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Chronic Psychological Stress and its Effects on the Human Body

Rhiannon Gagin
Sponsor: Dr. Chris Osgood
BIOL 405
15 April 2016

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Chronic stress has been known to cause harm to the body, but
what is really happening? Understanding the stress response that
occurs within the brain helps to shed light on this question. This
research delves into the effects of chronic stress on the human body in
relation to the cardiovascular, gastrointestinal, and immune system. It
was found that, with constant release of cortisol from the stress
response, the cardiovascular system tends to work harder. This can
increase the risk of cardiovascular disease, hypertension, heart attack,
and stroke. Stress takes a toll on the gastrointestinal tract as well by
exacerbating existing conditions of GERD and irritable bowel syndrome
as well as increasing incidence of peptic ulcer disease. The stress
response has been found to reduce immune response. A connection
was also observed between the release of cortisol from a stress
response and an increase in pro-inflammatory cytokines. Interleukin-6
(IL-6), a pro-inflammatory cytokine, is known to increase as one ages.
A study found that high-stress jobs such, as caring for a loved one with
Alzheimers disease, causes higher levels of IL-6, which shows a link
between chronic stress and immune system aging. The research also
looks into chronic stress and the effects at the cellular level. It was
found that chronic stress actually accelerates telomere shortening,
which is a marker for cellular aging. All of these effects can be slowed,
however, with control of stress. A study done at the University of

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California, San Francisco found that a better diet, stress management,
exercise, and increased social support, actually helps to increase
telomere length, which, in turn, slows down cellular aging. Another
study found that techniques such as meditation help to reduce stress
effects on the body. This research helped to illustrate the dangers of
chronic stress on the body. However, reducing these effects isnt about
finding the mythical fountain of youth. Instead, the true goal is
improving overall health and postponing the onset of age related
diseases by discovering ways to eliminate or reduce the damage to our
cells that happens over time.

What is stress? Stress is such a common thing that people often
forget how damaging it really is to the body. This epidemic of chronic
stress causes extra strain on bodily systems, which increases the risks
of cardiovascular or gastrointestinal issues down the road. This also
has an adverse effect on the immune system and even causes
problems at a cellular level causing premature aging. Although society
cannot completely eradicate stress, or find a fountain of youth, one can
find ways to reduce everyday stress to lead a healthier and longer life.

What is stress?

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Stress is defined as a physical, mental, or emotional factor that
causes bodily harm or mental tension (Definition of Stress, n.d.).
People of all ages, races, and genders undergo stress and this chronic
epidemic can eventually lead to physical and psychological health
issues down the road. Not all stress is detrimental to the body; stress
can act as a strong motivator.

The Stress Response

Stress is the bodys response to the experience of a stressor. A
stressor is something in the environment that an individual perceives
in their mind to be a threat. Examples of stressors are exams, loud
noises, rush-hour traffic, rude people, or deadlines at work. But,
stressors are neutral they arent what cause health problems down
the road. More so, its how one responds to a stressor and how they let
it affect them (Nordqvist, 2015). A study done at Penn State found that
people that frequently overreact to stress on a daily basis often suffer
from chronic health issues later in life (Science Daily, 2012).
The human body has a stress response, which is a mechanism
that is used in order to save ones life. Known as the fight or flight
response, the body secretes certain hormones, which help to enable
the body to overcome the stressful situation. The stress response

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starts in the brain. When placed in a stressful situation, the body sends
a message to the emotional processing part of the brain, or the
amygdala. The amygdala then sends a message to the hypothalamus,
which is the control center of the brain. The hypothalamus then
initiates the fight or flight response. This sends a signal to the
adrenal glands, causing them to release epinephrine or adrenaline into
the bloodstream. This causes blood pressure and oxygen intake to
increase. Epinephrine also causes the body to release glucose, which
supplies energy to muscles. After the epinephrine has run its course
through the body, the second stage of the response gets activated. As
shown below in Figure 1, stage 2 of the stress response requires
involvement of the HPA axis, otherwise known as the hypothalamus,
the pituitary gland and the adrenal glands. This stage of the response
works to keep the body on alert. If the body is still under stress, the
hypothalamus releases a hormone called corticotrophin-releasing
hormone (CRH). CRH activates the pituitary gland, which releases a
hormone called adrenocorticotropic hormone (ACTH). This hormone
causes the adrenal glands to release a glucocorticoid called cortisol,
which causes the body to remain energized by shutting down other
functions like the reproductive system or immune system. After the
body is free of the stressful situation it was in, the parasympathetic
nervous system kicks in, causing the cortisol levels to fall and thus
reaching a state of homeostasis (Understanding the Stress Response

