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Anti-Aging: A Historical Perspective by John Heidrick

Anti-Aging:  A Historical Perspective

Before jumping right into the middle of the anti-aging debate, I would like to offer everyone a brief historical perspective.  In the mid 1800's scientists and lay people alike scoffed at the very idea of being able to slow down the aging process.  They viewed all discussion of anti-aging as ridiculous and dangerous both to morality and to human order.  Aging and death were inevitable and there was nothing mere mortals could do to change it. 

Similar beliefs were held with regard to disease.  Disease was a natural event and there was nothing man could do to prevent God's will.  Well known scientists absolutely ridiculed the notion that tiny living organisms could exist and actually cause infection and disease. 

Then the 1870's came and forward thinkers like Koch and Pasteur proved the existence and the danger of the microbes we call germs.  Most of the miracles of modern medicine can be traced to those discoveries.

I mention this because, today, in 2003, the science of anti-aging is at a similar point as was infection and disease in the 1870's.  Science is embarking on a journey, that in the distant future, will look historically a lot like the history of disease treatment.

The real fact is that even in 2003 each of us, regardless of age, can do a substantial bit to slow the aging process and extend our lives.  It is very popular in today's technological world to liken our bodies to that of an automobile.  On the face of it the analogy seems to fit.  When new, each car is working perfectly and looking shiny and great.  As time goes on, wear and tear causes the need for replacement parts and the exterior shine begins to fade.  Eventually the car stops working and needs to be replaced.  This analogy is fine except for the fact that we are living beings and the car is not.  Incumbent in life are our miraculous powers of regeneration.  The difference between humans and autos are that we have tiny invisible "Mr. Goodwrenches" inside constantly working at fixing everything that is going wrong. 

The first indisputable fact that you need to assimilate is that as a human being you are continually repairing yourself, replacing dead cells and denatured proteins, creating new mitochondria and other cellular organelles.  That is the very nature of being human.

So what is aging?  Simply put, aging is the process by which the body slows it's repair processes.   It stands to reason then that if we can stimulate the repair process, in turn, we slow aging.

Let's look at some of the main areas of potential damage.

Free Radical Damage (oxidation)

A "free radical" is a specific type of atom (or molecule) that contains an unpaired electron in its outermost shell. 

Free radicals occur naturally as a result of normal biochemical reactions in the body.  For example, burning oxygen for energy or even simple immune system responses generate free radicals. Free-radical-generating substances can also be found in various foods we eat (especially oil fried foods), the drugs and medicines we take, the air we breathe and the water we drink..

As free radicals react with the various cellular structures, they produce cell damage which accumulates causing problems and sometimes cell death.  More specifically, the cell is the smallest totally self-sufficient unit of life. It can carry out all the processes needed for life.   The cell has various parts, including the nucleus (which stores the DNA), the mitochondria (which are the power plants), the golgi and ribosomes,(which are the manufacturing centers), and the lysosomes (a trash disposal system). All of these cellular parts are enclosed in a membrane called the cell wall.  Each of these individual parts as well as the cell wall can be damaged when free radicals come into contact with them.  Numerous studies have led to the accepted scientific fact that increased production of free radicals causes or accelerates cellular injury and also leads to disease.

Free radicals are also one of the fundamental reasons we age.  In fact, oxygen can be considered the ultimate paradox of life in that it is absolutely necessary for life but it is also the number one cause of free radical production which ages and ultimately costs us our lives.  Fortunately, although it is impossible to prevent all free radical damage, there is a way to eliminate a significant amount of damage.  The answer lies in the simple consumption of antioxidants.  Antioxidants, also known as "free radical scavengers," are compounds that either reduce the formation of free radicals or react with and neutralize them. Antioxidants often work by donating an electron to the outer shell of the free radical. Once the outer shell electrons of the free radical are paired, the free radical is stabilized and becomes non-toxic to cells. 

