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. New Scientist 10:45 03 October 02