The neuroendocrine system refers to the complex connections between the nervous system and our endocrine glands which are major controllers/regulators of body activity and functions. The hypothalamus, a structure at the base of the brain, stimulates and inhibits the pituitary gland, often called the “master gland,” which in turn regulates the glands of the body (ovaries, testes, adrenal glands, thyroid) and how and when they release their hormones into our circulation. Some types of hormones can be referred to as growth or trophic factors.

How does hormone (and growth factors) work to regulate various body processes and functions? These chemical messengers selectively stimulate cell activities. Generally, they bind to receptors on the cell membrane which trigger a complex cascade of events through activating some common signal transduction pathways (e.g NF-κB pathways as mentioned in “Genetic Clock” section), which in turn switch on gene expression and secretion of functional proteins (including other growth factors) that is biologically active for regulating body activities and various functions.

The hormone or endocrine theory of aging asserts that one of the most important factors in aging are the changes brought about in the body by the endocrine system. As we age, the endocrine systems become less efficient; the declines of hormone level appear to start around age 20 and affect just about every major hormone including Human Growth Hormone (HGH), estrogen, testosterone and melatonin, DHEA. These declines constitute a major cause of changes in our bodies (e.g. menopause).  As the hormones run down, so do all of the body systems which they regulate. Many body systems are re-regulated or affected by declining hormone levels including the immune system. The hormone theory of aging believes that these changes eventually cause the effects of aging. The actions that the various hormones on different facets of aging have been studied extensively. The transcription of many genes is affected by the changing hormone mix. Impacts are thought to exist in many spheres including energy level, metabolism and weight, endurance, sexual drive, mental acuity, ability to sleep, age-related bone loss, and disease resistance. Specific diseases are associated with various hormone deficiencies.

GROWTH HORMONE

Human Growth Hormone of the pituitary gland is released through the action of another trophic precursor called growth hormone releasing hormone, which is produced in the brain. After it is secreted, it passes from the pituitary to the liver. It works, in part, by stimulating the production of insulin-like growth factor (IGF-I), which comes mainly from the liver and mediates many of the actions of hGH. IGF-I enters and flows through the blood stream, seeking out special IGF-I receptors on the surface of various cells, including muscle cells. Through these receptors it signals for example, the muscle cells to increase in size and number, perhaps by stimulating their genes to produce more of special, muscle-specific proteins. hGH regulates a wide variety of biological activities including rate of cellular division, overall growth, metabolism and development of the body. It appears to play a role in body composition and muscle and bone strength. Typically HGH declines about 80% from age 20 to 60. The critical aspect is that beyond the ages of 20, it decreases every decade by about 14%. Since HGH and IGF-1 are mitogens which trigger cell division; lower levels of the GH/IGF-1 decreases cellular replication that could impact on some sort of cellular clock.

Growth factors might have an important role in longevity determination and aging. Many experiments in different model organisms associated the insulin/insulin-like pathways with aging. IGF-1 factor goes all over the body to reverse some of the first signs and symptoms we see in aging. It affects brain cells, hair color, and even cellulite. Patients with deficiencies in GH and IGF-1 show signs of early aging but their lifespan may actually be increased.

Please take a look at the list of mamalian genes that can modulate the aging phenotype available in Table 3, as many are related to the GH/IGF-1. One putative player in aging is the klotho gene, mutations in klotho appear to accelerate the aging process. In contrast, overexpression of klotho extend lifespan by about 30%. Its functions are largely unknown but it could be related to insulin/IGF-1 signaling.

Along with declines in levels of critical hormones, insulin resistance is another frequent hormone-related hallmark of aging, leading to hyperinsulinemia. Hyperinsulinemia shows up as a major risk factor for many age-related diseases, including cardiovascular diseases, Alzheimer’s disease, and stroke.

Decline in bone density and osteoporosis are also attributable to shifts in hormone levels with age. Inadequate bone growth and mineral density is responsible for many older people sustaining serious injuries from falls, losing their capabilities to move freely, or even to walk. All three hormones (hGH, hGH releasing hormone, and IGF-1) are being studied for their potential to strengthen muscle and bones and prevent frailty among older people.

In aging, there is not only a decrease of growth hormone, but there is also an increase in the production of somatostatin, a blocker to growth hormone. In order to block somatostatin, amino acid arginine (Arg) can be added which can take away the blocker and allows the production of your own growth hormone to be more effective.

HGH replacement Therapy is the widest used and most extensively studied anti-aging hormone replacement therapy. Visit our “anti-aging medicine” knowledge base to find our the pros and cons of HGH therapy.

ESTROGEN

Hormone levels appear to cause changes in male and female characteristics with age. As we age, production of sex hormones testosterone and estrogen, tends to decrease too. It has been proposed that ageing is regulated by reproductive hormones that act in an antagonistic pleiotropic manner i.e. they promote growth and development early in life in order to achieve reproduction, but later in life, it become deleterious and drive senescence (dyosis).

Although estrogen is primarily associated with women, men also produce small amounts of this sex hormone. Among its many roles, estrogen slows the bone thinning that accompanies aging. In premenopausal women the ovaries are the main manufacturers of estrogen. After menopause, fat tissue is the major source of smaller amounts and weaker forms of estrogen than that produced by the ovaries. While many women with menopausal symptoms are helped by estrogen hormone therapy during and after menopause, some are placed at higher risk for certain diseases if they take it.

TESTOSTERONE

In men, testosterone is produced in the testes (women also produce small amounts of this hormone). Production peaks in early adulthood. However, the range of normal testosterone production is vast. So while there are some declines in testosterone production with age, most older men stay well within normal limits. Incidences of testicular cancer and exotic-sounding diseases like cryptorchidism and hypospadias appear to be correlated with testosterone deficiency. The NIA is investigating the role of testosterone supplementation in delaying or preventing frailty.

DHEA

Short for dehydroepiandrosterone, DHEA is produced in the adrenal glands. It is a precursor to some other steriod hormones, including testosterone and estrogen. Production peaks in the mid-20s, and gradually declines with age. What this drop means or how it affects the aging process, if at all, is unclear. Investigators are working to find more definite answers about DHEA’s effects on aging, muscles, and the immune system. DHEA became credible to the medical establishment when the New York Academy of Sciences published a book entitled DHEA and Aging. This book provided scientific validation for the many life extending effects of DHEA although DHEA supplements, even when taken briefly, may cause liver damage and have other detrimental effects on the body.

MELATONIN

Contrary to some claims, secretion of this hormone, made by the pineal gland, does not necessarily diminish with age. Instead, a number of factors, including light, can affect production of this hormone, which seems to regulate various seasonal changes in the body. Claims that melatonin can slow or reverse aging are far from proven. Current research does indicate that melatonin in low dosages may help some older individuals with their sleep.

Other Hormones

Certain prostaglandins, hormone-like acids that affect important body processes such as body temperature and metabolism, tend to increase in old age and inhibit important immune cells from doing their jobs. Also, Older adults appear to be more sensitive to the action of prostaglandins than younger adults. And some researchers think this could be a major cause of immune deficiency in elderly people.