Reduce AGE’s and you improve circulation
Common blood-pressure drugs that help prevent the
life-threatening complications of diabetes may do so by slowing the accelerated
ageing from which diabetics suffer. The discovery could one day lead to drugs
that delay some of the symptoms of ageing in everyone.
People with diabetes tend to age rapidly,
particularly if they have type 1 diabetes, which strikes in childhood. Those
with the condition often go blind, and they suffer from heart and kidney disease
and high blood pressure far earlier than normal. Their skin can wrinkle in their
twenties.
"The rule of thumb is that people look as old as
their chronological age plus the duration of their diabetes," says team member
Merlin Thomas of the Baker Medical Research Institute in Melbourne.
That ageing occurs partly because high
blood-sugar levels encourage the body to produce gluey sugar-protein complexes
called advanced glycation end products. AGEs interfere with some cell functions
and make tissues such as blood vessels stiffer. In healthy people, AGEs form far
more slowly.
The Australian team, led by Mark Cooper of the
Baker Institute, has found that a common blood-pressure drug called ramipril
stops the build-up of AGEs in rats with diabetes. Those rats also had far less
damage to their kidneys. "There was complete prevention," says team member
Josephine Forbes. The results will appear in November's issue of the journal
Diabetes.
Ramipril is a type of blood-pressure drug called
an ACE inhibitor, and diabetic patients who take ACE inhibitors are known to
suffer less kidney and heart disease than those taking other types of
blood-pressure drugs. But until now the reason has not been clear.
ACE inhibitors reduce blood pressure by blocking
the formation of angiotensin II, a protein that makes blood vessels constrict.
Evidence is building that angiotensin II also increases oxidative stress,
creating free radicals that in turn stimulate production of AGEs.
Cooper's team is now measuring AGEs in the blood
of people with diabetes who take ACE inhibitors to find out whether their AGE
levels are lower. The team is also testing different types of AGEs to see which
ones cause the problems. The next step will be to find inhibitors that target
these AGEs.
And it is not just people with diabetes who may
reap the benefits of drugs designed to cut AGE levels. Many experts believe the
build-up of AGEs helps cause kidney disease and glaucoma as well as the
narrowing of the blood vessels in cardiovascular disease and the formation of
brain plaques in Alzheimer's. AGEs also accumulate in the skin, helping make it
wrinkly.
ACE inhibitors are unlikely to become an elixir of youth because they cause unpleasant side effects such as coughing and irregular heartbeat. But future drugs designed to block AGEs might have fewer side effects.
Source: Diabetes In Control Dot Com: New Scientist 10:45 03 October 02.