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320 Annals of Clinical & Laboratory Science, vol. 42, no. 3, 2012

Review:
Physical Inactivity: Associated Diseases and Disorders
Joseph A. Knight

Department of Pathology, University of Utah School of Medicine; Salt Lake City, Utah, USA

Abstract. A sedentary lifestyle is a very serious worldwide problem, especially in North America and Eu-
rope. Unfortunately, physical inactivity, which has progressively increased over the past several decades,
significantly increases the risk of numerous diseases/disorders, including several forms of cancer, diabetes,
hypertension, coronary and cerebrovascular diseases, overweight/obesity, and all-cause mortality, among
others. Unless there is a reversal of this sedentary lifestyle, the incidence of these diseases/disorders will
increase, life expectancy will decrease, and medical costs will continue to rise.

Key Words: physical inactivity, lifestyle, morbidity, mortality, guidelines

Introduction found in dietary restriction and whether these

Humans are not programmed to be physically in-
active. Indeed, the “sedentary death syndrome” is a
major risk factor for numerous worldwide diseases
and millions of premature deaths each year [1].
Studies have shown that long-lived species are more
efficient in cellular maintenance than short-lived
species, suggesting that enhancement of the body’s
maintenance systems may slow the aging process.
Since aging results from the accumulation of cel-
lular damage, interventions in poor lifestyles may
prevent damage, promote repair, and thereby in-
crease life expectancy. In fact, about two thirds of
the major causes of death are, to a significant de-
gree, lifestyle-related. As noted by Mokdad et al,
the major “actual causes of death” are physical in-
activity and poor nutrition [2,3].
Although a sedentary lifestyle is important in the
pathogenesis of many chronic diseases/disorders,
little is known about the mechanisms whereby
physical activity decreases their incidence. Since
caloric restriction (CR) is the only paradigm that
consistently increases the lifespan of flies, worms,
mice, rats, etc., a panel of aging experts examined
“whether changes in exercise behavior and body
composition produces similar changes as those
changes can be used to either replace or enhance
the beneficial effects of dietary restriction” [4].
Although no definitive conclusions were reached,
future research will determine if changes in physi-
cal activity and body composition act as CR
mimetics.
Physical inactivity results in the so-called “disuse
syndrome” (i.e., premature aging, obesity, cardio-
vascular vulnerability, musculoskeletal fragility,
and depression) [5]. Since this reproducible syn-
drome applies to the young and middle-aged, as
well as the elderly, age per se is not completely re-
sponsible for many of the diseases/disorders attrib-
uted to it. Thus, “illness as we see it has another
component that is due neither to disease per se nor
to time effects but to disuse, the third dimension”
[6]. Indeed, about 15% of the 1.6 million newly
diagnosed chronic diseases each year are due to a
sedentary lifestyle [7] (Table 1). Moreover, physical
activity also improves balance, flexibility, mental
health, and overall quality of life. Indeed, “physical
inactivity speeds the aging process in many people,
whereas increased physical activity slows it down in
others” [8]. Thus, the earlier in life one becomes
physically active, and remains so, the greater the
lifetime benefits.

Address correspondence to Joseph A. Knight M.D.; Department of Physical Activity Guidelines. The 1995 recom-
Pathology, University of Utah School of Medicine, 30 North 1900 mended guidelines indicated that at least 30 min-
East, Salt Lake City, Utah 84132; phone: 801 581 4516; fax: 801 585
2463; e-mail address: joe.knight@path.utah.edu utes of moderate intensity physical activity on

0091-7370/12/0300-320. © 2012 by the Association of Clinical Scientists, Inc.


Table 1. Physical Inactivity: Associated Diseases/Disorders
All-cause mortality
Cancer (colon, breast, prostate, others)
Diabetes mellitus (type 2)
Dyslipidemia (increased total/LDL cholesterol, decreased HDL cholesterol)
Hypertension
Immune deficiencies
Metabolic syndrome
Neurological disorders (functional decline, depression, dementia)
Osteoporosis (falls, fractures)
Overweight/obesity
Oxidative stress
Sarcopenia
most, but preferably all, days of the week would
result in significant health benefits [9,10]. However,
these guidelines were updated in 2007 [11]. Thus,
all healthy adults aged 18 to 65 years need moder-
ate-intensity aerobic (i.e., endurance) physical ac-
tivity for a minimum of 30 minutes on five days
each week or vigorous-intensity aerobic physical
activity for a minimum of 20 minutes on three
days each week. Although the recommendations
for older adults are similar, there are several differ-
ences including the following: aerobic intensity
should consider the older adult’s aerobic fitness, in-
clude activities that maintain or increase flexibility,
and balance exercises for those at risk of falls [12].
Moderate intensity is categorized as burning 3.5-
7.0 kcal/minute (e.g., walking on even terrain at
3.0-4.5 mph or biking 5.0-9.0 mph). Vigorous in-
tensity is classified as burning 7.0 or more kcal/
minute (i.e., race walking at > 5.0 mph; biking >
10.0 mph). To meet current guidelines, individuals
must walk a minimum of 3,000 steps in 30 min-
utes on five days each week. However, three bouts
of 1,000 steps in ten minutes each day also meets
the recommended goal. More recently, Wen et al
prospectively studied 416,175 men and women be-
tween 1996 and 2008 [13]. Compare with the inac-
tive group, those who exercised for 15 minutes/day
had a 14% reduced risk of all-cause mortality and a
3-year longer life expectancy. Each additional 15
minutes of daily exercise further reduced all-cause
mortality by 4% and all-cause cancer mortality by
1%.
Physical Inactivity: Associated Diseases and Disorders 321
Gait speed (meters/second)
has also been studied with re-
spect to survival in older
adults [14]. This analysis of 9
cohort studies involved 34,485
elderly adults with baseline
gait speed data and followed
for 6 to 21 years. The authors
concluded that “…gait speed
was associated with survival in
older adults.” Unfortunately,
at least 26% of American
adults are sedentary and more
than 50% are not regularly ac-
tive at the minimum recom-
mended level [15]. The objec-
tives of Healthy People 2010 were that at least 50%
of American adults will be regularly involved in
moderate to vigorous exercise, since approximately
250,000 premature deaths occur in the U.S. each
year as a result of physical inactivity [16].
To evaluate the dose-response relationship between
physical activity, various chronic diseases, and all-
cause mortality, Lee et al examined the parameters
of physical activity dose, volume intensity, dura-
tion, and frequency in 44 published studies [17].
Their findings showed the following: (a) there is
“clear evidence” that an inverse relationship exists
between volume of physical activity and all-cause
mortality rates in men, women, younger adults,
and older adults; (b) adherence to the current mini-
mal physical activity guidelines is associated with a
20-30% reduction in all-cause mortality; and (c)
further risk reductions occur at higher levels of en-
ergy expenditure.
