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Hydergine ® Developer Albert Hofmann Turns A Hundred
by David Jay Brown
The celebrated Swiss chemist Albert Hofmann turned a hundred last January. Thousands of people from around the world gathered in Basel, Switzerland to celebrate his centennial birthday and honor him for his numerous discoveries and contributions to the fields of chemistry and psychopharmacology.
When Dr. Hofmann addressed the large crowds that gathered in his honor, he spoke eloquently. He was unusually articulate and clear-headed for a man that was over a century old. Many people remarked how sharp his mind was and later, when I had an opportunity to interview Dr. Hofmann for a book that I’m working on, I too couldn’t help but marvel at his remarkable cognitive abilities. I wondered if part of the secret to his extraordinary mental clarity was a result of his development and periodic use of the ergot-derived pharmaceutical Hydergine ® (Ergoloid mesylate).
The development of Hydergine
When Dr. Hofmann began working for Sandoz Pharmaceuticals (now Novartis) in Switzerland during the 1930s his research goal was to work towards the isolation of active principles in known medicinal plants. Dr. Hofmann developed Hydergine in the 1940s, while researching the chemistry of ergot, a fungus that grows on rye and was traditionally used by midwives in Europe to lower blood pressure with birthing mothers. While purifying the ergot-derived substance ergotoxine, Dr. Hofmann had the intuition that this alkaloidal preparation was not homogenous. Dr. Hofmann’s intuition proved correct. Upon further analysis ergotoxine turned out to mixture of three different components. (1)
During testing by Professor Rothlin at Sandoz, medicinally useful properties were discovered, and from these three substances, two pharmaceutical preparations were developed: the blood-pressure-stabilizing compound Dihydergot and the cognitive enhancer Hydergine. Although Sandoz was initially interested in new blood-pressure medications, they began devoting a great deal of resources into researching Hydergine, after studies started to uncover its cognition-enhancing effects. Hydergine was developed because of its ability to improve peripheral circulation and cerebral function in the control of geriatric disorders, and it has proven to be an effective treatment for these indications. Hydergine was the first drug to show efficacy as a treatment for Alzheimer’s disease and dementias. (2)
Today Hydergine is widely used around the world as a treatment for senility, age-related cognitive decline, and as a treatment for a number of other problems. Extensive research has revealed a plethora of brain-boosting and anti-aging benefits that Hydergine has to offer. Hydergine is one of the most tested pharmaceuticals ever developed and it still remains one of Novartis’ most important pharmaceutical products. It has proven to be beneficial and nontoxic in numerous studies. Dr. Hofmann has periodically used Hydergine himself over the years, and I suspect that his use of this cognitive enhancer may play a significant role in his extraordinary mental clarity at the age of a hundred. (3)
The many benefits of Hydergine
Studies indicate that Hydergine has the ability to enhance memory and learning. It improves a range of cognitive abilities, such as concentration and recall (4,5,6) and helps to prevent damage to brain cells from insufficient oxygen. (7) A number of studies even suggest that Hydergine may be able to help reverse existing damage to brain cells. (8)
Some of Hydergine’s cognitive enhancement may be due to the fact that it increases oxygen and blood flow to the brain because it’s a mild vasodilator. (9) It also enhances brain cell metabolism and mitochondrial metabolism. Hydergine’s ability to improve cell metabolism inspired a team of Italian researchers to study how it affects the intracellular features of rat mitochondria, structures within cells that produce energy in the form of ATP (adenosine triphosphate) by respiratory metabolism. In these studies Hydergine not only increased the volume of the mitochondria, it also reduced their size, which is similar to the more efficient mitochondria in younger animals. (10)
Hydergine is an extremely powerful antioxidant. When I spoke with life extension researcher Durk Pearson he said, “We suspected that Hydergine might be a powerful antioxidant due to its structure, so we suggested an experiment that was done at NYU. Every time vitamin C is oxidized and then reduced by the iron in redox cycles, you produce a hydroxyl radical. And the hydroxyl radical is tremendously chemically reactive. It’s about as reactive as fluorine is at eight hundred degrees Fahrenheit–so it can rip up anything. What they found is that Hydergine was the most powerful antioxidant that they tested.”
Hydergine stimulates new interconnective growth between neurons. It causes the release of brain-derived neurotrophic factor (BDNF), which is involved in the repair of damaged neurons and the growth of neurons and neurites. (11) According to Pearson, “If you deprive the brain of BDNF the neurites die back and eventually the cell bodies connected to them die. The brain normally produces BDNF, but as you get older you produce less and less. You end up with some nuerites dying back and your brain sort of gets disconnected. The neurons get disconnected from each other.”
This is an important mechanism by which Hydergine may enhance learning and memory in the elderly. Hydergine mimics the effect of a substance found in the brain called nerve growth factor, which stimulates protein synthesis that results in the growth of new dendrites (tiny tree-like branches at the receiving ends of brain cells). (12) Many neuroscientists believe that intelligence is correlated with the number of interneural connections in the brain. Studies have demonstrated that Hydergine actually increases cortical thickness in the brain through this process and that it also raises levels of the neurotransmitter dopamine. (13)
Studies have shown that Hydergine helps to stabilize brain oxygen levels. (14) If brain oxygen levels are too low then Hydergine raises them, and if they’re too high then Hydergine lowers them. This is why some European countries use Hydergine preoperatively in surgery and after strokes, hemorrhages, and heart attacks to gain precious time. It is also sometimes used to gain more time after certain types of accidents, such as drowning, electrocution and drug overdoses.
Hydergine reduces deposits of the age-related toxin lipofuscin in the brain (15), and normalizes systolic blood pressure. (16) It has also been shown to reduce symptoms of lethargy and, in some cases, even lower abnormally high levels of cholesterol. (17) Many people report that their brain simply feels more awake and more lucid on Hydergine.
Some studies on Hydergine have demonstrated only mild effects, leading some people to believe that it’s not very effective. (18) However many European physicians believe that these studies were less dramatic than others simply because the dosages used were too low, and studies comparing the effects of a 3 mg daily dose to a 6 mg daily dose support this notion. (19) The U.S. recommended dose is 3 mg. per day, while the European recommended dose is 9 mg. per day in 3 divided doses. Some people need to take Hydergine for several months before they notice any significant effects.
Hydergine is extremely nontoxic and has very few side-effects. Initially, Hydergine may cause some mild nausea, gastric disturbances, and bradycardia. It is contraindicated for people who are allergic to it, who suffer from psychosis, or who have an abnormally slow heartbeat or low blood pressure. (20)
Combining Hydergine with other ergot derivatives or other cognitive enhancers may have a synergistic effect, so you may need to scale down the dosages of all the drugs. One should seek the advice of a physician when combining Hydergine with other cognitive enhancers in excess of 9 mg. per day. Most people do well at dosages of around 3 mg. to 9 mg. per day, in divided doses, with occasional breaks. The most common side effect is stomach upset. This can be avoided by using specially coated (FAS) tablets or by using a sublingual liquid preparation.
Other Ergot-derived cognitive enhancers
Albert Hofmann’s intuition about ergot turned out to be extremely fruitful. This remarkable fungus has proven itself to be a gold mine of medicinal treasures; Hydergine is only one of numerous drugs to be derived from ergot. Some of the other ergot-derived cognitive enhancers include the more potent pharmaceutical bromocriptine and the recently developed pharmaceutical nicergoline.
Bromocriptine
Bromocriptine is a dopamine receptor agonist, which activates dopaminergic neurons and mimics the effect of the excitatory neurotransmitter dopamine. (21) It is the most potent of the ergot derivatives and although it is primarily used to treat Parkinson’s disease, it also has profound antiaging effects because it enhances dopamine, which tends to decrease significantly with age. It also effects the pituitary gland production of the hormones prolactin and growth hormone (GH) in some very beneficial ways that appear to counteract some of the symptoms of aging. (22)
Bromocriptine inhibits prolactin, which tends to increase with age, and it increases GH secretion, which tends to decrease with age. Although bromocriptine increases GH secretion in healthy individuals with normal GH concentrations, it actually suppresses GH production in people with a condition known as acromegaly, which causes excessive GH production. Studies indicate that bromocriptine does not affect the release of any
Lipoic Acid:
Rejuvenate Your Antioxidants
By David Brown ipoic Acid (a.k.a. alpha-lipoic acid, thioctic acid, and referred to in this article as LA) is a fat-soluble enzyme, which operates as a cofactor in the metabolism of glucose and oxygen utilization. Soon after its discovery in 1950 it was shown to provide highly effective protection against toxin and radiation damage. LA is now recognized as a powerful antioxidant. It has a strong ability to disarm oxygen free-radicals and a high affinity for chelating undesirable ionized metals.
