Today's most promising therapy in the struggle against aging is deprenyl,
sold in the United States under the name of Eldepryl. Recent studies in both
animals and humans have shown that deprenyl has a variety of beneficial
effects on brain aging without producing toxic side effects. There is now
evidence that deprenyl is an antidepressant, a sexual stimulant, an effective
treatment for Parkinson's disease, a promising treatment for Alzheimer's
disease, and an antiaging therapy.
The most impressive clinical findings to date have been that deprenyl
treatment slows the progression of Parkinson's disease and extends the
lifespan of Parkinson's patients. In a retrospective comparison by Birkmayer,
et al., in Austria, Parkinson's patients receiving Madopar (L-Dopa plus a
decarboxylase inhibitor) and deprenyl lived an average of 15 months longer
than patients receiving only Madopar . When early stage Parkinson's patients
received deprenyl in a recent 810 patient study involving physicians
throughout the U.S. and Canada they were doing so much better than the
controls (who received a placebo) that the scientists directing the study
halted it in midstream so they could provide the control patients with the
benefits of deprenyl. At the time the study was concluded after a year of
treatment, deprenyl had doubled the time compared to the controls before
functional disability became severe enough to require L-Dopa therapy.


Preventing Parkinson's Disease
The fact that deprenyl works so well in early stage Parkinson's patients
suggests that it may help to protect the dopamine producing neurons in the
substantia nigra region of the brain from destruction. It is the loss of
these neurons, and the concomitant decline in the production of dopamine that
causes Parkinson's disease. Several of the scientists experimenting with
deprenyl are convinced that regular use of the drug prior to the onset of
Parkinson's symptoms could prevent the disease entirely.

According to neurologist J. Langston of the Institute for Medical Research,
San Jose, California, the evidence that deprenyl can prevent Parkinson's
disease is rather strong . Dr. Langston points to three compelling findings:

1 Deprenyl is a powerful selective inhibitor of monoamine oxidase B (MAO-B).
MAO-B is the specific form of the enzyme that breaks down dopamine into other
compounds, which are then excreted. There is a marked age related rise in MAO
levels, leading to an increased incidence of depression. Deprenyl functions
as an antidepressant without causing hypertensive reactions from cheese, wine
and other foods containing the amino acid tyramine, which can occur in
patients taking MAO inhibitors that block the action of MAO-A as well as
MAO-B. Dr. Langston thinks the specific type of MAO inhibition caused by
deprenyl may also exert a protective effect on the neurons that produce
dopamine.

2. There is evidence that dopamine producing neurons may be destroyed or made
dysfunctional as a result of side effects caused by dopamine metabolism
itself. Deprenyl inhibits the activity of one of the prime metabolites of
dopamine called 6-OHDA (6 hydroxydopamine), which generates oxidative free
radical reactions that have been shown to have neurotoxic effects on brain
neurons.

3. Deprenyl protects dopaminergic neurons from environmental toxicity caused
by agents such as MPTP ( I -methyl-4-phenyl-a, 2, 3, 6-tetrahydropyridine),
which produced severe Parkinsonian symptoms in young people who took it as a
"street drug" in the 1970's. It's been shown that toxic chemicals generated
during the oxidation of MPTP destroy dopamine-producing neurons and that
injections of deprenyl completely block this destructive process.


Slowing Down the Aging Process
Parkinson's Disease appears to be a form of accelerated aging caused by the
action of 6-OHDA or some other neurotoxin. Many older people suffer from
symptoms of Parkinson's disease, such as loss of coordination, shuffling and
diminuition of sex drive, because the same neurons destroyed in Parkinson's
Disease are also destroyed in normal aging, but at a slower rate. In fact, it
isn't until 80% of these brain cells are destroyed that we even begin to
suffer the symptoms of Parkinson's disease, which indicates that the dopamine
producing neurons in the substantia nigra are destroyed extensively with
advancing age in all of us, a conclusion supported by brain cell counts in
autopsy studies.
These findings suggest that long-term treatment with deprenyl could slow down
the aging process itself-a conclusion arrived at about 10 years ago by the
Hungarian pharmacologist Joseph Knoll, who developed deprenyl in 1965. In
order to test this hypothesis, Dr. Knoll conducted a study of the effects on
lifespan and sexual behavior of continuous deprenyl therapy in aging rats.
The reported results of this study were so remarkable that veteran life
extensionists experienced both exhilaration and disbelief.