Although healthcare providers are strongly encour-
aged to promote increased physical activity in older
people, many do not feel adequately prepared to
prescribe a specific exercise program [18]. Indeed, a
Center for Disease Control report indicated that
only 19% of physicians counseled their patients
about exercise [19]. Physical inactivity among chil-
dren and adolescents is also a major problem. For
example, Kimm et al prospectively followed black
and white girls for 10 years (ages 9 to 19 years) [20].
The median activity scores for black and white girls
were 27.3 and 30.8 metabolic equivalent times
(MET)/week at base line, respectively. By year 10
322 Annals of Clinical & Laboratory Science, vol. 42, no. 3, 2012
they declined to 0.0 and 11.0 MET/week (100%
decline for black girls, 64% decline for white girls).
Moreover, one-third of U.S. high school students
did not participate in the minimum recommended
level of moderate or vigorous physical activity in
2003 [21], and only 55.7% were enrolled in a PE
class where only 28.4% attended classes daily [22].
Physical Inactivity and All-Cause Mortality.
Life expectancy based on age and sex alone pro-
vides limited information since survival is also
significantly influenced by health and functional
abilities. Indeed, about 65% of the major causes of
death are lifestyle-related [2,3]. Although individu-
als with lower health risks generally live longer
than those with higher health risks, there is often
concern that increased life expectancy may result
in greater disability and increased medical costs.
However, the compression-of-morbidity hypothesis
suggests that it is possible to reduce lifetime mor-
bidity and thereby increase life expectancy [23].
Indeed, a study of university alumni showed that
those with high health risks (e.g., low exercise pat-
terns, smoking, excess body weight) had twice the
cumulative disability compared to those with a low
health risk after 32 years follow-up [24]. Thus, “not
only do persons with better health habits survive
longer, but in such persons, disability is postponed
and compressed into fewer years at the end of life.”
Television viewing time is associated with biomark-
ers of cardiometabolic risk, but since its relation-
ship with mortality had not been studied, Dunstan
et al examined adult viewing time [25]. After
adjustment for important variables, the hazard ra-
tio for each one-hour increment in television view-
ing time per day was 1.11 for all-cause mortality
and 1.18 for cardiovascular mortality. Compared
with viewing time of less than two hours/day, the
hazard ratios for all-cause mortality were 1.13 for
2-4 hours/ day and 1.46 for more than 4 hours/day.
For cardiovascular mortality, the corresponding
hazard ratios were 1.19 and 1.80.
In an early study, physical activity was compared
with all-cause mortality in 16,936 Harvard alumni
[26]. After 16 years follow-up, the death rate de-
clined steadily as the expended energy increased. A
subsequent prospective study of Harvard alumni
showed a graded inverse relationship between total
physical activity and all-cause mortality [27]. The
third study of this group showed that distance
walked and floors climbed were independent pre-
dictors of longevity [28].
Blair et al compared the degree of physical fitness
with all-cause and cause-specific mortality in men
and women over an 8-year period [29]. Here, the
age-adjusted all-cause mortality rate declined
across physical fitness quintiles from 64/10,000
person-years in the least fit men to 18.6/10,000 in
the most fit men (relative risk, 3.4) and 39.5/10,000
person-years to 8.5/10,000 for women (relative risk,
4.7). In a subsequent study, the relationship be-
tween changes in physical fitness and mortality risk
was evaluated in men [30]. Each man underwent
two clinical examinations (mean interval, 4.9
years) to assess any changes in physical fitness as
associated with risk of mortality during the follow-
up period. The highest age-adjusted all-cause death
rate was present in those who were unfit at both
examinations; the lowest death rate was in men
who were physically fit at both examinations.
Moreover, men who improved from unfit to fit be-
tween the two examinations also had a lower death
rate. In a recent review of physical activity and all-
cause mortality in women, the authors concluded
that “by adhering to current guidelines for physical
activity and expending about 4,200 kJ (about
1,000 kcal) of energy/week, women can postpone
mortality” [31].
Since little was known about the mortality risk and
physical activity in the elderly, Bijnen and associ-
ates evaluated 802 retired Dutch men at baseline
[32]. All-cause 10-year mortality in the highest ter-
tile decreased with increasing physical activity (rel-
ative risk, 0.77). More intense physical activity was
associated with greater decreased mortality.
Moreover, walking or bicycling at least 3 times/
week for 20 minutes significantly reduced all-cause
mortality compared with those who were physi-
cally inactive (relative risk, 0.70). More recently,
Newman et al evaluated the long-term positive ef-
fects of elderly adults at baseline who completed a
400 meter corridor walk [33]. After a mean period
of 4.9 years, those unable to complete the walk had
a significantly higher mortality risk, incident
coronary heart disease, disability, and mobility
limitation. Each additional minute of performance
time to complete the walk was associated with the
following hazard ratios: mortality, 1.29; incident
coronary heart disease, 1.20; mobility limitation,
1.52; and disability, 1.52. Those in the lowest
 Physical Inactivity: Associated Diseases and Disorders
quartile had a significantly higher risk of death
than those in the highest quartile.
Others evaluated the daily energy expenditure and
mortality among high functioning elderly individ-
uals for a mean of 6.15 years [34]. The free-living
activity energy expenditure was separated into the
following three tertiles: less than 521 kcal/day; 521
to 770 kcal/day; and greater than 770 kcal/day.
After adjusting for various confounders, those in
the highest tertile energy expenditure group were at
a significantly lower all-cause mortality risk than
those in the lowest tertile. Indeed, the least active
group was three times more likely to die. Benetos
and associates evaluated the role of physical activity
and other risk factors in older individuals who
could potentially reach the age of 80 years for men
and 85 years for women [35]. Their data showed a
significantly increased probability of reaching these
ages if they were involved in regular physical
activity. Wang et al added further support for
recommending physical activity in older persons
[36]. In this 13-year prospective study, runners’
club members 50 years and older were compared
with sedentary control subjects. Their findings
showed significantly lower disability levels in the
runners’ clubs members and the death rate in the
control group was 3.3 times greater. A recent meta-
analysis of 33 all-cause mortality studies also indi-
cated that better cardiorespiratory fitness (CRF)
was associated with a significantly lower risk of all-
cause mortality [37].
A recent study also suggested that leisure time
physical inactivity might accelerate the aging
process [38]. These researchers studied twin volun-
teers on physical activity level, smoking, and socio-
economic status, as well as determined their leuko-
cyte telomere length. After adjusting for age, sex,
BMI, smoking, socioeconomic status and physical
activity at work, telomere length was positively as-
sociated with leisure time physical activity and
thereby possibly slowed the aging process.
Heart Disease: Primary Prevention. Heart dis-
ease has been the leading cause of death in the U.S.
for the past four decades [39]. In 2007, cardiovas-
cular disease (CVD) accounted for 33.6% of all
deaths in the U.S.; 2,200 Americans died of CVD
each day [40]. Moreover, the myth that heart dis-
ease is only a “man’s disease” has been debunked.
