HEALTH PROMOTION AND AGING
"PHYSICAL EXERCISE"

andrew P. Goldberg, M.D., Associate Professor, Johns Hopkins University School of
Medicine and Francis Scott Key Medical Center, c/o General Clinical
Research Center, 4940 Eastern Ave., Baltimore, MD 21224

INTRODUCTION

Disuse invites dysfunction, while use favors function. At the most fundamental
level, use connotes viability and activity promotes productivity. Confinement to
enforced inactivity and immobility for a prolonged period of time results in
numerous undesirable physiologic changes, including a decline in cardiovascular
fitness, increase in body fat, decrease in lean body mass, loss of bone density,
increase in plasma lipids, decline jn glucose tolerance and deterioration in
cognitive-motor function, memory and mental acuity. This profile of inactivity is

similar to physiologic changes thought to occur with aging.

Aging is associated with a decline in time spent physically active - a behavior
"forced" upon many individuals due to their changing lifestyle of increased work
stresses, more family obligations and greater fatigue. It follows therefore,
that the reverse, 4 heightened degree of physical activity and fitness, may
confer protection or prevent declines in functional capacity. With aging,

regular physical activity may make it easier to participate in activities of
daily living, thereby prolonging an active, functional independent lifestyle.

Thus, for some older individuals the sequellae of physical inactivity may mimic
disease. Enforced physical activity may reverse. this process; such an outcome
would reenforce the causal relationship between reduced physical activity habits
and the declines in functional reserve capacity commonly observed with advancing

age.

RESEARCH IN GERONTOLOGY

RESEARLA in EE

Biological Aging and Declines in Functional Reserve Capacity

The empirical approach to defining the effects of aging in humans has been to
focus on time-related declines in organ function. These declines are commonly
attributed to a biological aging process; yet, closer inspection of the available
information indicates that there is a wide variance in the functional status of
individuals and that this diuversity in function increases with advancing age.
Unlike diseases which affect certain individuals, the aging process is universal
and results in gradual decline in the functional reserve capacity (defined as the
difference between basal and maximal function) of the cardiovascular, endocrine,
musculoskeletal, and other systems and changes in body composition and may be
considered a normal part of the human life experience. While it can be argued
that qualitative and quantitative differences in the organ function of older
individuals reflect heterogeneity in individual rates of aging per Sé, an
alternative hypothesis is that diversity in physiologic function is due to the
influence of extrinsic factors and diseases that covary with biological age to
affect functional reserve capacity in older humans. To what extent the rate of
decline and ability to maintain function into older age is dependent on factors
extrinsic to the aging processes is not known. Some of these extrinsic factors
may be classified as the purported lifestyle habits of physical activity, dietary
control of body weight and saturated fat consumption, and abstinence from

cigarettes and alcohol.

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The risk for declines in functional capacity of various organs with aging may be:
exaggerated and the prospects for reversal, delay or prevention of functional
loss with aging vastly underestimated. An examination of the effects of treating
disease and its consequences, maintaining regular physical activity habits, and
controlling body weight by dietary discretion on the functional reserve capacity
of the aging human being is necessary in order to understand the health-related
consequences of biological aging itself. The impact of diseases and purported
age-associated declines in physical activity increases in body weight,
indiscretions in diet, stresses of psychosocial or socioeconomic nature and
personal habits of alcohol consumption and cigarette smoking, which occur with
advancing age on the overall functional performance of the human being is
probably underestimated.

Disease and Declines in Functional Reserve Capacity with Aging

Susceptibility to disease increases with advancing age and available evidence
suggests that vulnerability to a number of chronic diseases (and subsequent
disease-related declines in function) can be attenuated by changing lifestyle
habits. For example, reducing body weight lowers risk for non-insulin dependent
or type II diabetes; a low fat, low cholesterol diet reduces risk for coronary
artery disease; smoking cessation reduces risk for lung cancer and heart attacks;
a low salt diet reduces blood pressure and risk for stroke; and avoidance of
excess sun lowers the incidence of skin cancer. There is a consistent
relationship between physical activity status and the incidence of coronary
artery disease that is comparable in magnitude to that related to serum
cholesterol, smoking >1 pack/day of cigarettes and systolic hypertension (1).
Physical exercise also is associated with a lower risk factor profile (lower
lipids, better blood pressure and glucose tolerance, elevated high density
lipoprotein cholesterol) for coronary artery disease (2). The interaction among
diseases, lifestyle variables, and putative aging makes it difficult to assess*
the effects of each of these processes on the overall functional capacity of the
aging human being unless the influence of all the factors on functional capacity
are delineated or controlled while the physiologic effects of one single process
are measured. This is not always feasible because change in one usually alters
the others, thereby limiting the ability to distinguish the physiological effects
of each process independently.

One approach to studying the effects of extrinsic variables on age-related
declines in organ function might be to first differentiate the effects of disease
from those of biological aging. To identify the effects of one disease is not
difficult when clinical signs and symptoms of other diseases are not present;
however, the effects of asymptomatic disease can be easily overlooked and may
cause substantial functional impairments. Furthermore, the effects of several
diseases on functional capacity can be synergistic.