There are numerous antioxidants available for use today in speeding the repair process.   Vitamin C, beta carotene, vitamin E, glutathione, and superoxide dismutase are among the most popular.

Cross Linking Damage (Glycosylation):

The body is made up, largely, of proteins.  As we age, during normal metabolic activities, sugar molecules sometimes erroneously attach to protein molecules.  The resulting bond is called a "cross-link."  Cross-linked proteins are, in essence, virtually indestructible, damaged proteins.  Cross-linking can occur on a variety of different protein molecules, for example, collagen, elastin, enzymes, etc.  Cross-linked proteins not only accelerate the process of aging but they also directly cause a variety of serious problems including skin damage and wrinkles, cataracts in the eyes and neurological degeneration.

Worse, cross-linked proteins that interact with free radicals cause even more greatly accelerated damage to cells. 

Until recently, biochemists believed that cross-linked protein molecules were totally impervious to change.  Once they occurred, they would exist in your body forever, causing increased aging related damage.  In other words, they were a natural phase of the aging process.

This entire body of knowledge was turned totally upside down with the discovery of Carnosine and the effect that it has on cross-linked proteins   Carnosine is an amino acid based compound; multifunctional di-peptide made up of a chemical combination of the amino acids beta-alanine and L-histidine.

Long-lived cells such as nerve cells (neurons) and muscle cells (myocytes) contain naturally high levels of carnosine. Carnosine levels decline with age. Muscle levels decline 63% from age 10 to age 70, which may account for the normal age-related decline in muscle mass and function (Stuerenberg HJ et al., 1999). In fact, it has been found that muscle levels of carnosine correlate with the maximum life spans of animal species (Hipkiss AR et al., 1995).

Laboratory research on cellular senescence (the end of the life cycle of dividing cells)
suggests that these facts may not be coincidences. Carnosine has the remarkable ability to
rejuvenate cells approaching senescence, restoring normal appearance and dramatically extending cellular life span. 500 mgs. of supplemented Carnosine can eliminate destructive "cross-linking" and bring Carnosine levels back to youthful levels.  There have been no negative effects seen with carnosine supplementation however it has been suggested that mega doses (2000 mgs. or more) might be associated with an increase in allergy type symptoms like runny nose or sniffles.

A second treatment that shows great promise is Metaformin.  Metaformin (also called Glucophage or Metforal) is a standard anti-diabetic drug that used throughout the world to treat both insulin dependent and non-insulin dependent diabetes.  Although its FDA approved use is to increase sensitivity of insulin and to lower blood glucose levels, there are many other important actions coming to be seen.

Metaformin lowers cholesterol, reduces body fat, stimulates antioxidant defenses, decreases the incidence of thrombosis and heart attacks and inhibits protein cross linking, especially when associated with collagen and with blood.

Hormonal Decrease

The body's natural repair processes also slow as a result of a normal decrease in certain critical age related hormones belonging to the Growth Hormone family.

First, let me admit to being a firm advocate of the role that the various growth hormones play in anti-aging, in decreasing body fat and increasing lean muscle and in promoting general health.  I, personally, have tried every type of Growth Hormone Therapy available and have drawn definite conclusions on each.  I am willing to share both my academic and practical knowledge on all of these with you.

Let's begin by differentiating between the three most powerful Growth Hormone substances known to medical science:

HGH:  Human Growth Hormone

IGF-1:  Insulin Like Growth Factor-1

GHRH:  Growth Hormone Releasing Hormone

I have used pharmaceutical injections for each of these, as well as what I refer to as more readily available "intermediate" substances that "turn on" the body's natural biochemical processes that enable higher blood levels of the particular hormone.