323
Indeed, it is the major worldwide cause of death in
women since it accounts for one-third of all female
deaths. In many countries, including the U.S.,
more women die of CVD than men [41]. Primary
heart disease prevention, a reduction in coronary
heart disease (CHD) risk factors in healthy people,
results in a four-fold higher reduction in mortality
from CHD than secondary prevention (i.e., risk
factor reduction in people with established CHD)
[42]. Although about 40% of 40 year old adults
will develop heart failure during their lifetime, the
Physicians’ Health Study indicated that adherence
to healthy lifestyle is associated with a significantly
lower risk of heart failure [43].
Morris et al reported in the early 1950s that active
conductors in the London double-decker buses
were protected against CHD compared with the
sedentary bus drivers [44,45]. Similarly, postmen
were protected from CHD compared with less ac-
tive government employees. Three decades later,
Paffenbarger and associates examined 16,936
Harvard alumni for lifestyle experiences related to
CHD and longevity [46]. Those expending 2,000
kcal/week in walking, stair climbing, and sports
play were at a 39% lower risk for CHD than the
less active alumni and 16% fewer CHD deaths
would have occurred if everyone had expended the
same amount of energy in some form of exercise.
Since that time, there has been a growing interest
in using walking speed to assess functional status
and motor performance in older people, 3,208 el-
derly men and women were followed for an average
of 5.1 years [47]. Here, persons with low walking
speed had a three-fold increased risk of cardiovas-
cular death compared with those who walked
faster.
In their study of the association of 400 meters
corridor walk performance with the total mortality
in elderly individuals, Newman et al also evaluated
its effect on incident CHD [33]. Here, inability to
complete the walk was associated with a signifi-
cantly higher risk of incident CHD. Of those who
completed the walk, each additional minute was
associated with a hazard ratio of 1.2 for incident
CHD. Others studied the consequences of differ-
ent physical activity levels on total life expectancy
with and without CHD in both men and women
[48]. Compared with low levels of physical activity,
moderate and high levels led to 1.3 and 3.7 and 1.1
324 Annals of Clinical & Laboratory Science, vol. 42, no. 3, 2012
and 3.5 more years in total life expectancy, respec-
tively, as well as 1.3 and 3.3 more years free of
CHD.
Since the role of walking compared with vigorous
exercise in the prevention of coronary heart disease
remains somewhat controversial, especially among
women, healthy postmenopausal women were pro-
spectively studied [49]. The results showed that
increasing quintiles of energy expenditure had age-
adjusted relative risks for coronary events of 1.00,
0.73, 0.69, 0.68 and 0.47, respectively. To further
understand these variables, Duncan et al random-
ized 492 sedentary adults to 1 of 4 exercise-coun-
seling conditions or to a physician advice compari-
son group [50]. The duration (30 minutes) and type
(walking) of exercise were held constant while exer-
cise intensity and frequency consisted of moderate
intensity-low frequency (3-4 days/week) and hard
intensity-high frequency (5-7 days/week). After 24
months, participants in the high-intensity exercise
group showed significant increases in cardiorespi-
ratory fitness.
Although exercise capacity is an important prog-
nostic factor in people with CHD, it had been un-
certain whether it predicts mortality equally well
among healthy individuals. To evaluate this, Myers
and associates studied 6,713 men referred for tread-
mill exercise testing [51]. The participants were
classified into two groups: 3,679 had an abnormal
exercise test result, history of CHD, or both; 2,534
had a normal exercise test result and no history of
CHD. The peak exercise capacity, measured in
metabolic equivalents (MET), was the strongest
predictor of death between both groups. Each
MET increase in exercise capacity conferred a 12%
improvement in survival.
To evaluate increased physical activity in the frail
elderly, Ehsani et al randomly assigned frail octoge-
narians to a control sedentary group or an exercise
group in a 6-month training program followed by
3-months of more intense endurance exercise [52].
Compared with the sedentary group, the exercise
group showed a 14% increase in both the peak oxy-
gen consumption and exercise cardiac output. The
authors concluded that “although frail octogenari-
ans have a diminished capacity for improvement in
aerobic power in response to exercise training, this
adaptation is mediated most by an increase in Q
(peak exercise cardiac output) during peak effort.”
Heart Disease: Secondary Prevention. Although
rest and physical inactivity have been recommend-
ed for patients with established CHD for decades,
it is important to recognize that recent studies
clearly show that the benefits of physical activity
and fitness also apply to those with coronary and
other vascular diseases. For example, a recent pro-
spective Nurses’ Health Study showed that regular
exercise significantly minimizes the risk [53].
Indeed, the absolute risk of sudden cardiac death
associated with moderate to vigorous exertion was
“exceedingly low.” A prospective study of U.S.
male physicians also indicated that habitual vigor-
ous exercise “diminishes the risk of sudden death
during vigorous exertion” [54]. The following re-
ports further document the importance of physical
activity in patients with established CHD.
A British study involving men with established
CHD compared the relative risks of death from
cardiovascular disease and all-cause with the level
of physical activity [55]. Compared with the inac-
tive or occasionally active group, the relative risks
(RR) were as follows: light activity, 0.42; moderate
activity, 0.47; and moderately vigorous or vigorous
activity, 0.63. In addition, recreational activity of
four or more hours/week, moderate or heavy gar-
dening, and regular walking 40 or more minutes/
day were also associated with a significant reduc-
tion in mortality. Those who were initially seden-
tary, but began a light or more active program, also
lived longer (RR, 0.58). Similarly, Hung et al com-
pared the effect of aerobic training (AT) or com-
bined AT and strength training (CT) on peak aero-
bic power (VO2 peak), distance walked in 6
minutes, upper and lower extremity maximal
strength, and quality of life in elderly women with
CHD [56]. The subjects, randomly assigned to AT
or CT, exercised 3 days/week for 8 weeks. Both AT
and CT improved similarly in VO2 peak, 6 minute
walking distance, lower extremity strength, and
emotional as well as and global quality of life.
Since the association between long-term outcomes
and the number of cardiac rehabilitation sessions
attended were unknown, Hammill et al identified
30,161 elderly patients who attended at least one
session over a four-year period [57]. After adjust-
ment for several confounders, the results showed
the following: those who attended 36 sessions had
a 14% lower risk of death and a 12% lower risk of
 Physical Inactivity: Associated Diseases and Disorders
MI than those who attended 24 sessions; a 22%
lower risk of death and a 23% lower risk of MI
than those who attended 12 sessions; and a 47%
lower risk of death and a 31% lower risk of MI than
those who attended one session. In an early meta-
analysis of 48 clinical trials involving patients with
CHD, exercise-based cardiac rehabilitation de-
creased all-cause mortality (20%), cardiac mortali-
ty (26%), nonfatal MI (21%), coronary artery by-
pass graft surgery (13%), and percutaneous
coronary angioplasty (19%) [58].
