494

Effects of Aging, Sex, and Physical Training on

Cardiovascular Responses to Exercise
Takeshi Ogawa, MD; Robert J. Spina, PhD; Wade H. Martin III, MD; Wendy M. Kohrt, PhD;
Kenneth B. Schechtman, PhD; John 0. Holloszy, MD; and Ali A. Ehsani, MD

Background. The relative contributions of decreases in maximal heart rate, stroke volume, and oxygen
extraction and of changes in body weight and composition to the age-related decline in maximal oxygen
uptake (Vo2max) are unclear and may be influenced by sex and level of physical activity.
Methods and Results. To investigate mechanisms by which aging, sex, and physical activity influence
Vo2max, we quantified Vo2, cardiac output, and heart rate during submaximal and maximal treadmill
exercise and assessed weight and fat-free mass in healthy younger and older sedentary and endurance
exercise-trained men and women. For results expressed in milliliters per kilogram per minute, a
three-to-four-decade greater age was associated with a 40-41% lower Vo2max in sedentary subjects and
a 25-32% lower Vo2max in trained individuals (p<0.001). A smaller stroke volume accounted for nearly
50%o of these age-related differences, and the remainder was explained by a lower maximal heart rate and
reduced oxygen extraction (allp< 0.001). Age-related effects on maximal heart rate and oxygen extraction
were attenuated in trained subjects (p<0.05). After normalization of Vo2max and maximal cardiac output
to fat-free mass, age- and training-related differences were reduced by 24-47% but remained significant
(p<O.OS). For trained but not sedentary subjects, maximal cardiac output and stroke volume normalized
to fat-free mass were greater in men than in women (p<O.OS).
Conclusions. A lower stroke volume, heart rate, and arteriovenous oxygen difference at maximal exercise
all contribute to the age-related decline in Vo2max. Effects of age and training on Vo2max, maximal
cardiac output, and stroke volume cannot be fully explained by differences in body composition. In
sedentary subjects, however, the sex difference in maximal cardiac output and stroke volume can be
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accounted for by the greater percentage of body fat in women than in men. (Circulation 1992;86:494-503)
KEY WoRDs * body composition * cardiac output * maximal oxygen consumption * stroke
volume

