Aging & Hormones
Annie Sawyer, Ph. D.
There are multiple factors and symptoms or syndromes of aging that negatively affect our quality of life, such as increased body fat, loss of lean muscle tissue, lower energy levels due to low mitochondrial supply, decreased sexual function, common depressive symptoms, and weakened immune function or decreased skin turgor (Scuteri et al. 2005 & Gause-Nilson et al. 2006). The increasing prevalence of the metabolic syndrome among U.S. adults is proved to be a major aging factor as well (Ford et al. 2004). Not known as metabolic syndrome at first, this constellation of abnormalities is recognized as placing individuals at dramatically increased risk for cardiovascular disease.
A study published in 2004 in the Journal of the American Medical Association (JAMA) followed more than 1,200 men for 11 years. Some researchers (Lakka et al. 2002), found that men with metabolic syndrome were 160-320% more likely to die from coronary heart disease than those without metabolic syndrome. Besides the increased prevalence of metabolic syndrome and, in general, the worse cardiovascular risk profile and clinical outcomes, people with a lower social position have often to face a worse medical assistance, which can increase the rate of missing diagnoses of cardiovascular risk factors and target organ damage (Perel at al 2006).
The “neuroendocrine theory of aging” explains the intimate connection between hormones and degenerative diseases as postulated by Dilman Dean (1960). The metabolic pattern of aging is explained as a combination of: a) reduced receptor sensitivity to insulin (insulin resistance); b) obesity c) altered lipid profile (elevated VLDL, LDL, triglycerides, and total cholesterol; d) hypercortisolemia (elevated cortisol and decreased DHEA); e) decreased androgen output in men; f) increased gonadotropins (LH and FSH); g) decreased immunity and increased incidence of autoimmune antibodies; h) elevated blood pressure and i) functional hypothyroidism. The entire aging cascade causes hormonal and metabolic shifts that can lead to aging, degenerative diseases and future mortality. Although it may seem strange, abdominal fat could affect the human brain, and be responsible for dementia in advanced age (Earl et al. 2002).
As seen from the HERS (2002) study, the low circulating level of hormones (HGH and testosterone in particular) promotes an increase in adipose tissue bulk. This leads to free fatty acids release, which are immediately transported to the liver, stimulating the production of Apo-B containing very low density lipoproteins (VLDL). Insulin resistance leads to overproduction of triglyceride-rich lipoproteins and there is also a reduced activity of peripheral lipoprotein lipase which in turn supports the accumulation of triglyceride-rich lipoproteins in the circulation. Hlatky and co-authors (2002) explain that via the action of cholesterol ester transfer protein, triglycerides are transferred from these lipoproteins to high density lipoproteins in exchange for cholesterol esters. The enrichment of the triglyceride-rich remnant particles with cholesterol ester leads to formation of small dense LDL. Moreover, because of this exchange, the level of high density lipoprotein cholesterol falls (Hlatky et al. 2002).
According to Giampapa (2004), as people age the body’s ability to metabolize glucose, a factor also referred to as “glucose tolerance” progressively diminishes. In his proper words: “The aging body simply does not respond to the action of insulin, resulting in elevated levels of glucose in the bloodstream. This is referred to as ‘glucose intolerance,’, and its causes as well as main consequences include being overweight, due to continual wear and tear on the pancreas from years of eating and a decrease in the overall amount of insulin and other important hormone production. Another cause is that the human cells are not able to absorb glucose like they did when younger.” As the author states, glucose intolerance renders glucose less available for use by muscle tissue, leading to higher insulin levels (hyperinsulinemia) and higher blood sugar levels (hyperglycemia). The hypothalamus senses this condition and sends signals to the pituitary gland to inhibit secondarily the secretion of human growth hormone (HGH). HGH stimulates the process of fat burning. At the same time, the pancreas is stimulated to release insulin, secondarily diminishing HGH production. Thus the elevation in blood sugar not only creates insulin resistance, obesity, type 2 diabetes and cardiovascular disease, but can also decrease the secretion of HGH (the main hormone of youth) leading to premature aging. In another study it is proved that complementary human growth hormone replacement can improve body composition in healthy older men, without changes in functional ability (Papadakis et al. 1996). In conclusion, HGH production is a complex process and requires the normal function of other organs and hormones to work.