Arteriosclerosis is the main disease process which correlates directly with
biological age, and has the greatest impact on cardiovascular function and
longterm survival in the elderly (3). Asymptomatic coronary disease was probably
responsible for the decline in the peak exercise ejection fraction below resting
levels in 72% of apparently healthy volunteers over 60 yrs of age (4). The
coexistence of wall motion abnormalities in 50% of individuals older than 70
years of age with an abnormal ejection fraction response to exercise suggests
that regional ischemia was indeed present. In contrast, during maximal cycle
exercise there was neither a decline in the ejection fraction below resting
levels nor were there regional wall motion abnormalities in normotensive older

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subjects intensively screened for coronary artery disease by exercise thallium
scintigraphy (5). This suggests that biological aging per se does not reduce
cardiac function in older individuals who are properly screen for cardiovascular
disease. Hypertensive disease also has a substantial effect on cardiac
performance by increasing arterial stiffness and pressure, pulse wave velocity
and left ventricular wall thickness, decreasing the early diastolic filling rate
and prolonging ventricular relaxation (6). There is a 25% increase in left
ventricular wall thickness and a 50% reduction an early diastolic filling rate at
rest between the third and ninth decades in clinically normotensive individuals
(7,8)3 thus, hypertension might accelerate age-related changes in cardiac
function. This would increase afterload in the aging heart, alter the pulsatile
component of external cardiac work, reduce arterial distensibility and raise
systolic arterial blood pressure, pulse wave velocity and peripheral vascular
resistance. Physical conditioning modestly lowers both systolic and diastolic
blood pressure, and reduces peripheral vascular resistance in hypertensive
middle-aged patients (9), and increases stroke volume, cardiac output and left
ventricular wall thickness without changing peripheral vascular resistance in
normotensive younger subjects (10). Whether exercise training would increase
arterial distensibility and reduce pulse wave velocity and systolic arterial
pressure in older subjects is not known; but lower pulse wave velocity and
systolic arterial pressure are common in cultures where levels of physical

activity are high and the sodium content of diets are Tow (11).

Rigorous screening for silent ischemia and hypertension at rest and by maximal
treadmill exercise testing with electrocardiography and thallium scanning (12)
can provide individuals free from coronary artery and other asymptomatic
cardiovascular disease in which to study the physiological effects of exercise
training, independent of disease, on cardiovascular and endocrine-metabolic
functions in aging man. Using these techniques the prevalence of coronary artery
disease in subjects over the age of 70 years was estimated to approach the post-
mortem finding of greater than 70% narrowing of at least one major coronary
artery in 40-60% of unselected hearts (13). Similarly, screening the older
individuals for diabetes with the glucose tolerance test by the criteria of the
National Diabetes Data Group (14,15) and for hyperlipidemia using criteria from
the Lipid Research Clinics Prevalence Study (16,17) allows detection and
exclusion of older people with generally accepted abnormalities in glucose and
lipoprotein lipid metabolism who may be at high risk for asymptomatic disease or
organ dysfunction. While disease causes demonstrable and clearly significant
impainments in functional capacity, increased physical activity by raising
aerobic capacity, lean body mass and energy level and reducing body fat can have
a substantial impact on the functional status of the aging human being.

Physical Activity and Maintenance of Functional Reserve Capacity

An emphasis on maintenance or improvement in functional capacity with advancing
age has not been a major focus of gerontologic research. A substantial amount of
information regarding the effects of aging on physiologic function is derived
from cross-sectional studies which report declines in performance among different
age groups. . In the analysis of measurements of the various functional status
within group data, there is substantial heterogeneity in the physiologic function
of individuals within the various age groups. While mean data may show a decline
in the functional reserve capacity among the elderly, there are older individuals
with either minimal or no loss, and sometimes equal or even better functional
capacity than that of the average younger person. This information has come to
the forefront in evaluating the physiologic effects of factors extrinsic to

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primary biologic aging, such as regular, intense physical activity, on functional
reserve capacity. In master athletes, individuals over the age of 50 years who
are very physically active, highly conditioned and compete regularly in athletic
events, there is minimal loss in cardiovascular function with advancing age, and
glucose tolerance, insulin sensitivity, and lipoprotein lipids are comparable to
those of younger athletes (18-21). Master athletes, and other older individuals
without specific pathologic linked losses in function commonly associated with
disease, who have maintained functional reserve capacity comparable to younger
counterparts might constitute that category of non-diseased elderly who have aged
successfully (22). This suggests there are more important determinants of health
than biological (as opposed to functional) age in disease-free older people. The
role of these extrinsic factors or lifestyle behaviors, especially physical
activity habits, as significant modulators of physiologic function in the elderly

requires further evaluation.

A profound effect of physical exercise training on cardiovascular, endocrine-
metabolic and musculoskeletal function in younger individuals is now well
recognized, and it is likely that many changes in functional reserve capacity
that have been previously attributed to an "aging process" are in part due to the
sedentary lifestyle and dietary indiscretion that accompanies advancing age. It
is not known how much of an improvement in physiological function can be expected
in response to varying levels of physical exercise in sedentary elderly subjects,
nor is it known to what extent and under what conditions medically unsupervised
physical activity can be recommended for healthy or disease-afflicted elderly.
Further investigation is needed to understand the mechanisms by which aging
affects physiologic responses to acute and long-term physical activity and to
define the roles that physical conditioning can play in the promotion and
maintenance of health and the prevention of diseases attributed to biological
aging.

