:Glycation:

:Advanced Glycation Endproducts (AGE) are a major feature of aging besides oxidation and carbonylation.

Glycation is a destructive process that binds a protein molecule to a glucose molecule resulting in the formation of damaged, nonfunctioning structures and enzymes. By altering protein structure glycation decreases biological activity. Glycated proteins accumulate in the tissue and are reliable markers of disease. Many age-related diseases such as arterial stiffening, cataract and neurological impairment are at least partially attributable to glycation.

Carnosine, which prevents glycation, may also play a role in the recycling or disposal of glycated protein. Carnosinylation, where carnosine attaches to denaturated molecules, tags glycated proteins for removal.

Glycation, known in biochemistry as the Maillard reaction, occurring between proteins and glucose, is recognized as a major contributor to aging and perhaps cancer, as well as the complications arising from diabetes. Glucose provides the fuel for glycation, the insidious protein/glucose combination that, following several steps including the oxidation process, results in the formation of advanced glycation end-products or AGE.

Once AGEs are formed, they interact with neighboring proteins to produce pathological cross linkages that toughen tissues. It has been speculated that no other molecule has the potential toxic effects on proteins as advanced glycation end-products. Diabetic individuals form excessive amounts of AGEs earlier in life than non-diabetics, a process that especially disrupts organs that depend on flexibility for function. It is glycation that hardens the arteries of diabetics, contributing to retinopathy and nephropathy.

AGEs trigger a cascade of destructive events as they cling to cellular binding sites. One of the consequences of AGEs is a 50-fold increase in free radical formation. As diabetes, a condition of accelerated aging, spawns a harvest of AGEs, the arteries, the lens and the retina of the eye, peripheral nerves and the kidneys are under specific attack. By opposing glycation with inhibitors like Carnosine and Calcium Pyruvate, glomerular damage and the resulting inflammation and renal degeneration is reduced. Diabetic rats, not treated with glycation inhibitors, show a twofold increase in glomerular staining for advanced glycation end-products compared with a similar group of diabetic rats receiving treatment (Forbes et al., 2001).

Cataract, another complication common to diabetics, is likely to form as a result of glycation, while glycation inhibitors protect against the damage. Supplementation with glycation inhibitors enable humans to prevent many of the adversities that accompany aging. Because Carnosine, a dipeptide, structurally resembles the sites that glycating agents attack, it is able to sacrifice itself to spare the functional and structural components of the tissue. Carnosine also bolsters proteolytic pathways responsible for disposal of damaged, excess and leaking proteins.

Because of its anti-glycation actions, carnosine and pyruvate may be useful against diabetic complications such as cataract, neuropathy, arteriosclerosis and kidney failure. They can also help all of us since AGEs age us all, just not a rapidly as diabetics.