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Harvard Health, 2011). This is a very normal and necessary response
to stressful situations. However, the true problem occurs when the
body releases those same hormones on a regular basis due to chronic,

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uncontrolled stress (Sapolsky, 2000).

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Figure 1 Shows pathway of stress in the body. Displays actions of the HPA axis and
what hormones get released into the body (Reiche, 2004).

Stress and the Cardiovascular System

When the body is in a constant state of alertness, various bodily
systems are affected. Due to the frequent release in epinephrine and
cortisol, the cardiovascular system can suffer from issues down the
road. Constant release of these stress hormones causes the heart to
work harder than normal, which can cause increased heart rate, higher

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blood pressure, and cardiovascular tone to increase (Sapolsky, 2000).
Constant elevations over long periods of time can increase the risk of
cardiovascular disease, hypertension, myocardial infarction, and
stroke. Studies involving animals proved that prolonged activation of
the sympathomedullary pathway (SAM) causes a stress-related
increase in risk for coronary artery disease (Cohen et. al. 2007).

Stress and the Gastrointestinal Tract

When cortisol is released by the adrenal glands, other systems
get shut down in order to direct the energy towards keeping the body
alert. One of the systems in which blood flow gets reduced is the
gastrointestinal tract (Understanding the Stress Response, 2011).
Chronic stress has been shown to exacerbate already existing GI
disorders. It aggravates gastroesophageal reflux disease (GERD) and
irritable bowel syndrome (IBS). Studies have found a connection
between jobs with higher levels of stress and increased incidence of
peptic ulcer disease. This was first noted when men in supervisory
positions and air traffic controllers were found to display higher
occurrences of peptic ulcers than craftsman or civilian co-pilots,
respectively. Though not yet proven, there seems to be a minor
association between higher levels of stress causing aggravation of
symptoms of gastro-esophageal reflux disease (GERD). Patients are
reporting increases of heartburn symptoms when they experience

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higher levels of stress. However, research has shown that the role
stress plays in acid reflux is minor, and anti-anxiety medications have
no effect on treatment of reflux disease. The perception that stress
caused the reflux related heartburn is likely a result of the patients
attempting to connect their stress to their symptoms. It was found that
patients with GI symptoms of irritable bowel syndrome (IBS), present
with higher levels of cortisol in samples of saliva and urine than those
of control subjects. This is an indicator of chronic stress being
experienced in IBS patients (Bhatia et. al. 2005).

Stress and the Immune System

Can stress make me sick? Well, in a word, yes. Studies have
provided convincing evidence that the elevated hormones and
dopamine resulting from chronic stress inhibit the immune system from
T-Cell and macrophage activation. The state of mood of a patient also
affects the ability of T-lymphocytes to respond to stimulation of
mitogen, or something that triggers cell division. Patients that are
being treated for depressive disorder also have inhibited lymphocyte
response to mitogens (Khansari et. al. 1990). Stressful life events
appear to provide a greater reduction of immune response than
depression alone. When college students are compared with patients
being treated for depression, students experiencing periods of stress
due to academic demands had a greater decrease in lymphocyte