The perspective gained in this area of gerontologic investigation will be limited
if only cross-sectional data are examined, especially when all that is reported
are mean data. Only through longitudinal investigations of medically defined,
carefully selected cohorts can the impact of physical activity on the functional
reserve capacity of aging humans be distinguished from other extrinsic factors,
disease and biological aging itself. Several longitudinal studies examining the
potential of exercise training to slow age-related declines in cardiovascular,
musculoskeletal, bone-mineral, and glucose and lipoprotein lipid metabolism are
currently, supported by the National Institute on Aging. There are also studies
in progress to investigate the mechanisms by which physical exercise may improve
the functional reserve capacity and the medical condition of elderly people
afflicted with diseases such as coronary artery disease, hypertension, type II
diabetes mellitus and osteoporosis. If the results of these studies are to
provide insight into the efficacy of aerobic exercise as a therapeutic modality
to improve the well-being of the rapidly expanding population of older people,
the common experimental problems distinguishing confounding effects of aging,
cohort, secular and time effects on the experimental measures must be considered

and may require an age-time matrix type of study design (23).
DEFINITION OF THE ISSUES

The specific contributions of physical inactivity and deconditioning to the
commonly observed declines in the functional reserve capacity of major organ
systems with aging have not been thoroughly delineated. The maintenance of
physical activity and conditioning status measured as maximal aerobic capacity

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(the ability of the cardiovascular system to deliver blood and oxygen to working
muscles and of exercising muscles to utilize the oxygen and energy substrate to
perform work in response to a maximal exercise stimulus) (24) into older age may
have substantial health and socioeconomic benefits for the elderly. The fact
that high levels of maximal aerobic capacity (VO max) observed in selected master
athletes are associated with improved metabolic function and the maintenance of a
high level of functional reserve capacity compared to- their sedentary peers
suggests that this is the case. Although maximal] aerobic capacity 1s probably
the best measure of physical work capacity and fitness in younger individuals, it
may not be the only measure of organ performance or necessarily the best measure
of functional reserve capacity in the elderly. Energy expenditure, measured as
oxygen consumed, or other physiologic responses (hemodynamic, muscular, hormonal,
cognitive-motor or otherwise) to submaximal] isotonic work on a bicycle or
treadmill, to an qsometric (weight) stimulus, or to environmental and mental
stressors are also important, useful measures of human performance.

The goal of remaining physically active with advancing age is to delay the
declines in functional capacity with aging. Not only does regular aerobic
exercise maintain muscle strength, coordination, speed, endurance and agility,
but it reduces body fat and other risk factors for coronary artery disease,
heightens mental acuity, maintains self esteem and enhances quality of lifestyle.
The rehabilitative capacity of regularly performed aerobic exercise also is
demonstrated in human disease. Physical activity has improved physiological
function and overall performance in some patients with ischemic coronary artery
disease, hypertension, endstage renal disease, diabetes mellitus, weakness due to
muscle wasting and depression. The salutary effects of physical conditioning on
behavior include enhanced motivation, increased confidence in the ability to
perform daily tasks and activities, successful return to a regular work schedule,
and a heightened level of energy for activity; all presumed due to increased
aerobic capacity. Such improvements could maintain the functional capacity of
older people afflicted with disease, in spite of concomitant physical
limitations. This suggests that regular physical activity may be a suitable
mode of rehabilitation for older individuals with limited function due to disease
and for maintaining the functional reserve capacity of the healthy elderly.

If physical conditioning status is maintained by regular exercise, can age-
associated declines in functional capacity be avoided? Can vigorous exercise
successfully restore the declines in organ function and vulnerability to diseases
and stresses associated with aging? If so, how much exercise is needed? How
often and at what intensity? Is there a threshold for activity or set point for
VOomax at which beneficial adaptations will occur or deteriorations ensue? Can
the observations in master athletes with high Jevels of maximal aerobic capacity
or in disease-afflicted individuals who regain functional capacity through
regular physical activity be solely ascribed to exercise? Many questions need
be answered regarding the potential for physical exercise to promote successful,
healthy aging and to restore the functional capacity of those afflicted with
disease. Substantial research is needed to understand the relationship of
regular physical exercise and the maintenance of heightened aerobic capacity to
the functional status of the aging human being.

Major Areas Which Require Investigation

Evaluation of the potential role for regularly performed physical exercise
in the prevention and/or reduction in the extent of age-related diseases
and disorders in humans, and the determination of the exercise

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prescription (type, frequency, intensity and duration) and magnitude of
the increase in aerobic capacity required to produce these effects.

Assessment as to whether or not there is a threshold for the increase in
maximal aerobic exercise capacity required to achieve a specific
functional reserve capacity. Are there different benefits for different
degrees of exercise intensity?

Investigation of the mechanisms by which regularly performed exercise
increases cardiovascular, endocrine-metabolic, cerebral, and other organ
function, maximal aerobic capacity, and the ability to work and function
independently, and reduces risk factors for disease in the elderly.

