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Selenium
 There
has never been a study to test the effects on lifespan of the trace
mineral selenium, but an early study, which examined the toxicity of
selenium (and other minerals) found, by accident, that it extended the
lifespan of laboratory mice. There have been dozens of studies showing
that dietary selenium can help to prevent a wide variety of cancers, and
that it may be useful in the treatment of cancer. Anyone taking selenium
on a daily basis for antiaging purpose should be careful to keep their
doses low to avoid the possibility of toxic side effects.
Procaine (GH3 And KH3)
 The
two most popular antiaging drugs in the world are Gerovital-H3 from
Romania (GH3) and KH3 from Germany. The active ingredient in both these
drugs is procaine, which is also the active ingredient in the numbing
dental drug Novocaine. The benefits of procaine were initially touted by
Romanian physician Ana Aslan, who claimed that her GH3 formula could be
used in the treatment of virtually all the diseases of aging. Subsequent
studies in Europe and the U.S. with both GH3 and KH3 showed that these
drugs are effective antidepressants, and that they may be useful in
treating arthritis. A large animal study conducted by Aslan showed that
GH3 extended the lifespan of laboratory mice by 20%. A subsequent, much
smaller study, using higher doses of GH3, did not show prolongation of
lifespan.
DMAE
In three experiments, the drug DMAE, sold in the U.S. and Europe under
the names Deaner and Lucidril extended the lifespan of mice up to 49.5%
when given in the animals' drinking water. In the early 1980s, Riker
Laboratories, the manufacturer of DMAE decided to withdraw the drug from
the market because of poor sales for its FDA-approved use (hyperactivity
in children). Since then, a similar version, commonly sold under the name
DMAE has become available as a dietary supplement. The combination of DMAE
and the herb gingko has become popular as a cognitive-enhancing therapy or
"smart drug".
Centrophenoxine
Centrophenoxine extended the mean lifespan of laboratory animals, in one
study, perhaps through its active component, dimethylaminoethanol (DMAE).
It has also been shown to be effective in treating neurologic impairment
due to aging, and in reducing the age-associated accumulation of
pigmentation in neurons, muscle cells and skin cells. Studies in humans
have shown that Centrophenoxine can improve both learning and memory, and,
as a result, it is commonly used as a "smart drug".
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Aminoguanidine
Glycosylation is the pathological binding of glucose to an amino acid
that results in the formation of a non-functioning structure in the body.
Diabetics suffer from an accelerated rate of glycosylation, and many of
the premature degenerative diseases common in Type I and Type II diabetes
is attributed to the glycosylation process.
As organisms age, glycosylation becomes a major factor in the
development of aging-relating diseases. Some gerontologists believe that
glycosylation is the most significant biologic event responsible for the
degenerative diseases of arterial system, the eye and the brain. Those
seeking to add healthy years to their lives have a significant interest in
interfering with the glycosylation process.
Oxidative damage plays a role in the glycosylation process, which helps
to explain why antioxidant supplements have shown benefit in preventing
diseases associated with diabetes. It requires a lot more than
antioxidants, however, to adequately block age-related glycosylation.
While a number of antiglycating agents are in the development stage,
aminoguanidine has been available to Life Extension members for many
years.
When reports of toxicity were reported in a FDA-sanctioned human
clinical study conducted two years ago, The Life Extension Foundation
sought to ascertain what dose of aminoguanidine was causing toxic
reactions. The company conducting the studies, and the FDA, refused to
provide this information.
After two years of painstaking investigation, The Foundation has
learned that when 300 mg of aminoguanidine where administered three times
a day (900 mg/day) to diabetic patients, toxicity was noted. When the dose
was lowered to 200 mg three times a day (600 mg/day), the signs of
toxicity vanished. These results confirm The Foundation's previous
recommendations, based on extrapolations from the published literature,
that healthy adults may consider taking 300 mg of aminoguanidine a day (or
every other day), while diabetics could consider a maximum dose of 600 mg
a day. Semi-monthly CBC-chemistry blood tests should be considered in
order to protect against any unknown liver or kidney toxicities.
As more European suppliers have begun offering aminoguanidine, the cost
has declined sharply, making this an inexpensive addition to one's life
extension regimen.
