Aging Clock - Pineal Gland and other Pacemakers

Is there a centralized aging clock in humans that dictates the pace at which all of the bodily systems run? Yes and No... Studies have not yet found a specific central mechanism that is solely responsible for aging. However, there is a system of development. An example of this is that there is a system that takes a single cell (zygote) and evolves it into a complex organism. Certain parts of this developmental system are not programmed to stop even after their roles in the organism's development have been finished. These systems are key to the growth and sexual maturation of the human but without an "off switch" they seem to have a number of delayed side effects. In reality these systems can harm the mature adult because they behave as if the body was still developing. The result is an increased aging process that can lead to age related disease. This means that the central aging clock could be seen as a by-product of the body's developmental systems when they do not shut off at maturity.

This rather unusual theory of development is the premise of the neuroendocrine theory of aging. Neuroendocrine refers to the fact that there is a synergy between the endocrine systems (the system which controls the body's functions via hormones) and the central nervous system. Vladimir Dilman, a well known Russian scientist and physician developed the neuroendocrine theory of aging in the 1950s. In the years since, a large body of evidence has been developed to support his theory on aging.

The next important function that we need to understand is the idea of homeostasis. Basically, homeostasis is the way that the body maintains a proper balance of all of it systems. To be able to function in a normal manner the body has to have its physiological framework kept within an optimal range: body temperature should be about 98.6F (37 C), blood pressure at about 120/80, blood sugar at 70-120 mg/dl and so on. Homeostasis in the way the system keeps the systems stable. If homeostasis is disrupted, the system works to bring it back to normal function. Failure to maintain homeostasis can lead to death.

Homeostasis is different at all stages of life. An example of this is that the average level of hemoglobin (the molecule that moves oxygen in the blood) is about 11mg/100ml in infant males, while 10 year olds would have a level of approximately 12mg/100ml and adult males would have and average of 15mg/100ml. This simply means that homeostasis has to change the rate it works at according to where the body is in the aging process.

The main function of growth is to increase levels of homeostasis with the expending of more energy, growing in size and the development of the reproductive organs. The issue at hand is that the homeostasis continues to take place event after the body reaches maturity. It continues to occur throughout the lifespan of the individual. After maturity, instead of stimulating growth, homeostasis ages you instead. This means that the developmental system turns into an aging clock as time goes on.

An interesting question is why doesn't the developmental system in the body shut off at a certain point instead of stimulating accelerated aging after the body reaches maturity. No one knows the answer to this question. The good news is that biological clocks can be speeded up or slowed if need be.

In order to understand an explanation of possible ways to slow down the body clock first we need to understand some of the physiology. The hypothalamus is the part of the brain that is the mechanism that is primarily responsible for the process of homeostasis in the body. The hypothalamus continually monitors the numerous internal systems of the body. If one of the systems goes out of the appropriate range of function then the hypothalamus sends out a message to the pituitary, which is the primary gland of the endocrine system. The pituitary gland then transmits the signals it has received from the hypothalamus into hormonal messages to the peripheral endocrine glands such as the adrenals or the thyroid. The peripheral endocrine glands then regulate the functions of the organs and tissues.

Another key concept that needs to be understood in the discussion of the body clock is that of negative feedback (that is with regards to feedback inhibition). In the winter the metabolic rate of the body needs to go up in order to compensate for the colder temperature of the air. In order to do this the hypothalamus sends the appropriate message to the pituitary which in turn transmits a message to the thyroid to secrete more thyroxin (thyroxin is the hormone that raises the metabolic rate). The rise in thyroxin levels is then sensed by the hypothalamus which in turn stops it from sending a further signal. This is how negative feedback works. Basically it is the ability of the body's systems to end a stimulatory signal when the request has been fulfilled.

To summarize: the body needs a slow shift in homeostasis in order to develop. The hypothalamus is the main directing force behind that work of homeostasis. The neuroendocrine theory of aging therefore suggests that the hypothalamus runs the body's developmental systems until maturity at which point it becomes an aging clock. This switch of function can be explained by the process of negative feedback.

A good example of this is the sexual maturation process of women. As young girls the ovaries produce a small amount of estrogen, but enough to still trigger a negative feedback reaction from the hypothalamus. As the young woman grows older the hypothalamus reacts less readily to the negative feedback messages and thereby stimulates the ovaries to produce a higher level of estrogen. This raised level of estrogen production leads then leads to sexual maturity. Comparable processes of homeostasis occur during the maturation of all bodily systems. Sadly, after maturity, the hypothalamus doesn't react to negative feedback as quickly therefore resulting in further homeostatic shifts which begin to have a negative role, leading to aging and degenerative diseases.

The next question to look at is what the actual effects of the homeostatic system is on the body clock and how age related diseases can result from this. A complicated set of systems seems to be involved in this process. Examples of the age related diseases are abnormal stress response, age related depression, insulin excess and syndrome X - a carbohydrate tolerance.