Measurement of the biological adaptations to increased exercise/physical
activity in man in vivo at functional levels ranging from the whole body
to the specific organ systems, tissues and to the cellular and molecular
level, and the determination of the influences of advancing age on these
processes.

Evaluation of whether or not maximal aerobic capacity (VOomax) is the best
measure of physical conditioning status, cardiovascular function and
overall functional reserve capacity in the elderly.

Determination whether functional declines with short- and long-term
deconditioning are more rapid and of greater magnitude in older active
individuals than in comparably conditioned younger individuals, and an
assessment as to whether or not deconditioned older individuals are
capable of rehabilitation to previous levels of performance after
deconditioning.

Assessment whether the recommendation for increased physical activity in
older individuals is medically safe for healthy as well as disease-
afflicted elderly. If affirmative, then studies are needed to develop
guidelines for baseline medical evaluations and appropriate prescriptions
(type, frequency, duration and intensity of activity) for exercise
training older people that maximize the benefits of exercise while
preventing injury.

THE ELDERLY BE PHYSICALLY CONDITIONED?

; of the longitudinal studies documenting improvements in functional reserve
icity with aerobic conditioning are in younger and middle-aged individuals;
ss-sectional comparisons in epidemiologic studies provide most of the
yymation on the potential of physical exercise training to increase aerobic
icity and improve functional reserve capacity in the elderly (2, 25-27). In

few longitudinal studies examining the effects of exercise training on
sntary people over the age of 60 years, the training stimulus was of short
ition and low intensity, and sample sizes were small. As a result, a
stantial change in maximal aerobic capacity was documented in some (28-30),
not in other studies (31-33). These inconsistencies have limited the ability
seach a conclusion about the trainability of older individuals (34). However,

physiological results of longitudinal studies in which high intensity
“cise was used to condition older individuals (30,35), the benefits achieved
middle-aged and older patients with coronary artery disease (36), type II
yetes (37,38) and chronic renal disease (39) with participation in vigorous

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aerobic exercise programs, and the observations in master athletes (18-21)
support the view that exercise has the potential to improve functional capacity
and prevent disease in the elderly.

Several studies have attempted to determine the training intensity required to
raise VOomax substantially in older individuals. In an early study (28), 60% of
people aged 60-79 yrs increased their aerobic capacity an average of 7% after
participation in a 6 week walking and jogging program at an intensity of 40-50%
of heart rate reserve. In another study, there were comparable increases in the
peak VOomax of 60-70 year olds after 9 weeks of exercise at an intensity of
either é or 70% of VOgmax (29). The most comprehensive study to date involved,
a 6 month program of walking at 40% of heart rate reserve which increased VO .max
by 12% in 11 healthy subjects ages 65+3 years (30,35); however, in spite of the
rise in VOgmax during the lower intensity exercise, glucose and lipoprotein lipid
metabolism did not improve. Subsequently, higher intensity exercise at 80-85%
heart rate reserve for 6 months raised VOgmax an additional 18% and substantially
improved hemodynamic, metabolic and pulmonary responses (30,35,40,41). It is not
clear whether it was the duration or the intensity of the training stimulus which
limited the improvement in the functional reserve capacity of these older
subjects. Although the older individuals increased their VOogmax an additional
18% in response to the vigorous aerobic exercise program, the lower intensity
training stimulus was sufficient to improve cardiac performance, but not the
metabolic function of these individuals. While VOsmax increased in older
subjects at these lower intensities, higher intensity training programs and a
more significant rise in maximal aerobic capacity over a longer time period might
be required for older subjects to achieve the metabolic improvements observed in
younger and middle-aged subjects after endurance training (42-45). The high
VOomax and associated cardiovascular and metabolic benefits achieved by master
athletes who have trained intensely for a long period of time lends credence to
this hypothesis (18-21,46,47).

In some older subjects, the cardiovascular and metabolic adaptations to exercise
programs may be significantly less than in younger individuals. This may reflect
the presence of asymptomatic disease or irreversible changes in cardiac,
respiratory and/or skeletal muscle structure and function in older subjects which
limits the ability of the exercise stimulus to produce physiologic adaptations in
the function of various organs comparable to those observed in healthy younger
subjects (48,49). The suggestion that enhanced muscular adaptations, rather than
increased cardiac output may be responsible for the greater oxygen extraction at
maximal exercise in master athletes suggests that peripheral, not central
adaptations are primarily responsible for their elevated VOomax (49). These
changes in skeletal muscle structure and function may take Yonger to occur in
older individuals. Whether or not endurance exercise can induce these peripheral
adaptations in sedentary older individuals and raise their VO max to levels
comparable to those found in younger individuals may require longterm
longitudinal studies.

The ability of master athletes to maintain high levels of VOgmax and have glucose
tolerance, insulin sensitivity, and plasma lipoprotein lipid levels comparable to
those found in younger active individuals (18-21) suggests that maintenance of a
high level of physical activity into older age can slow the decline in the
functional reserve Capacity of the cardiovascular and endocrine-metabolic systems
previously attributed to biological aging (48). Preliminary results in several
highly conditioned master athletes who began intensive physical exercise training
in their 6th decade of life and in one who deconditioned for 10 weeks (VOgmax

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declined from 53 to 39 ml/kg-min) suggest that these cardiovascular and metabolic
adaptations are probably not inherited (50).

