***Cortisol –Death Hormone

Hydrocortisone, otherwise referred to as cortisol, is known to play vital functions in the body’s response to threats. The glucocorticoid is primarily released to counter stress, and achieves that through a number of responses – increases blood sugar, represses the immune system, and increases metabolism of carbohydrates, fats and proteins.   Cortisol is a neuroendocrine hormone same as epinephrine, norepinephrine, and dopamine which are often released into plasma in the process of “activating the hypothalamic-pituitary – adrenal axis, sympathetic nervous system, and adrenal medulla” (Parks, et al., 2009) .  All these function to control the physiologic stress response, and the urinary levels are indicative of the levels in plasma.

Increasing evidence indicates that the hormone could be playing a more complex role than currently understood.  This follows the finding that the cortisol is present in much higher levels in older people compared to the young. Moreover,  after experiencing stressful moments, cortisol levels drop rapidly in young people, as opposed to older persons in whom it takes days for cortisol to go back to normal levels.  Could cortisol be a death hormone? Well, findings of various studies could be pointing in that direction.  

Several studies have been carried out to understand the ways in which stressful experiences shape the biological process of aging.  Scientists have long believed that every individual has an intrinsic biological clock that determines his/her aging process.  Telomeres have been cited to be powerful markers of aging.  (reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1876843/)

Telomeres are DNA-protein complexes that function by capping the ends of chromosomes to ensure chromosomal stability. Telomeres are protected by the enzyme telomerase.  Doctors Elizabeth Blackburn, Carol Greider and Jack Szostak received the Nobel prize in Medicine in 2009 for their research that proved that chromosomes are protected by telomeres, and telomeres are protected by telomerase. (http://www.nobelprize.org/nobel_prizes/medicine/laureates/2009/advanced-medicineprize2009.pdf )

Telomeres shorten as humans grow older. In vitro studies have shown that cells grow old and ultimately die when the telomere shortens significantly. 

Indeed, telomere shortening has been linked to high mortality rates and cardiovascular events in the elderly.  Studies indicate that shorter telomere lengths are associated with high levels of perceived stress (reference: http://www.molecularpain.com/content/8/1/12 ); however, the association is not always predictable and may vary depending on other factors such as the response to neuroendocrine hormones, external stress, and age related factors (Parks, et al., 2009) .

New evidence indicates that environmental factors that work both internally and externally could be responsible for telomere shortening and aging.  The health variability observed among the elderly is clearly as result of telomere length.  Though scientists have long speculated on the existence of a relationship between stressors – both social and psychological – and variations in health status, evidence has never been clearer is it seems to appear now (Berkman & Gylmour, 2006) .  Cortisol is one of the physiological pathways that influence a number of diseases in the aging process. A study conducted by Epel et al. associated telomere length with elevations in urinary catecholamines and cortisol in a section of caregiver subjects (2006) .

Though it is not easy to understand the exact pathogenic mechanism of stress, current research indicates that premature aging in people can be triggered by chronic stress. As indicated above, there are a number of pathways through which a psychological stressor can affect the aging of cells. These might include “immune cell function or distribution, oxidative stress or telomerase activity” (Elissa S. Epel, Morrow, & Cawthon, 2004) . Stress could negatively impact on the population of naïve T cells, and cause an increase in the number of memory T cells, which could result in or contribute to weakening of the immune system.

Stress has also been implicated in the chronic activation of oxidative stress (damaging free radicals) through autonomic neuroendocrine responses (McIntosh & Sapolsky, 1996) .   Although this has not been tested in vivo, the link between stress and hormones has long been demonstrated at the cellular level.  Glucocorticoids are the primary adrenal hormones that are released during stressful times, and have been shown to cause neuron damage resulting from oxidative stress (Kiecolt-Glaser & Glaser, 2010) . This takes place partly through the decrease of antioxidant enzymes while increasing levels of calcium and glutamate.  Previous studies have related “self-reported distress” in women to oxidative DNA damage (Elissa S. Epel, Morrow, & Cawthon, 2004) .  In-vitro studies have shown that oxidative stress shortens telomeres in cell cultures.

There has been evidence suggesting that the aging of the immune system could be closely associated with chronic stress and other stress factors. Normal aging is linked to emotional distress that goes hand in hand with increased ration of cortisol to dehydroepiandrosterone (DHEA) (Bauer, Jeckel, & Luz, 2009) .  A malfunction in DHEA secretion results in the increased exposure of lymphoid cells to harmful effects of glucocorticoids (Bauer, Jeckel, & Luz, 2009) . 