Flynn et al tested the effects of exercise training on
the health status of individuals with heart failure
[59]. This multi-center, randomized controlled trial
involved stable outpatients with heart failure, of
which 1,172 underwent usual care plus aerobic ex-
ercise training consisting of 36 supervised sessions
followed by home-based training. The control
group only received usual care. The researchers
concluded that “exercise training conferred modest
but statistically significant improvements in self-
reported health status compared with usual care
without training.”
Ischemic Stroke. In 2008, stroke was the third
leading cause of death in the United States [60],
and each year an estimated 795,000 people experi-
enced a new or recurrent stroke [61]. However,
physical activity has been shown to reduce the risk
of ischemic stroke in both women and men. For
example, Hu et al examined the association be-
tween physical activity and risk of stroke in 72,488
women [62]. After eight years of follow-up, the
relative risks for ischemic stroke across increasing
metabolic equivalent tasks from lowest to highest
quintiles were 1.00, 0.87, 0.83, 0.76, and 0.52.
Similarly, Lee and Blair examined the association
between cardiorespiratory fitness and stroke mor-
tality in men over a ten year period [63]. After ad-
justment for age and other risk factors, the high-fit
men had a 68% lower risk and moderately-fit men
a 63% lower risk of stroke mortality compared with
the low-fit men.
More recent studies confirm the importance of
physical activity in reducing the risk of ischemic
stroke. For example, a prospective cohort of stroke-
free older individuals in the Northern Manhattan
Study indicated that moderate to heavy physical
activity was protective against the risk of ischemic
325
stroke in men, but not women [64]. However, their
later study found that increased levels of physical
activity were associated with a lower risk of silent
brain infarcts in both men and women [65].
Hypertension. Aging is accompanied by cardio-
vascular changes that include a decrease in elastic-
ity and an increase in stiffness of the coronary ar-
teries, which increases the afterload on the left
ventricle resulting in systolic hypertension.
Unfortunately, hypertension is a major public
health problem and appears to be increasing. For
example, in a community-based prospective study,
Vasan et al evaluated the lifetime risk of developing
hypertension in 55- to 65-year-old individuals who
were free of hypertension at baseline [66]. The re-
sidual lifetime risk for developing hypertension was
90% in both groups. Compared with an earlier pe-
riod, the risk for hypertension remained unchanged
for women, but increased approximately 60% for
men.
Since exercise is a cornerstone therapy for the pre-
vention, treatment, and control of hypertension,
lifestyle modifications are strongly encouraged. In
an early study of 14,998 Harvard male alumni,
those who did not engage in vigorous sports play
were at a 35% greater risk for hypertension than
those who did [67]. Moreover, increased levels of
BMI, weight gain since college, history of parental
hypertension, and lack of strenuous exercise inde-
pendently predicted an increased risk. The follow-
ing year, Blair et al reported on the association of
physical fitness with hypertension in men and
women over a period of one to twelve years [68].
Those with low levels of physical fitness had a rela-
tive risk of 1.52 compared with the highly fit group.
As noted by Brennan et al, isolated systolic hyper-
tension is present in most older women [69]. To
evaluate the possible effect of lower levels of physi-
cal exertion on blood pressure, they studied 109
elderly women, of whom 63.3% were hypertensive.
The mean systolic BP was lower among women
moving 5 or more hours/day than those moving
less than 5 hours/day. Others carried out a similar
six-month randomized controlled trial of combined
aerobic and resistance training in persons with un-
treated systolic BP of 130-159 mm Hg or a diastolic
BP of 85-99 mm Hg [70]. Although the mean dia-
stolic BP was significantly reduced, the systolic BP
326 Annals of Clinical & Laboratory Science, vol. 42, no. 3, 2012
was not, suggesting that “older persons may be re-
sistant to exercise-induced reduction in systolic
BP,” perhaps due to “the lack of improvement in
aortic stiffness….” Based on current evidence, the
American College of Sports Medicine recommends
30 or more minutes of moderate-intensity physical
activity for hypertensive people on most, but pref-
erably all, days of the week [71].
Type 2 Diabetes Mellitus. Aging is commonly as-
sociated with an increased incidence of insulin re-
sistance and type 2 diabetes mellitus. Unfortunately,
the number of diagnosed cases in the U.S. rose
from 1.5 million in 1958 to 17.9 million in 2007
and as of 2009, 23.6 million Americans had type 2
diabetes [72]. In the U.S., diabetes is currently the
seventh most common cause of death. However,
since it is also a major risk factor for cardiovascular,
cerebrovascular disease, and peripheral vascular
diseases, hypertension, and renal disease, its actual
cause of death is significantly higher.
Type 2 diabetes constitutes from 92% to 96% of all
diabetes cases. For decades, it was termed “late-
onset diabetes” since it was uncommon prior to
aged 40 years. It was also commonly referred to as
the “3-Fs”- female, fat, and forty. However, because
of the marked lifestyle changes over the past several
decades, the disease is now common in males, ado-
lescents and young adults. Indeed, the major risk
factors for type 2 diabetes are abdominal obesity
and physical inactivity. Although a familial risk
factor is often present, it is significantly less impor-
tant than lifestyle.
Numerous studies have clearly demonstrated that
exercise improves glucose metabolism. To evaluate
the effect of lifestyle intervention, the Diabetes
Prevention Program Research Group assigned
3,234 non-diabetic middle-aged persons with ele-
vated fasting and post-load plasma glucose concen-
trations to one of three groups: placebo, metfor-
min, or lifestyle change [73]. After an average
follow-up of 2.8 years, lifestyle intervention de-
creased the incidence by 58% and metformin use
by 31%. Moreover, after a median follow-up of
23.1 years, the Physicians Health Study reported
that the hazard ratios of inactive men with normal,
overweight or obese BMIs were 1.41, 3.14, and
6.57, respectively [74]. Active but overweight and
obese men had hazard ratios of 2.39 and 6.22.
In an early study, Pan et al randomized 577 Chinese
men and women with impaired glucose tolerance
to either a control group or one of three treatment
groups: diet only, exercise only, or diet plus exercise
[75]. After six years of follow-up, 67.7% of the con-
trol group developed diabetes compared with
43.8%, 41.1% and 46.0% in the diet only, exercise
only, and diet plus exercise groups, respectively.
Similarly, 522 middle-aged overweight/obese
Finnish subjects with impaired glucose tolerance
were randomly assigned to an intervention group
or a control group [76]. Each interventional group
member received counseling for reducing weight,
improving diet, and increasing physical activity.
After 4 years follow-up, the incidence of diabetes
was 11% in the intervention group and 23% in the
control group.
Hu et al. followed 84,941 female nurses who were
free of cardiovascular disease, diabetes, and cancer
at baseline for 16 years [77]. They concluded that
91% of the 3,300 new cases of type 2 diabetes were
attributable to poor lifestyles. Although over-
weight/obesity was the single most important risk
factor, physical inactivity was the second most im-
portant factor. Similar findings were also reported
in children [78]. In this study, insulin resistance
was evaluated in 9 to 11.5 year-old obese and lean
children. As with adults, total and central adiposity
were positively associated with increased insulin re-
sistance while physical activity was negatively as-
sociated with insulin resistance.