In studies examining the effect of regular chronic wheel exercise on cardiac
function in sedentary adult rats there was a mild augmentation in cardiac
oxidative enzyme capacity and an attenuation of the age-related decline in
myocardial calcium activated actomyosin ATPase activity. This indicates that
exercise conditioning can partially reverse the decline in cardiac muscle
oxidative capacity observed in aging sedentary rats (51), suggesting that the
relative efficacy of chronic exercise to modulate myocardial performance is
possible into older age, and apparent age-related declines in myocardial
function, at least in rodents, can be reversed by physical conditioning.

It is possible that the vigorous high intensity training program required to test
the hypothesis that physical exercise will improve functional reserve capacity in
the elderly may not be possible in all] older individuals. The ability to
condition some older individuals may be limited by obesity or coexistent diseass
or other medical conditions. Obesity, defined as a body mass index >30 Kg/m
(52) is associated with hypertension, diabetes, hyperlipidemia and
arteriosclerosis (53), and an increased mortality from coronary heart disease
(54). Thus, overweight individuals are at increased risk for complications
during exercise training and require careful screening for overt and asymptomatic
disease prior to onset of exercise training. Furthermore, oxygen consumption and
cardiac work are increased in overweight individuals during exercise (55),
increasing risk for cardiovascular complications. Weight reduction prior to
participation in a physical exercise program may reduce risk for complications
during training and enhance the ability of overweight individuals to raise their
maximal aerobic capacity. Simultaneous programs of weight reduction by
hypocaloric feeding and behavior modification combined with physical exercise may
be even more beneficial, since increased energy expenditure during exercise will
enhance the caloric deficit produced by hypocaloric feeding (55,56). Preliminary
results in healthy overweight, middle-aged and older men screened for occult
coronary disease by maximal treadmill stress testing suggests that such a
combined intervention promotes a greater reduction in adipose tissue mass than
achieved either by hypocaloric feeding or exercise alone (57). Such an approach
seems attractive if confounding extrinsic factors such as disease do not limit
the exercise capacity of these sedentary, overweight individuals or place them at
risk for injury. Thus, prior screening for disease, especially symptomatic and
asymptomatic coronary artery disease by careful medical exam and exercise stress
testing’ with electrocardiography and thallium scans would provide a_ healthy
population of older individuals at low risk for exercise-induced complications in
which to test whether prolonged, intensive physical exercise in elderly
individuals will cause cardiovascular, metabolic and other physiologic
adaptations comparable to those seen in younger individuals.

ARE AGE-RELATED DECLINES IN CARDIOVASCULAR FUNCTION MODIFIABLE BY PHYSICAL EXERCISE’

The most effective test to evaluate the maximal functional capacity of the
cardiovascular system is to measure maximal oxygen uptake during strenuous
exercise. This test determines the capacity of the cardiovascular system to
deliver oxygen to working muscles and for exercising muscles to utilize the
oxygen to perform the work (24). Most of the studies examining the effects of
aging on VOgmax are cross-sectional comparisons of the changes in physiologic
responses to maximal exercise stress with age in active, but non-athletic men.
They report a rather uniform average 10% per decade or 0.45 ml/kg-min per year

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mean decline in VOgmax from age 25-80 years (25,58). However, in highly trained
master athletes there was a decline in VO2max of only 5% per decade (18). The
rate of decline in VOomax with advancing age in longitudinal studies 1s
heterogeneous, and dependent on the physical activity status of the population
studied. In subjects aged 40-72 years divided into active and inactive
categories, the VO max of active men who jogged an average of 3 miles/week
declined by much less rapidly than that of sedentary men (59). In men aged 40-60
yrs old who ran an average of 25 km/week, there was no decline in VOomax over a
10 year period of follow-up (60). In a recent longitudinal study there was a
decline in VOpmax of less than 2% per decade in highly conditioned master
athletes aged 50-82 yrs who remained competitive and a significant 12% decline
per decade in the VOgmax of those who ceased competition but remained highly
active during the 10 year period (19). In that study, maximal heart rate and fat
free mass decreased and percent body fat increased comparable amounts in both
groups, suggesting that the competitive group either increased arteriovenous
oxygen difference (i.e., muscular adaptations occurred) or raised stroke volume
(i.e., cardiac adaptations occurred since maximal heart rate decreased) during
the 10 year period of intensive training. Thus, while maximal heart rate
declines with advancing age, it appears that highly conditioned elderly subjects
without evidence cardiovascular disease can maintain their aerobic capacity by
increasing muscle oxidative capacity (arteriovenous oxygen difference) and by
increasing stroke volume and diastolic filling (Frank Starling mechanism) to
compensate for the progressive decline in maximal heart rate with advancing age
(46-49). In addition to the physiologic adaptations observed with regular high
intensity endurance exercise in healthy conditioned older athletes, Tong term,
high intensity aerobic training produces both cardiac and peripheral adaptations
jn middle-aged patients with ischemic heart disease (36,61,62). In these
patients the peripheral adaptations also may be of greater significance then
central (cardiac) ones, since left ventricular wall thickness, contractility and
function during systole did not change (46).