Hydergine
Hydergine is another "smart drug", which has been shown to improve
learning and memory in both young and old men and women. In clinical
trials, Hydergine has been shown to improve blood supply to the brain,
increase the amount of oxygen available to the brain, enhance metabolism
in brain cells, prevent free radical damage in brain cells, increase ATP
levels in the brain, and enhance the use of energy-generating glucose in
the brain. Hydergine is available as a prescription drug in the United
States, but is available at higher doses in Europe.
Piracetam
Piracetam is the foremost of the so-called nootropic "smart drugs". It is
a derivative of the amino acid GABA that increases the sensitivity of
receptors involved in learning and memory in brain neurons. Studies in
both animals and humans have shown that Piracetam can improve memory,
increase attention and concentration, and improve spatial learning.
Piracetam is, perhaps, the most potent of the "smart drugs", and is used
commonly to increase intelligence, information processing ability and
creativity. Piracetam has been shown to harmonize and synchronize the
spheres of the brain by modulating electrical activity within the brain.
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Vinpocetin
Vinpocetin is another of a new class of "smart drugs", whose effects are
similar to that of Hydergine. Among the clinical benefits of taking
vinpocetin, which have been demonstrated in humans, are therapeutic
benefits for dizziness, headache, poor hearing, poor eyesight, insomnia,
mood instability, vertigo, irritability and nervousness. Vinpocetin
improves blood circulation to the brain, which improves cognitive function
and protects against stroke. It is not available in the U.S., but can be
obtained from offshore companies offering unapproved drugs to Americans
for their own personal use.
Chromium Picolinate
 This
patented form of the trace mineral chromium has been shown to lower blood
glucose (sugar) and is considered a potential antiglycosylation agent. In
one study, supplementation with chromium picolinate reportedly extended
the lifespan of laboratory rats. After 41 months, 80% of rats receiving
chromium were still alive, while all the control rats had died. There was
also a reduction in AGES (Advanced Glycation End products) in the animals
receiving chromium. In human studies, chromium picolinate has been found
to decrease body fat and enhance lean body mass, while lowering blood
cholesterol levels. Other studies with chromium picolinate have not
produced the same kind of results.
Dilantin (Phenytoin) And
Phenformin
 In 1980,
Russian scientists reported that the drugs Dilantin (phenytoin) and
Phenformin had extended animal lifespan by 25% and 23% respectively in a
strain of mice prone to autoimmune disease. Dilantin is an FDA-approved
drug commonly prescribed to normalize electrical activity in epilepsy
patients. Studies around the world have shown that Dilantin is useful for
a wide variety of conditions including depression, headache, and
neurologic disorders. Phenformin is a prescription antidiabetic drug,
which lowers blood sugar in patients suffering from this disease, which
suggests that it might have antiglycosylation effects. Both drugs have
serious side effects, which makes them relatively poor candidates for
long-term use.
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Picamilon
 The
hottest new "smart drug" is the Russian therapy Picamilon, which has been
shown to be better than Hydergine and Vinpocetin in improving blood flow
to the cerebral vessels in the brain, as well as reduced oxygen flow
(ischemia) to the brain. Picamilon is sold as a pharmaceutical in Russia,
but is really a vitamin-like compound, consisting of a niacin analog (N-Nicotinoyl)
bonded to GABA. This combination creates a molecule that readily
penetrates the blood- brain barrier to enhance cerebral and peripheral
circulation, and improve cognitive function.
Pyritinol
Recent evidence suggests that a European medication called Pyritinol may
be an effective treatment for Alzheimer's disease. When compared Hydergine
and placebo, Pyritinol produced continuous improvement in cognitive
function, which was more pronounced than in the Hydergine group. Pyritinol
is used in Europe for the treatment of a wide variety of neurologic
disorders. The Pyritinol molecule is structurally similar to Vitamin B6
(Pyridoxine), but functions in a different way within the body. Pyritinol
is not available in the U.S.
Pregnenolone
Pregnenolone is known as the "mother hormone" because it is the
precursor of a number of of hormones including DHEA, Testosterone and
estrogen. Studies have demonstrated that the neurosteroid Pregnenolone has
a potent stimulatory effect on memory, and that it can be taken to improve
several types of cognitive function. Because there have been no studies on
the effects of Pregnenolone on aging and lifespan, these are being
investigated in The Lifespan Project.