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response to mitogens and T-cell replication. This also found a reduction
in numbers of natural killer cells and interferon production by white
blood cells. This was also observed in other groups that had
experienced other stressful events such as divorce, death in the family,
and sudden unemployment (Dantzer et. al. 1989). Further studies
demonstrate that cortisol is released in greater concentration during
stressful events and has a more profound effect in suppressing the
immune system. Cortisol is also shown to suppress reduction of
inflammation mediators and cytokines (Reiche et. al. 2004). Stress
related reduction of immune response reduces the bodys ability to
fight infection and heal.
Further studies have been investigating the connection between
the cytokine interleukin-6 (IL-6) and diseases associated with aging. IL6 is a pro-inflammatory cytokine that controls the bodys response to
infection and injury. These cytokines also work to activate the HPA axis,
causing the release of cortisol, which works as an anti-inflammatory
agent to counteract the pro-inflammatory cytokines. Pro-inflammatory
cytokines, especially IL-6, are not like other components of the immune
system that weaken with age. IL-6 actually increases to higher levels
with age as well as negative lifestyle choices such as smoking, higher
BMI, and lack of physical activity. More than 30 years of research
focused on the connection of depression and stress to weakened
immune systems. Conventional wisdom was that pro-inflammatory

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cytokines were reduced along with other immune system functions,
but there is overwhelming evidence to the contrary chronic stress
and depression actually accelerate cytokine production (Robles et. al
There was research performed by Susan K. Lutgendorf from the
University of Iowa that studied four groups of women with different
levels of stress in order to observe differences in their levels of
interleukin-6. The first group included 18 women who provided care to
patients with Alzheimers. The remaining three groups were composed
of 17 women who were in the process of moving, 15 women that did
not experience either of these stressors, and 20 younger women.
Researchers utilized Profile of Mood States (POMS) and early morning
blood draws in order to study the subjects. POMS is a test that allows
the subject to indicate the emotions they experienced in the past
week. Research found that Alzheimers caregivers had significantly
higher scores in the categories of anxiety, depression, anger, fatigue,
and confusion than the other women in the study.
Table 2 Profile of Mood State scores from women in the study. It can be seen that
Alzheimers caregivers have significantly higher scores in categories of anxiety,
depression, anger, fatigue and confusion than women from the other 3 groups
(Lutgendorf et al., 1999).

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Regarding IL-6 levels, it was discovered that the women who were
caring for Alzheimers patients had the highest levels of IL-6. (See
Figure 3. The younger women had the lowest levels compared to the
older non-caregivers. (Lutgendorf et al., 1999).

Figure 3 Levels of interleukin-6 found in women of the study. The caregivers were
found to have the highest levels among the 4 groups. (Lutgendorf et al., 1999).

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The startling factor in this study was that the women providing
care were actually 6-9 years younger than the other two groups of
women. Knowing that IL-6 naturally increases with age, it was noted in
another group of older subjects that were dealing with chronic stress
related to caring for a spouse with Alzheimers disease that their IL-6
levels were four times those of a similarly aged control group. The
conclusion of these studies is that chronic stress could indeed be
contributing to premature immune system aging (Robles et. al. 2005).

Stress and Effects at a Cellular Level

Chronic psychological stress also breaks down human bodies at a
cellular level and accelerates the aging process. This is due to
premature shortening of DNA strands. Each cell contains 46
chromosomes that form DNA. At the end of each strand of DNA are
telomeres, shown in Figure 4, which are nucleoprotein structures that

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serve as the protection and prevent deterioration of the chromosome
(Bergland, 2014).

Figure 4: DNA strands showing telomeres at the ends. Telomeres are the protective
caps that prevent unraveling of the DNA (Bergland, 2014).

Telomeres are made up of a repeat sequence of TTAGGG. As cells

undergo replication in S phase, a part of the telomere is unable to
replicate which causes them to become shorter over time. This gradual
shortening of the telomeric DNA is what causes cellular aging (Epel,
2009). Cells are only able to divide a certain number of times before