Thus, while maximal aerobic capacity declines with advancing age, this decline
can be attenuated by central and peripheral circulatory adaptations. In highly
conditioned master athletes there is a decline in VOzmax with advancing age that
can be attributed to a decline in maximal cardiac output caused by the well-
documented age-related decline in maximal heart rate (46-48). However, this can
be attenuated by continued high intensity aerobic training (19). Thus, because
of variability in lifestyle habits there may be diversity in VOomax and cardiac
hemodynamics in elderly individuals such that some older jndividuals have a
VOomax’ comparable to that of younger individuals.

In addition to differences in the disease status, physical activity habits and
body composition of older subjects, studies in disease-free older subjects
indicate that there are at least three significant age-associated alterations in
cardiac structure and function. These are a mild increase in left ventricular
wall thickness (8,48), slowed and delayed ventricular relaxation (6,8), and
diminished contractile performance during physical exercise (46,48). The first
two age-related changes probably reflect a compensatory response to the increased
workload imposed by vascular changes (increased peripheral vascular resistance),
which increase pulse wave velocity and afterload. This increases the pulsatile
component of external cardiac work and raises systolic arterial pressure (11).
These changes are magnified in individuals with hypertension (6) and are an
independent risk factor for cardiovascular mortality (63). The clinical
relevance of the left ventricular hypertrophy observed with advancing age is not
clear, but under conditions of acute volume overload or exercise stress may raise

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ventricular and pulmonary pressures and increase shortness of breath. Physical
conditioning profoundly affects the circulatory system in younger individuals by
increasing stroke volume, decreasing peripheral vascular resistance, and
increasing left ventricular mass (10,48); in older subjects it might also
increase arterial distensibility, reduce pulse wave velocity and lower systolic
blood pressure. The effects of physical conditioning on these processes are not
known in older people.

The third age-related change in cardiovascular function, a decline in maximal
aerobic capacity, defined by the Fick equation as the product of cardiac output
and arteriovenous oxygen difference during maximal exercise stress is dependent
on the population studied, and age-related changes in the peripheral and central
circulation (46-48). In disease-free individuals cardiac output, measured at
peak oxygen consumption using the gated blood pool scan technique during cycle
exercise to exhaustion, was maintained with advancing age (5,12). However,
neither arteriovenous oxygen difference nor cardiac output or their determinants
have been measured at VOo.max; and in preliminary studies evaluating. the
mechanisms regulating aerobic capacity in master athletes and sedentary older
subjects, peripheral and not central adaptations seem responsible for the higher
levels of VOgmax in highly conditioned master athletes (49). Other possible
reasons for differences in VOgmax among older individuals may be _ the
inappropriate normalization of oxygen consumption during maximal exercise stress
to total body mass rather than to lean body mass since muscle mass decreases with
advancing age (64,65) and the additive effects of the age-associated decline in
blood flow to muscle during maximal exercise in elderly subjects (66). While
there is a progressive decline in pulmonary function with advancing age that may
be caused by effects of biological aging or environmental exposures and lifestyle
(67,68), they do not seem to limit exercise capacity in individuals without
evidence of pulmonary disease because maximal ventilatory capacity is rarely
achieved at VOomax. Hence, the pulmonary system is usually not rate-limiting in
exercise performance, although oxygen exchange in the lung may hinder performance
during prolonged exercise.

Thus, the health status and lifestyle habits of the individuals studied seem to
have the most profound affect on cardiovascular performance during maximal
exercise stress testing. Coronary artery disease, whether overt or asymptomatic
has the most significant impact on cardiac function and screening out individuals
with cardiovascular disease especially in older populations, dramatically alters

cardiac performance (5,12,48). In healthy older individuals, screened for
coronaryzartery disease, differences in cardiac function may be primarily due to
physical conditioning status. In the only study addressing this issue, both

cardiac output and end diastolic volume were higher at the same level of exercise
intensity after a 12 week aerobic training program, but end systolic volume did
not change (69). The extent to which the peripheral (muscle mass, blood flow and
oxygen extraction) and central (ventricular function, cardiac output, and oxygen
exchange) factors determining maximal aerobic capacity (Fick Equation) differ
among healthy elderly subjects with varied physical activity habits, and the
effects of physical conditioning on these parameters is not known.

ARE GLUCOSE AND LIPID METABOLISM MODIFIABLE BY PHYSICAL EXERCISE IN THE ELDERLY?

Some of the alterations in glucose and lipoprotein metabolism which occur with
advancing age predispose older people to ‘diabetes mellitus and hyperlipidemia
(15,16), major risk factors for coronary artery disease, the leading cause of
death in older Americans (3). If physical inactivity and a reduced aerobic

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capacity are major determinants of the decline in metabolic function and increase
in adiposity which predispose older individuals to develop atherosclerosis, then
anterventions which improve physical conditioning status and VOomax should
improve metabolism, reduce risk factors for atherosclerosis and decrease
cardiovascular complications during stress. A better understanding of the
effects of change in lifestyle habits on glucose and lipid metabolism with
advancing age might have important health implications for reducing the
revalence of coronary artery disease and prolonging the survival of older
individuals.

