Cortisol is a hormone secreted by the adrenal glands in response to stress. Among its main actions in the body are the increase in gluconeogenesis (formation of glucose from non-carbohydrate compounds), the suppression of the immune response, intervention in the metabolism of macronutrients, and decrease in new bone formation (osteopenia or osteoporosis). Cortisol has been used for many years in medicine to treat some diseases under the synthetic form of hydrocortisone. Cortisol levels tend to rise with age, and cortisol is the only hormone to do so. Faced with a stressful situation, cortisol is released by the adrenal glands atop the kidneys, and cortisol levels in the blood increase rapidly. These levels decline rapidly in young people, however, this rapid decline does not occur in older people. The concentration of cortisol in the blood tends to stay high for longer periods, causing toxicity in the body's cells and other adverse biochemical and metabolic effects.
A study conducted among elderly patients showed that high concentrations of cortisol measured in saliva were associated with a significantly increased risk of mortality and higher prevalence of hypertension and diabetes mellitus. (Schoorlemmer, Peeters, van Schoor and Lips, 2009). Chronic stress can affect health through various mechanisms, foremost among which is the hormonal pathway. Chronic stress and elevated cortisol causes people to be more prone to suffer from chronic (non-communicable) diseases and the ravages of accelerated aging. Aging is associated with alterations to certain biologic parameters such as adverse elevations in proinflammatory cytokines (such as TNF-alpha and IL-6), blood pressure and blood lipids (decreases in HDL “good” cholesterol, and increases in atherogenic LDL cholesterol and triglycerides). These markers are commonly known as "allostatic load", and indicate the damage that is caused by repeated fluctuations of cortisol in response to stress. Among the biochemical stressors are the imbalance between anabolic and catabolic hormones, which can be caused by chronic exposure to psychological stress; inflammatory factors, and oxidative stress (free radicals). Other stressors are health behaviors and cellular processes associated with aging.
The hormonal imbalance caused by stress is characterized by low levels of beneficial anabolic hormones that promote growth of lean muscle and bone mass, and prevent adiposity (abdominal weight gain). These beneficial anabolic hormones reduced by stress and antagonized by cortisol include androgens and IGF-1. This hormonal imbalance is also characterized by high levels of cortisol that cannot be compensated by increased insulin. In this way, high concentrations of cortisol coexist with elevated insulin levels. This condition causes a rise in abdominal fat deposits. Visceral fat is the most responsive to hormonal imbalance caused by stress as the abdominal adipocytes contain more receptors for glucocorticoids. In addition, elevated concentrations of cortisol causes increased levels of lipoprotein lipase, the enzyme responsible for catabolizing the conversion of triglycerides into free fatty acids.
Elevated levels of serum cortisol that characterize the states of chronic stress and increased intra-abdominal fat deposits are accompanied by an increase in the concentration of other biochemical stressor compounds such as oxidative stress markers. This adverse metabolic state is characterized by a decrease in the concentration of antioxidants (vitamin C, vitamin E, glutathione), and increased concentration of lipid and inflammatory markers such as Tumor Necrosis Factor (TNF-alpha) and Interleukin-6 (IL-6). Monocytes infiltrate the fat and create a state of constant systemic inflammation.
Shortened Telomeres and Metabolic Syndrome:
Certain behaviors can affect cortisol levels in blood and generate a hormonal imbalance. Among these behaviors are activities, diet and sleep patterns. Overeating can lead to increased aerobic metabolism, overproduction of damaging free radicals, and an increase in fat deposition. Excess fat (especially visceral fat) can lead to the development of insulin resistance with hyperinsulinemia, hyperglycemia, and decreased antioxidants. This is related to metabolic proinflammatory state and oxidative stress. Food restriction followed by overeating is associated with higher levels of serum cortisol and chronic stress. As a result, elevated serum cortisol also decreases the length of telomeres and cells ages faster. Telomeres are the terminal ends of the chromosomes, and serve as biologic clocks, determining when our cells will die. Decreasing the length of telomeres (which is seen when cortisol is elevated) hastens the death of the cell. This is why cortisol has been called the “Death Hormone”. When telomeres are shortened in the cells of the immune system, there is an adverse effect on immune function and an increased risk of communicable diseases, non-communicable chronic diseases and mortality from all causes. (Epel, 2009).
Brain Shrinkage and Senile Dementia:
Oxidative stress caused by hormonal imbalance (high concentrations of cortisol) affects the production of free radicals and increases the risk of neurodegenerative diseases such as Parkinson’s Disease and Alzheimer’s disease. Nervous system cells are extremely sensitive to the effects of cortisol. While this hormone is essential for the viability of the brain, long-held high concentrations cause neuronal damage which is in part due to oxidative stress. A prospective study of 51 healthy persons (followed for 5 years) in whom serum cortisol was assessed through saliva samples over 24 hours showed that those undergoing higher levels of stress had higher levels of cortisol in the blood. These researchers also evaluated the functionality of the hippocampus, which is not only influenced by glucocorticoid levels, but also involved in the regulation of these hormones. The results showed that higher glucocorticoid levels increased the likelihood of injury in the hippocampus. Older people with persistently high cortisol levels showed a reduction in hippocampal volume and a deficit in memory-related functions (i.e. increased senile dementia), compared with people with normal serum cortisol. Hippocampal atrophy is a paradoxically both a cause and a result of high levels of cortisol in the blood for long periods of time. The reduction of hippocampal volume is associated with memory impairment and reduced cognitive functions. (Lupien, de Leon, Santi, Convit, Tarshish, Nair, Thakur, McEwen, Hauger, Meaney, 1998).