In the past 49 years there have been over 800 research papers published on LA, and new discoveries continue to evolve. UC Berkeley researcher, Dr Lester Packer, has referred to LA as the “ideal antioxidant” not only becauseLA works as a powerful antioxidant on its own, but also because it acts in a synergistic fashion with other antioxidants.
LA is now recognized as a powerful antioxidant.
It has a strong ability to disarm oxygen
free-radicals and a high affinity for
chelating undesirable ionized metals.
LA works to recycle and reactivate such free radical scavengers as Vitamins C and E, thereby maximizing utilization of these vitamins as antioxidants. LA has the same effect on naturally-occurring antioxidants such as thioredoxin and glutathione (the most abundant antioxidant, selenium-containing proteins in mammals). Even after these vitamins have already been oxidized, LA can reactivate them.1 So if you are not getting enough Vitamin C or E in your diet, LA supplements can help compensate for the difference.
 Although LA is not currently considered to be a vitamin by most researchers, it was originally thought to be a vitamin. Most researchers currently believe that the liver synthesizes LA in small amounts.2 Due to the way it functions synergistically with certain vitamins (the antioxidant B vitamins, Vitamin C, and Vitamin E), some researchers suspect that it still might be an essential vitamin. However the ultimate answer to this question will be determined by whether it is an essential nutrient which is not synthesized in the body. Packer claims that, even though LA’s pathway is not clearly explained, lipoic acid is made in the body.3 But one thing researchers do agree on is that LA levels decrease with age, and with that decline many of the body’s rejuvenating abilities are lost.
Dr Lester Packer has referred to LA as the
“ideal antioxidant” not only because LA works
as a powerful antioxidant on its own, but also
because it acts in a synergistic
fashion with other antioxidants.
LA supplementation has been shown to be beneficial in helping to treat a variety of medical problems. Beneficial results were found especially in the treatment of those with diabetes and neurodegenerative disorders.4 LA can also help lower elevated cholesterol levels which protects against cardiovascular dysfunctions.5 It can retard HIV activation and cataract formation.6 There is also evidence that LA helps to slow down numerous aspects of the aging process by protecting the brain, and by preserving intracellular mitochondria (which supply the basic energy that regulates every cell in the human body).7
LA’s ability to recycle other antioxidants in the body makes it a great potential protector against atherosclerosis. Atherosclerosis is the condition which underlies both heart disease and stroke. There is good evidence that free radicals negatively modify LDL (low density lipoprotein) cholesterol. LDL cholesterol is one of the primary contributors to the undesirable cholesterol deposits which form atherosclerotic plaques. That’s why LDL cholesterol is referred to as the “bad cholesterol.” There is also ample evidence that sufficient levels of Vitamin E can protect against this type of free radical damage. Since LA can extend the life of Vitamin E, it can also increase protection from this type of damage.8
LA recycles and reactivates free radical
scavengers Vitamins C and E – maximizing
their antioxidant abilities.
Several important research findings indicate that LA may offer some hope for those who suffer from AIDS. Research reveals HIV patients have low levels of a potent endogenous (from within the body) antioxidant called glutathione. One study demonstrates that when LA is administered to the body’s T cells (cells involved in immune protection), there is a dramatic rise in intracellular glutathione levels.9
Another study found that LA has a buffering effect on detrimental gene activation, a process which is induced by the rampage of free radicals. Expression of HIV is dependant upon aberrant gene activation. In several studies LAand other antioxidants were effective in inhibiting the activation of this mechanism. Because of these findings, researchers have proposed using LA as a therapeutic adjunct to treating HIV infection.10
Researchers agree that LA levels decrease
with age, as do many of the
body’s rejuvenating abilities.
| David Jay Brown earned his master’s degree in psychobiology at NYU, and researched learning and memory while in USC’s doctoral program in Behavioral Neuroscience. He is the author of Brainchild, and coauthor of Mavericks of the Mind and Voices from the Edge. His new science fiction novel, Virus, will be published this Fall by New Falcon, and he is currently working on a book with British biologist, Rupert Sheldrake, about the unexplained abilities of animals. |
LA may help to prevent brain damage when the brain is deprived of oxygen due to stroke or cardiac arrest. Damage to the brain commonly occurs during these situations because of the combination of ischemia (lack of oxygen) and reperfusion (rapid reoxygenation). Most of the brain damage usually occurs during reperfusion, which is primarily attributed to injury from oxygen free radicals. When experimental animals are treated with lipoic acid, before being exposed to both ischemia and reperfusion, there is a significant improvement in the reduction of brain damage.11
LA may also help with age-related memory decline, and could also have the potential for enhancing or preserving cognitive abilities. In one experiment with mice, LA demonstrated an improvement in the long-term memory of older mice, after being administered for a period of 15 days. However, there was no change among the younger mice. It appears that LA alleviated certain neurotransmitter (NMDA) receptor deficits in the older animals.12
There is reason to believe that LA may also be helpful in preventing cancer, since free radical damage to DNA is thought to be a main factor in causing cells to become cancerous.13
LA’s ability to recycle other antioxidants
in the body make it a helpful
protector against atherosclerosis.
LIPOIC ACID IS FOR EVERYONE
LA can revive and rejuvenate other antioxidant substrates present in the body, like the spent ascorbate and tocopherol radicals produced when Vitamin C and Vitamin E disarm higher-energy free radicals. Thus LA can maximize their utilization, giving you more miles per gallon on your health and a bigger bang for your buck, minimizing the draw on your pocketbook. LA stands alone as a powerful antioxidant.
There are growing numbers of studies substantiating the multiple benefits of LA and showing that doses of 600-1,000 mg/day produce the greatest benefits for health maintenance and preventive purposes. Whether you have particular health concerns which might be benefited by LA supplementation or whether you’re just concerned about the fact that the need for LA increases with age14
New Evidence for Free Radical Theory of Aging Suggests
Antioxidants Extend Life
by David Jay Brown
Caenorhabditis elegans is a type of nematode that normally lives for about three weeks. These microscopic roundworms can live for up to twelve weeks, however, when mutations are engineered in certain genes that control a period of slowed-down metabolism in their life cycle, called the dauer state. In this state they can move around and respond to their environment, but they are sealed up (front and back) and cannot eat. This ability to extend their lifespan has been of interest to longevity researchers, but, because humans do not have a dauer state in their life cycle, skeptics have claimed that it probably has little relevance for extending human life.
The recent discovery of a new catalase gene in these tiny creatures, however, provides additional evidence for the free radical theory of aging, which proposes that one of the primary reasons cells age is the damage to DNA caused by free radicals and reactive oxygen species.1 New evidence for this theory is important because free radical and oxidative damage can greatly affect human health and longevity.2 This newly discovered gene controls the production of catalase, an endogenous (produced by the body) enzyme that neutralizes reactive oxidants and protects cells from oxidative damage.
Free radicals are atoms or molecules that contain at least one unpaired electron (in most stable chemical species, the electrons are paired). This makes them chemically unstable and allows them to react readily with other compounds. In so doing, free radicals and other reactive oxidants can cause extensive damage to cells and tissue, impairing the immune system and leading to infections and various degenerative disorders, such as cardiovascular disease, joint disease, and mental decline. Perhaps worst of all, they can damage the DNA in our cells and put us at risk for cancer.3
Figure 1. The nematode C. elegans in reproductive embrace.Many researchers believe that the havoc that free radicals and other reactive oxidants wreak on our bodies is the basis for the aging process. These dangerously reactive chemicals can be caused by exposure to radiation and toxic compounds, but they also result from necessary and seemingly harmless metabolic processes, such as the breaking down of stored fat molecules for use as an energy source, or simply from metabolizing oxygen. In other words, free radicals are generated from simply eating food and breathing air.
Dr Martin Chalfie and his colleagues at Columbia University recently discovered a new gene for a catalase in nematodes. Catalases promote the decomposition of hydrogen peroxide, a strong oxidant. They are found in the blood and most living cells of animals, including humans (they are also found in breast milk). If this particular gene is disabled in the normal, nonmutated nematode, the catalase that it codes for is diminished, resulting in significant cellular damage. When this same gene is disabled in the genetically mutated nematode (which has an extended lifespan), the nematode incurs not only the same cellular damage but loses its life extension capabilities. This strongly suggests that catalase is necessary for extending the life of the nematode.
“What that says genetically,” Dr Chalfie stated, “is that this particular catalase is a necessary component – perhaps not a sufficient one, though, because we haven’t proved that yet – for the extension of lifespan in this animal. If you can control the catalase gene, then that can have a profound effect on how long the worms will live. We’ve shown that animals that do live longer have more catalase activity and that this particular catalase is greatly increased in those animals.”