A beneficial effect of physical conditioning on glucose and lipoprotein
metabolism and body composition is recognized in younger and middle-aged
individuals (2,26,27,42-45) and several studies indicate that similar changes
occur in older subjects (28-30). The longitudinal studies in older individuals
are few in number and most are descriptive, not mechanistic. Furthermore,
changes in body fat and diet during training, the duration and intensity of the
exercise, and the timing of the last exercise session relative to the performance
of the research tests affect glucose and lipoprotein metabolism and may limit the
ability to distinguish effects of physical conditioning per se from those of
other extrinsic factors affecting metabolism.

Declines in metabolic function with advancing age are highly variable, and in a
substantial percentage of older subjects measures of lipoprotein lipids, glucose
metabolism and body composition are comparable to those in younger subjects. The
reduction in overall muscle mass and blood flow to muscle in elderly individuals
contributes to the decline in metabolic function by decreasing muscle structure
and function and reducing the peripheral utilization of substrates. Thus, while
glucose utilization and lipoprotein turnover traditionally have been normalized
to body weight or the pool size of a substrate, it may be appropriate to
normalize these parameters for lean body mass and organ function in older
individuals.

Glucose Metabolism with Advancing Age

The 5 mg/d1 deterioration in glucose tolerance per decade observed with advancing
age is primarily caused by peripheral tissue resistance to the action of insulin
(14,15). Studies using the glucose clamp technique indicate that at submaximal
insulin concentrations both glucose disposal and the suppressibility of hepatic
glucose production by insulin on the average are reduced in older subjects
despite normal insulin receptor binding (70-72). This raises plasma insulin
levels and reduces glucose tolerance, both of which increase risk for accelerated
atherosclerosis (73). Tissue responsiveness to insulin, defined as the glucose
disposal rate at maximal insulin concentration, is normal in some and reduced in
other elderly subjects depending on their degree of hyperinsulinemia and glucose
intolerance. This suggests that in some older people there may be a post-
insulin receptor defect in insulin action, yet this has not been examined
directly at the cellular level. Other mechanisms, such as reduced insulin
secretion (74) and increased levels of norepinephrine resulting in impaired
insulin secretion and action (75), also may worsen glucose metabolism in older
individuals.

Cross-sectional data in master athletes (20) and sedentary younger and older
individuals (38,42,43) suggest that the maintenance of high levels of physical
activity into older age protects against the age-related deterioration in glucose
tolerance and insulin sensitivity. In only one study examining the effects of

c -ll
aging on glucose metabolism was VOomax and percent body fat of the subjects
measured directly (21); and there are no longitudinal studies of the effects of
change in physical conditioning status and body fat on the mechanisms regulating
glucose metabolism in older individuals. Thus, the relationship of physical
conditioning status to glucose metabolism in older individuals, independent from
hereditary factors and other extrinsic variables, is not known.

Lipoprotein Lipid Metabolism with Advancing Aqe

The finding of elevated levels of high density lipoprotein cholesterol (HDL-C)
and lower triglyceride and low density lipoprotein cholesterol (LDL-C) levels in
master athletes that are comparable to those in athletic younger individuals
suggests that physical conditioning may improve lipoprotein lipid metabolism and
reduce risk for coronary artery disease in older individuals. There is little
known about the regulation of lipoprotein metabolism in elderly subjects, but the
impact of extrinsic factors, genetics and disease on metabolic function is
substantial (76). For example, obesity and diets high in cholesterol and
saturated fat lower HDL-C, raise LDL-C and increase plasma triglyceride levels
(77,78). Alcohol intake (79), medications (80) and chronic diseases also have
substantial effects on lipoprotein lipids, most of them undesirable. Chronic
diseases, such as diabetes, renal and liver disease, common in elderly
populations lower HDL-C and raise plasma LDL-C and triglyceride levels. These
abnormalities in lipoproteins are associated with increased risk for
atherosclerosis and coronary artery disease (16,76). If the presence of these
conditions is undetected, lipoprotein lipid profiles will be altered independent
of biological aging.

Thus, the accurate study of the effects of physical activity on lipoprotein
metabolism in older individuals requires rigorous screening to select healthy
people of comparable body weight and diet without evidence of disease or genetic
factors which affect lipoprotein metabolism. Such a design would distinguish
the metabolic effects of exercise capacity from those erroneously attributed to
biological aging per se. Studies of this type have not been performed in the
elderly and might provide insight into the role of physical exercise programs in
reducing risk for coronary artery disease in seniors.

CAN AGE-RELATED LOSS OF BONE DENSITY BE PREVENTED BY PHYSICAL EXERCISE?

There is a progressive decline in bone density in both males and females with
advancing age. These losses may be so severe in elderly females to result in
fractures causing progressive disability, limited activity and substantial
declines in functional capacity (81). Although biological aging is considered a
major factor in the loss of skeletal bone, the effects of estrogen and vitamin D
deficiency, physical inactivity, cigarette smoking and excessive alcohol also
contribute to the development of osteoporosis in the elderly (81-84). In
postmenopausal females the rate of loss in skeletal mass and bone density is
greatly accelerated due to estrogen deficiency; however, this decline can be
accelerated by the present of the aforementioned additional extrinsic risk

factors which enhance osteopenia.