Importantly, diabetic adults 18 years and older who
walked at least two hours/week reportedly had a
39% lower all-cause mortality rate and a 34% low-
er cardiovascular mortality rate compared with
sedentary persons [79]. The mortality rates were
lowest for individuals who walked three to four
hours/week. The authors concluded that “one death
per year may be preventable for every 61 people
who could be persuaded to walk at least 2 hr/wk.”
Cancer. Cancer is the second leading cause of
death in the U.S., Canada, and most of Europe. In
addition to poor nutrition and tobacco use, physi-
cal inactivity is a major risk factor for several can-
cers. Indeed, “The adoption of an active lifestyle
could reduce all-cause cancer rates by as much as
46%” [80]. Although the mechanism(s) whereby
regular physical activity may prevent site-specific
 Physical Inactivity: Associated Diseases and Disorders
Table 2. Cancer and Physical Inactivity
Prostate
Breast
Colon
Lung
Ovary
Endometrium
cancers is unknown, evidence suggests that compo-
nents of the innate immune system are involved, as
well as a better overall lifestyle, lower body fat, de-
creased stool transit time, lower estrogen levels, and
enhancement of antioxidant enzyme systems [81].
The major cancers associated with physical inactiv-
ity are listed in Table 2.
1. Prostate Cancer. Studies of the relationship be-
tween physical activity and prostate cancer have
been inconsistent. A literature review between 1989
and 2001 identified 13 cohorts of U.S. and interna-
tional studies, nine of which showed an association
between increased physical activity and decreased
risk of prostate cancer [82]. Five of 11 case-control
studies also indicated that high physical activity
levels decreased prostate cancer risk. Of all studies
between 1976 and 2002, 16 of the 27 reported a
reduced risk in the most active men. More specifi-
cally, a recent Chinese case-control study showed
that moderate physical activity was inversely asso-
ciated with prostate cancer risk [83]. There was also
a dose-response relationship. However, a popula-
tion-based case-control Canadian study reported
mixed evidence for an association between prostate
cancer risk and physical activity [84]. Although oc-
cupational activity decreased the risk, only vigor-
ous physical activity decreased the risk.
Nilsen et al prospectively examined the association
between physical activity and prostate cancer in
29,110 Norwegian men [85]. After 17 years of fol-
low-up, multivariable analysis showed that exercise
frequency and duration were inversely associated
with the risk of advanced prostate cancer and can-
cer death. However, the results of a Health
Professionals Follow-up Study showed no associa-
tion between total prostate cancer and total, vigor-
ous, or non-vigorous physical activity, although in
men 65 years and older there was a lower risk in the
327
highest category of vigorous activity for advanced
and fatal prostate cancer [86].
Since vigorous activity after diagnosis had been re-
ported to be inversely associated with prostate can-
cer-specific mortality, Richman et al examined vig-
orous activity and brisk walking among 1,455 men
with clinically localized prostate cancer [87]. After
2,750 person-years, men who walked briskly for 3
hours/week or more had a 57% lower rate of pro-
gression than those who walked at an easy pace for
less than 3 hours/week.
2. Breast Cancer. Studies clearly demonstrate that
increased physical activity reduces the risk of breast
cancer. Although the positive effect of exercise ap-
plies to both pre- and postmenopausal women, the
association is stronger for the latter [88]. Among
women of the French E3N cohort, there was a lin-
ear decrease in breast cancer risk with increasing
amounts of moderate (P < 0.01) and vigorous (P <
0.0001) recreational activities [89]. Moreover,
women in the Women’s Contraceptive and
Reproductive Experiences Study, which involved
both black and white women with newly diagnosed
breast cancer, were compared with cancer-free
women matched for age, race/ethnicity, and study
site [90]. Here, breast cancer risk was significantly
decreased with increased levels of lifetime exercise
activity in all women. Similarly, John et al con-
ducted a population-based case-control breast can-
cer study in African Americans, Latinos, and
whites to assess the association with a lifetime of
moderate and vigorous physical activity [91]. The
results showed significant breast cancer risk reduc-
tions in both pre- and postmenopausal women and
were similar in the three racial/ethnic groups.
Interestingly, the Women’s Health Initiative
Observational Study of older women reported that
those who had engaged in strenuous physical activ-
ity three or more times/week and worked up a
sweat at age 35 years, had a relative risk for breast
cancer of 0.86 compared with women who did not
[92]. Thus, “An hour every day of moderate or
strenuous activity provides the most benefit.” It
should also be noted that obesity, which can be
controlled to a significant degree by physical activ-
ity, is also a major risk factor for postmenopausal
breast cancer [93].
328 Annals of Clinical & Laboratory Science, vol. 42, no. 3, 2012
3. Colorectal Cancer. There is a strong inverse as-
sociation between risk of colon cancer and physical
activity. In a case-control study, data collected on
lifetime occupational and recreational physical ac-
tivity for ages 20, 30, 40, 50 and 60 years from
patients with colon cancer were compared with a
cancer-free control group [94]. For lifetime physi-
cal activity, the multivariate odds ratio for the
highest quartile was 0.37. For life-long high exer-
cisers, compared with non-exercisers, the odds ra-
tio was 0.26.
Others examined the association between occupa-
tional and leisure-time physical activity and
colorectal cancer in a cohort of male smokers [95].
After 12 follow-up years, the relative risks for light
and moderate/heavy occupational activity were
0.60 and 0.45, respectively. In addition, the relative
risk for distal colon cancer in moderate/heavy oc-
cupation activity was 0.21. For rectal cancer, the
relative risk reductions for light and moderate/
heavy occupational activity were 0.71 and 0.50, re-
spectively. Slatterly et al also reported that vigorous
physical activity reduced the risk of rectal cancer
among both men and women [96].
Although the incidence of colorectal cancer in
Japan is among the highest in the world, increased
job-related physical activity in males is associated
with a significant risk reduction in both distal co-
lon and rectal carcinoma [97]. However, only total
and moderate or “hard” non-job physical activity
averted a positive affect on rectal cancer. In fe-
males, job-related physical activity and moderate or
“hard” non-job physical activity were protective
only in the distal colon. In a recent review of 52
studies, 37 found a significant association between
the level of physical activity and decreased colon
cancer [98].
4. Lung Cancer. Population studies of the associa-
tion between physical activity and lung cancer have
yielded inconsistent results. For example, Bak et al
examined the relationship between physical activi-
ty and risk of lung cancer in a Danish cohort aged
50 to 64 years [99]. After adjustments for smoking,
education level, possible occupational exposure to
carcinogens, and diet, there was “no convincing
protective effect of physical activity on lung cancer
risk.” Similarly, a large European study showed “no
consistent protective association of physical activity
with lung cancer risk” [100].