Human Growth Hormone:

Human Growth Hormone (HGH or GH) is a hormone produced by the anterior pituitary gland located in the brain.  HGH is a very complex hormone made up of 191 amino acids. HGH secretion reaches its peak in the body during adolescence and steadily declines each additional year through a person's eighties.  If you are a numbers person, here are some average HGH secretion levels:

At 20 years old we average 500 micrograms/day
At 40 years old we average 200 micrograms/day
At 80 years old we average 25 micrograms/day

As secretion of HGH lowers, our ability to repair damaged tissue as well as our ability to engage in a number of other positive, powerful metabolic activities declines.

The amount of HGH secreted is a direct result of the ratio of Growth Hormone Releasing Hormone, technically referred to as Sermorelin, versus Growth Hormone Inhibiting Hormone, technically referred to as Somatostatin.  This is probably a new concept to most everyone.  The literature is absolutely full of talk about HGH increasing substances but there is almost never a mention of the equally important counterbalance, that being, the hormone that actually inhibits HGH release.  It stands to reason that interfering with the inhibitory chemical is at least as important, if not more so, than simply increasing systemic HGH.

Let's talk, first, about increasing HGH.  Secondly, we will discuss the absolutely essential matter of blocking the effects of Somatostatin, the HGH inhibiting hormone.

The most obvious way of increasing circulating amounts of HGH is with synthetic HGH injections.  We refer to this as Recombinant Growth Hormone Therapy.  All this really amounts to are subcutaneous injections of a lab synthesized biosynthetic hormone that is identical to naturally occurring human growth hormone. A company called Genentech made the first synthetic GH in 1985 but it was a 190 amino acid match; they were one amino acid off from natural HGH. One year later Eli Lilly patented a 191 amino acid hormone that was identical to the HGH produced by the pituitary gland. The drug is called Humatrope and is the most widely used recombinant growth hormone today.

HGH injections are extraordinarily expensive, often causing the average patient over $30,000 a year.  I was obtaining Humatrope far less expensively in Mexico (less than 1/10 the cost of the same product in the US) but needed a dosage regime still costing me close to $200.00 every 8-10 days to see even the most minimal of results. 

Frankly, between the cost and the inconvenience of daily injections, despite what all the medical researchers tell you, Humatrope injections are not the best answer for raising HGH levels.  Anyone who tells you they are, well, they have probably never tried a therapy regime themselves.  One notable exception would be bodybuilders who sometimes mega dose their systems with massive amounts of HGH two to three times a week for three to six week cycles.  In that case, a huge rise in GH related effects can be seen but many of these are not at all healthy or positive. It is important to distinguish between sensible clinical doses of HGH for anti-aging and ridiculous massive doses for rapid muscle gain and fat loss.

After rejecting the idea of becoming a cash poor pin cushion, I turned to HGH sprays and homeopathic preparations for increasing GH.  These worked about as well as water and cereal would for raising GH.  If they aren't a scam, I am not sure what to call them.  One possible exception is Somtrop Pro w/ IGF-1.  This oral spray quickly exerted itself as functional product in that it made my skin feel tighter and better, improved the quality of my sleep and perhaps even improved my mood a small bit.  I wouldn't say it rejuvenated me but I did feel different being on it than being off it.

Finally I tried all the various "intermediates."  I tried the amino acids, the secretagogues and the various voodoo based lotions and potions.  Most all of them were an utter waste.  One notable exception which in my opinion is far and away the best method I have found to promote the secretion of HGH, is the amino compound GABA.  Five to ten grams of the natural amino GABA before bed caused a stunning number of nearly immediate changes.  My sleep became unbelievably deep and restful.  My skin became incredibly even and I was able to hold tans far longer.  Excess body fat began to disappear.  My memory and mood improved and many of the small aches and pains associated with middle age began to disappear.  And best of all my 10 grams of GABA a night before bed cost me less than $1.00 a day!