M aximal oxygen uptake (Vo2max) declines with
age.'-6 Although the rate of this decline is
estimated to be =10% per decade in seden-
tary subjects,1-4 some investigators have reported that
neither stroke volume nor maximal cardiac output de-
creases with advancing age,78 and others have found no
evidence of reduced oxygen extraction in older versus
younger individuals.9 Thus, the role of a lower stroke
volume and arteriovenous oxygen difference in explain-
ing the age-related decline in Vo2max is controver-
sial.6-14 The discordant results of previous studies may
be related, in part, to differences in sex, level of physical
activity, weight, and body composition of the sub-
jects.13-'6 Therefore, it is important to characterize the
effect of age on physiological responses to exercise in
From the Section of Applied Physiology, Department of Med-
icine, and the Irene Walter Johnson Institute of Rehabilitation,
Washington University School of Medicine, St. Louis, Mo.
Supported by Program Project grant AG-05562 and by grant
RR-00036 to the General Clinical Research Center. R.J.S. was
supported by Institutional National Research Service Award
AG-00078, W.H.M. by National Heart, Lung, and Blood Institute
(NHLBI) grant HL-41290, and W.M.K. by NHLBI grant
HL-07456.
Address for reprints: Wade Martin, MD, Washington University
School of Medicine, Department of Medicine, 4566 Scott Avenue,
Campus Box 8113, St. Louis, MO 63110.
Received January 16, 1992; revision accepted May 6, 1992.
the context of these factors. To investigate the mecha-
nism of the age-related decline in exercise capacity, we
measured oxygen uptake, cardiac output, heart rate,
and other cardiovascular responses to submaximal and
maximal treadmill exercise in healthy sedentary and
endurance exercise-trained younger and older men and
women. To delineate the extent to which age-related
effects on exercise capacity, maximal cardiac output,
and stroke volume may be accounted for by differences
in body composition, we estimated fat-free mass in the
same individuals from measurements of body weight
and density. Age-related differences in Vo2max, maxi-
mal heart rate, stroke volume, and arteriovenous oxygen
difference were quantified in subjects of the same sex
and training status and, when appropriate, were ex-
pressed in relation to both weight and fat-free mass.
Methods
Subjects
We studied 110 healthy subjects. Participants were
categorized on the basis of age, sex, and training status
into the following eight groups: 14 sedentary men aged
27±3 years (mean±SD), 13 sedentary men aged 63±3
years, 14 sedentary women aged 23±2 years, 14 seden-
tary women aged 64±4 years, 15 trained men aged
28±3 years, 14 trained men aged 63±4 years, 13 trained
women aged 26±3 years, and 13 trained women aged
 Ogawa et al Aging and Cardiovascular Responses to Exercise
57±3 years. The older group of exercising women was
younger than the comparable groups of older trained
men and sedentary women because we could find only
three women aged 60-70 years whose training volume
and intensity approached those of the trained groups of
older men and younger women.
All subjects were healthy nonsmokers and had a
resting blood pressure .140/90 mm Hg. The physical
examination and resting ECG were within normal lim-
its, and a maximal treadmill exercise ECG was without
evidence of cardiovascular disease by criteria described
below. No subjects took regular medications except five
women treated with estrogen and/or progesterone
replacements.
Sedentary subjects were normally active but did not
engage in regular exercise. Approximately 20% of the
older individuals were employed, but none had occupa-
tions requiring strenuous exertion. Young sedentary
subjects were students or were employed at jobs that did
not involve more than light activity. All four groups of
trained subjects were composed of individuals who had
been exercising strenuously for at least 30 minutes three
or four times per week for several years.
Exercise Stress Testing
Older subjects were evaluated for clinical evidence of
cardiovascular disease with a maximal treadmill exercise
test. Immediately before the test, a 12-lead ECG was
recorded and supine blood pressure was determined.
The exercise test was conducted with the Bruce proto-
col17 and had an end point of exhaustion as described
previously.18 Criteria for exclusion from the study were
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as follows: symptoms of chest discomfort consistent with
angina, cardiac dysrhythmias more severe than occa-
sional atrial or ventricular premature contractions, flat
or downsloping ST segment depression .0.1 mV, and
an abnormal blood pressure response to exercise de-
fined as a decrease in systolic pressure to a value 20
mm Hg or more below that in any preceding stage.
Maximal Oxygen Uptake
Several days after completion of the exercise stress
test, maximal oxygen uptake (Vo2max) was quantified
by respiratory gas analysis during treadmill exercise. An
automated on-line system was used to measure oxygen
uptake (Vo2) and carbon dioxide production every 30
seconds. A progressive incremental protocol 5-12 min-
utes in duration having an end point of exhaustion was
selected to measure maximal oxygen uptake as de-
scribed previously.18 Maximal oxygen uptake was de-
fined by leveling off of oxygen uptake despite a further
increment in exercise work rate or by the attainment of
a respiratory exchange ratio >1.1. Data for Vo2max
were expressed in liters per minute, milliliters per
kilogram per minute, and milliliters per kilogram fat-
free mass per minute.
Body Composition
Fat-free mass was estimated from measurements of
body weight and density. The hydrostatic weighing
procedure used to determine body density has been
described in detail previously.19 Percent body fat was
calculated with the equation recommended by Brozek
et al.20
495
Cardiac Output
Cardiac output was measured after 15 minutes of
seated rest and during submaximal and maximal tread-
mill exercise with the acetylene (C2H2) rebreathing
technique as described previously.21 Resting trials were
conducted in triplicate, and the results were averaged.
Subjects then completed two separate 4-6-minute
bouts of walking or running at 50% of Vo2max followed
by two sessions of similar duration at 75% of Vo2max
and a final 4-6-minute bout of progressively more
intense work that elicited Vo2max in the last 60-90
seconds of exercise. Individual trials of resting and
exercise cardiac output were separated by 10-minute
intervals to permit washout of C2H2 from the body.
During each exercise trial, oxygen uptake was moni-
tored every 30 seconds, and cardiac output and blood
pressure were determined in the final 60 seconds while
an ECG was recorded simultaneously. Results of the
two exercise trials at the same submaximal work rate
were averaged. The test-retest correlation for duplicate
measurements of cardiac output at the same work rate
was 0.97 in both younger and older people. Heart rate
was determined from three consecutive sinus beats of
the ECG. Stroke volume, arteriovenous oxygen differ-
ence, mean blood pressure, total peripheral resistance,
and left ventricular stroke work were derived using
standard formulas.22
Statistics
Data were analyzed with the SAS package as imple-
mented on the SUN computer system of the Division of
Biostatistics of Washington University. ANOVA was
used to determine whether age, sex, and training status
had independent or interacting effects on physiological
variables. Differences between specific subject groups
were evaluated with Student's t tests. Means were
considered significantly different at p<0.05. Data are
expressed as mean±+SD.
Results
Effect ofAge
Vo2max, unadjusted for differences in weight and
fat-free mass among subject groups, was 28-37% lower
in older than in younger subjects (p<0.001) (Table 1).
Figures show relations between oxygen uptake, ex-
pressed in liters per minute, and cardiac output (Figure
1), the arteriovenous oxygen difference (Figure 2), heart
rate (Figure 3), and stroke volume (Figure 4) at rest and
during submaximal and maximal exercise. Table 2 shows
the data for measurements made at maximal exercise.
Vo2max, expressed in milliliters per kilogram per
minute, was 41% lower in older than in younger seden-
tary men (p<0.001) (Table 1). This was nearly identical
to the 40% difference in Vo2max between older and
younger untrained women (p<0.001). In the trained
groups, the Vo2max of older male subjects was 25%
lower than in younger men (p<0.001), and older women
had a Vo2max 32% below that of younger female subjects
(p<0.001). For results normalized to weight, 72% of the
age-related difference in Vo2max in sedentary individu-
als was explained by a smaller maximal cardiac output
(p<0.001) (Tables 3 and 4) and the remainder by
reduced oxygen extraction (p<0.001) (Tables 2 and 4).
In trained subjects, the difference in maximal cardiac
 496 Circulation Vol 86, No 2 August 1992