In Dr. Knoll's study, 24-month old rats (about 65 years old in human terms)
were given injections 3 times a week of 0.25 mg/kg of deprenyl, while the
control animals received saline injections. These injections were continued
until the animals died.

The degree of lifespan extension reported by Dr. Knoll is unprecedented for a
clinically available therapy. After 60 years of scientific inquiry into
methods to extend lifespan, gerontologists have found only one method (food
restriction) that can radically extend maximum lifespan in mammals and in
order to get the degree of lifespan extension claimed by Dr. Knoll, it is
necessary to severely restrict food intake in rats at a very young age, with
side effects such as stunted growth, seizures and premature death.

If Dr. Knoll's findings are valid, it could mean that we could live for as
long as 150 years by simply taking deprenyl for the rest of our lives.
Moreover, since the ability to live to 150 years would constitute a highly
extraordinary extension of maximum lifespan, it would mean that deprenyl
therapy slows down the aging process in dramatic fashion.

Such a demonstration of aging control would be the most important
breakthrough in the history of medicine. It would not only mean that we could
add decades of healthy life to our lifespan, but that we would know that the
control of human aging is feasible, so that the search for other methods to
control aging could be done with far greater confidence. One of the first
steps would be to discover the biochemical mechanism(s) by which deprenyl
slows down aging, so that we can develop more effective aging control drugs.

Dr. Knoll's claims for lifespan extension might be dismissed out-of-hand, if
it wasn't for all the other evidence suggesting that deprenyl might very well
be able to slow down aging. Deprenyl is the best candidate we've ever had for
an antiaging therapy and so we have to take Dr. Knoll's claim s seriously.
What we're all looking for is further evidence conceming the effects of
deprenyl on lifespan, so it's good to report that the results of a new study
have just been published.


The University of Toronto Study
Scientists at the University of Toronto tried to duplicate Dr. Knoll's
results in another strain of rats. They performed two experiments with male
Fischer 344 rats. In the fist experiment, 62 animals, 24 to 25 months of age,
were assigned to random groups, with the animals in one group receiving
injections 3 times a week of a 0.25% solution of deprenyl and others
receiving saline injections. Blood samples were taken at the start of the
experiment and again after 3 months, with a battery of tests administered to
measure the effects of deprenyl on blood chemistry.

In the second experiment, the same drug dosage and route of administration
were used, starting at 23 to 24 months of age in 70 rats randomly assigned
either to deprenyl or placebo groups. After these animals died, autopsies
were perforrned to determine the cause of death. The animals were weighed
regularly to find out if food restriction was involved in any lifespan
extending effect found in the experiment.


Results of the Study
In the analysis of longevity, the animals were assigned a score equal to the
number of days they survived following the start of treatment, with the data
from both experiments pooled. The results included data from four deprenyl
treated animals and one saline treated animal which were sacrificed because
they had tumors.

The major finding of the study was that the deprenyl group survived
significantly longer than the control group. The mean survival time of the
deprenyl group was 133.7 days compared to 114.7 days in the control group.
The maximum survival time (the longest surviving 10% of the population) of
the de- prenyl group was 248.4 days compared to 212.1 days in the control
group. The longest surviving animal in the deprenyl group lived for 315 days
(beyond the start of the experiment), while the longest survivor in the
control group lived for 251 days.

In the majority of cases of the animals autopsied, death could not be
attributed to any single factor. Many of the animals, for example, had tumors
in addition to liver and kidney problems.

There was no difference in body weight between the two groups during the
first four months of
/END OF PART I/

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