A newly discovered nematode gene neutralizes free radicals thereby protecting cells from oxidative damage and slowing down aging.
I asked Dr Chalfie how the discovery of this gene might affect our understanding of how to lengthen human lifespan. “I think,” he replied, “the first thing we have to ask is, is there an equivalent gene in any animal other than this nematode? Is it in humans? So far, by looking at the publicly available human DNA sequences, we have not found it. I suspect that we will get a definite answer for this after the human genome sequence is completed in the next three to five years. Then we’ll know whether there is, in fact, a catalase like this.”
But whether or not there are any human genes that can be engineered to extend life, Dr Chalfie’s discovery of the role that catalase plays in nematodes lends strong plausibility to the free radical and oxidative damage theory of aging. Dr Chalfie believes the most important implication of his discovery is that, “It gives support to the idea that a major contributor to aging, at least as we see it in this worm, is oxidative damage. This is an important controlling aspect for the aging of this animal. It’s not only free radicals that cause the damage, it’s also reactive oxygen species, of which hydrogen peroxide is one.* They’re often called oxygen radicals, but that’s a misnomer. So here’s an enzyme that controls reactive oxygen damage, and when you disable it, the animals live shorter lives. They appear to age more rapidly, and the genetic mutations that normally extend lifespan no longer do so. This suggests that it’s the action of this enzyme that was important for that lifespan extension.”
To learn more about the implications of Dr Chalfie’s discovery, I spoke with Dr Bruce Ames, an expert on oxidant damage and antioxidants at the University of California, Berkeley. Dr Ames said the discovery was important because, “It confirms the idea that aging in animals results from accidental damage to DNA, like that caused by free radicals, and not from a genetically directed clock. I don’t think aging is built in, as with telomeres, where you have a certain number of ticks and then you die. I think it has more to do with wear and tear, and that mitochondrial decay has a lot to do with it. I think the evidence for the free radical theory of aging is getting much stronger.”
In addition to catalase, a number of important free radical scavengers occur naturally in the body, such as superoxide dismutase, methionine reductase, and glutathione peroxidase. However, these enzymes are not enough to arrest the free radical damage that is imposed upon our cells virtually every moment, so antioxidant supplementation is advisable.
Some examples of nutrients that act as antioxidants are Vitamin A, Vitamins B1, B5, and B6, and Vitamins Cand E; other tocopherols, such as tocotrienol; beta-carotene and other carotenoids, such as lycopene; the amino acids taurine and cysteine; alpha-lipoic acid; and the trace minerals selenium and zinc. Many of these compounds can work synergistically to neutralize free radicals and other oxidants.
Many researchers believe that the havoc free radicals wreak on our bodies is the basis for the aging process.
Melatonin, the hormone that many people use as a supplement to help them sleep at night, has also been shown to be a powerful antioxidant. The components of certain herbs, such as green tea, marijuana, and ginkgo biloba,have been shown to have these properties as well. Then there are the food additives BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) . . . and the list goes on.
According to Dr Ames, “If you don’t get enough of Vitamins C or E, it’s like irradiating yourself. Oxidant byproducts of normal metabolism – notably superoxide, hydrogen peroxide, and hydroxyl radical – are some of the same mutagens produced by radiation. Ingesting a diet with inadequate antioxidants, such as Vitamins C and E, mimics radiation exposure. Oxidative damage to DNA and other macromolecules appears to play a major role in aging and degenerative diseases associated with aging, such as cancer.”
Many antioxidants are found naturally in sprouted grains and in fresh fruits and vegetables. Dr Ames states that “The quarter of the population eating the fewest fruits and vegetables has double the cancer rate – for most types of cancer – compared to the quarter eating the most fruits and vegetables. Antioxidant and other micronutrient deficiencies may explain much of why this is so, as inadequate intake of these substances can cause broken chromosomes and lead to cancer.
We can arrest and possibly reverse damage caused by free radicals by using a broad spectrum of antioxidants.
“Much of the population does not get enough of the required antioxidants and other essential micronutrients from fruits and vegetables. To maintain the maximum possible protection from the constant onslaught of free radicals and to prevent chromosome breakage, it is necessary to eat at least five portions of fruits and vegetables per day. We can also minimize damage by taking multivitamins as insurance. It may be desirable to take Vitamin E in addition, as it appears difficult to get the optimal amount of this antioxidant through diet alone.”
At present we can’t do anything about our own levels of the antioxidant catalase. However, we can do something about arresting, and possibly even reversing, some of the damage caused by free radicals by using a broad spectrum of antioxidants. These antioxidants may be able to do a lot to ensure that we remain healthy.
What excites Dr Ames most about his own work, he told me, is that “We’re making progress in rejuvenating old rats by feeding them normal mitochondrial
ROBOT MEDICINE, EXTREMIPHILIC INSIGHT,
CRYONIC SUSPENSION, NANOPROTECTANTS,
HEAT SHOCK PROTEINS, NAKED DNA …
Life Extension: Looking into the Next Millennium
By David Jay Brown
The quest for eternal life is one of humanity’s oldest dreams, perhaps the ultimate goal of medicine all along. In recent years, life extension research has made great strides toward reaching this lofty goal. If the current trend continues, we can expect that much more radical developments will be along soon, and ultimately it may be possible to extend human life indefinitely.
For this article I interviewed several experts in varying fields about what life extension breakthroughs they think might occur in the next century. These pioneers delve into scientifically-sound possibilities that stretch the imagination – such as the ability to manipulate our own DNA, revive people from cryonic (frozen) suspension, and extend human life for hundreds of years through “bush robots” (extraordinarily powerful machines that will eventually be able to repair virtually any type of damage to the human body), and nanotechnology (repair machines made of our own biomaterial and so small that they can operate within the cells of our bodies with advanced super-computer skills).
 I spoke first with two of the world’s experts on life extension, Durk Pearson and Sandy Shaw®, and asked them about possible longevity developments in the near future. Shaw told me, “There is a class of organisms calledextremiphiles. These are bacteria that live under extreme conditions, in places where nobody thought anything could live – like down in deep vent sites under the ocean where there is extremely hot water coming out.”
Pearson added, “Obviously there’s some sort of repair mechanism going on there. I think that a genetic engineering company might very well make themselves a bundle someday by finding out exactly how these cells are able to repair their DNA so well … One of the most surprising things that’s been discovered in genetic engineering is that if you simply inject naked DNA into muscle cells, the DNA is somehow transported into the cells. There, it is incorporated into the nucleus and expressed as proteins. It’s not a very efficient process, but naked DNA is real cheap, and just injecting it with a hypodermic syringe is not a difficult task. So perhaps it may be possible to equip people with some of these bacterial repair enzymes, and improve their ability to repair DNA.”
Ultimately it may be possible to extend human life indefinitely.
But, even with such genetic repair techniques, say that you still don’t live long enough to see the major age-reversing breakthroughs of the next century. You might wish to consider the option of cryonic suspension. This involves having your body cooled down at the time of death, having cryo-protectants pumped through your cardiovascular system, and then being immersed (head first) in a vertical tank filled with ultra-frigid (320 degrees below zero Fahrenheit) liquid nitrogen to preserve your body. This is done in anticipation of nanotechnology, advances in molecular engineering which will be capable of rebuilding the human body atom-by-atom. Then, if all goes well and there isn’t too much structural damage from the cryo-preservation techniques, you will be thawed, repaired, resuscitated, and brought back to full health.
I spoke with Brian Shock – editor of Cryonics magazine, at the Alcor Life Extension Foundation in Scottsdale, Arizona – to learn more about the current state of cryonics. Alcor is the largest provider of cryonic services in the world and have been doing cryobiology research for more than 25 years. They currently have 35 people in suspension, and 456 are signed up. Based on the current rate of nanotechnological development, Alcor believes that they will be able to revive their clients in between 50 and 150 years. I asked Shock about Alcor’s research.
With incredible speed, replicating molecular machines that are capable of precisely sequencing atoms could be programmed to repair any cellular damage in the body; they could also completely reverse the aging process, as simply as if you were changing graphics on your computer screen.
Shock replied, “We’ve done a number of experiments with cold ischemia [lack of oxygen] in animals. We basically cooled animals down to near the freezing point and recovered them to demonstrate that at least the first part of our procedure works. We found that actually getting an animal down below the freezing point is something of a barrier. It could be done with Arctic-adapted animals, frogs, squirrels, and those kinds of creatures. But for regular mammals, especially humans, that’s really just too damaging – especially if done at the temperatures needed to store our patients … The next step involves fine-tuning the profusion system we use. There are questions of whether we should oxygenate patients in ischemic conditions; we’re still determining that. We are adding medications in the initial step of suspension that we think will keep the person in a much better condition. We’re also looking at some new and better cryo-protectants.”