TABLE 1. Anthropometric Characteristics, Resting Heart Rate, Blood Pressure, and Exercise Capacity of Subjects
Age groups (years)
Sedentary men Trained men Sedentary women Trained women
23-31 60-68 21-31 59-72 20-27 60-72 18-30 51-63
Height (cm) 176.8+7.7 176.5+5.8 179.6+5.2 173.4+6.4* 164.5±6.5k 164.5±8.3# 166.6±6.2* 164.6±6.2#
Weight (kg) 75.3±11.8 83.4±11.5 68.4±8.4 65.9±6.7§ 57.7±9.2# 66.9±14.6** 55.4±6.7# 59.4+5.8**
Body surface area (n2) 1.83+0.14 1.91+0.15 1.79±0.11 1.70+0.11*§ 1.54±0.13# 1.65±0.19** 1.55±0.11# 1.57±0.10**
Fat (%) 17.1+7.1 28.9±5.8* 9.4±2.8§ 17.5±3.7*§ 21.7±6.7 36.0±6.3*,** 17.1+4.51# 25.3±5.7§#
Fat-free mass (kg) 61.9+6.4 59.0±7.5 61.9±6.7 54.3±6.1t 44.9+5.9# 42.2±6.7# 45.9+5.5# 44.0±4.1#
Resting heart rate (bpm) 72+13 75±10 61±911 60±7§ 81±12 77±10 66±1311 70±13tt
Resting BP (mm Hg)
Systolic 113±13 120±10 115±9 122±12 93±6# 117±18* 103±8f# 114±15l
Diastolic 78±8 76±8 74±8 77±11 61±8# 74±8* 68±5litt 73±10
Vo2max (1/min) 3.41±0.39 2.24±0.33* 4.35±0.53§ 3.14±0.43*§ 2.13±0.35# 1.46±0.24*# 2.89+0.37f# 2.09±0.19*§*
Vo2max (ml/kg/min) 45.9±6.1 27.2+5.1* 63.5±4.4§ 47.6±4.3*§ 37.0+4.3# 22.2±3.1*,** 52.1±3.1f* 35.3±3.3*§#
Vo2max (ml/kg fat-free
mass/min) 55.2±6.0 38.0±4.8* 70.3±4.9§ 58.0±6.2*§ 47.3±4.7# 34.8±3.0*tt 63.0±5.2*# 48.9±4.2*5#
bpm, Beats per minute; BP, blood pressure. Values are mean±SD.
*p<0.001; tp<0.01; tp<0.05 vs. younger subjects of the same sex and training status.
§p<0.001; lp<0.01; lp<0.05 vs. sedentary subjects of the same sex and similar age.
#p<0.001; **p<O.0l; ttp<0.05 vs. men of similar age and training status.
output between younger and older individuals was also trained individuals (Tables 2 and 4) and about 40% of it
responsible for most (81-89%) of the age-related effect in sedentary subjects.
on Vo2max. A lower maximal heart rate in older persons The highest values for stroke volume were attained at
(p<O.OOl) accounted for only 26-30% of the difference 50% of Vo2max, and a decrease in stroke volume
in maximal cardiac output between younger and older
18 r
32 r
15
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66 ,+6
0
0 1 2 3 4 0 1 2
VO2 (Lmin ) V02 (Lmin
FIGURE 1. Graphs showing cardiac output at rest and
during submaximal and maximal treadmill exercise in younger
and older sedentary men, trained men, sedentary women, and
trained women. Statistically significant differences are desig-
nated for corresponding values at rest and during maximal
exercise. * p<0.001 and * * * p <0. 05 vs. younger subjects of the
same sex and training status. + p<0.001 and + + p<0.01 vs.
sedentary subjects ofsimilar age and the same sex. 8p <0.001
and 58p<0.01 vs. men of similar age and training status.
V
0 1 2 3 4 0 1 2 3 4 5
3 4 5 V02 (L.mln -1) V02 (L'mIn')
)
FIGURE 2. Graphs showing arteriovenous oxygen difference
(AVO2D) at rest and during submaximal and maximal tread-
mill exercise in younger and older sedentary men, trained
men, sedentary women, and trained women. Statistically
significant differences are designated for corresponding values
at rest and during maximal exercise. *p<0.001, **p<0.01,
and ***p<0.05 vs. younger subjects of the same sex and
training status. +p<O.001 and + + +p<O.05 vs. sedentary
subjects of similar age and the same sex. 8p<0.001 and
85p<0.01 vs. men of similar age and training status.
 Ogawa et al Aging and Cardiovascular Responses to Exercise 497

200
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VO2 WLmin 1) VO2 (L.mln ) 0 1 2 3 4 0 1 2 3 4 5

FIGURE 3. Graphs showing heart rate at rest and during
submaximal and maximal treadmill exercise in younger and
older sedentary men, trained men, sedentary women, and
trained women. Statisticall significant differences are desig-
nated for corresponding values at rest and during maJcmal
ex>ercise. *p<0.001 vs. younger subjects of the same sex and
training status. +p<0.001, ++p<0.01, +++p<0.05 vs.
sedentary subjects of similar age and the same sex, and
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VO2 (Lmin -') VO2 (L.min )
FIGURE 4. Graphs showing stroke volume at rest and during
submaximal and maximal treadmill exercise in younger and
older sedentary men, trained men, sedentary women, and
trained women. Statistically significant differences are desig-
nated for corresponding values at rest and at each level of
submaximal or maximal exercise. *p<0.001, **p<O.Ol, and
* * * p<0.05 vs. younger subjects of the same sex and training

