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Tuesday

Cortisol, Telomere Length, and Stress

In the 1920s, American  physiologist Walter Cannon was the first to describe the 'fight or flight' response wherein stress hormones prepare our  bodies for battle, or give sufficient energy and speed for us to flee from  danger (Cannon 1915).  Hans Selye  (1907-1982), however,  is considered to  be the father of stress research, and was one of the earliest scientists who  published numerous manuscripts on stress, the hormone cortisol, and their impact on health and disease in the early  decades of the 20th century.   Selye authored the book Stress  without Distress,  where he called  stress 'the spice of life' (Selye 1974).    Selye  recognized stress had positive values when integrated properly into life, but  also recognized that an improper reaction  to stress in life was a major cause of disease, and that cortisol moderated  these effects (Selye 1954).

Cortisol is a hormone that is secreted by the adrenal glands which are located  atop the kidneys.  Cortisol and  noradrenaline initiate a stress response, known as 'the fight or flight  response';.  A massive burst of energy and  feelings of alertness follow the release of cortisol into the bloodstream.  This physiologic event is fueled by dramatic  increases in respiration and increased levels of glucose in the blood stream,  which allows the muscles to work harder, faster and for a longer periods of  time. This response has one purpose: to get you out of harm’s way.  Classic examples could be avoiding an  approaching vehicle or escaping from predators.

For most  of us the word stress has intrinsically negative connotations. The stress  response enables an individual to deal with the stressor (stress causing event),  whatever it may be. Stress is an“experience  accompanied by predictable biochemical, physiological, cognitive, and  behavioral changes that are directed either toward altering the stressful event  or accommodating to its effects” (Taylor 2010).  Stress can be positive or negative depending  on individual context.  Cortisol is  beneficial only while the dangerous stressing event is present: it makes you  alert in the workplace, it aids your concentration and overall sharpens your  mental and physical faculties.  The  problem is that it has been known for decades that elevated and prolonged cortisol levels present health risks which  cannot be understated.

Since Selye's research beginning in the  mid-thirties, scientific evidence has supported the hypothesis that chronic  stress results in long term chemical changes in the body which manifest  themselves in conditions such as, heart and arterial disease, diabetes, high  blood pressure, immunosuppression, obesity and increased body mass index (BMI),  neuron damage,  insomnia,  depression,   increased risk of suicide, osteoporosis, dementia and Alzheimer’s  disease.  The latter two may be caused by  cortisol-associated damage to the hippocampus (the area of the brain associated  with memory processing and organization). 

Cortisol, Telomere Length, and Stress
In fact, researchers have found that prolonged elevations of cortisol literally  caused brain shrinkage (reduced  hippocampal volume) and memory deficits compared to individuals with normal cortisol  levels (Lupien 1998). This does not suggest that the stress  response is in itself dangerous or life threatening.  As stated above, the stress response is essential to our survival.  For humans the  very real danger is that stress is unavoidable and that each stressing event  instigates the same response: cortisol is secreted by  the adrenal glands in times of emotional stress.  The stressor and subsequent release of  cortisol  can be unrelenting, and may  last for extended periods of time.  Accumulated  cycles of cortisol release can lead to adrenal exhaustion from excess depletion  of the adrenal hormones during long-term stress, or alternately to cortisol resistance where cortisol  levels are dangerously physiologically high in the bloodstream, but at low  levels within the cell.  Cortisol  resistance may lead to a curious combination of both fatigue and agitation  (Cohen et al 2012, and Menke et al 2012).   Some examples of long-term stressors could be a messy divorce, an  ongoing conflict in the workplace, or even the stress of the daily rush hour  each morning and afternoon.

The list is  endless, and we all have different triggers. It is not always the stressor, but  how we as individuals react to that stressor.   Each person's reaction to the same stressor can be remarkably  different.  For this reason alone,  'stress has long been suspected in the etiology [study  of causation] of many diseases, and can be immunosuppressive and hence may be  detrimental to health' (Dhaber and Mckewen 1999). The basic inference is that after the  stressing event has passed, the body needs time to breakdown the stress  hormones circulating in our blood stream into harmless substances. If the body  does not have the metabolic efficiency or the time to do this effectively, cortisol  subsequently will become a toxin.  The time taken for cortisol to turn from  beneficial (where we feel energized, and elated) to bad (where we feel wired,  jittery, and fatigued) has been called, “the  cortisol switch” and has been measured at approximately 16 minutes.  (Gottfried 2012)

The action of cortisol in the blood stream is  analogous to the 'oxygen debt' where aerobic respiration enables the body to  function at its peak; overstepping this peak initiates anaerobic (oxygen-free)  respiration in the muscles. The result of this anaerobic respiration is a  build-up of lactic acid: we recognize this by feeling an increased heaviness  and tiredness in the muscles, accompanied by progressively more rapid and  deeper breathing. There comes a point where you have to stop the activity and  pay back the 'oxygen debt' by inhaling large amounts of oxygen, and allowing  the lactic acid to be transported by the circulatory system to the liver where  it is oxidized to carbon dioxide and water.   Similarly, we must be removed from a stressing event, or learn adequate coping mechanisms to react to the  stressing event in a more healthy fashion in order to allow cortisol levels to  return to normal.  If this is not  accomplished, cortisol levels remain elevated and can quickly become  deadly. 