Nanotechnology - on another radical front of development and intimately connected to all others – offers hope that we will be able to repair the structural damage caused by freezing, and revive people from cryonic suspension. It also promises the greatest possible advance in life extension. With incredible speed, replicating-molecular machines that are capable of precisely sequencing atoms could be programmed to repair any cellular damage in the body; they could also completely reverse the aging process, as simply as if they were changing graphics on a computer screen. We know that this powerful sub-Lilliputian technology is possible because the idea for it comes from nature. All living things are already built by biological molecular assemblers. This is simply the most precise way to build (or rebuild) material forms, as well as the cheapest and the fastest. K. Eric Drexler, author of Engines of Creation, says that this sub-microscopic technology is inevitable given our present line of technological development in micro-electronics, computers, and genetic engineering.
If you apply nanotechnology to the human body, you basically cure disease and stop aging.
I spoke with Christine Peterson about nanotechnology and human longevity. Peterson is the executive director of the Foresight Institute – a non-profit educational organization that has been keeping abreast of nanotechnology since 1986. She is also the coauthor of Unbounding the Future: The Nanotechnology Revolution. Peterson told me, “I think that we can anticipate fairly astounding medical technologies based on molecular nanotechnology – in other words, getting every molecule in the desired location. If you apply that technology to the human body, you basically cure disease and stop aging. So what you end up with is the ability to bring about a state of health in any given human body, which is about as much as you can ask from health-care technology. That’s pretty much the ultimate.”
The first nanomachine parts are already here. Virtually every week in Science there’s a paper about how a new type of molecular-sized lever, gear, rotor, tube, switch, or piston has been engineered. Some of the most exciting recent news involves the building of machines out of synthetic DNA. Previously, the ability to build a “DNA nanomanipulator” had been blocked by the excessive floppiness of the DNA-junction molecules. But back in August of 1998, Nadrian Seeman and his colleagues at New York University reported that branched DNA junctions could be made more rigid by incorporating “double-crossover molecules of DNA.”
 This development opened up the door for a whole new avenue of molecular-machine design. Dr Seeman and his colleagues recently announced that they built a “nano-robotic arm” from synthetic DNA molecules. The device has two rigid arms that can be rotated between fixed positions, like a movable switch. Dr Seeman said, “Using synthetic DNA as a building material, we have constructed a controllable-molecular mechanical system. In the short run, this is an exciting technical achievement. In the long term, the work will have implications for the development of nanoscale robots and for molecular manufacturing.”
Pushing into the future even farther, I spoke with Hans Moravec. Dr Moravec is the founder and Director of the Mobile Robot Laboratory of Carnegie Mellon University, the world’s largest robotics program. He is also the author of Robot and Mind Children. Dr Moravec predicts that by the middle of the 21st Century, extremely powerful robots will be built with greater than human intelligence.
I spoke with Dr Moravec about the future development of robotics. With regard to extending human life, he doesn’t think that there will be enough technological advancement for much robotic help in the near future, “except in that, robots are helping in the biomedical labs. A lot of molecular biology is done by these little laboratory robots that perform hundreds of tests at once.”
Dr Moravec envisions that “bush robots” will eventually be able to repair virtually any type of damage to the human body.
Dr Moravec has suggested that we may eventually be able to transplant our brains into the bodies of super-human robots, and transfer
Nicotinamide Improves Health and May Extend Life
Applying the Secrets of Caloric Restriction
By David Jay BrownMany life-extension seekers have viewed the dramatic results from longevity studies involving caloric restriction as one of life’s cruelest jokes. Calorically restricted animals (that receive all their proper nutrients) develop fewer diseases in general and are known to live significantly longer than animals that are allowed to eat as much as they like. Numerous animal studies – dating all the way back to the 1920s – have shown this to be the case with worms, flies, mice, and monkeys. 1
While living longer by adhering to a partial-starvation diet may not seem particularly appealing to most people, the results of these studies have been so impressive that anyone seriously interested in life extension has to be more than a little intrigued.
Caloric restriction doesn’t just increase average lifespan in animals; it also increases maximum lifespan - dramatically so. This means that animals on calorically restricted diets live significantly longer than the longest-lived members of their own species that are not calorically restricted. Many things increase average lifespan in animals – a healthy diet, nutritional supplements, exercise, good genes, etc. – however, increasing maximum lifespan is a whole new ball game. The maximum lifespan for a human being is somewhere between 110 and 120 years. The longest-lived human ever documented was a French woman who died in 1997 at 122 years. The rodents in the calorie-restriction studies lived to be the human equivalent of 140 to 160 years!3
Rhesus monkeys used in the NIA caloric-restriction study had much lower incidence of cancer and other diseases involving cell proliferation.
LESS CANCER AND PROLIFERATIVE DISEASES
The primate studies involving caloric restriction suggest that these results probably apply to humans as well, and exciting new research suggests that the life-extending benefits of caloric restriction may be available without having to struggle with a near-starvation diet. New evidence from a recent study at the National Institute on Aging in Bethesda, Maryland sheds some light on the mechanism involved in caloric restriction and suggests thatnicotinamide supplements (with the proper cofactors) may mimic the benefits of caloric restriction.
Recently, Mark Lane, Ph.D., Angela Black, Ph.D., and colleagues at NIA revealed that calorically restricted monkeys develop fewer proliferative diseases (such as cancer and endometriosis) than controls.4 The NIA study, which followed 120 rhesus monkeys for more than a decade, found that monkeys who consumed 30% fewer calories than controls had fewer chronic diseases in general, but, more specifically, they had a much lower incidence of diseases involving cell proliferation. “I think the main implication for potential human application of this would be that it’s going to reduce the incidence of age-related diseases, in particular cancer. Cancerous tumors in the animals were noticeably reduced,” said Dr. Lane. This finding is not unique to the NIA study. It has been generally accepted that caloric restriction – the practice of undernutrition without malnutrition – doesn’t just slow the progress of cardiovascular disease; it slows cancer too.
CALORIC RESTRICTION MECHANISM UNKNOWN
Although there have been hundreds of studies on caloric restriction, the exact biological mechanism responsible for the increase in longevity and the reduction of proliferative diseases remains a mystery. However, a number of important clues are now available. “Caloric restriction reduces insulin, insulin-like growth factor-1 (IGF-1) [a measure of growth hormone release], and other growth factors in the body. That’s been shown many times. So that would have obvious effects on proliferative or runaway-growth kinds of diseases. That may be the proximate mechanism here, but we really don’t know that for sure,” said Lane. However, most longevity researchers agree that caloric restriction probably extends animal life because fewer calories means less energy production, less wear and tear, and less oxidative damage.5
THE GENE-SILENCING THEORY
MIT researcher Leonard Guarente, Ph.D., offers an alternative explanation.6 His gene-silencing theory proposes that caloric restriction reduces the overall metabolism of an essential cofactor called nicotinamide adenine dinucleotide, or NAD for short. NAD is normally shunted into the breakdown of glucose in cellular energy production. But when increased in availability through caloric restriction, there is an abundance of NAD beyond that needed for cellular energy production. This extra NAD is available to act as a catalyst for an enzymatic protein called silent information regulator no. 2 (Sir2p). NAD increases the effectiveness of Sir2p, and the result disables the transmission of certain genetic messages that ultimately lead to cell death.
The mechanism involves a process called deacetylation, in which acetyl groups are removed from a substance called chromatin, which normally fits around the chromosomes like a loose sleeve. However, once deacetylated, the chromatin tightens itself snugly around the DNA. This blocks the DNA from broadcasting genetic instructions that would ultimately have devastating consequences for the cell and are thought to be responsible for a cellular aging process. When the chromatin tightens itself snugly around the DNA, the instructions that would eventually lead to the cell’s death are squelched. When NAD is abundant, the effectiveness of Sir2p is increased, and cell life is preserved. Thus, NAD helps prevent the expression of certain genes responsible for a cellular aging process involving damage to DNA molecules.
When NAD is abundant, Sir2p prevents the release of circular DNA fragments that proliferate inside cells during the aging process. These replicating rings of genetic “noise” accumulate to the point where they eventually strangle the cell from within. However, when NAD and Sir2p join forces, the possibility of this happening is significantly reduced because of gene silencing. If caloric restriction helps increase longevity by decreasing the incidence of cancer, runaway cell proliferation – the mechanism of cancer – is likely to be fueled by more, rather than fewer, calories.