Testosterone
The hormonal stimulus for sex drive in both men and women is
Testosterone, which declines with advancing age in both sexes.
Testosterone also plays an important role in maintaining muscle mass and
strength and bone density. The hormone is often administered to aging men
and women as a topical cream, but also is available in oral and injectable
forms.
Estrogen and Progesterone
 The
"female" steroid hormones estrogen and progesterone play important roles
in maintaining bone density and strength, sexual function, mental function
and, in women, in countering the effects of the menopause. Recent studies
indicate that estrogen may be an effective treatment for Alzheimer's
disease, and that estrogen supplementation may protect women from
Alzheimer's and other neurologic diseases. Both estrogen and progesterone
are available in a variety of forms -- natural or synthetic, oral or
topical. There is considerable interest in the use of plant-derived
phytoestrogens, which have weak (but safe) estrogenic activity as a
possible replacement for drug forms of estrogen. One product, Natural
Estrogen, has been specially designed for this purpose.
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Deprenyl is another chemical name for Selegiline hydrochloride. It is
available in the U.S. under the name Eldepryl. It is also available by
mail from offshore companies. In a number of clinical trials, deprenyl has
improved the condition of both Parkinson's and Alzheimer's disease. In
controlled studies, however, its long-term use for Parkinson's disease was
called into question. Evidence that deprenyl may slow aging includes
studies showing it protects brain neurons from neurotoxins (in tissue
culture), elevates levels of antioxidant enzymes, reduces levels of the
dopamine-degrading enzyme monoamine oxidase-B, and extends the lifespan of
both mice and rats. 
Human
growth hormone helps maintain the immune system and builds youthful
DHEA (dehydroepiandrosterone) is an adrenal hormone that is the precursor
for steroid hormones such as testosterone and estrogen. DHEA declines
precipitously with advancing age in both men and women. There have been
many studies showing that oral DHEA can improve neurological function,
immune function, stress disorders, and that it can be protective against
some types of cancer and cardiovascular disease. In one clinical study at
the
Melatonin
is a hormone produced by the pineal gland, which is located beneath the
brain. Melatonin is a highly potent antioxidant, which has been described
as the pacemaker of the aging clock in humans. It is released every night
as part of our time-dependent biorhythms to help induce sleep and
recuperation from fatigue. Melatonin has been shown to have anticancer
effects. In animal studies in Italy, melatonin and transplants of pineal
gland tissue from young animals extended the lifespan of old animals,
however the mice used in these studies had suboptimal lifespans. The Life
Extension Foundation is funding a study to further assess the effects of
melatonin on aging and lifespan in mice. 
Acetyl-L-Carnitine (ALC) is an energy-stimulating compound similar to an
amino acid. It has been shown to improve cognitive function in both
normally aging individuals and Alzheimer's patients, and to strengthen the
heart muscle. The basis for theorizing that ALC may be able to slow aging
comes from evidence that ALC improves mitochondrial function in several
ways. Mitochondria are the power plants of the cells, where energy for all
life processes is generated. Scientists have speculated that the decline
in mitochondrial function may be a cause of aging in humans. 
Coenzyme
Q10 (coQ10) is a cardioprotective, energy stimulating compound that has
been shown to be effective as a means of preventing and treating certain
forms of cardiovascular disease and cancer. In a study by Bliznakov, the
lifespan of mice was increased by 50% by injections of coQ10. In another
study at UCLA Medical Center, the mean but not maximum lifespan of mice
was increased by very high oral doses of coQ10. In both studies, mice
receiving coQ10 looked especially good and healthy at advanced ages. coQ10
is being assessed further for its effects on aging and lifespan in mice.
NADH is a form of nicotinamide adenine dinucleotide, a coenzyme that
assists enzymes involved in energy production within mitochondria, the
power plants of the cell. NADH plays an important role in the generation
of ATP (adenosine triphosphate), the body's energy currency, and has been
found to be effective in Europe in treating Parkinson's and Alzheimer's
disease. NADH is also needed for the regeneration of glutathione after it
has become oxidized. 
Lycopene is a member (along with beta-carotene) of a family of plant
pigments called carotenoids. There are more than 600 different carotenoids,
but lycopene and the carotenes are the most important ones. They are the
pigments that give leaves, tomatoes and other plants their bright colors.
