. Physiol. Appl. Histochemical and metabolic characteristics of human skeletal muscle in relation to age. P. Am. P. 7. Acta Physiol. even though muscle size was smaller in the older trained men. Grassi et al. S. M. C. 63: 257-261. MARTIN. D. B. Muscle respiratory capacity and vo 2 max in identically trained young and old rats. J. ERMINI. Rick Schaal. . D. J. 1992. 1993. 1976.. NEMETH. J. ROGERS. NEMETH. R.. W. M. P. 1992. L. Gerontol. Interestingly. This study was supported in part by a University Seed Grant from the Ohio State University Research Foundation. AND 0. T. SPINA. 711: 219-226. accepted in final form 22 June 1993.. Appl. Effect of prolonged exercise on muscle citrate concentration before and after endurance training in men. D. 1987. ABDULJALIL. HOLLOSZY.. A. G. S. Physiol. COGGAN. This appeared to be due to the 25% lower muscle citrate synthase activity of the older athletes. M. M. Sci. 1986. COGGAN. M. R. Stand.-Y. metabolic responses. AND K.. A. A. J. G. J. However. FITTS. the young and older athletes were also matched on the basis of absolute training intensity and absolute performance ability. ROBITAILLE. similar to the 12 and 18% differences observed between the young and older untrained men. AND M.. HOLLOSZY. R. NEMETH. WITZMANN. Plasma glucose kinetics during exercise in subjects with high and low lactate thresholds. A.. M. it is possible that the decrease in maximal cardiac output and therefore in VO 2maxwith age eventually limits absolute training intensity and therefore indirectly accounts for this small reduction in muscle respiratory capacity. NEMETH. Sports. 0. C. 14. in our prior study. 9. M. Metab. AND J. BROWN. A. J. FLECK. J. WHITE. F. Received 19 February 1993. AND J. 0.to 26-yr-old) endurance athletes and that this decline paralleled that of nonathletes. J. KENT. R. Gerontology 22: 301-316.2132 AGING AND HUMAN MUSCLE METABOLISM those of untrained men -40 yr younger. D. J. H. (17) found that leg muscle (plus bone) volume was reduced by -10% in older (60. R. 5. Thus a small but functionally significant reduction in muscle respiratory capacity may be an inevitable consequence of aging (34). 815 Market St. DUDLEY. J.&hydroxyacyl-CoA dehydrogenase activies are -15% higher in elite young orienteers than in elite older orienteers. 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