THE “CANCER-SILENCING” LINK
“A link between aging and cancer is suggested by the delay of cancers in calorically restricted mice,” write Drs. Leonard Guarente and Cynthia Kenyon (also an aging-gene researcher, but at University of California, San Francisco), “and by the striking correlation between physiological age and the likelihood of cancer in animals with very different lifespans. This suggests that any treatment that slows the aging process, whether it acts directly on hormone signaling, gene silencing, or oxidative stress, may have the potential to delay cancer and possibly other diseases of aging.“7
Understanding the mechanism of slowing the aging process leads one to predict that caloric restriction might be most effective in slowing down the incidence of runaway cell growth and proliferative disease, and this is exactly what Lane and Black found in their most recent study.
THE RACE FOR CALORIC-RESTRICTION-MIMICKING DRUGS
These findings have stimulated an aggressive search for drugs that mimic the process of caloric deprivation. Lane is currently studying a synthetic molecule similar to the sugar glucose. He has demonstrated that cells take up this glucose analog as if it were glucose, but they cannot metabolize it to obtain energy, as they do from glucose.
In rodent studies, administering this synthetic molecule produces some of the same responses as caloric restriction, such as reducing body temperature and lowering the amount of insulin in the blood.4 Lane and his colleagues at NIA are now testing whether these treatments will extend the lifespans of rodents.
ALTERNATIVES TO CALORIC RESTRICTION?
“By disrupting the normal metabolic pathway for the metabolism of glucose with a glucose analog,” Lane explained, “we were able to reproduce many of the biological effects of [caloric] restriction – such as a reduction in insulin levels, a reduction in body temperature, and even a slight reduction in body weight. Those animals did not exhibit any significant reduction in food intake, so they were essentially eating as much as they wanted of a diet with this glucose analog in it. . . . We think that caloric restriction has many of its effects by acting as a metabolic stressor on the body. You’re basically reducing metabolic output of the cells by inhibiting glycolysis, and this is what this glucose analog also does.”
THE LIMITATIONS OF DRUGS
It’s unfortunate that the glucose analog that Lane is studying has significant drawbacks; at high doses it’s toxic throughout the body and can kill brain cells. But there may be less toxic alternatives to mimicking the effects of caloric restriction. “There are other compounds that inhibit glycolysis as well that may not have these toxic effects,” said Lane. “Right now we’re focusing on really trying to study the mechanism using this glucose analog because it’s well characterized and well studied in other model systems. Once we get a better handle on its workings, and if indeed it is mimetic of caloric restriction, then we’re going to move into developing other compounds. The end point of this research would be to develop other compounds that are
An Overview of the Theories of Aging
Why Do We Age?
By David Jay Brown  lthough many of the factors involved in human aging still remain a mystery, our understanding of the aging process has advanced significantly over the past few decades. This article provides an overview of some of the leading theories of aging, with a particular focus on their implications regarding life extension.
In researching this article, I spoke with Ward Dean, MD, and Arthur Balin, MD – two experts on human aging – to find out what they think the primary causes of aging are and what they think can be done to stop, slow down, or reverse the aging process. Dr. Dean is the medical director of the Center for BioGerontology in Pensacola, Florida, and is the author or coauthor of a number of popular books, includingBiological Aging Measurement and Smart Drugs & Nutrients. Dr. Balin was the executive director of the American Association of Aging and is the author of such influential books as Human Biologic Age Determination and The Life of the Skin.
In general, current theories of aging can be separated into two basic groups. One group suggests that aging is caused primarily by the accumulation of DNA damage due to the wear and tear caused by free radicals. When genes are this damaged, they can no longer adequately control the functions of cells. The other group centers around the notion that aging is built into our DNA from the start and is a direct consequence of our genetic programming.
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DNA Damage Theories
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THE FREE RADICAL/OXIDATION THEORY OF AGING
Probably the most influential of current theories, the free radical/oxidation theory of aging is supported by a large and growing body of evidence. Developed by Dr. Denham Harman in 1956, the theory postulates that changes due to aging are caused by free radical reactions. Free radicals are atoms or molecules that contain at least one unpaired electron. This makes the molecules chemically unstable and allows them to react easily with other compounds in the body. In so doing, free radicals and other reactive oxidants can cause extensive damage to cells and tissues, impairing the immune system and leading to infections and various degenerative disorders, such as cardiovascular disease. Perhaps worst of all, they can damage the DNA in our cells and put us at risk for cancer.
Many researchers believe that the havoc that free radicals and other reactive oxidants wreak on our bodies is the basis for the aging process. It has been shown that accumulation of free radical damage increases with age.1 Support for the free radical theory of aging has increased progressively over the years, and growing numbers of studies implicate free radical reactions in the pathogenesis of specific diseases, such as cancer and arteriosclerosis.2
Free radicals can be caused by exposure to radiation and toxic chemicals, but they also result from seemingly harmless and necessary metabolic processes, such as the breakdown of stored fat molecules for use as an energy source, or simply from metabolizing oxygen. Sun exposure can cause the generation of free radicals too. An effective antioxidant regimen would include a well-designed multivitamin/multimineral antioxidant formulation. A booster formulation containing added amounts of Vitamin C and E, and various flavonoids would also be useful for additional protection. Polyphenols such as are found in green tea can add yet another important range of protection.
DNA DAMAGE AND REPAIR THEORY OF AGING
Oxidative damages to DNA are among the best documented and most prevalent of DNA injuries and are likely to be a prominent cause of aging. (This theory is similar to the free radical/oxidation theory, with more emphasis placed on direct DNA damage and repair.) DNA is particularly sensitive to oxidative damage, and breakages occur continuously in the cells of living organisms. While most of these damages are quickly repaired, some accumulate, because the DNA repair mechanisms cannot correct defects as fast as they are produced.
Many researchers suspect that the overall aging of the organism is caused by these accumulated genetic alterations, which inhibit the cells’ ability to function properly and can lead to their death.1
An example of a substance that does direct damage to DNA, hydrogen peroxide is considered to be one of the most dangerous oxidants, because it easily diffuses through cell membranes and can injure the delicate biological machinery. High concentrations of hydrogen peroxide can lead to cell death and even lower concentrations that can cause permanent genetic alterations. This DNA damage could lead to mutations and ultimately to the malignant transformation of cells (carcinogenesis).
Bulletin: Confirmation of Free Radical Theory
Just in. As we go to press, an important article has just appeared in Science magazine that may fundamentally alter our knowledge about the different theories of aging.6 Authored by Dr. Richard Weindruch (whose work has found caloric restriction to extend life in animals) and three other researchers, the Science article shows that certain antiaging genes, which repair damage caused by free radicals, are significantly reduced in their activity in animals on high caloric diets, as compared with animals on low caloric diets (calorically restricted diets).According to research scientist Dr. Raj Sohal of Southern Methodist University, the study “helps confirm that the formation of free radicals are at the heart of aging, and that gives us ways to seek out medicines that may prevent free radical damage.”7 This is very exciting. It should now be possible to rapidly determine the best protocols for slowing the aging process, given that many of the antiaging genes have now been identified. And the evidence thus far points to genes that repair free radical damage. |
MITOCHONDRIAL DNA THEORY OF AGING
This theory, also originated by Denham Harman, proposes that the accumulation of mitochondrial mutations during life is an important contributor to both the aging process and to several human degenerative diseases. (This theory is distinguished by its emphasis on mitochondrial damage and repair.) The mitochondria - a specialized part of cells that are responsible for producing the energy within cells - have their own genetic material (mtDNA), which is distinct from the nuclear DNA in the cell. The mtDNA is produced at the inner mitochondrial membrane, near the sites where free radicals are formed. Mitochondrial DNA appears unable to counteract the damage inflicted by these free radicals (byproducts of respiration) because, unlike the nuclear DNA, they lack advanced repair mechanisms.
Oxidative damage to mitochondria leads to a loss of energy resources within the cell. This in turn increases the probability of the cells dying under stressful conditions. Observations have confirmed that mutation rates occur at a much higher frequency in mtDNA than in nuclear DNA. There is also evidence that, with increasing age, genetic damage increases, and there is a decline in mitochondrial activity in nondividing cells, such as heart and kidney cells.3
Mitochondrial scientists Linnane and Ozawa have suggested that clinical interventions may be able to counteract the oxidative damage done to the mitochondrial DNA.4 Among the nutrients that can help comprise a mitochondrial protection program are acetyl L-carnitine, coenzyme Q10, DHEA, and alpha-lipoic acid. MCT oil (medium chain triglycerides) also deserves inclusion in such a program.