b88p<0. 05 vs. men of similar age and training status.
Occurred between 50% and 100% of maximal effort
(p<0.05), in all groups of subjects (Figure 4). Never-
theless, stroke volume was higher at maximal exercise
than at rest (p<0.05) in every group except older
sedentary women. For results normalized to weight, a
smaller stroke volume in older versus younger persons
(p<0.01) explained the largest proportion of the aver-
age age-related difference in both'V02max and maximal
cardiac output (53% and 66%, respectively) (Tables 3
and 4). The average effect of age on maximal heart rate,
stroke volume, and the arteriovenous oxygen difference
was similar in men and women. However, age-related
differences in both maximal heart rate and oxygen
extraction were smaller (p <0.001 and p <0.05, respec-
tively) in trained than in untrained individuals.
Effect of Training Status
'V02max, expressed in milliliters per kilogram per
minute, was 38% greater in physically conditioned than
in sedentary young men (p<0.001), which is similar to
the 41% difference between trained and untrained
young women (p<50.001). In older subjects, however,
the difference in V02max between exercising and sed-
entary individuals (p<0.001) was 75% for men and
59% for women. The higher exercise capacity in physi-
cally conditioned subjects was related primarily to a
larger maxmal cardiac output (p<0.001), particularly
in men, in whom it explained 88-99% of the effect of
training status on mo2max. In women, the higher maxi-
mal cardiac output in the trained group (p <0.001)
status. + p <0. 001 and + + p <0. 01 vs. sedentary subjects of
similar age and the same sex. 8p<0.001 and 58p<0.01 vs.
men of similar age and training status.
accounted for only :65% of the difference in Vo2max
between conditioned and sedentary subjects. Regard-
less of age or sex, the effect of training status on
maximal cardiac output was explained by a larger stroke
volume in the physically conditioned groups (p<0.001).
Thus, the effect of training status on stroke volume was
greater in men than in women (p<0.05). Training was
associated with a lower maximal heart rate in younger
(p<0.001) but not older people (Table 2).
Effect of Sex
Men were taller and heavier than women (p<0.01),
but even after normalization of results to weight,
Vo2max was higher (p<0.001) in male than in female
subjects (Table 1). For younger individuals, the sex
difference in Vo2max, expressed in milliliters per kilo-
gram per minute, was similar in the trained (22%) and
untrained (24%) groups. In older individuals, however,
the sex difference averaged 23% in sedentary subjects
and 35% in those who exercised. For results normalized
to weight, a larger maximal cardiac output in men
(p<0.001) explained less than 40% of the sex difference
in Vo2max of sedentary subjects but 86-95% of it in
physically conditioned individuals (Table 3). Maximal
heart rate was similar in men and women, regardless of
training status or age. Thus, a sex difference in stroke
volume (p<0.001) was responsible for virtually all of
the effect of sex on maximal cardiac output.
 498 Circulation Vol 86, No 2 August 1992
TABLE 2. Effects of Age, Sex, and Training Status on Cardiac Output, Heart Rate, Stroke Volume, Stroke Work, and Arteriovenous
Oxygen Difference at Maximal Exercise
Age groups (years)
Sedentary men Trained men Sedentary women Trained women
23-31 60-68 21-31 59-72 20-27 60-72 18-30 51-63
Cardiac output (I/min) 21.2+2.4 16.3±2.5* 27.4±3.2§ 20.5±2.1*§ 15.2±2.7# 11.9±1.7*# 18.4±2.0§# 14.3±1.5*§#
Heart rate (bpm) 185±9 163±15* 178±t6l 165+9* 189±5 162±10* 181±911 167±9*
Stroke volume (ml) 115±16 101 ± 19* 154+20§ 124± 14*§ 80± 12# 74 ±8t* 102± 12§# 85±9*§#
Stroke work (g m) 161±33 161±34 215±36§ 188+18t¶W 100±16# 117±21*# 128±19§# 120±16#
Arteriovenous 02
difference (ml/100 ml) 15.4±1.4 13.6±1.1* 15.5±1.0 14.7±1.4f 13.5±1.0# 11.9±1.6t** 15.0±1.0§ 14.5±1.1§
bpm, Beats per minute. Values are mean+SD.
*p<.OOJl; tp<0.Ol; *p<O.OS vs. young subjects of the same sex and training status.
§p<0.001; lp<0.01; lp<0.o5 vs. sedentary subjects of the same sex and similar age.
#p<O.OOl; **p<0.01 vs. men of similar age and training status.

Body Composition and Age-Related Effects
Older subjects were not as lean (p<0.001) and
tended to be heavier than younger individuals of the
same sex and training status (Table 1). Normalization of
results to fat-free mass rather than weight reduced the
average difference in Vo2max between younger and
older subjects from 34% to 24% (Table 1). Thus, nearly
one third of the age-related effect on maximal exercise
capacity can be explained by the larger adipose tissue
mass in the older group.
For maximal cardiac output expressed in liters per
minute or milliliters per kilogram per minute, the
difference between groups of younger and older indi-
viduals of corresponding sex and training status ranged
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younger and older groups averaged 19% (range, 17-
22%) (p<0.001) for results normalized to weight but
was no longer present in sedentary subjects and was
reduced to 9-13% in trained individuals after normal-
ization to fat-free mass (p<0.001) (Table 3).
Body Composition and Training Status Effects
Physically conditioned individuals tended to weigh
less and were significantly leaner (p<0.001) than their
sedentary counterparts (Table 1). The 38-75% differ-
ence in maximal oxygen uptake between groups of
trained and untrained subjects was reduced by nearly
one third but remained highly significant (p<0.001)
after data were normalized to fat-free mass (Table 1).