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the telomeres become too short, causing the cell to become senescent
or inactive, which means the cell is no longer able to divide. This is a
stage called replicative senescence. When cells become worn out,
after dividing 50-70 times, and need to be replaced, cellular
senescence is used to stop the cell from dividing ("Are telomeres the
key to aging and cancer," n.d.). The downside is, this seems to also be
contributing to aging and shorter lifespan in humans.
Working in conjunction with telomeres is an enzyme called
telomerase. Telomerase is a ribonucleoprotein reverse transcriptase
enzyme, which functions as a form of maintenance for telomeres by
providing added length to counteract the telomere shortening that
occurs from cell division (Puterman et. al. 2010). As the cell ages,
telomerase gradually decreases until the cell reaches senescence. In a
new cell, the telomerase functions to reinforce the telomeres (Epel,
2009). Chronic stress causes the adrenal glands to release
glucocorticoid hormones that cause damage to DNA by reducing antioxidant proteins and accelerates the shortening of telomeres as well as
reduces telomerase activity in the cell (Shammas, 2011). The length of
the telomeres is an indicator of the biological age of a person, but
when stress causes premature shortening of the telomeres, there is an
adverse effect on the longevity of the person.

How to Counteract Stress

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Just knowing the effects of stress on the body is itself stressful, but
there are ways to counter the negative aspects of chronic stress by
various methods that have been in practice for many years. As shown
in Figure 5, this study has proven that well-managed diet, stress
management, exercise, and positive social contact can actually
increase telomere length.

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Figure 5: Diet, exercise, stress management and increased social support, telomere
length can increase (Fernandez, 2013).

A five-year study done by researchers at University of California, San

Francisco (UCSF) observed a group of 35 men with an early stage of
prostate cancer. They demonstrated that a group of 10 men out of the

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35 participants actually had significant increases to telomere length
of about 10 percent after participating in controlled lifestyle changes of
better diet, stress management, exercise and social support. The
control group of 25 men did not change their lifestyles and were found
to have lost 3 percent of their telomere length by the end of the 5-year
study (Fernandez, 2013). This goes to show that positive lifestyle
changes can slow down telomere shortening, which, in turn, can slow
down the aging process.
In addition to lifestyle changes, activities such as meditation
have also been shown to reduce the bodys stress response. Meditation
is an exercise in which a person focuses their mind in order to ease
themselves of stress to promote relaxation. There are many different
types of meditation, such as Transcendental Meditation, which is a type
that involves concentrating on mentally repeating a word or phrase
(Epel et. al. 2009). This particular technique has been found to reduce
blood pressure. A study was performed which observed methods of
stress reduction and the effects on hypertension in African American
men and women over the course of one year. The methods of stress
reduction included Transcendental Meditation (TM), progressive muscle
relaxation (PMR) or attending a health education class (HE). It was
found that the subjects who practiced Transcendental Meditation had
lower systolic and diastolic blood pressures, more than methods of
progressive muscle relaxation and attending health education classes

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(Figure 6) (Schneider et. al. 2005). In addition to reducing
hypertension, Transcendental Meditation has also been found to reduce
basal cortisol levels (Maclean et. al. 1997). Therefore, meditation,
when performed alongside lifestyle changes, helps to reduce the
effects of stress on the body.

Figure 6 Changes in blood pressure in stress-reducing methods of Transcendental

Meditation (TM), progressive muscle relaxation (PMR) or attending a heath
education class (HE). TM shows to have the greatest reduction in both systolic (SBP)
and diastolic (DBP) blood pressures out of the 3 methods (Schneider et. al. 2005).

Chronic stress is indeed very harmful to the body. The ongoing
release of cortisol from the bodys natural stress response has been
found to have negative, long-term effects on the body. Vital parts of
the body, such as the cardiovascular system, the gastrointestinal tract,
and the immune system are harmed. A connection was also found
between chronic stress and damage at a cellular level, which causes

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premature aging. However, all is not lost, as the effects of stress can
be slowed with stress management, a better diet, exercise, and
relaxation techniques.
This research was done in order to provide a deeper
understanding of something that is a commonality in everyones dayto-day lives. We often forget the damage we are causing to our bodies
by letting stressors take control of us. Though it is easier said than
done, I hope that this research can help shed light on this silent killer. It
is important to try and get this problem of chronic stress under control
in order to live healthier and longer lives.

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