SUPPLEMENTS CAN HELP PROTECT YOU
FROM OXIDATIVE INJURY AND DNA DAMAGE
Biological systems have evolved a multiplicity of defenses against oxidative attack. To protect the body from free radical and oxidative damage, our cells utilize free radical scavengers - a mixed bag of vitamins, minerals, enzymes, flavonoids, and other compounds that function as antioxidants to neutralize free radicals and other oxidants. A number of important free radical scavengers occur naturally in the body, and many can be found in fruits and vegetables.
While many antioxidants can be obtained from food sources, it is often difficult to get enough from these sources to obtain optimal protection from the constant formation of free radicals. We can minimize free radical damage by taking antioxidant supplements. Researchers have identified a whole arsenal of nutritional antioxidants. These include beta-carotene, C and E, alpha-lipoic acid, and the mineral selenium. Melatonin, the hormone that many people use as a supplement to help them sleep at night, and the components of certain herbs, such as green teaand Ginkgo biloba, also have been shown to have these properties as well.
Many studies have demonstrated the protective benefits that result from taking antioxidant supplements. There is evidence that suggests a protective effect from antioxidant vitamins for ischemic heart disease, cataracts, and
Doctors Report
How Their Patients are Doing on 5-HTPBy David Jay Brown David Jay Brown interviewed several physicians and other health practitioners about their patients’ experiences with 5-hydroxytryptophan (5-HTP). Various problems discussed included: sleep disorders, depression, anxiety, migraines, fibromyalgia, and weight management.
MY PERSONAL PERILS WITH SEROTONIN DEFICIENCY
 have suffered from Serotonin Deficiency Syndrome (SDS) for many years. From 1988 until 1996 I needed to drink – virtually every night – a half-quart of cow’s milk (which has relatively high levels of the amino acid tryptophan) to help me sleep, enhance my mood, and reduce anxiety. Drinking milk was necessary for me because the FDA banned the sale of tryptophan in 1988. I had previously used tryptophan with great success to treat my SDS. My brain simply craved serotonin. Large quantities of milk helped, although I got awfully sick of drinking milk. But the tryptophan supplements had provided exquisite relief.
During two periods of significant depression I tried the pharmaceutical compounds Prozac® and Zoloft®. Like tryptophan, these drugs increase the activity of serotonin in the brain, but I found the side effects intolerable. With both drugs I found it incredibly difficult, if not impossible, to reach orgasm during sex. Both drugs dampened my creativity, which being a writer, is my life-blood. And, while the drugs raised the floor on my emotional lows, they also lowered the ceiling on my emotional highs. I felt as though my emotions were trapped in a box. I never had any of these side effects with tryptophan. This made sense to me since tryptophan is natural to the body and is simply the metabolic precursor to serotonin.
| David Jay Brown earned his master’s degree in psychobiology at NYU, and researched learning and memory while in USC’s doctoral program in Behavioral Neuroscience. He is the author of Brainchild, and coauthor of Mavericks of the Mind and Voices from the Edge. His new science fiction novel, Virus, will be published this Fall by New Falcon, and he is currently working on a book with British biologist, Rupert Sheldrake, about the unexplained abilities of animals. |
The FDA prohibition resulted from a single contaminated batch of tryptophan. It was synthesized by a Japanese manufacturer who used a new and untested raw-material source and skimped on filtering. Several people suffered serious adverse reactions due to the contaminated batch. For the FDA to universally and permanently ban all tryptophan – which is found naturally in mother’s milk – seems extremely questionable to me. Aside from two exceptions, infant formulas and parenteral care IVs, the moratorium on the use of tryptophan continues to this day to the extent that it can only be obtained by prescription. The ban is not based on FDA ignorance, since the Center for Disease Control’s reports acknowledge the adverse effects were due to a contamination by one manufacturer. This simply gave the FDA their perfect excuse to exile the natural tryptophan for their vested interest in pharmaceutical companies, who are unable to patent naturally-occurring substances such as tryptophan. The FDA/prescription company alliances don’t want tryptophan competing, however effective and safe, with their highly profitable drugs, such as Prozac, Zoloft, and Paxil®.
Exploring the Frontiers of Anti-Aging Medicine:
An Interview with Dr. Marios Kyriazis
By David Jay Brown
Marios Kyriazis, M.D. is both a clinician and a researcher in the field of anti-aging medicine. He has made significant contributions in the science and application of anti-aging medicine, and he is considered one of Britain’s leading longevity specialists. Dr. Kyriazis is one of the world’s experts on the subject of how carnosine effects the aging process, and his research into the effects of this mighty amino acid dipeptide have revealed how it can offer a number of unique and substantial health benefits.
Dr. Kyriazis has a postgraduate degree in Gerontology from the King’s College, University of London, and another in Geriatric Medicine, granted by the Royal College of Physicians. He is also a Chartered Biologist, and a Member of the Institute of Biology for his work in the biology of aging. Dr. Kyriazis is the founder and medical advisor to the British Longevity Society, and he is a certified member of the American Academy of Anti-Aging Medicine. He is also an adviser to several other age-related organizations.
Dr. Kyriazis has extensive experience with nutritional supplements and anti-aging drugs. He is the author of several books on these subjects, including The Anti-Aging Plan, Stay Young Longer–Naturally, The Anti-Aging Cookbook, The Look Young Bible, and Carnosine And Other Elixirs Of Youth.
Dr. Kyriazis lives Hertfordshire, England. I interviewed him on November 6, 2004. Dr. Kyriazis has a warm and thoughtful manner about him. We spoke about the best ways to slow down the aging process, his research and clinical experience with carnosine, and how just the right amount of stress can actually benefit our health.
David: What do you think are the primary causes of aging?
Dr. Kyriazis: When I think about the primary causes of aging I divide them into two groups–fifty percent genetic and fifty percent environmental. From the environment we get free radicals, glycosylation, and hormonal changes. At the moment I don’t think there is anything that we can do about the genetic part, but we can of course influence the environmental part of aging. So I am working in clinical medicine to offer ways of counteracting the environmental causes, or the environmental basis of aging.
David: How do you differentiate between the biological symptoms of aging and those bodily changes that are actually caused by one’s belief about aging?
Dr. Kyriazis: It depends at what level one looks. I am more interested in the clinical level, although I have done biological research as well. I think there are different ways of looking at it. Biology will start with the molecules and the cells, and say this is an age-related phenomenon, a disease-related phenomenon. From my point of view I see individual patients. People usually come to see me because they have an age-related illness. So they come with, say, heart disease, or a prostate problem, which are age-related. Then when we expand on the actual causes of their problem they want to know more and find out about other age-related processes which may affect them. So it is a combined thing. I don’t necessarily make a distinction myself in my work.
David: What do you think are currently the best ways to slow down, or reverse, the aging process and extend the human life span?
Dr. Kyriazis: I offer a combination of different therapies affecting the entire body. For example, I recommend antioxidants and anti-glycator drugs or supplements. Apart from the ordinary vitamins and nutrients, I recommend carnosine, DHEA, and other hormones, depending upon whether the individual is deficient in those hormones or not. I also recommend a nutritional lifestyle and exercise–but not ordinary exercise. It’s a combination of different unusual exercises (which I discuss in my book The Anti-Aging Plan) plus mental and sense exercises as well.
I try to make it easy for the individual to follow this, because many times people think that it’s much easier to just take a tablet or a capsule, rather than change their lifestyle. But I think it is very important to find a way to motivate the individual to change their lifestyle. So, in other words, it’s a combination approach. Different things all working together. Some people say, oh take four different supplements, or four different hormones, and you are covered. I don’t agree with that. I think that there are so many different aspects of aging, and that we need to use different treatments, a multi-pronged approach. So that’s what I say to my patients.
David: Can you talk a little about some of the beneficial effects your patients have had with carnosine supplements?
Dr. Kyriazis: Yes. I think I was the first person to use carnosine for anti-aging purposes. Carnosine has been around for quite some time, and athletes used to use it to enhance muscle and a performance. But I began using it specifically for anti-aging back in 1999. And the first person who took carnosine under my guidance still takes it today, five years later, and everyone says how young she looks generally. Her head hasn’t got a single grey hair–not one–although she’s now 48 or 49. This corresponds with experiences we have had with other patients. In other words, they generally look younger. Their hair grows better, and it stays black, or whatever color it is, but not grey. Many people experience increased energy. Mental performance, memory, and other brain functions improve as well.
But I always say to people that carnosine is not something that you can notice yourself. It’s something that works inside the body over the long-term, over ten or twenty years to prevent all the different age-related processes and damages that happen. I see carnosine mainly as a preventative treatment, not so much as an immediate treatment for some specific disorder, or to be noticeable. It doesn’t immediately produce noticeable effects, although there are ways of doing different biochemical tests, blood tests, and so on, that show an overall improvement over the years.