The effect of Human Growth Hormone (HGH) in metabolic syndrome healing can be easily explained: it has important effects on protein, lipid and carbohydrate metabolism. A validated age report and correlation with HGH in centenarian prevalence are discussed in a study by Perls et al. (1999). In some cases a direct effect of growth hormone has been clearly demonstrated, in others IGF-I has been postulated to be the critical mediator, and in some cases it appears that both (direct and indirect) effects are at play (Giampapa et al. 2004 & Papadakis et al. 1996):
a) Protein metabolism: In general, growth hormone stimulates protein anabolism in many tissues. This effect reflects increased amino acid uptake, increased protein synthesis and decreased oxidation of proteins.
b) Fat metabolism: Growth hormone enhances the utilization of fat by stimulating triglyceride breakdown and oxidation in adipocytes.
c) Carbohydrate metabolism: Growth hormone is one of a battery of hormones that serves to maintain blood glucose within a normal range. HGH is often said to have anti-insulin activity, because it suppresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver. Somewhat paradoxically, administration of growth hormone stimulates insulin secretion, leading to hyperinsulinemia.
Another hormone, called Cortisol, concomitantly increases its production from the suprarenal glands. Cortisol is known as the “age accelerating” or the hormone of "aging" as it is also produced in times of elevated stress. Generally it promotes the aging process through memory loss, decreased cognitive function, interrupted sleep problems (insomnia), nervous system damage, decreased immune function, increased pro-inflammatory signaling factors (eicosanoids and interleukins), body fluid retention, elevated triglycerides, high total cholesterol, low HDL, high LDL. and low good to bad cholesterol ratios, increased sugar cravings due to increased insulin levels, insulin resistance, skin problems (wrinkles, adult acne, psoriasis, seborrhea, alopecia (hair loss) and many others. Data from In Chianti study (a community-based study in 867 persons aged 65 and over), showed that depression combined with high levels of 24-hour urinary cortisol increases probability of the metabolic syndrome by about 20%, and can be used for predicting the syndrome (Vogelzangs et al. 2007). The study concluded that people with depression and high levels of urinary cortisol (> 111 µg) had an 84% increased probability of the metabolic syndrome compared to non-depressed persons with normal cortisol levels.
A study by Björntorp (2001) suggests that a hyperactive hypothalamic-pituitary-adrenal HPA) axis can cause significant abdominal fat accumulation- representing the whole mark of the syndrome. The author describes cortisol binding to the glucocorticoids receptors, which are multiple in the visceral fat, activating the enzyme lipoprotein lipase, and inhibiting lipid mobilization, which leads to rapid accumulation of triglycerides in the visceral area. Results from the Health ABC study are suggesting that the above effects are more pronounced when combined with low levels of sex steroid hormones, which have also been associated with depression (Morsink et al. 2007). As a conclusion from the above and multiple other studies, a recent trial draws the conclusion that depression is an important co-morbidity with metabolic syndrome in a general population (Dunbar et al. 2008).
Ghrelin is a peptide hormone secreted from the stomach that binds to receptors on somatotrophs and potently stimulates secretion of growth hormone.
HGH secretion requires the following:
a) Pituitary/hypothalamus stimulation;
b) Pancreatic regulation for optimum production of insulin and blood sugar in the blood, glucagon, leptin and cortisol levels;
c) Correct hepatic (liver) nourishment and functioning for the conversion of HGH to insulin growth factor 1 (IGF-1) according to Rudman’s HGH theory, published in The Journal of American Geriatrics Society(1985).