Other studies, however, have shown that physical
activity decreases the risk of lung cancer. For ex-
ample, an Iowa Women’s Health Study found that
women with high physical activity levels were less
likely to develop lung cancer than those who were
relatively inactive [101]. Similarly, a case-control
study of women from the Czech Republic reported
an inverse association for lung cancer between
smokers and physical exercise [102]. Moreover, re-
searchers of an extensive Norwegian study reported
that men who exercise four or more hours each
week had a lower lung cancer risk for both small
cell and adenocarcinoma than men who did not
exercise (relative risk, 0.71) [103].
Furthermore, a sub-cohort of these men in which
physical activity was assessed twice, the relative risk
for lung cancer was 0.39 for those who were most
active at both assessments. Moreover, in a meta-
analysis “of all relevant reports published from
1966 through October 2003”, the odds ratios for
lung cancer were 0.87 for moderate leisure-time
physical activity and 0.70 for high activity [104].
5. Ovarian Cancer. Increased physical activity
may lower the risk for ovarian cancer by decreasing
circulating sex hormones, ovulation frequency,
body fat or chronic inflammation. To investigate
this possible association, Hannan et al carried out a
prospective cohort study of 27,365 women [105].
Although there was no overall significant associa-
tion between physical activity and ovarian cancer
over the previous year, “the results are suggestive of
an inverse association.” However, in the
Copenhagen City Heart Study “a highly signifi-
cant inverse association was seen between vigorous
physical activity in leisure-time and cancer of the
ovary…” [106]. Similarly, a case-control Canadian
study reported that, compared to women in the
lowest tertiles of moderate, vigorous and total rec-
reational activity, those in the highest tertiles had a
significantly lower risk [107]. In a case-controlled
Chinese study, the risk for ovarian cancer also de-
clined with increasing duration of strenuous sports
and frequency of “activity-induced sweating among
pre-menopausal women….” [108]. In addition, a
literature review concluded that “physical activity
protects against ovarian, endometrial and post-
menopausal breast cancer independently of BMI”
[109].
 Physical Inactivity: Associated Diseases and Disorders
6. Endometrial Cancer. The results of an early
population-based case-control study of physical ac-
tivity at work and outside work showed that non-
retired women holding sedentary jobs or with sed-
entary lifestyles were at a “somewhat increased risk
of endometrial cancer” [110]. Similarly, the authors
of an early British study concluded that “physically
inactive women may be at increased risk of endo-
metrial cancer because they are more likely to be
overweight or obese” [111].
More recently Moradi et al reported results from a
population-based case-control study in the “entire
Swedish female population aged 50-74 years…”
[112]. Compared with the lowest levels of physical
exercise, there was a significant reduction in endo-
metrial cancer for those in the highest exercise lev-
els. Another population-based case-control study
that examined the relationship between endome-
trial cancer and physical activity from exercise,
household activities, and transportation showed
the following: exercise participation in both adoles-
cence and adulthood reduced the cancer risk by
40%; postmenopausal women who initiated exer-
cise in adulthood significantly reduced their cancer
risk; and reductions in risk were found for house-
hold activities and walking for transportation [113].
A review of physical activity and individual cancer
risk concluded that “a convincing risk reduction
was found for colon cancer and estrogen-depen-
dent malignancies such as breast and endometrial
cancer” [114].
Sarcopenia. By the age of 50 years, most humans
become aware that they are losing endurance and
muscle strength due to a loss of muscle mass and
adaptive ability (sarcopenia). The most apparent
causes are lack of use, depletion of muscle regenera-
tion stem cells, a decline in anabolic hormones, and
decreased physical activity. As a result, muscle
strength decreases approximately 50% from age 30
to 80 years [115], and by the seventh and eighth
decades of life, maximal voluntary strength is de-
creased by 20-40% for men and women in both
proximal and distal muscles [116].
A recent study evaluated the effects of aging on the
functional and morphological properties of cardi-
ac, skeletal, intestinal muscles, and oxidative status
in mice to determine whether a moderate lifelong
exercise program would be protective against some
329
harmful aging effects [117]. Indeed, moderate
treadmill running during murine lifespan reversed
all of the aging effects on intestinal, skeletal, and
heart muscles. It also prevented the enhancement
of lipid peroxidation and sarcopenia.
Raguso et al evaluated the association between
physical activity on body composition in healthy
elderly men and women [118]. After a 3-year peri-
od, increased physical activity was associated with
greater muscle mass and less truncal body fat.
Exercise not only reverses the age-associated de-
cline in muscle mass, but also muscle strength
[119]. After 12 weeks of exercise training, about
40% of the 10-year strength loss and 75% of the
muscle mass loss were restored.
When exercise intensity is low, only modest in-
creases in strength are achieved in the elderly.
However, progressive resistance training shows
similar or even greater strength gains compared
with young individuals. For example, after a 12-
week progressive training program involving older
men, the extensor strength more than doubled,
flexor strength more than tripled, and total muscle
area increased by 11.4% [120,121]. Strength train-
ing also leads to significant improvement in muscle
strength in frail individuals aged 90 years and older
[122]. After eight weeks of high-intensity resistance
training, strength gains averaged 174%, mid-thigh
muscle area increased 9%, and mean tandem gait
speed improved 48%.
Osteoporosis and Fractures. Osteoporosis, a very
common problem in postmenopausal women and
the elderly, is associated with a decrease in bone
mineral density (BMD) and increased fractures re-
sulting in a high percentage of late-life disability
and death. Unfortunately, 20 million Americans
have osteoporosis and another million will develop
the disease unless preventive action is taken [123].
An estimated 26% of U.S. women 65 years and
older and more than 50% 85 years and older have
osteoporosis [124]. However, osteoporosis is not
just a woman’s disease. Although men are com-
monly affected, it is not well appreciated by the
medical community. In fact, two million American
men have osteoporosis compared with eight mil-
lion women [125]. Moreover, 24% of men 45 years
and older will have an osteoporosis-related fracture
compared with 47% of women and 31% will die
330 Annals of Clinical & Laboratory Science, vol. 42, no. 3, 2012
within one year compared with 17% of women.
Osteoporosis is responsible for over 1.5 million
fractures each year in the U.S. resulting in 500,000
hospitalizations, 800,000 emergency room visits,
2.6 million physician visits, 180,000 nursing home
admissions, and 12 -18 billion dollars in healthcare
costs.
Numerous studies have shown that physical activi-
ty is an important factor in reducing/preventing
osteoporosis. Furthermore, increased physical ac-
tivity during childhood and adolescence is an im-
portant prevention factor. For example, athletically
active adolescent females have higher bone mass
than their sedentary counterparts [126]. Moreover,
weight bearing physical activity during the years of
peak bone acquisition (age 12 to 18 years) “appears
to have lasting benefits for lumbar spine and proxi-
mal femoral aBMD (areal bone mineral density) in
postmenopausal women.” Similarly, an Eastern
Finland study that compared the walking distance
at ages 9 to 11 years with femoral BMD in peri-
menopausal women showed that the greater the
walking distance, the higher the BMD [127].