I use carnosine on patients who are normally healthy, who don’t have a disease. For example, I don’t use it on people who have muscular dystrophy or other muscular diseases. I think some people take it for that, but I don’t know whether it works or not. So it is difficult to differentiate and see a noticeable improvement on a healthy person. It’s much easier to notice if somebody is ill and he or she gets better after taking it. But this supplement is mainly used by healthy people in the long-term.
David: Can you talk a little about carnosine’s anti-glycosylation effect, and how it protects the body from dangerous cross-linked, oxidized proteins?
Dr. Kyriazis: Everybody thinks that free radicals and oxidation are the main causes of aging, but there’s another important one, which is glycosylation, and this happens all the time. It is due to glucose or other molecules attaching to proteins. This causes cross-linking and “advanced glycosylation end-products” or AGEs. I would say that this causes more damage to the body than free radicals, and carnosine prevents this damage in different ways.
First of all, it prevents free radical attacks because it’s an antioxidant. But it is also an anti-glycosylator. In other words, it prevents the proteins from being cross-linked. If two proteins that are not supposed to attach to each other, become attached and combine together, then they become useless. That’s what happens in cross-linking, and carnosine prevents that. Carnosine is like a shield that protects proteins. So when two proteins come together they don’t attach to each other. They remain free to function normally.
So the first stage is that carnosine prevents glycosylation in the first place. The second stage is that if glycosylation has already happened, if the two proteins have become cross-linked, carnosine will facilitate the removal of these useless proteins. Actually, our body is trying to eliminate abnormal proteins all the time, but with aging this rate of elimination slows down. Therefore we have an accumulation of abnormal proteins. But carnosine speeds up the rate of elimination, so all the junk material we have in our body gets eliminated quicker.
There is also some evidence that carnosine can actually break the existing bonds between the two cross-linked proteins. So if the proteins have become attached to each other, and they are cross-linked, in some circumstances carnosine can break the bond and allow them to be free again, and to function normally. So carnosine has three different benefits in addition to being an antioxidant.
David: What kind of dosage do you recommend a healthy person take?
Dr. Kyriazis: I started with fifty milligrams a day, but now I recommend a higher dose–perhaps about two hundred milligrams a day. I know that some people use a thousand or more milligrams a day, but I don’t see the reason for that. I think about two hundred milligrams a day, in association with other supplements, should be enough for a healthy person.
David: What are your thoughts about using N-Acetylcarnosine eye drops–which breakdown into carnosine in the eye–as a way to protect the health of one’s eyes?
Dr. Kyriazis: This is also a very promising development. I was involved with advising the different researchers at the companies that are now marketing acetylcarnosine. The things that carnosine does as a tablet doesn’t work as well as
Chemo-Eroticism:
Exploring the New Prosexual Drugs &
the Art of Feeling Really Good
by David Jay Brown
Like immortality and the fountain of eternal youth, every culture since the beginning of time has sought out aphrodisiacs and methods for enhancing the sexual experience. Biological organisms like us seem to find sex and drug ingestion fairly irresistible because these activities activate ancient pleasure centers in our brains. Our ancestors discovered long ago that by combining these two biochemical art forms new dimensions in the realm of “feeling really good” can be achieved. For example, although alcohol intoxication actually interferes with sexual functioning, many people have their first sexual experiences while drunk as a teenager, due to its disinhibiting properties. Maybe not knowing much about history or biology is fine when love is in the air, but knowing your chemistry sure can be helpful in making this a more wonderful world.
Marijuana is a very erotic plant, and the majority of High Times readers are, I’m sure, hip to the fact that if you smoke cannabis prior to sex, every sensation becomes greatly enhanced because it increases the sensitivity of one’s senses. The sensual photo profiles and centerfolds in High Times of the plant itself reflect this erotic quality, as they are clearly modeled after the pictorials of beautiful nude women in Playboy and Penthouse. And as the infamous Playboy interview with Timothy Leary during the Sixties made clear, the popularity of LSD is partially due to acid’s ability to turn sexual activity into a full-blown ecstatic mystical experience. So sex and drugs have always had an intimate relationship, but true aphrodisiacs– substances that actually ignite the feelings of sexual passion– have always just been a myth– conjuring up images of those ridiculous “Spanish fly” ads in the back of sleazy magazines– right?
Maybe not. Contemporary neuroscience research is leading many people to question that assumption, and the beacon of modern pharmacology has created a whole new class of chemical tools to explore this ancient neurochemical connection. On a medical level, effective chemical treatments for such age-old problems as impotence, premature ejaculation, loss of interest in sex, as well as difficulty achieving erection, sufficient lubrication, and orgasm are now available. There is also a variety of chemical means to increase one’s physical sensitivity and subjective enjoyment of the sexual experience. These substances can be used to help make disabled people healthier, and they can also be used by erotic engineers to make great sex even better. Most significantly, there are now chemicals available that appear to actually make you horny.
John Morgenthaler, co-author of Smart Drugs and Nutrients, recently published a new book– Better Sex Through Chemistry(with Dan Joy)– which reveals how to safely enhance one’s sex life through nutrients and a new class of pharmaceuticals which they call “prosexual drugs”. In conversation with Morgenthaler he told me that in researching the book they started “by doing computer searches of Medline and Embase. These are the largest medical science databases in the world with millions of scientific abstracts. We searched on key words like “impotence” and “aphrodisiac” and to our surprise, we downloaded nearly 15 megabytes of data directly related to prosexual enhancement. This is a huge body of scientific work. We had no idea there would be that much substantial information.”
Morgenthaler coined the term “smart drugs” and played a significant role increasing awareness about them. In writing this book he has now made public another popular underground phenomena– which has been picked up on recently by the mainstream media– letting the pussy out of the bag, but providing an extremely valuable resource, which overflows with otherwise obscure hard-to-find information. The media’s recent attention to the subject has got some people, at least in California, somewhat nervous that the FDA or DEA will crackdown on the usage of prosexual drugs, just as they did with smart drugs and MDMA once their popularity began to increase, and they hit the mainstream. But the chemical revolution currently in motion is not taking place exhibitionistically this time at Raves or in dance halls, rather it is occurring discretely in the bedroom. There are now over a dozen important and fascinating nutrients and pharmaceuticals of interest to sexual enthusiasts and biochemical gourmets which are currently available. Some of the most significant of these are discussed below, and I tested a number of them myself in writing this article. (About myself: I’m 34 years old and sexually healthy. My sex drive tends to run higher than most men I know my age, and the only times that I’ve ever encountered any sexual problems is when I’ve been nervous, chemically altered, or overextended.)
Smart drugs and prosexual drugs have a lot in common. As in the case with the majority of smart drugs, all of the major substances discussed in this article share exceptionally low levels of toxicity, and they are all legal. Some of the prosexual substances, such as deprenyl and bromocriptine have also been shown to increase intelligence, booster attention, and benefit memory consolidation. Inversely, some of the smart drugs such as piracetam and vasopressin have been reported to have sexually beneficial effects. According to gerontologist and life extension researcher Ward Dean, M.D., “…anything that improves brain function is probably going to improve sexual functioning.”
All of the prosexual substances discussed in this article are also extremely safe, remarkably free of side-effects, non-addictive, and in general improve overall health. This would have to be the case with any substance that improved sexual vitality over an extended period of time, as sex and health are intimately linked. So great is their connection that a healthy sex life is one of the primary indicators of overall good physical health. In fact, Morgenthaler told me that he is “really much more interested in health and longevity than sexual enhancement. For me, this was a way of writing a life extension book that would sell. We are using sex as the hook to sell life extension.” Better sex, I’ll admit, certainly provides me with additional motivation to want to live a longer and healthier life.
It has long been known that proper nutrition is essential for maintaining the desire, capacity, and stamina necessary for a healthy sex life. Many nutrients and amino acids play vital roles in facilitating the process of neurotransmission and/or bloodflow in regions of the brain and genitals which are responsible for sexual function and sensation. Taking supplements can sometimes be beneficial. For example, L-Arginine– an essential amino acid readily available in most health food stores– has been shown to increase the ability to obtain erections and maintain stamina, as well as overall increasing libido, and is reported to also increase the intensity of sexual sensations.