from 22% to 30% (p<0.001) (Tables 2-4). However,
normalization of results to fat-free mass (Table 3)
reduced the average magnitude of the age-related effect
to only 17% (range, 16-20%) (p<0.001), suggesting
that up to one third of the difference between younger
and older people may be a result of the greater adipos-
ity of the older individuals.
Stroke volume, unadjusted for weight or body com-
position, was an average of 14% smaller (range, 8-20%)
in older than in younger subjects at maximal exercise
(p<0.01) (Table 2). The difference between the
For maximal cardiac output, the average difference
between groups of physically conditioned and sedentary
subjects was 39% (range, 26-57%) for results normal-
ized to weight (p<0.001) (Table 3) but only 25%
(range, 14-37%) for data expressed in milliliters per
kilogram fat-free mass per minute (p<0.01) (Table 3).
Exercise training was associated with a 40% larger
stroke volume per kilogram of body weight (range,
27-53%) than was found in sedentary subjects
(p<O.OOl). Expression of results in terms of fat-free
mass reduced the average difference to 25% (range,

TABLE 3. Effects of Age, Sex, and Training Status on Cardiac Output, Stroke Volume, and Stroke Work at Maximal Exercise With
Results Expressed in Terms of Weight and Fat-Free Mass
Age groups (years)
Sedentary men Trained men Sedentary women Trained women
23-31 60-68 21-31 59-72 20-27 60-72 18-30 51-63
Cardiac output
(ml/kg/min) 282+48 199±38* 401 +29§ 312+34*§ 263 ±30 183±29* 332±22§# 242±33*§#
Stroke volume (ml/kg) 1.53+0.26 1.22±0.22* 2.25+0.17§ 1.87±0.20*§ 1.39±0.16 1.14±0.21t 1.85±0.16§# 1.45±+0.21*fO
Stroke work (g in/kg) 2.14+0.41 1.93±0.27 3.14+0.49§ 2.86+0.33§ 1.73±0.2 4** 1.81±0.26 2.32±0.290# 2.03±0.32*1#
Cardiac output
(ml/kg fat-free mass/min) 344±45 277±35* 443+30§ 380±46*§ 340±27 285±32* 403±30§** 326±33*1I**
Stroke volume
(ml/kg fat-free mass) 1.86+0.23 1.71±0.22 2.50+0.20§ 2.27±0.26*5 1.82+0.16 1.79±0.27 2.25±0.20§** 1.95+0.24*¶**
Stroke work
(g. m/kg fat-free mass) 2.61±0.45 2.72+0.32 3.48+0.49§ 3.47±0.4311 2.24±0.22** 2.85+±0.50* 2.81 ±0.39§# 2.73±0.27#
Values are mean+SD.
*p<0.fO1; tp<O.0l; *p<0.05 vs. younger subjects of the same sex and training status.
§p<0.001; lp<O.O1; 1p<0.05 vs. sedentary subjects of the same sex and similar age.
#p<0.001; **p<O.0l vs. men of similar age and training status.
 Ogawa et al Aging and Cardiovascular Responses to Exercise 499

TABLE 4. Effect of Age on Determinants of Maximal Oxygen Uptake (Vo2max) and Cardiac Output (Q)
Sedentary men Trained men Sedentary women Trained women
Cardiac output
% A age -29.4 -22.2 -30.4 -27.1
% A Vo2max 71.5 81.0 71.9 89.1
Arteriovenous oxygen difference*
% A age -11.7 -5.2 -11.9 -3.3
% A Vo2max 28.5 19.0 28.1 10.9
Maximal heart rate
% A age -11.9 -7.3 -14.3 -7.7
% 'A Vo2max 27.1 24.8 32.4 23.6
%AQ 37.0 30.2 44.3 26.3
Stroke volume
% A age -20.3 -16.9 -18.0 -21.6
% A1 Vo2max 46.2 57.5 40.7 66.3
% AQ 63.0 69.8 55.7 73.7
Cardiac output is expressed in milliliters per kilogram per minute. For physiological variables, the percent difference
between younger and older subjects of corresponding sex and training status is given on the first line (% A age), and
the percent contribution of the same variable to age-related differences in maximal oxygen uptake and cardiac output
is given on the second and third lines (% A Vo2max and % A Q, respectively).
*The percent contribution of the arteriovenous oxygen difference is given relative to cardiac output. Therefore, the
sum of contributions of arteriovenous oxygen difference, maximal heart rate, and stroke volume to age-related
differences in Vo2max slightly exceeds 100%.