Insulin Like Growth Factor 1

IGF-1 stands for Insulin-like Growth Factor 1. IGF-1 is also known as Somatomedin-C. IGF-1 is directly synthesized from HGH.  As important as HGH is, it does not last long in our bloodstream. In fact, in just a few short minutes, our liver absorbs HGH and converts it into other growth factors. IGF-1 is the most important growth factor that is produced from HGH.  You can think of HGH as the hormone that gets the ball rolling, but IGF-1 as the hormone that does most of the does most of the work.  Therefore, it is not surprising that, in theory, IGF-1 injections will do for you what GH does-and a whole lot more. After injecting IGF-1, it is expected that you will see increases in lean body mass, fat reduction, bone building and increased muscle and nerve repair.

IGF-1 is also thought to improve glucose metabolism.  As its name indicates IGF-I, or insulinlike growth factor-I, has similar properties to insulin, and it has improved blood sugar profiles in type 2 diabetic patients.

One of the most exciting potential uses of IGF-1 is the repair of peripheral nerve tissue that has been damaged by injury or illness. If a nerve is torn in the arm or leg, the connection to the muscle is impaired, there is loss of movement and the muscle atrophies. While peripheral nerves call regenerate to a small extent, severe tears of more than a few millimeters may result in permanent injury. Fantastically, IGF-1 has repaired and reconnected severed nerve endings of up to a distance of 6 millimeters, an effect previously thought impossible.

Additionally, in studies of cells in culture and in animals, IGF-1 has been shown to have
remarkable effects on the spinal cord motor neurons. It increased motor neuron activity in spinal cord cultures by 150 to 270 percent and it increased intramuscular nerve sprouting a whopping tenfold when it was given to normal adult rats.

Unfortunately, as interesting as all this sounds, injections of Somatomedin-C are ridiculously expensive and near impossible to find.  I imagine that no one sells it because very few could afford the price. 

After a very short treatment regime with Somatomedin-C, I saw decent results, better than with sub-q injections of HGH but no effects appreciably better than simple GABA powder which I already told you about. 

As with most pharmaceutical agents, there are nutrient manufacturers trying to convince you that their combination of aminos or their extracts of deer or elk antler works even better than the drug.  Hey, it doesn't hurt to try things, I know, I've made a life-long study of such things.  But my experience and the experience of scores of others I have watched have far and away proven to me that if I had the choice of taking injections of GH or IGF-1, any homeopathic substance and any nutrient type precursor, I would absolutely positively take 5-10 grams of GABA powder before bed.  Not only has GABA proven to create more positive change; it is actually the least expensive of all the alternatives.  Imagine that!

Growth Hormone-Releasing Hormone (GHRH)

GHRH is the faucet that turns on human growth hormone in the body, so it stands to reason that it may be the most natural method for inducing a rise in HGH levels  Synthetic GHRH is made by Serano Laboratories in Nowell, Massachusetts and is sold under the brand name of Geref.  It has only limited approval as a drug in the United States; that approval granted for the treatment of Growth Hormone deficiencies in children.

I can give GHRH a strong and hearty stamp of approval.  I have found that injecting GHRH leads to near immediate results.  You can see the change in musculature and in adipose tissue within three to five days. Muscle definition increases very dramatically and fatty tissue is reduced. The fat just burns away. It gave me increased energy and strength in the gym while making me feel, literally, like a teenager.

If you are having trouble conceptualizing GHRH think of it as an umbrella with Growth Hormone under it, and below that insulin growth factors 1 and 2, and under that the myriad growth factors, which carry out the specific actions on the cells and tissues of the body. Therapeutically, it is difficult to imagine anything working better than GHRH injections.

