Glycation - Irreversible Wrinkles and How to Prevent Them

You may not know this...not all wrinkles are created equal. While wrinkles from sundamage and intrinsic aging can be improved, those from a process known as glycation cannot.

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.

In the 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.

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?
  Treatment is best started with prevention by diet control, reducing total calories, avoiding high sugar foods and not cooking at high temperatures. Supplements such as aminoguanidine, pyridoxamine, carnosine and benfotiamine are excellent glycation preventors.

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:

Beautymag Online, Glycosylation and the Ageing Process

Peter T. Pugliese, MD, April 14, 2008, from the April 2008 issue of Skin Inc. magazine.