Glycation

Certain substances that contribute to the aging process can be avoided. A good example of this is tobacco tar. Other contributory substances are not as easily avoided as they are key parts of the metabolism. The best example of this is glucose.

The most common carbohydrate found in food is glucose; it is the primary structural unit of starch and a component of sucrose (table sugar) as well. The bulk of the energy that we get from eating cereals, bread, pasta and many other common foods is derived from glucose. One of the key physiological measurements is the level of glucose found in the bloodstream. Glucose levels are very important because the glucose is the main fuel for the central nervous system. If the glucose level of the blood drops below a certain level for long enough then consciousness will be lost. This can lead to a comatose state and even death. Raised levels of glucose, such as those that occur in diabetes can also be dangerous. The body maintains a complex system for maintaining the levels of glucose in the blood at a safe level. The liver stores a reserve of glucose in the form of glycogen (which is a polymer that is similar to starch). The liver can also make its own glucose by converting protein to glucose if need be. Starvation causes the body to slowly break down muscle protein in order to provide glucose to the central nervous system.

Glucose is always present in the bloodstream whether or not it is present in the food that we eat. It is a key cellular fuel in the body. Glucose can also cause damage to the body as well as fueling it. This damage is a negative reaction with DNA and proteins. This negative reaction is called glycation or the Maillard reaction. In glycation, enzymes fail to work at their regular level of effectiveness thus causing glycated proteins to lose their shape, become insoluble or unstable. A great example of this is cataracts which occur when protein glycation takes place. The process of glycation lowers the level of solubility of the lens proteins which in turn leads to a loss of transparency in the lens.

Complications caused by diabetes are an extreme example of the damage that can be caused by glycation and cross linking. The main clinical symptom of diabetes is a raised level of glucose present in the bloodstream. Because the rate of chemical reactions is in direct proportion to the concentration of the reagent, the more raised the glucose level, the more increased the level of glycation and cross linking is. Cross linked arterial walls become brittle, less able to pulse, and the capillaries become less open to the permutation of nutrients and oxygen. The result is the loss of sufficient blood flow to the tissues, which in turn leads to slow healing of wounds, nerve damage and the formation of ulcers. The majority of tissues, including the nerves, retina and kidney allow glucose to penetrate without the presence of insulin when this happens the damage is particularly severe. These tissues are particularly badly affected by high levels of blood glucose, which explains why kidney failure, blindness and nerve damage (neuropathy) are the most common complications of diabetes.

Research shows that the most commonly found type of glucose cross linking that occurs in aging tissues is glucosepane. Glucosepane is a chemical bridge that is created when glycated proteins react with specific amino acids from other proteins. There are generally twice as many glucosepane cross links found in diabetics then there are in non-diabetics of the same age range. The levels of glucosepane also correlate with the incidence of age related diseases.

There are other probably causes of cross linking including cigarette smoke, heavy metals, peroxides, UV radiation, and acetaldehyde (a byproduct of alcohol). Free radicals can also promote and accelerate the cross linking and can even be cross linkers themselves.

How can cross linking be made minimal or reduced? The best way to eliminate cross linking is to avoid exposure to the environmental factors that cause it. Use good sunscreen, spend minimal amounts of time in the sun, reduce amounts of alcohol consumption and don't smoke. By keeping your antioxidant defenses healthy, particularly during stressful times you can minimize or reduce the risk of cross linking.

Maintaining good carbohydrate tolerance can be one of the most important steps that you can take to minimize glycation and cross linking. High levels of carbohydrate tolerance is one of the most common features found in metabolic processes of people over 100 and could very well be the reason for their long lifespan. A glycated hemoglobin test (HbA1c test) can determine how well your body processes carbohydrates. There is an over the counter version of the HbA1c test, although this may be less accurate. The HbA1c test determines the amount of your hemoglobin that has reacted with glucose and therefore is also a good way of determining the levels of glycation and cross linking in the body. HbA1c also corresponds with the average level of blood sugar in the 3 months before the test. Healthy people maintain an average HbA1c range of 4% to 5.9%. Some studies have shown that the lower part of this range is the optimal level for promoting health and longevity. Above average readings in the HbA1c range mean that there should be a change in lifestyle in order to improve higher levels of carbohydrate metabolism. This can include exercise, weight loss and a diet based on foods with low glycemic levels as well as taking supplements that lower the blood sugar levels.

What treatments have been developed to stop or reverse glycation and cross linking? Carnosine has been shown to slow the process of cross linking in animals. Carnosine is a particularly effective inhibitor of protein to protein and DNA to protein cross linking that is caused by different aldehydes including glucose. It has yet to be seen if people taking Carnosine supplements will see an increase in longevity. Vitamin derivatives, including a fat soluble form of B1 known as benfothiamine as well as B6 (in the form of pyridoxamine) are good inhibitors of certain kinds of glycation and cross linking. Their long term effects on humans remain unclear. There is research being done on the use of serrapeptidase and bromelain (both of which are protease supplements) as a way of breaking up existing protein to protein cross links. Other scientists are trying to determine a specific supplement that is capable of preventing or reversing glucosepane cross links.

Aging is a complex set of processes that involve a diverse set of conditions and reactions. This is why the aging process has been very difficult to define; it is also why there are multiple theories on the process of aging. The processes of aging can be divided into two groups: the amassing of various degrees of damage to the cells and the genetically programmed process of aging.
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The greater our comprehension of the aging process the more ways that scientists find to try to extend the average life span. Ironically, the most effective means of anti-aging intervention has been the same for the past 50 years; eating less!!