Dr. Emiliano Corpas and his colleagues at the Gerontology Research Center,
Francis Scott Key Medical Center, and Johns Hopkins University School of Medicine,
found that twice-daily subcutaneous injections of GHRH restored the levels of growth hormone and IGF-1 levels in older men to that of men three decades younger. All the older men had reduced levels of GH and IGF-1 to start. The study was set up so that the older men were given injections of either low dose GHRH (.5 milligram) or high dose (1 milligram) twice daily for fourteen days, then no treatment for another fourteen days. At that point those who had gotten low doses received high doses and vice versa for another two-week period. At the end of the study period, the men who received the high dose of GHRH had levels of growth hormone peaks and IGF-1 that were comparable to those of the younger groups. None of the subjects reported any problems or side effects with GHRH and there were no adverse changes in function, such as increased blood glucose or blood pressure. The researchers concluded that "short" term subcutaneous administration of GHRH to healthy old men reverses age-related decreases in HGH and IGF-1, suggesting that prolonged treatment could improve age-related alterations in body composition."

Another group of researchers found that doses of only 80 micrograms of GHRH given intravenously were enough to raise growth hormone levels significantly in a group of young healthy men without causing unwanted side effects. There was no difference in GFI response above that dosage.

It has been tested on animals as well as humans.  For example, in pigs, it increased the muscle weight by 16 percent and decreased fat weight by 25 percent. It also increased skin and bone weights by 29 percent and 19 percent, respectively. While the researchers in this case were interested in producing leaner pork, presumably what works for Ms. Piggy should work for us as well.

Right now GHRH is being used almost entirely for research purposes. It is available in synthetic form from Serano Laboratoriy. and Hoffman-La Roche. And it is sold in pharmacies across the border in Mexico.  Of course, that is where I first used the product.

More studies, including long-term treatment, have to be carried out in humans before the hormone can be sold for therapeutic purposes. But the potential is great for GHRH because it more closely mimics the way growth hormone is released in the body, and the studies of the Baltimore group show that it can actually reverse the loss of growth hormone that occurs with age.

I am not aware of any proven natural precursors to real GHRH although I am sure in the coming months that we will all be bombarded with some outlandish marketing claims from the less reputable nutrient hucksters.  In summary, it is my educated opinion that if you want to increase circulating HGH naturally you would choose pure GABA hcl powder.  If you were interested in going the pharmaceutical route, I found the best success with Geref. 

Earlier we discussed Somatostatin or Growth Hormone Inhibiting Hormone.  Since this naturally occurring hormone increases with age and inhibits the release of a number of critical substances including HGH, insulin and gastrin; it doesn't take much imagination to envision the negative role this hormone plays in our health and general vigor. 

Unfortunately, since this is a relatively new field of biochemical study, there are no current pharmaceuticals offered for sale to lessen the inhibitory effects of Somatostatin in healthy adults.  In fact, there will never be, as the FDA does not recognize HGH promotion in healthy adults as a valid medical issue for clinical trials to be undertaken.

Furthermore, there are no known nutrients that directly block Somatostatin. But there is hope in that we know that the neurotransmitter acetylcholine markedly interferes with Somatostatin.  In other words, as acetylcholine levels rise, Somatostatin falls and as acetylcholine levels fall, Somatostatin absolutely skyrockets.  It appears then that keeping acetylcholine levels high is the best way to lower the negative effects of Somatostatin and increase the positive effects of HGH precursers.

There is a preponderance of clinical findings indicating that acetylcholine levels can be increased by ingesting 50 mcgs of Huperzine A.  Additional studies indicate simple Choline to be effective in this regard as well.  To achieve maximal HGH secretion it is important to take the Huperzine A anywhere from 30 minutes to 4 hours before taking any Growth Hormone promoter (such as GABA) or any direct injection of HGH.  I recommend Trigger Factor's Thin Stat product an affordably priced combination of the critical Somatostatin inhibiting ingredients Huperzine A and Choline.


To Block Somatostatin:

One Thin State cap (Trigger Factors) upon rising and one additional cap about every six hours as remembered.  It is very important to take one cap before bed, preferably at least an hour before sleep.


To Increase HGH:

Pharmaceutical Injection Route.  The recommended product would be Geref, a growth hormone releasing hormone.


Natural Promotion Route.  2-5 grams of GABA capsules or powder with water before bed.


This article was published on Tuesday 02 January, 2007.
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