This effect is due to the fact that L-Arginine increases the production of an excitatory neurotransmitter called NO (nitric oxide, the only known gaseous neurotransmitter), which is widely recognized as the sole chemical responsible for causing penile erections. Although less studied in women, one 21 year old female taking L-Arginine supplements has been quoted as saying, “My god, that stuff! I had to stop taking it. I was doing it with every guy that came along.” (Could this be what Nancy Reagon meant by “Just say NO.”?) So I tried the stuff. My research notes for L-Arginine read as follows:
10:30 am: I swallow two teaspoons of “ProSexual Plus”, a passion-fruit flavored cocktail with 3 grams of L-Arginine, some ginko baloba, along with other vitamins and nutrients packed into it. It tastes pretty good. My research partner says “no thanks”, and doesn’t want to try it. 11:45: Feeling horny for sure, but also a bit edgy and anxious. Kissing and cuddling with my partner is exquisite, but no more so than usual I don’t think. No problem getting an erection, but this hasn’t been a problem. 12:00: Smoke some grass, which helps to reduce some of the edginess, and allow me to more enjoy the heightened sexual desire. Entering my partner is divine, but not significantly different from the night before. 12:20: Climax is powerful, although not significantly enhanced or altered. 2:00: Still feel energized and slighly anxious, although less so.
Niacin, or vitamin B-3, when taken on an empty stomach causes blood vessels near the skin to dilate for several minutes, which produces the well-known “niacin flush.” Sexual activity also causes the skin to flush, through the natural release of histamines. Taking niacin prior to sex, many claim, increases tactile sensations, electrifying the sense of touch, and enhancing orgasms. The niacin rush feels prickly and uncomfortable for me in general, but during sex the flood of histamines seems to feel warm and make me glow. This stuff is certainly worth trying. Many people swear by it and it’s very popular. Niacin is inexpensive and available in every vitamin store and
Truth, Freedom, and the FDA: An Interview with Durk Pearson and Sandy Shaw
By David Jay Brown
Durk Pearson and Sandy Shaw co-authored two of the first and most widely read books on the subject of human longevity–Life Extension: A Practical Scientific Approach and The Life Extension Companion–which triggered a large amount of popular interest in the subject (including my own), and their many television talk show appearances have reached a large number of people over the years.
Although, perhaps, the ultimate goal of medicine all along, the idea of extending human life in otherwise healthy individuals was a relatively novel concept for most people when Pearson and Shaw published their first book back in 1982. How many people could have predicted back in the early eighties that in just a few years after the publication of Pearson and Shaw’s groundbreaking book that there would be such a huge worldwide interest in life extension, anti-aging, and preventative medicine? Pearson and Shaw were not surprised by this new and growing interest and had, in fact, been anticipating it.
Pearson and Shaw have been studying life extension since 1968. They are largely self-educated. Pearson graduated from MIT with a triple major in physics, biology, and psychology, and Shaw graduated from UCLA with a double-major in chemistry and zoology. However, most of their knowledge comes from consuming scientific and medical journals with a voracious appetite, talking with colleagues, and experimenting on themselves. In this manner, they have become two of the most well-informed people on the planet regarding the biochemical mechanisms of aging, and they continue to study it full- time. Pearson and Shaw then apply this knowledge in designing nutritional supplement formulations for their own use, some of which are available commercially.
Pearson and Shaw have also been very politically-active over the years with regard to protecting people’s rights in America to access nutritional supplements, and to easily obtain available accurate information about the supplements which may benefit their health. To this effect, they wrote the book Freedom of Informed Choice: FDA Versus Nutritional Supplements (Common Sense Press, 1993), and won a landmark lawsuit against the FDA–Pearson v. Shalala–charging the government agency with unconstitutionally restricting manufacturers from distributing truthful health information (which was viewed as a violation of the constitution’s First Amendment guarantee of free speech) that could save many people’s lives. This was a landmark achievement for the dietary supplement industry and for the availability of truthful scientific information to consumers.
This interview occurred on December 16, 2005. Durk and Sandy are responsible for inspiring my own interest in life extension and they have long fascinated me. The couple makes a great team, often completing one another’s sentences, and bouncing ideas and facts back and forth off each other as they speak. It’s as though their nervous systems are symbiotically intertwined, and the breadth of their knowledge is staggering. It doesn’t take much to get them talking passionately about their favorite subjects–life extension and freedom. A few questions can ignite an information explosion. We spoke about how fish oil can improve cardiovascular health, about how the FDA tried to suppress this information, and how they legally forced the FDA into reversing their unconstitutional attempt to suppress the distribution of truthful information.
David: What do you think are the most important nutritional supplements that people should be taking?
Durk: Let me just preface my answer to this question by stating that we’re dealing with a system here–a system for handling free radicals and for doing a lot of other things–and just saying, here’s the most important three or four nutritional supplements really does a disservice to people. This is because free radicals are in fact handled by a rather elaborate system that’s evolved over the past few billion years that the planet’s had oxygen, and just having one of them doesn’t really do you anywhere as much good as having a set of them. But If I wanted to mention just one, I would say EPA and DHA, particularly DHA found in oils from cold water fatty fishes. The reason for that is that it can reduce the risk of a sudden-death heart attack by anywhere from about fifty percent to eighty percent, depending on the dose. As little as two meals per week of fatty cold water fish could give you about a forty to fifty percent reduction on your risk of sudden-death heart attacks.
Sandy: Three hundred thousand people die of sudden death heart attacks every year in the United States, so if all of those people were taking the recommended amounts of fish oil supplements, or the two fatty fish meals a week, then there’d be about fifty percent fewer that would have died. In other words, a hundred and fifty thousand people would not have died.
Durk: They’re very inexpensive, very safe, and very effective. You see these sort of heart attacks on TV all the time. Somebody has a heart attack, the ambulance arrives, and they defibrillate and resuscitate the person and everything is okay. Well, it doesn’t work that way outside the hospital, because they have to get that defibrillator to the person within a few minutes.
Sandy: But most of the incidences of fibrillation occur outside of a hospital, usually in a person’s home or where they work, and they don’t get to the hospital right away. If you lose several minutes, by that time you’ve either already died or you’ve suffered irreversible brain damage, so if you do survive you’re in very damaged condition.
Durk: Under the usual conditions, your brain starts dying after about five minutes from a lack of circulation, which occurs when your heart fibrillates–just vibrates and stops pumping blood. Incidentally, that’s what happens when you are electrocuted. At about ten minutes your brain is irreversibly and completely gone. A response time for a really good paramedic operation is about eight minutes. So you can see that there’s not much of chance for revival, and in fact, paramedics in the field are actually able to revive about two percent of people whose hearts have gone into fibrillation from a sudden-death heart attack. The DHA is very effective in preventing this from occurring. It doesn’t stop the heart attack from happening, but it turns a sudden-death heart attack, which gives you very little chance, into a…
Sandy: …survivable heart attack, where you do recover, and you don’t have irreversible damage to the brain. You can have a full recovery.
Durk: They can get you to the hospital, and then they can do angioplasty, or put in a standard, quadruple bypass or whatever.
One thing that’s very important for people to know about this is that the FDA tried to suppress this information…
Sandy: …about the benefits of fish oil. We actually sued the FDA in 1994 because they would not permit a health claim that fish oils may reduce the risk of cardiovascular disease.
Durk: It’s not that they merely would not permit it, they actually issued a regulation that stated that it was a crime to state that the cold water fish oils, with omega-3 fatty acids, could reduce the risk of cardiovascular disease. It was actually illegal. They specifically made it illegal.
Sandy: So we filed suit for violation of the First Amendment, because they were not permitting the communication of truthful information.
Durk: At the time we filed suit against them in 1994 there were one hundred and seventy-four papers on the subject in the scientific literature. A hundred and seventy of them supported our position; four did not. The four that did not were very small preliminary studies that didn’t have the statistical power to detect the fifty percent reduction in sudden-death heart attacks. During the seven years that we litigated against the FDA, one million Americans died premature preventable deaths.
Sandy: Half of the three hundred thousand people dying every year from that wouldn’t have died if they’d have been taking fish oil. However, dietary supplement companies, and also food companies offering fish, couldn’t tell people about the benefits of fish oil. And because of that people simply didn’t have the information.
Durk: Since the legal case was resolved in our favor in 2001, you’re now starting to see claims on fish oil supplements, and recently the FDA even caved in and is allowing claims on fish. So I think we’re going to see a very dramatic reduction in people dying of heart attacks as a result of this.
Sandy: I wanted to add that one of the ways that we study the effects of the various supplements is to look at metabolic pathway charts. You see, what happens with free radicals is that they’re handled by a chain of antioxidants in the body. It’s not just one or a couple that take care of the free radicals that are constantly around in the body. They’re constantly there because you’re producing them naturally through metabolic activity, and your body has got to handle these free radicals.
The metabolic pathways show you that once a free radical scavenger like vitamin C reacts with a free radical, then it becomes a free radical itself. It becomes an ascorbyl radical. That radical then has to be taken care of by another antioxidant. Glutathione usually takes care of the vitamin C radical, and converts vitamin C back to it’s reduced state.
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