9-34%) (p<O.OO1). However, the magnitude of the

training status effect was sex-dependent (50% in men
versus 30% in women [p<0.05] for results normalized 230

to weight and 34% in men versus 16% in women 200

[p<0.05] for results normalized to fat-free mass). Fur- E
E
thermore, the effect of training status on stroke volume 170
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normalized to fat-free mass was greater in younger than 0 140

in older women (24% versus 9%; p<O.05), but an
age-training status interaction was not observed in m
110

male subjects (34% versus 33%; NS). s0

Body Composition and Sex-Related Effects 50

Vo2max, expressed in milliliters per kilogram per
minute, was 22-35% greater (p<0.01 to p<O.OO1) in 230
male than in female subjects (Table 1). Normalization :C 200
of results to fat-free mass eliminated nearly 50% of this E
***+++6
E
sex difference, but Vo2max remained ~=15% higher 170 T 1 ..-
(range, 9-19%) in men than in women (p<0.05 to
p<O.OOl) (Table 1). Maximal cardiac output, expressed 0
140 ' I - A X .;x - 5
j
110
in milliliters per kilogram per minute, was 7-22% , --- 4s-i-..
greater in men than in women (p<O.OO1) (Table 3). 0, 80
However, the average sex difference was more than so
twice as large in trained as in untrained subjects (22% X,. 1 T .
versus 8%; p<0.05). Expression of maximal cardiac REST 25 50 75 100 REST 25 50 75 100
output in terms of fat-free mass (Table 3) eliminated IVO2max %VO2max
the sex effect entirely in the sedentary groups, but a
10-17% difference between men and women remained FIGURE 5. Graphs showing systolic and diastolic blood
in trained individuals (p<O.OO1). The findings for pressure at rest and during exercise at 50%o, 75%, and 100%
stroke volume at maximal exercise (Tables 2 and 3) of Voynax in younger and older sedentary men, trained men,
were very similar to those for maximal cardiac output. sedentary women, and trained women. Statistically significant
differences are designated for corresponding values at rest and
Blood Pressure and Total Peripheral Resistance at each level of submaximal or maximal exercise. Oxygen
The smaller exercise stroke volume in older versus uptake at each data point is shown in preceding figures.
younger subjects was associated with higher values for * p < 0. 001, * * p < 0. 01, and * * * p <0 05 vs. younger subjects of
blood pressure and total peripheral resistance (p<0.05 the same sex and training status. + p0. 001, + +p.<0.01, and
to p<O.OO1) (Figures 5 and 6) regardless of sex or + + +p<0.c05 vs. sedentary subjects of similar age and the
training status. However, the age-related effect on sys- same sex. Op < 0. 001, &Sp < 0. 01, and b8&p < 0. 05 vs. men of
tolic pressure during exercise of similar relative inten- similar age and training status.
 500 Circulation Vol 86, No 2 August 1992

1800
SEDENTARY MEN TRAINED MEN
age because of the higher blood pressure in older
O YOUNGER
individuals. Exercise stroke work was greater in all
1500

I groups of physically conditioned than in sedentary

0
* OLDER

U
m
G!
c
0.
1200

900
I subjects except older women (p<0.05 top<0.001). Men
had higher stroke work values at maximal exercise than
women (p<0.001) regardless of age or training status.
T4++
More than half of this sex difference was accounted for
600 by the greater weight of men. After normalization of
results to fat-free mass, a sex effect was no longer
300 1 present in older sedentary people, but in trained indi-
viduals and younger sedentary subjects, stroke work at
0 maximal exercise was =20% greater in men than in
180 women (p<0.01).
SEDENTARY WOMEN TRAINED WOMEN
150
In

0
Discussion
Ui
to
120 TT . d Our findings provide evidence that the decline in
E
c

90
Vo2max with age is related primarily to a lower maximal
cardiac output. Although a slower maximal heart rate
60 accounts for a portion of this effect, a smaller stroke
° L
dd
volume is of greater importance. These results are in
df \ +*ed
30 agreement with the data of Julius et al0 showing that
v I,,,,,,,, , stroke volume during heavy treadmill exercise is smaller in
0 1 2 3 4 0 1 2 3 4 5
sedentary subjects in their sixth or seventh decade than in
V02 (L-min t) VOz (L.min 1) those aged 18-34 years. Our data are also consistent with
FIGURE 6. Graphs showing total peripheral resistance the findings of Port et al23 that left ventricular ejection
(TPR) at rest and during exercise in younger and older fraction is lower in older individuals than in younger
sedentary men, trained men, sedentary women, and trained persons during peak cycle ergometer exercise. In contrast,
Becklake et al7 observed that stroke volume is higher in
women. Statistically significant differences are designated for
older than in younger men during peak cycle ergometer
corresponding values at rest and at each level of submaximal work, but they found no effect of age on exercise stroke
or maximal exercise. *p<0.001, **p<0.0J, and ***p<0.05 volume in women. Even more surprisingly, Rodeheffer et
vs. younger subjects of the same sex and training status. a18 reported that peak cardiac output during cycle ergom-
+ p<O.OOJ and + + p<O.OJ vs. sedentary subjects of similar
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eter exercise does not decrease with age. In the latter

