AMINOGUANIDINE: AN AGE INHIBITOR!
By Phil Micans
PharmB
Aminoguanidine (pronounced a-mean-o-gwan-I-din) is a “new” anti-aging therapy
and recent interest has been aroused by the fact that it may be able to prevent
some of the signs of aging from occurring.
THE GLUCOSE CROSS-LINKING PROBLEM
It is believed that the cross-linking of the proteins that make up the human
body play a role in the human aging process. Everyone is familiar with the
effects of cross-linking reactions, because the process causes food to turn
yellow and become tough, (i.e. watch what happens after you cut an apple in
half).
Cross-linking may be responsible for many of the problems of old age,
including senile cataracts, thickening of the arteries, some cancers and damage
to the immune system.
A damaged immune system leads to increased susceptibility to infection and
some cancers may arise from the effects of glucose on DNA. DNA contains all the
information necessary to create a normal cell, however it can react with glucose
to produce damaged DNA, which in turn causes abnormal cells to be produced.
CROSS LINKING, AGING AND THE HEART
Aging is associated with cardiac enlargement and arterial stiffening, one
theory for this is an age-related accumulation of Advanced Glycation End
products (AGE).
Glycosylation is the product of reaction between a sugar and the free amino
group of proteins and it is referred to as cross-linking. The linking of
glycosylation by-products to proteins results in the development of large,
cross-linked molecules that inhibit the ability of the cell to function
normally.
One study conducted on animals showed that aminoguanidine prevented
age-related cardiac enlargement. In fact, the membrane surface area was reduced
by 30%. Furthermore, the collagen content of their arterial walls was increased
by 24-30%. Aminoguanidine is therefore acting to improve overall heart and
arterial condition and not just by preventing or slowing proteins from
cross-linking, but also by decreasing the AGE-induced cross-linking of the
extra-cellular matrix.
Studies conducted at the University of Milan over the last 25 years have
shown aminoguanidine’s ability to do two things. Firstly, in tests on animals,
aminoguanidine has reduced the ability of very low density lipoprotein, (the bad
form if cholesterol), to bind itself to blood vessel walls. In turn, blood
platelets are less likely to coagulate and form dangerous clots.
Secondly, aminoguanidine has an ability to treat patients whose blood vessels
are constricted by arteriosclerosis. In 1992 at the University of Milan, 11
patients with peripheral vascular disease were treated with aminoguanidine.
Their blood vessels were so clogged that they couldn’t walk for more than 500
yards, but after treatment the patients blood flow improved on average by 30%
and the patients exercise abilities improved by 50% to 105%.
DIABETES
Diabetes is often seen as a form of accelerated aging and research into
diabetes has provided support for the idea that cross-linking causes aging. The
levels of cross-linking products in diabetics are two to three times those than
their equivalent “normal” non-diabetics.
It is believed that AGE is increased in diabetes and plays an important role
in the development of diabetic complications. As aminoguanidine acts to bind to
sugars, thus preventing them from binding to the lysine group of proteins it was
only a matter of time before various trials began.
A number of different studies with diabetic rats indicate that aminoguanidine
administered rats have significantly superior survival rates than those who are
untreated.
Diabetic clinical trials with humans have also highlighted aminoguanidine’s
ability to prevent oxidative modification of low-density lipoproteins (LDL) and
inhibit the formation of atherosclerotic plaques.
Trials conducted by the American corporation, Alteon Corporation (who are
using aminoguanidine under the name of Pimagidine) and another drug development
called ALT-711 (more of that at the end of this article), indicate that
aminoguanidine can significantly reduce albuminuria, (proteins present in urine,
usually as a result of kidney disease), delay the onset of end-stage renal
disease and improve the cholesterol profiles of diabetic patients.
CONCLUSION
Research has shown that glucose is partly responsible for the cross-linking
of proteins, which in turn leads to aging damage. Glucose is found in every cell
of the body and is relatively stable, but it can join with protein to form a
glucose/ protein combination. It is this combination that will continue through
a number of steps, to eventually cause active cross-links. But the formation of
this process appears to be reversible. Glucose/ protein substances stay in the
body for months, even years, cross-linking with the proteins around them. This
continuous cross-linking may be prevented by using glycosylation inhibitors
because their primary use is to stabilize the metabolism of glucose.
Aminoguanidine is able to join up with substances that cause links and to
stop cross-links from developing. Therefore it may be able to help alleviate or
prevent senile cataracts, thickening of the arteries, kidney failure, thinning
bones, osteo-arthritis, skin wrinkles and many other signs of aging.
Aminoguanidine’s ability to stabilize the metabolism of glucose, to help
prevent and treat adult onset diabetes, it’s role in reducing very low density
lipoprotein cholesterol, and the evidence that it can improve blood flow,
helping to reverse the conditions of arteriosclerosis and blood clots, indicates
that aminoguanidine has a wide reaching ability to help prevent and treat a
number of aging disorders.
Aminoguanidine has the potential to slow the aging process by protecting the
proteins that make up the human body, such as the skin proteins (collagen and
elastin), eye lens protein, nerve protein and kidney proteins from aging damage.
All the body’s proteins deteriorate with advancing age and more so in diabetes.
Aminoguanidine is able to combat some of the adverse effects of diabetes and
improve the quality and duration of life. As diabetes is an age-related
disorder, and in-fact effects everyone over the age of 30 (physicians alter the
parameter of the test based upon chronological age), aminoguanidine offers
itself as a true anti-aging medicine.
DOSAGES AND SIDE EFFECTS
Both animal and human trials indicate that aminoguanidine has very low
toxicity and appears safe to use with “normal” dosages. Side effects in human
trials have been limited to nausea and headache, but as presently there is still
relatively little human data and clinical trials, aminoguanidine use is probably
best undertaken whilst under the supervision of a physician.
LATEST NEWS
The Alteon Corporation in the USA currently has aminoguanidine (Pimagidine)
in stage III trials for diabetes. Interestingly it has also developed ALT-711
(thiazolium salt) which is now in stage II trials. Whilst aminoguanidine and
other agents (such as Carnosine and Acetyl-L-Carnitine) have been shown to help
prevent cross-linking, ALT-711 is claimed to break existing links. If this is
substantiated, this could be a major anti-aging medicine of the future.
It is becoming clear that agents that can slow, prevent and even reverse the
effects of cross-linking will have a major impact in the role of preventative
medicine, and indeed could be one of the keys to true anti-aging medicine.
Copyright 2003. This article may not be reproduced for public
broadcast in any form, without the written permission of: International Antiaging Systems
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