Aminoguanidine:
An AGE Inhibitor!
By Phil Micans PharmB
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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.
About
the author:
Phil Micans, PharmB., has degrees in Food and Vitamin Technology
and Pharmacology. He has been actively involved in Anti-Aging
Medicine since 1986 and became initially interested after reading
Pearson and Shaw's book; Life Extension. His current accreditations
include being Editor of the Anti-Aging Bulletin, consultant to
the International Journal of Anti-Aging Medicine, co-writer of
The New Millennium Guide to Anti-Aging Medicine and the A4M Anti-Aging
PDR. He is also Vice President of International Anti-Aging Systems.
DISCLAIMER;
ALL INFORMATION IS EDUCATIONAL AND
PROVIDED UNDER IAS TERMS AND CONDITIONS.
IT DOES NOT AND SHOULD NOT REPLACE THE ADVICE OF YOUR PHYSICIAN.
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Feb. 3, 1998. |