Others studied the effect of daily physical activity
on the proximal femur in women aged 35-40 years
[128]. After 12 months, there was a significant rela-
tionship between physical activity and proximal
femoral BMD. Similarly, after comparing the
BMD of long distance male runners with age-
matched healthy controls, the runners had signifi-
cantly higher BMD at the calcaneus, lower limbs,
femoral neck, pelvis, and trabecular lumbar spine
[129]. However, a meta-analysis of 10 studies that
examined the effect of walking on BMD in men
and postmenopausal women indicated that walk-
ing only had a significant positive effect on lumbar
BMD, but the effect was not significant on the fe-
mur or calcaneus [130]. Nevertheless, when com-
bined with a weight-bearing program, the results
are more significant. For example, in a 12-month
prospective randomized trial, elderly women as-
signed to the exercise group showed a significant
increase in BMD of the Ward’s triangle,
improvement in walking speed, and isometric grip
strength [131].
Physical Disability. As a person ages, there is a
significant increased risk of becoming frail and dis-
abled. In an early study, predictors of disability
were compared between 50- to 80-year old mem-
bers of a runners’ club and a university population
[132]. The runners’ club members had significantly
better overall health and less disability at baseline
and after a six-year follow-up. Predictors of greater
subsequent disability were greater baseline disabil-
ity, medication, pack-years of smoking, and age, as
well as increased blood pressure, arthritis, and less
physical activity. Similarly, a six-year prospective
longitudinal disability study compared older men
and women with general community members
[133]. The authors concluded that “older persons
who engage in vigorous running and other aerobic
activities have lower mortality and slower develop-
ment of disability than do members of the general
population.”
To further appreciate the benefits of aerobic
exercise on disability and mortality in older per-
sons, Wang et al examined whether regular exer-
cise could compress morbidity into later years of
life [134]. Compared with the control group, their
findings showed the following: (a) disability levels
were significantly lower in the runners’ club mem-
bers; (b) relative disability was postponed 8.7 years;
(c) runners’ club membership and participation in
other aerobic activities were protective against mor-
tality; and (d) controls had a 3.3 times higher death
rate in every disease category.
Overweight/Obesity. Physical inactivity and obe-
sity are major public health concerns throughout
the industrialized world. Indeed, obesity and phys-
ical inactivity independently contribute to all-cause
and cause-specific mortality among young and
middle-aged adults [135]. These researchers com-
pared adiposity with physical activity in predicting
mortality over a 24-year period involving 116,564
women who were free of cancer and coronary heart
disease at baseline. Compared with physically ac-
tive lean women, the multivariate relative risks of
death were 1.55 for lean inactive women, 1.91 for
active obese women, and 2.42 for inactive obese
women. Moreover, a BMI greater than 25 and
physical activity less than 3.5 hours each week to-
gether accounted for 31% of all premature deaths.
Since the amount of physical activity needed to
prevent long-term weight gain in older persons was
unclear, Lee and associates carried out a prospec-
tive 15 year study involving 34,079 healthy women
 Physical Inactivity: Associated Diseases and Disorders
[136]. At the end of the study, the average weight
gain was 2.6 kg. However, those who were success-
ful in maintaining normal weight and gaining less
than 2.3 kg averaged 60 minutes of daily moderate
intensity activity (mostly walking).
Menschik et al studied 3,345 adolescents over a
five-year period and found that the likelihood of
being an overweight young adult was reduced by
48% in those involved in various extracurricular
wheel-related activities (i.e., rollerblading, roller
skating, skate boarding, or bicycling) more than
four times each week [137]. Moreover, each week-
day the students who participated in curricular
physical education decreased the odds of being
overweight adults by 5%; participation in physical
education every weekday decreased the odds by
28%.
The HALE project investigated the single and
combined effect of the Mediterranean diet, being
physically active, moderate alcohol use, and non-
smoking on all-cause and cause-specific mortality
in elderly Europeans [138]. After 10 years of follow-
up, the hazard ratios were as follows: adherence to
a Mediterranean diet, 0.77; moderate alcohol use,
0.78; physical activity, 0.63; and non-smoking,
0.65. The combination of these risk factors lowered
the all-cause mortality rate to 0.35. Indeed,
Mokdad et al noted that combined physical inac-
tivity and obesity/poor diet was the second highest
“actual” cause of death in the United States in 1990
and 2000 [2,3].
Depression and Dementia/Alzheimer’s Disease.
Depression. Depression is reportedly the leading
cause of nonfatal medical disability in developed
countries among those aged 15 to 44 years [139].
Indeed, depression is the major cause of suicide, the
10th leading cause of death in the U.S. Although
aging is strongly associated with functional decline
and depression, increased physical activity has been
shown to delay these disorders. For example, 158
men and women aged 50 years and older with a
major depressive disorder were randomly assigned
to a program of aerobic exercise, antidepressants, or
combined exercise and medication [140]. Although
persons receiving medication alone exhibited the
quickest initial response, exercise was equally effec-
tive in reducing depression after 15 weeks.
331
More recently, Lindwall et al investigated the rela-
tionship between light and strenuous exercise and
depression in elderly Swedish men and women
[141]. Here, the inactive elderly had higher depres-
sion scores both in terms of light and strenuous ex-
ercise. Moreover, those who were continuously ac-
tive had lower depression scores than both the
continuously inactive persons and those who shift-
ed from activity to inactivity during the previous
year. Similarly, a Finnish study found that those
who exercised at least two to three times each week
experienced significantly less depression, anger,
cynical distrust, and stress than those exercising
less frequently or not at all [142]. Others evaluated
the effect of treadmill walking in a group of U.S.
men and women with a major depressive episode
[143]. Following an interval training pattern, tread-
mill walking 30 minutes daily for ten days resulted
in “a substantial improvement in those with major
depressive disorders.”
Dementia/Alzheimer’s Disease. Under normal
conditions, the production of neurons (i.e., neuro-
genesis) occurs only in the hippocampus and olfac-
tory systems of the adult brain. Since aging causes
changes in the hippocampus, it may lead to cogni-
tion decline in the elderly. However, several studies
have shown that regular exercise ameliorates some
of the deleterious morphological and behavioral
consequences in aging mice and thereby increases
the potential for neurogenesis [144-147]. Moreover,
as in mice, exercise was shown to have a primary
effect on dentate gyrus cerebral blood volume,
which correlated with cardiopulmonary and cogni-
tive function in humans [148].