age and the same sex. 8p<O.OOJ, 88p<O.OJ, and 83&p<0.05
vs. men of similar age and training status.
sity was greater in women than in men (p<0.05). At
maximal exercise, there was a less pronounced effect of
age on total peripheral resistance in trained than in
sedentary subjects (p<0.05).
Blood pressure at a similar relative work rate was not
significantly influenced by training status except in
women during heavy exercise. Younger trained women
had a higher systolic pressure at maximal effort than
their sedentary peers (p<0.05), whereas older trained
women had a lower blood pressure at 75% and 100% of
Vo2max than their untrained counterparts (p<0.05).
Total peripheral resistance at a given relative work rate
was lower in all groups of trained than in untrained
subjects (p<0.01).
Systolic and mean blood pressures at equivalent
relative exercise intensities were lower in young women
than in young men, regardless of training status
(p<0.05 top<0.001) (Figure 5). In older subjects, a sex
effect on blood pressure was not observed in sedentary
individuals but was evident in trained subjects at 75%
and 100% of maximal effort (women less than men;
p<0.01). Women had a higher total peripheral resis-
tance than men (p<0.05 to p<0.001) at all levels of
exercise (Figure 6).
Stroke Work
Unlike stroke volume, stroke work at maximal exer-
cise (Tables 2 and 3) was not consistently influenced by
study, a larger left ventricular end-diastolic volume more
than compensated for the lower left ventricular ejection
fraction in older individuals, and peak cardiac output
during cycle ergometer work was similar in younger and
older people. However, younger and older subjects were
not matched by sex or level of physical activity, both of
which have significant effects on left ventricular end-dia-
stolic volume, stroke volume, and cardiac output during
exercise.13-15,22 In addition, a number of the older subjects
in the Rodeheffer study had an elevated resting systolic
blood pressure, which possibly explained their greater left
ventricular end-diastolic volume. Finally, oxygen uptake
was not measured in the latter investigation, although the
peak power output was lower in the older group. Thus, it
is likely that Vo2max was also reduced in these older
individuals. Multiple investigations, including the current
one, indicate that differences in Vo2max between 25- and
65-year-old sedentary subjects of the same sex are approx-
imately 40%.134 If maximal cardiac output is not influ-
enced by age, then the arteriovenous oxygen difference
at maximal exercise also would have to be 40% lower in
older individuals to account for their 40% lower Vo2max.
A 40% decrease in arteriovenous oxygen difference from
values of 15-16 ml/100 ml blood typically observed in
young healthy subjects at peak exercise14,24 would result
in a peak arteriovenous oxygen difference of 9-10 ml/100
ml blood in older individuals under these conditions.
Such values are well below those actually found in even
the most sedentary older persons.10"',4 Our data are
well within normal physiological ranges reported in other
investigations in which a variety of techniques were
employed.'-4,11-14,22,24
 Ogawa et al Aging and Cardiovascular Responses to Exercise
The magnitude of age-related effects on Vo2max,
maximal cardiac output, and stroke volume was greatest
for data normalized to weight and least for results
expressed in terms of fat-free mass. Because the capac-
ity for high-intensity, weight-bearing exercise is thought
to be most closely approximated by Vo2max expressed
in milliliters per kilogram per minute, these data suggest
that a significant portion of the difference in maximal
exercise responses between younger and older subjects
can be attributed to the larger mass of adipose tissue in
the latter group. Even after normalization of results to
fat-free mass, however, Vo2max, maximal cardiac out-
put, and stroke volume were an average of 24%, 17%,
and 8% lower, respectively, in older than in younger
individuals. These findings provide clear evidence that
age-related effects on cardiovascular function during
maximal exercise cannot be explained entirely by differ-
ences in body composition and weight.
The smaller stroke volume observed in older subjects
at maximal exercise was associated with a higher mean
blood pressure in women and sedentary men. For these
groups, stroke work in the older subjects was equal to or
greater than that in younger individuals. Thus, part of
the cardiac volume work performed in younger subjects
during exercise was replaced by pressure work in these
older persons. Left ventricular wall thickness and mus-
cle mass increase with age,2526 and left ventricular
hypertrophy is more prevalent in older than in younger
subjects.27 In addition, left ventricular mass is reported
to be more closely related to exercise than to resting
blood pressure.28 A greater left ventricular mass may be
an adaptive response to the larger proportion of cardiac
energy expended as pressure work during exercise and
Downloaded from http://ahajournals.org by on June 15, 2021
other forms of stress in older individuals. The latter
effect has been attributed, in part, to higher aortic
characteristic impedance.29
In the present investigation, the arteriovenous oxygen
difference at maximal exercise was lower in older than
in younger sedentary subjects. These results are consis-
tent with the findings of Julius et al10 and Hossack et
al.14 The absence of a smaller arteriovenous oxygen
difference in our older trained subjects suggests that the
age-related effect in sedentary individuals may be a
consequence of decreased physical activity. This possi-
bility is supported by recent data from our laboratory
indicating that skeletal muscle oxidative capacity and
capillary density are lower in older than in younger
sedentary subjects30 but are not different in younger and
older trained individuals.31 Other potential mechanisms
of an age-related decrease in arteriovenous oxygen
difference in sedentary individuals at maximal exercise
include a decline in absolute or relative blood flow to
active skeletal muscle and a smaller ratio of skeletal
muscle to total body mass.9'16
In the current investigation, the estimated rate of
decline in Vo2max between the ages of 25 and 65 years
was about 40% slower in trained than in sedentary male
subjects (7.1% versus 11.3% per decade). Although this
difference only approached statistical significance, it is
likely to be physiologically important and is consistent
with results of earlier studies in which the age-related
decline in Vo2max was only half as great in trained men