Physical inactivity is one potentially modifiable factor contributing to the loss
of skeletal integrity and bone density. A number of cross-sectional studies
suggest that bone loss can be attenuated by physical exercise (84-86); thereby
slowing the emergence of osteoporosis and reducing the heightened risk of bone
fracture in the elderly. If estrogen is replaced in the postmenopausal female,

c = 12
bone resorption will decrease; simultaneous weight bearing exercise may further
augment bone accretion and increase bone mass (87). Estrogen administration (in
the postmenopausal female), cessation of cigarette smoking, reduction in alcohol
intake, dietary supplementation with vitamin D (and perhaps calcium) and other
extrinsic factors may be additive with the effects of exercise to reduce the
progression of osteopenia in the elderly. Although supplemental calcium
administration alone or with estrogen does not increase bone density (88), its
effects when administered during exercise are not known.

The increase in muscle mass and strength, and enhancement of agility associated
with physical exercise may substantially reduce the vulnerability of older
individuals, especially postmenopausal women, to risks of bone fracture. While
the 1984 Consensus Conference on Osteoporosis (89) recommended modest weight
bearing exercise for the possible prevention of bone loss, closer inspection of
the literature indicates that more information is needed (90). If it is decided
which older individuals might benefit from physical activity, it will be
necessary to determine the type, intensity and duration of the exercise program
best suited to increase bone density; assess whether there are additional
requirements for supplemental hormones, vitamins and minerals to maximize the
effects of exercise; and develop measures of bone density and aerobic capacity to
accurately evaluate the effects of exercise on bone-mineral metabolism. Many
factors can affect the progression/remission of osteoporosis; hence the selection
of subjects, size of the sample studied and method of randomization to treatment

will be critical.

ARE ADAPTATIONS TO ENVIRONMENTAL STRESS IMPROVED BY PHYSICAL EXERCISE?

The ability to adapt to changes or stresses in the environment declines with
advancing age. Older individuals are on the average less tolerant to extremes of
temperature (91,92), more prone to orthostatic hypotension after rapid positional
change (93) and more often remain tachycardic, hypertensive and fatigued after
physical exertion than younger people (94). Tolerance to temperature and
recovery from exhaustive exercise are improved in younger and middle-aged
individuals after physical conditioning (95-97), but the results of exercise
training on these responses are not known in the elderly. Paradoxically, exercise
training worsens orthostatic tolerance in younger subjects (98,99), but the
effects in older sedentary individuals with impaired baseline orthostetic
tolerance are not known. Blood volume, blood flow and thermoregulation (swea ing
and shivering) affect responses to these environmental conditions; these
parameters have neither been measured in healthy older individuals nor related to
maximal aerobic capacity, body composition or diet. One would suspect that more

physically active older individuals would be more tolerant to these stresses, but
this requires investigation.

SUMMARY AND FUTURE PROSPECTS

There is evidence that regularly performed exercise may improve the quality of
life and protect against the development of disease in elderly subjects. Several
studies have shown that the functional reserve capacity of the cardiovascular,
endocrine-metabolic and musculoskeletal systems can be maintained and/or improved
by regular exercise in healthy, elderly subjects. Controlled longitudinal
studies have shown that regularly performed exercise is associated with fewer
risk factors for arteriosclerosis and coronary artery disease in middle-aged men
and women and a few studies have documented similar effects in older subjects.

Results in master athletes and in patients with disease support the hypothesis

Cc - 13
that physical activity will improve the functional capacity of older people.
More information is needed to determine the extent to which physical conditioning
will benefit the elderly and type and quantity of regular exercise which should
be prescribed for older populations. This can be achieved both by large scale
longitudinal studies as well as by small short and long term evaluations in
healthy and disease afflicted older subjects of the mechanisms by which exercise
training improves functional capacity, reduces risk factors for arteriosclerosis
and improves the quality of life. If it can be documented that exercise training
slows or prevents the age-related deterioration in functional capacity and makes
it easier for the elderly to complete activities of daily living with more energy
and less fatigue, then regular exercise could be incorporated into programs of
public health and preventive medicine as a means by which the productivity,
independence, and active lifestyle of the aging population can be prolonged.

In studying the effects of exercise on the functional reserve capacity of the
elderly it will be important to determine the age, gender and clinical
characteristics of the older subjects most likely to benefit. Guidelines for
medical screening and baseline evaluations of functional reserve capacity will be
needed to determine the exercise prescription most likely to achieve the desired
physiologic result without risking injury to the older participant. This will
require determination of the type, intensity, duration and frequency of exercise
for each functional decline and risk factor which develops with advancing age.
Standardized methods will be required to monitor physiologic responses to
exercise, determine the rate of progression to higher levels of exercise and
document the physiologic effects of the exercise program. Safeguards will be
needed to maintain diet, drugs and other lifestyle habits constant to permit
accurate assessment of the physiological effects of physical exercise.

Progress in this area of investigation will require Support for centers of
excellence to perform large scale exercise studies to document the physiological
effects of physical exercise, and its role in the prevention of disease,
reduction in the utilization of health resources and improvement in the mental
health and the quality of life of elderly populations (100). Longitudinal
Studies of this type would ultimately have sufficient data to determine the
impact of exercise training on morbidity and mortality in the elderly and
establish the relationship of physical activity to survival in healthy and
disease-affected older individuals.

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