Glycation and the Ageing Process

Glycation of skin
Blood sugar, or more accurately blood glucose level, is a very important aspect of human physiology because glucose is the primary fuel for the central nervous system. If the blood level of glucose drops below a certain point for a long enough period of time, a person will lose consciousness, fall into coma and die. Very high blood glucose seen in diabetes is also harmful, although the immediate consequences are usually less dramatic.

It is less widely known that blood sugar has an important bearing on the aging process. Unfortunately, in addition to being a vital cellular fuel, glucose is also a substance that can cause damage to cells and tissues by randomly reacting with proteins, DNA and other vital molecules.

Glycation
The mechanism of skin glycation

Advanced Glycosylation
One of the processes that carbonylates proteins, glycation, is itself recognized as a major cause of aging and degenerative disease. Glycation occurs when protein react with sugars. Then, through a series of reactions including oxidation, advanced glycation end products (aptly called AGEs) form.

Glycation: A process called non-enzymatic glycosylation or glycation, glucose molecules attach themselves to proteins, setting in motion a chain of chemical reactions that ends in the proteins binding together or crosslinking, thus altering their biological and structural roles. The process is slow but increases with time.

 Advanced Glycosylation End products (AGEs), is the term given to Crosslinks of proteins like collagen and elastin, which seem to toughen tissues and may cause some of the deterioration associated with aging. AGEs have been linked to stiffening connective tissue (collagen), hardened arteries, clouded eyes, loss of nerve function, and less efficient kidneys. These are deficiencies that often accompany aging.[1][2]

 AGEs exert their harmful effects on two levels. Most obviously, they physically impair protein, DNA and lipids, altering their chemical properties. They also act as cellular signals, triggering a cascade of destructive events when they attach to their cellular binding sites. The main binding site for AGEs is appropriately called RAGE (receptor for AGEs). The binding of AGEs to RAGE induces cellular activation and intracellular oxidative stress, AGE binding to RAGE tends to be self-amplifying, since the more AGEs bind to RAGE, the more RAGE binding sites develop. This creates a “positive feedback loop” leading to spreading waves of cellular activation and tissue damage.

One happy finding is that the body has its own defense system against crosslinking. Just as it has anti-oxidants to fight free-radical damage, it has other guardians, immune system cells called macrophages, that combat glycation.

Macrophages with special receptors for AGEs seek them out, engulf them, break them down, and eject them into the blood stream where they are filtered out by the kidneys and eliminated in urine. The only apparent drawback to this defense system is that it is not complete and levels of AGEs increase steadily with age. One reason is that kidney function tends to decline with advancing age.

Is there an answer to glycation?

The natural dipeptide carnosine may be the answer. Carnosine is a multifunctional dipeptide made up of a chemical combination of the amino acids beta-alanine and 1-histidine. Caronsine has the remarkable ability to rejuvenate cells approaching senescence, restoring normal appearance and extending cellular life span.[2][3]

Carnosine not only inhibits the formation of AGEs, it can also protect normal proteins fron the toxic effects of AGEs that have already formed. Carnosine is by far the safest and most effective natural anti-glycating agent. Studies have shown that carnosine can stop protein damage from spreading to healthy proteins. It also found evidence that canosine reacts with and removes the carbonyl groups in glycated proteins. These studies reinforces the body of research demonstrating carnosines unique three-stage protection against accumulation of aberrant proteins: carnosine protects against protein carbonylation, inhibits damaged proteins from damaging healthy proteins, and helps the proteolytic system dispose of damaged and unneded proteins.

Carnosine levels decline with age, and now that many people are cutting down on meat – the main dietary source of carnosine – supplementation becomes expecially important. Expect to see carnosine in the ‘new generation’ of actives of the future.

References

[1] Scientific Backgrounders, “Alpha Lipoic Acid“, page 2 http://www.nnfa.org/services/science/bg, March 19th 2003

[2] Carosine; anti-aging actve ingredient, “A free radical scavenger and anti-glycation dipeptide”, http://www.flamma.it/carosine.htm, March 2nd 2004

[3] Alpha-Lipoic Acid 1-3, http://www.usadrug.com,  March 19th 2004