as in their sedentary peers.313'32 The latter effect was
explained by the absence of an age-related decline in
stroke volume in the physically conditioned group.13 In
501
contrast, the current investigation demonstrates that
stroke volume at maximal exercise is lower in older than
in younger trained men. The most likely explanation for
this discrepancy is that the present group of 63-year-old
men was several years older and exercised less strenu-
ously and frequently than the competitive master ath-
letes studied earlier. Support for this explanation is
provided by the fact that the Vo2max of the current
group was nearly 20% below that of the subjects in the
previous studies.313 However, we cannot rule out the
possibility that the dissimilar stroke volume results are
caused by a difference in techniques used to measure
cardiac output. In the current investigation, cardiac
output was measured at maximal exercise by the acety-
lene rebreathing technique. In the earlier studies, stroke
volume at maximal exercise was estimated from deter-
minations of cardiac output made during submaximal
work by the CO2 rebreathing technique. The present
stroke volume results are consistent with data of Rivera
et a16 obtained by the acetylene rebreathing technique
to measure cardiac output in a group of runners similar
in age and Vo2max to the older trained participants in
the current investigation.
Stroke volume and cardiac output at maximal exercise
were lower in women than in men, even after normal-
ization to weight. Normalization of results to fat-free
mass eliminated the sex difference entirely in sedentary
subjects and substantially reduced it in trained individ-
uals. Thus, the sex difference is largely a result of the
greater percentage of body fat in women. However,
there were sex differences in mechanisms by which
exercise capacity was enhanced in conditioned versus
sedentary subjects. Training status had a larger effect on
stroke volume and maximal cardiac output but a smaller
effect on maximal arteriovenous oxygen difference in
men than in women. Sex differences in the nature and
magnitude of adaptations to training were particularly
evident in older subjects. These findings are consistent
with data of Scheuer et a133 and Schaible et a134 that sex
and sex hormones may influence cardiac function and
the nature of training-induced cardiac adaptations in
rats.
Hossack et al14 found that age-related differences in
maximal oxygen uptake, cardiac output, and heart rate
were greater in men than in women. Our results are
consistent with these data if absolute differences in
Vo2max and maximal cardiac output are compared.
However, younger men had higher values for Vo2max
and maximal cardiac output than younger women. In
percentage terms, there was no significant effect of sex
on age-related differences in exercise capacity, maximal
heart rate, or stroke volume. Nevertheless, we observed
a larger decrease in stroke volume as exercise intensity
was increased from 50% to 100% of Vo2max in older
sedentary women than in the other groups of subjects.
There was also a greater influence of age on exercise
blood pressure of women than men regardless of
whether absolute or percentage changes were com-
pared. Studies from other laboratories indicate that the
prevalence of left ventricular hypertrophy is greater in
older women than in older men.27 Recent data from our
laboratory suggest that the age-related increase in ex-
ercise blood pressure of women may be partly a conse-
quence of estrogen deficiency.18
 502 Circulation Vol 86, No 2 August 1992
Limitations
We cannot rule out the possibility that the cross-
sectional design of this study may have introduced
selection bias. The potential for this confounding effect
is likely to be greatest in older subjects because cardio-
vascular and other forms of chronic disease are present
in more than 50% of such individuals.35'36 Although the
inadvertent selection of older subjects with cardiovas-
cular disease could spuriously enhance the magnitude of
effects attributed to aging per se, a number of precau-
tions were taken to minimize this possibility. Smokers
and subjects with a resting blood pressure above 140/90
were specifically excluded. Signs or symptoms of cardio-
vascular disease identified by medical history, physical
examination, or maximal exercise testing were also
criteria for exclusion. Approximately 30% of older
sedentary subjects screened during the 2-year recruit-
ment period for this study were excluded for these
reasons. Because only healthy individuals were re-
cruited, few subjects with symptoms of cardiovascular
disease volunteered to participate. Thus, the total per-
centage of potential participants who either did not
volunteer or were excluded during the screening process
is likely to approach the more than 50% of individuals in
this age group expected to have cardiovascular disease.
It is conceivable that some older subjects, particularly
those in the trained groups, were genetically endowed
with superior health or cardiovascular function that
would tend to minimize the observed effects of aging.
However, the difference in Vo2max values of younger
and older subjects of the same sex and training status is
similar to that reported in a number of previous inves-
Downloaded from http://ahajournals.org by on June 15, 2021
tigations.1-4.6.14 Therefore, there is no good evidence
that our results can be attributed to selection bias.
Nevertheless, longitudinal studies continuing over sev-
eral decades will be necessary to quantify with certainty
the effect of aging on cardiovascular function during
exercise.
In summary, our results indicate that increased age is
associated with a lower Vo2max and maximal cardiac
output. Nearly half of the age-related difference in
Vo2max is explained by a smaller stroke volume and the
remainder by a lower heart rate and arteriovenous
oxygen difference at maximal exercise. The relative
magnitude of these differences is similar in men and
women. However, endurance exercise training may at-
tenuate age-related decreases in maximal heart rate and
arteriovenous oxygen difference. Age- and training-
related effects on Vo2max, maximal cardiac output, and
stroke volume cannot be fully accounted for by differ-
ences in body composition. The effect of sex can be
explained on this basis in sedentary but not trained
subjects.
Acknowledgments
We thank Sarah Jilka, Shari Clark, Kevin Kincaid, and Mary
Malley for technical assistance and Phyllis Anderson for
preparation of the typescript.
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