Recognizing that increased physical activity may
also maintain cognitive function in older adults,
Weuve and associates examined the association be-
tween regular long-term physical activity, includ-
ing walking, and cognitive function in 18,766 el-
derly women [149]. They found that when
combining the tests of cognition, verbal memory,
category fluency and attention, women in the high-
est activity quintile had a 20% lower risk of cogni-
tive impairment. Indeed, an American study noted
that greater energy expenditure is protective against
cognitive impairment in a dose-response manner
[150]. However, since low-intensity physical activi-
ty, such as walking, had not been evaluated with
332 Annals of Clinical & Laboratory Science, vol. 42, no. 3, 2012
regards to dementia, Abbott et al examined this as-
sociation in men aged 71 to 93 years [151]. After
five years of follow-up, those who walked less than
0.25 miles each day experienced a 1.8-fold higher
risk for dementia than those who walked two or
more miles each day.
Colcombe and associates reported that increased
cardiovascular fitness results in increased function-
ing of the attentional brain network during a cog-
nitively challenging task [152]. Here, highly fit or
aeraobically trained individuals showed greater
task-related activity of the prefrontal and parietal
cortices compared with low fit or the non-aerobic
control group. More recently, they reported a sig-
nificant increase in brain volume in 50 to 79 year
old individuals who participated in aerobic fitness
compared with those who participated in the non-
aerobic group [153].
Alzheimer’s disease (AD) is the sixth leading cause
of death in the U.S. The major risk factors include
age, family history, educational level, and the pres-
ence of the apolipoprotein E (APOE) genotype e4
[154]. A leading explanation for AD is an increase
in cerebral beta-amyloid protein. Importantly,
Lazarov et al recently reported that “environmental
enrichment” decreases the accumulation of amy-
loid protein and alters the gene expression changes
in a double transgenic mouse model [155]. These
genetically modified mice were placed in an “en-
riched” environment containing exercise equip-
ment and toys, as well as the usual food, water, and
bedding material for the control mice. After five
months, the brains of the mice housed in the en-
riched environment showed a significant reduction
in amyloid protein, which was primarily related to
increased physical activity.
At about this same time, Podewills and associates
reported that persons regularly engaged in a variety
of physical activities may decrease the risk of devel-
oping AD by as much as 50% [156]. Increased
physical activity also decreased the risk of all-cause
and ischemic dementia. However, physical activity
did not affect individuals who carried APOE4, a
gene variant that increases the risk for AD. Others
also reported that leisure-time physical activity at
midlife is associated with a decreased risk of AD
[157]. Thus, “regular physical activity may reduce
the risk or delay the onset of dementia and AD,
especially among genetically susceptible
individuals.”
Both physical activity and diet were recently evalu-
ated in a prospective study of two cohorts compris-
ing community-dwelling elders without dementia
at baseline [158]. After 14 years, the hazard ratio for
“some” physical activity was 0.75 and 0.67 for
“much” activity. A literature review of the positive
effects of exercise on the aging brain and cognition
has been published [159].
Miscellaneous Diseases/Disorders.
Inflammation and Atherosclerosis. Although the
pathogenesis of atherosclerosis is incompletely un-
derstood, inflammation is a widely accepted mech-
anism. Since CHD is the number one cause of
death in the U.S. and in most other Western coun-
tries, and cerebrovascular disease is number three,
the prevention or delay of these diseases would not
only improve the quality of life but increase longev-
ity. As of 2005, twenty-two prospective epidemio-
logic studies demonstrated that increased blood
levels of high sensitivity C-reactive protein (hs-
CRP), a sensitive marker of inflammation, is a
strong predictor of future CHD. Other studies also
showed that physical activity decreases the inflam-
matory process. For example, a group of 197 pa-
tients with CHD was randomized to either a com-
prehensive lifestyle program (regular physical
activity, low fat diet, smoking cessation) or usual
care with routine follow-up for six months [160].
Independent of diet and smoking, physical perfor-
mance was significantly and inversely correlated
with levels of C-reactive protein, interleukin-6, and
soluble cell adhesion molecule-1 in patients with
CHD “possibly retarding the process of
atherosclerosis.”
Immune System. Aging is commonly accompa-
nied by a decrease in immune function, which can
lead to an increased incidence of infectious diseas-
es, malignancy, and autoimmune disorders; thus,
the immune theory of aging. Since the aging pro-
cess does not uniformly affect the immune system,
a possible explanation may be due, at least in part,
to differences in the level of physical activity.
Indeed, many studies have shown that moderate
exercise training attenuates immunosenescence in
the elderly. For example, Chubak et al studied the
effects of moderate-intensity exercise on the risk of
colds and upper respiratory tract infections in over-
weight and obese sedentary postmenopausal wom-
en [161]. After several months, the risk of colds in
 Physical Inactivity: Associated Diseases and Disorders
the control group was three times that of the
exercisers.
Although moderate regular physical activity bene-
fits the immune system by augmenting resistance
to infections and some forms of cancer, intense
long-term exercise (e.g., marathon runners) appar-
ently has a negative effect. For example, the suscep-
tibility to upper respiratory tract infections (URTI)
after chronic physical exercise at various intensities
is described with a “J-shaped” curve. In this review,
Nieman presented data from several studies indi-
cating that individuals engaging in marathon-type
events and/or very heavy training are at increased
risk of URTI [162].
Regular exercise also accelerates wound healing in
the elderly. For example, in a group of healthy older
men and women, wound healing occurred at a sig-
nificantly faster rate in the exercise group compared
with the sedentary group [163].
Metabolic Syndrome. The metabolic syndrome is
a combination of cardio-metabolic risk determi-
nants including central obesity, insulin resistance,
glucose intolerance, dyslipidemia, hypertension,
hyperinsulinemia, and microalbuminuria. Sisson
and associates examined the association of leisure
time sedentary behavior (LTSB) and usual occupa-
tional/domestic activity with metabolic syndrome
and cardiovascular disease (CVD) risk factors in
men and women [164]. After four years, the odds
of developing the metabolic syndrome were 1.94 in
men for four or more LTSB hours/day, compared
with one or less hour/day. LTSB of four or more
hours/day was also associated with increased waist
circumference, low HDL-cholesterol, hyperten-
sion, and increased blood glucose in men. In wom-
en, high LTSB was only associated with an in-
creased risk of the metabolic syndrome.
Summary
Physical activity clearly leads to increased physical
fitness, exercise capacity, and risk reduction of a
wide variety of pathological diseases and clinical
disorders resulting in lower rates of morbidity, all-
cause and cause-specific mortality, and increased
life expectancy. More specifically, physical inactiv-
ity increases the risk of coronary heart and cerebro-
vascular diseases, type 2 diabetes mellitus, hyper-
tension, several cancers (e.g., lung, prostate, breast,
colon, others), osteoporosis/fractures and
333
dementia, among others. However, even among the
very old “not only continuing but also initiating”
physical activity is associated with better survival
and function [165]. Moreover, since there is a linear
relationship between the level of physical activity
and health status, children and adolescents should
participate daily in 60 minutes or more of moder-
ate to vigorous physical activity that is enjoyable,
involves a variety of activities, and is developmen-
tally beneficial.
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