Energy usage is the driving force in the homeostatic shifts that cause age related insulin excess and impaired carbohydrate tolerance. The pancreas secretes a hormone known as insulin. Insulin is secreted as a response to the body's glucose level (blood sugar) which normally rises after eating. It then assists with the moving of glucose, amino acids and fats into the relevant cells where they are either used for energy, stored or used as structural materials. The normal pattern is that when a meal has been consumed the food is digested and absorbed causing the blood sugar (glucose) level to rise thereby setting off the secretion of insulin; after about an hour the insulin raises the blood sugar level back to its original level. As we age, the absorbency of muscle and other tissues in response to insulin declines and the amount of insulin produced after a meal goes up. The net result is that after eating older people have a higher level of blood sugar for a more prolonged period of time and increased levels of insulin circulating through the bloodstream. There has been a lot of debate as to whether a raised sensitivity of the muscle to insulin causes excessive insulin secretion or vice versa. The neuroendocrine theory of aging explains that the central hypothalamic clock contributes to both factors.

Raised levels of insulin and impaired glucose tolerance can raise the levels of LDL, triglycerides and cholesterol. The higher levels of these substances can cause cell damage via glycation and cross linking. They can also lead to salt (sodium) retention and many other problems. The aforementioned metabolic shifts often lead to the development of most age related diseases including heart disease, diabetes, hypertension, obesity, cancer and lowered levels of immunity.

Type II diabetes (noninsulin dependent diabetes) is the most common manifestation of glucose intolerance. Patients suffering from type II diabetes have raised levels of glucose despite still being able to produce insulin. In the early stages of type II diabetes it isn't unusual for the level of insulin to be at an abnormally high level. When diabetes goes untreated it can lead to complications which cause a speeding up of the aging process as well as degenerative diseases.

In one scientific study, insulin production and glucose tolerance was examined in Italian people over the age of 100. It was found that in these elderly people both the insulin production levels and the glucose tolerance were at the same levels as they were in adults under the age of 50 and better than those of between 50 and 75. This shows that in people over 100 there is often only a minimal shift in the level of homeostasis which could be the explanation for their advanced age.

There are many ways to raise levels of glucose tolerance and prevent excessive levels of insulin in the body. These effects can be brought about through exercise, weight loss, and a diet high in fiber and lower in saturated fats as well as a careful correction of nutrient levels. Negative effects to glucose tolerance and insulin levels can be brought on by stress, a lack of physical exercise, a diet that is heavy on saturated fats and low in fiber, as well as overeating and nutrient deficiencies.

Another key contributor to the aging process is the disruption of stress response. The neuroendocrine theory of aging explains that the hypothalamus slowly loses its responsiveness to the feedback inhibition of corticosteroids, which are the key stress hormones in the body. Corticosteroids are created in and released by the adrenal glands (the main corticosteroid in people is cortisol). There is a higher level of corticosteroid production in older people as a response to normal stresses. Older people can also have to high a level of corticosteroids in their bloodstream even when stress levels are low. This is the equivalent of living with chronic stress. This state of chronic stress is a vicious circle in which the central aging clock slowly disrupts the normal stress response which then speeds up the clock itself. Corticosteroid excess is a key contributing factor to glucose intolerance, which slows the immune system, raises blood pressure and can contribute to the onset of age related diseases.

The central aging clock appears to contribute to many other age related issues including the production of sex hormones, abnormal appetites and so on.

How can the aging clock be slowed down? Improving the level of sensitivity in the hypothalamus to negative feedback can slow the clock down. To date, very little research has been done to develop practical means of slowing the aging clock. The research that has been done shows that the levels of the chemicals that transmit messages between the brain cells (neurotransmitters) in the hypothalamus are directly related to the responsiveness to the process of negative feedback. Alternatively, when neurotransmitter levels in the hypothalamus are higher than the aging clock slows down. The table below shows some of the factors that appear to have an effect of the central aging clock.
 

Speeding up of the central aging clock is related to:Slowing down of the central aging clock is related to:
Stress; abnormal response to stressImproving stress resistance; restoration of optimal response to stress; avoidance of intense or prolonged stress
Overeating, excess caloriesCaloric restriction (in rodents), maintenance of ideal body weight (in humans)
Impaired carbohydrate toleranceImproved carbohydrate tolerance
Insulin excessOptimal insulin release
Depression; decreased neurotransmitter levels in the hypothalamusOptimal emotional state, elevation of neurotransmitter levels in the hypothalamus
Lack of melatonin and other pineal gland hormonesRestoration of the levels of melatonin and other pineal gland hormones
Free radical damage to the brain due to oxidation, ionizing radiation or environmental toxins.Prevention of free radical damage to the brain
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