Toxicity results with high cortisol levels in blood.  A study conducted by Schoorlemmer et al. showed an association between high cortisol levels with chronic diseases and mortality (2009) . Citing the hormone’s mechanism of action, the study established how elevated levels are associated with hypertension, diabetes mellitus (DM), depression, and susceptibility to infections. Gender was to found to play a significant role in the association between cortisol and mortality (P< 0.003). The levels of cortisol were measured in the second (1995/1996) and the fourth cycle (2001/2002) of the ongoing “multidisciplinary cohort study on predictors and consequences of changing physical, cognitive, emotional and social function in older persons” (Schoorlemmer, Peeters, Schoor, & Lips, 2009) .   Further investigations were conducted by separating the different serum cortisol levels into tertiles. In the fourth cycle, it was found that higher a higher risk of mortality was found in the third tertile compared to the reference tertile for salivary morning cortisol . In women, higher mortality risk was found in the third tertile compared to the second tertile (Schoorlemmer, Peeters, Schoor, & Lips, 2009) . All mortality data was collected from municipal registers. (another reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2968721/)

Investigations conducted on the social and physical environmental factors, and disparities in the risk for cardiovascular have linked cortisol to cardiovascular disease (CVD).  According to Bjorntorp 2001; and Esch et al. 2002, the excess cortisol released during chronically stressful situations contributes to central adiposity (the deposit of fats in the midsection of the body) (Schulz, et al., 2005) . This has been established as an important risk factor for CVD.  These findings are consistent with those of a study conducted in 2000 (Psychosomatic Medicine 62: 623 – 632) that stress induced cortisol secretion was consistently greater in women with central fat.

Cortisol has also been associated with progression of ovarian cancer. A study investigating “diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer” showed a greater association of cortisol dysregulation with functional disability, fatigue and vegetative depression (Weinrib, et al., 2010) .  

In summary, levels of cortisol increase with age and stress levels; elevated levels of cortisol are inversely proportionate to telomere length (or ‘death clocks”); cortisol contributes to telomere shortening; and elevated levels of cortisol may significantly increase both morbidity and mortality in humans.  Cortisol is indeed the “death hormone”.

Parks, C. G., Miller, D. B., McCanlies, E. C., Cawthon, R. M., Andrew, M. E., DeRoo, L. A., & Sandler, D. P. (2009). Telomere Length, Current Percieved Stress, and Urinary Stress Hormones in Women. Cancer Epidemiol Biomarkers, 18 (2):551-560.

Parks et al. (2009).

Berkman, L. F., & Gylmour, M. (2006). How soceity shapes aging: the centrality of variability. Daedalus, 135,1: 105-114.

E S Epel, J. L. (2006). Cell aging in relation to stress arousal and cardiovascular disease risk factors. Psychoneuroendocrinology, 31:277-287.

Elissa S. Epel, E. H., Morrow, J., & Cawthon, R. (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences of the United States of America, 101, 49: 17312 - 17315.

McIntosh, L., & Sapolsky, R. M. (1996). Neurotoxicology, 17,873 - 882 .

Kiecolt-Glaser, J. K., & Glaser, R. (2010). Psychological Stress, Telomeres, and Telomerase. Brain Behav Immun, 24(4):529-530.

Elissa S. Epel, E. H., Morrow, J., & Cawthon, R. (2004)

Bauer, M. E., Jeckel, C. M., & Luz, C. (2009). The role of stress factors during Aging of the Immune System. Neuroimmunomodulation , 1153:139 -152.

Bauer, M. E., Jeckel, C. M., & Luz, C. (2009)

Schoorlemmer, R. M., Peeters, G. M., Schoor, N. M., & Lips, P. (2009). Relationship between cortisol level, mortality and chronic diseases in older persons. Clinical Endocrinology , 71,779-787.

Schoorlemmer, R. M., Peeters, G. M., Schoor, N. M., & Lips, P. (2009).

Schoorlemmer, R. M., Peeters, G. M., Schoor, N. M., & Lips, P. (2009).

Schoorlemmer, R. M., Peeters, G. M., Schoor, N. M., & Lips, P. (2009).

Schulz, A. J., Kannaan, S., Dvonch, T., Israel, B. A., Allen, A., James, S. A., . . . Lepkowski, J. (2005). Social and Physical Environments and Disparities in Risk for Cardiovascular Disease: The Healthy Environments Partnership Conceptual Model. Environmental Health Perspectives, Vol. 113, 12: 1817 - 1825.

Weinrib, A., Sephton, S. E., Degeest, K., Penedo, F., Bender, D., Zimmerman, B., . . . Lubaroff, D. M. (2010). Diurnal Cortisol Dysregulation, Functional Disability, and Depression in Women with Ovarian Cancer. Cancer, 116(18): 4410-4419.