***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).  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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