Lycopene is the best anti-aging candidate of this class of compounds
because it is the most efficient quencher of an especially dangerous free
radical called singlet oxygen. Equally important is the fact that lycopene
is regenerated after quenching singlet oxygen, and can then detoxify
dangerous molecules without being destroyed. Lycopene levels drop off with
age, even if we continue eating the fruits and vegetables that contain it.
Lycopene has been shown to increase the survival of irradiated mice, and
to decrease the incidence of various types of cancer in mice. It is now
the subject of study in The Foundation's Lifespan Project. 
Vitamin E is the major fat-soluble compound that protects our cell
membranes against oxidative damage. It can break the self-perpetuating
chain of oxidative reactions in unsaturated fatty acids in membranes.
Vitamin E also helps maintain the antioxidant activity of selenium, and
works with this trace mineral to help boost immune function. There have
been highly persuasive studies in humans showing that regular vitamin E
intake can reduce the risk of heart attacks in both men and women, and
that it can protect us from several types of cancer. In one study, the
combination of vitamin E and vitamin C reduced death from all causes.
(FYI: Not taking at least your daily requirement of Vitamin E has been
compared to the equivalent of smoking Cigarettes). 
In 1958, biochemists Roger J. Williams and Richard Pelton fed large
amounts of vitamin B5 to male and female mice. They found that the treated
mice lived an average of 19% longer than controls. A previous study had
found that B5 increased the lifespan of fruit flies. The major biochemical
role of vitamin B5 appears to be as a constituent of coenzyme A, which is
involved in many chemical reactions essential to life, including the
detoxification of many dangerous substances. When high doses of vitamin B5
were given to rats they were able to survive in cold water twice as long
as controls. Similar results have been found in humans. 
In an experiment conducted at NASA's Ames Research Center in a long-lived
strain of mice already in middle-age (18 months of age), the scientists
found an 11% increase in lifespan in animals fed vitamin B6 compared to
controls. Vitamin B6 plays an important role in many life processes. It is
needed for the metabolism of amino acids such as tyrosine and
phenylalanine, and is an essential cofactor (along with vitamin B6 and
folic acid) in the body's defense against elevated homocysteine levels,
which have been linked to arteriosclerosis, heart disease and stroke. 
In the 1950s and 60s, Denham Harman of the University of Nebraska Medical
Center, the originator of the free radical theory of aging, conducted a
series of experiments in which he extended the lifespan of short-lived
mice with various synthetic antioxidants. The antioxidants included BHT (butylated
hydroxytoluene), Ethoxyquin (dihydroethoxytrimethylquinolone),
2-mercapto-ethylamine (2-MEA), and NDGA (nordihydroguaretic acid). Dr.
Harman found mean lifespan increases of up to 61% with these compounds.
Subsequent studies confirmed the lifespan-extending ability of Ethoxyquin
and NDGA. These supplements have never become popular because of concern
about adverse effects from their chronic use. 
In 1977, George Cotzias, et al. reported a 50% increase in the mean
lifespan of rats fed very high doses of L-Dopa, the precursor to the
neurotransmitter dopamine. In another study in rats, it was shown that the
incidence of movement disorders among aged rats were almost totally
reversed by L-Dopa, which enabled the rats to swim almost as well as young
rats. L-Dopa is used to treat Parkinson's disease patients, with major
improvements usually occurring for several years followed by a steep
decline in function coupled with adverse side effects. The problem with L-Dopa
as an anti-aging drug is its side effects at high doses, which include
abnormal heart rhythms, movement disorders, mental disturbances, and a
greater risk of at least one type of cancer. 
Since the 1930's it has been known that a diet restricted in Calories, but
otherwise rich in nutrients, dramatically extends the life span of
experimental animals. Over two thousand studies have confirmed the
effectiveness of Calorie restriction (or "undernutrition without
malnutrition, " as Roy Walford calls it) in a wide variety of species. The
diet is currently being studied in monkeys, as well as in humans. While
the effectiveness of this anti-aging regimen is likely far greater than
others currently available, the difficulty of the regimen for most people
is also far greater. Serious life-extensionists should nevertheless
consider trying at least a mild version of the diet. 