Cortisol is unique among hormones because it is  the only hormone whose concentration in the body increases as we age. Part of the reason for this is that younger  people metabolize (breakdown) the hormone more rapidly than older people.  So if our lives are overly stressful for an  extended period of time the result is elevated levels of cortisol which effectively  have nowhere to go.  In essence, the body  fails to ensure that cortisol levels rapidly return to normal and remain within  homeostatic limits.

In Chronically stressed persons the body  simply does not have the time to recover and re-energize after a expereincing a  stressful event, because the body is in a near constant state of alertness or  “stress-response mode”.  Speaking  personally [Mark] my last teaching job resulted in an incredibly painful knot  in the pit of my belly on a Friday, that did not fully subside until Sunday,  just in time for the whole cycle to start again.  This is just one of the many symptoms that  fall under the category of adrenal  fatigue (i.e. resulting from stress and not a pathological condition such  as Addison’s disease). The end result is a complete breakdown of the normal  stress response and the transformation of a beneficial substance (short term) into  a toxin (long term).  Some of the long  term implications for cortisol's effect on cellular metabolism are discussed  below.

On the tips   of our chromosomes, which contain our DNA, located in the nucleus of  every cell in our body (aside from red blood cells), lies a structure called a telomere.  Telomeres have protective and stabilizing  functions.  A telomere is like the  plastic cap at the end of a shoelace, which keeps the shoelace from  unraveling.  With each cell division the  length of the telomere is reduced, so as we age the telomeres on all of our  chromosomes progressively shorten.  Eventually,  when telomere length is greatly reduced, a condition called cell senescence  occurs; the cell is metabolically active but is incapable of division. Research  over the last decade provides a picture of how at the cellular  level, stress may promote earlier onset of age-related disease, (Epal et al.  2004).  This  research suggests that the stress response has a detrimental effect on cell  metabolism, and in particular cell division (mitosis). 

Equally  concerning is the stress response (i.e. cortisol) effect on telomere length and consequently on cell  longevity.  Cortisol has a destructive  effect on the enzyme telomerase which “relengthens the telomeres so that they get the same length as  before embarking on cell division” (Bojesen et al 2013).  Research shows that chronic stress can  subtract 10 years to your lifespan.

The cell's environment directly regulates both the activity of  telomerase and telomere length with profound consequences such that chronic  stress is associated with 'telomeres shorter on average by the  equivalent of at least one decade of additional aging' (Epal et al 2004), as compared with less  stressed persons.  There is now a  significant body of research documenting the detrimental effect of ether stress  (or the associated release of cortisol during stress) on telomere shortening (Daubenmier et al. 2012; Tomiyama et al 2012; Parks et  al 2009).  When the telomere length is zero, cell apoptosis  (self-suicide) occurs. Therefore, telomere length is one of the determining  factors of cell longevity and senescence. Reduced telomere length has  been associated with high death rates in elderly people. The implication is  that elevated and persistent cortisol levels accelerate this process such that  the mapping of telomeres has profound implications for the cellular basis of  chronic stress and age related diseases, in addition to boosting understanding  regarding cancers, the appropriate treatment of those cancers, and the genetic  links between telomere length and the subsequent development of cancer. (Bojesen et al 2013).

Any high school biology book or fitness  schedule tells us that a balanced diet is essential for overall health and well-being. If it is impossible to avoid  the stressing events, is it possible to alleviate the impact of elevated  cortisol levels, or is it possible to block stress response pathways?  In essence we are asking if it is possible to  inhibit the production of cortisol.  Research  and clinical trials since the mid-nineties have shown that a substance derived  from the whites of fertilized chicken eggs called Young Tissue Extract, or YTE,  may play a crucial role in reducing cortisol levels in young as well as in  elderly subjects, and thus this substance may play a role in stress management.  It is important to clarify that YTE does not inhibit normal stress response but,  “restores the ability of chronically stressed subjects to adapt to acute  stress” (Schult et al 2009).

YTE is marketed internationally under the  name Laminine, and because it is not  a prescription drug, but is a nutritional supplement, the manufacturer cannot  make any claims for the prevention, mitigation, treatment, or cure of any  disease. The freeze-dried supplement does contain a combination of essential  amino acids, peptides and growth factors which have been shown to elevate  levels of a substance called 17-ketosteroid.   This steroid (a critically important  class of biological molecule) has many functions, but one result of ingestion  is, that it reduces the rate of the body's production of cortisol. Laminine has  been shown to inhibit the stress response by elevating the body's production of serotonin, which promotes feelings  of wellbeing and relaxation (Solberg 2011).

Effectively, our stress hormone levels drop  because we lose our feelings of anxiety, worry, insecurity and related negative  emotions. We all know the short term consequences of stress include insomnia,  reduced appetite, feeling overwhelmed or powerless and increased alcohol intake  to cope with these feelings. The long-term consequences can be severly  debilitating, or even life threatening. It is important to note that chronic stress should be avoided at all  costs, however, sometimes this is just not possible and it may be unrealistic  to say, 'just remove the stressing event'.

For persons enduring an extended  stressful period Laminine may be an answer as people who  are chronically stressed “profit both psychologically and physiologically from YTE.  (Schult et al 2009), along with  proper diet, exercise, stress reduction and relaxation techniques, and the  moderation of alcohol (Mendelson et  al 1966; Thayer et al 2006; Stalder et al 2010) and coffee intake (Bennett et al 2013), the latter two of which are also  associated with elevated cortisol levels.

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