Depression, Impaired Memory and Cognition:
Individuals who are under high levels of stress for long periods of time may experience (reversible) nervous system lesions, and symptoms of impaired memory, memory lapses, and reduced concentration. Elevated cortisol can adversely affect behavior and high levels are associated with depressive symptoms. High cortisol levels over long periods of time can lead to a depletion of the adrenal glands (adrenal exhaustion) and low levels of cortisol. This can lead to some confusion and a false interpretation of the tests that are performed to evaluate the concentration of cortisol in the blood. Those who suffer from chronic fatigue syndrome (CFIDS), depressive symptoms, insomnia, among others, may paradoxically have low blood cortisol levels alternating with moments of greater concentration (imbalance and wild fluctuations). For this reason, there must be an adequate sample period and the ability to evaluate test results in conjunction with the patient's symptomatology in recent months.
Cortisol and Heart Disease:
Increased levels of serum cortisol steadily raise the risk of heart disease. A study conducted in 861 patients over 65 years old, who were studied for over six years through measurements of 24-hour urinary cortisol, showed that high levels of the stress hormone were associated with a dramatic increase in cardiovascular deaths. Those individuals who held to the highest concentrations of blood cortisol were 5 times more prone to suffer a heart attack, stroke or other cardiovascular events. This was the first study that directly associates cardiovascular death and increased levels of stress hormones. (Vogelzangs, Beekman, Milaneschi, Bandinelli, Ferrucci, Penninx, 2010).
Cortisol and Immunity:
Aging of the cells of the immune system is highly correlated with, and directly related to chronic stress. Alterations in the secretion of the hormone dehydroepiandrosterone (DHEA) along with the increase in plasmatic cortisol levels cause damage to the cells of the immune system. The characteristics of accelerated aging induced by chronic stress include increased oxidative stress, reduction in the length of telomeres, chronic exposure to the action of glucocorticoids, reduction of cell-mediated immunity, resistance to the action of steroids and chronic inflammation of low-grade. For these reasons, older people suffering chronic stress have higher morbidity and mortality risk. (Bauer, Jeckel and Luz, 2009).
Telomerase and Cortisol:
Chronic stress induces cellular changes that accelerate aging. One of these cellular changes is the decrease in the length of telomeres and telomerase activity. Telomeres are nucleoprotein structures formed by lining the ends of chromosomes and protect them. Every time that cells divide (reproduce), they lose some of these telomeres and the telomeres are shortened. Because the cells have a limited capacity for mitosis, telomerase acts by adding telomeric DNA fractions to prevent this shortening. Cells with shorter telomeres are those that have aged or have experienced reduced telomerase activity. Telomerase is highly expressed in cells that must divide regularly (such as the cells of the immune system) and is found in lower levels in most somatic (bodily) cells. Telomerase also reduces the likelihood that a cell will hit its Hayflick limit, which is the number of times that a normal (non-cancerous) human cell population will continue to divide until all cellular division stops. (Hayflick and Moorhead, 1961).
Oxidative stress and excess of visceral fat are two of the factors that reduce the activity of telomerase and damage telomeric DNA. One study showed that psychological stress with increased serum cortisol levels is highly associated with greater oxidative stress, lower telomerase activity and reduced telomere length, all determinants of accelerated aging and cellular senescence. (Epel, Blackburn, Lin, Dhabhar, Adler, Morrow, Cawthon, 2004).
As discussed above, elevated levels of cortisol maintained over time are highly injurious to health. The medical approach for the reduction of elevated control levels and prevention of metabolic and psychological stress should be a priority, especially in older people in order to reduce morbidity and mortality.
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Dr. Steven Petrosino received his Baccalaureate (BA) degree in both Science and English from Penn State University in 1975, pursued his Masters degree (American Studies) with honors at Penn State in 1977-1978, and graduated Summa Cum Laude with a Doctorate in Nutrition from Lasalle University in 1995. He currently is enrolled in a Ph.D. program at Walden University (Public Health). In 1996-1998 he was involved in external post-doctoral research at the Ohio State University in the Department of Cancer Prevention and Natural Products Research. In 2002, he was enrolled in a post-doctoral external course (Immunobiology) at the University of Pennsylvania.
Dr. Petrosino is currently employed as a Senior Medical Science Liaison with Human Genome Sciences, Inc. He is married to the former Lynn Tutoli, and he and his wife reside in Dublin, OH. They have two children, Angela Petrosino Johnson, (32) and Aaron (28). Visit his website here: http://www.nutritionadvisor.com