There’s a big difference between glycation and glycosylation. Glycation is unhealthy, glycosylation is predominantly beneficial.

Glycosylation refers to an enzyme-mediated modification that alters protein function, for example, extending their life span by protecting against denaturation or proteolytic degradation. Glycosylation can also enhance a protein’s interactions with other proteins. By contrast, glycation refers to a monosaccharide (usually glucose) attaching nonenzymatically to the amino group of a protein. In other words, the enzymatic cross-linking of carbohydrates to other organic molecules, such as proteins, is called glycosylation and is an important post-translational modifications of proteins, essential for human cell signaling and metabolism. Glycation is different than glycosylation. Less commonly known is the non-enzymatic and less specific reaction called the Maillard reaction, after its discoverer Louis-Camille Maillard. This is the reaction that underlies the browning of bread. The Maillard reaction takes place in multiple steps, leading to the irreversible formation of advanced glycation end products (AGEs). In the early steps of the reaction, the sugars can react irreversibly with amino acid residues of peptides or proteins to form protein adducts or protein crosslinks. Initially this step of glycation affects the interactions of collagen with cells and extracellular matrix components. However, the most damaging effects of glycation are caused by the formation of glucose-mediated intermolecular cross-links. The cross-linking decreases the critical flexibility and permeability of the tissues and reduces cellular turnover. Advanced glycation end products form and bind to long-lived proteins in the skin, cross-linking them, damaging their structure, deforming their fibers. Many proteins in the skin, including collagen, can be long lived. That is, these long lived proteins don’t turnover for years, sometimes decades. As such, they are susceptible to damage, including through glycation. This glycation of collagen in the skin, noticeable as browning skin, likely means glycation of the collagen is happening in other parts of the body, including the cardiovascular system.

In the last step, when oxidation is involved, the products are called advanced glycation end products (AGEs). AGEs are formed through four pathways: (1) the Maillard reaction, (2) sugars auto-oxidation pathway, (3) lipid peroxidation pathway, and (4) polyols pathway. Glucose is converted into fructose via the polyol pathway (based on aldo-keto reductase enzymes), which accelerates the production of AGEs. The formation of AGEs is a slow process that occurs physiologically in vivo, with higher accumulation of AGEs in tissues with slow renewal rates, such as the skin’s long lived proteins. AGE levels are increased in patients due to increased production, but they are also increased due to impaired excretion. In conditions such as metabolic and oxidative stress, AGE accumulates more rapidly. New, non-invasive assessment techniques of AGE are now available. The measurement is made using skin autofluorescence.

Not only is the skin autofluorescence (SAF) a measure of AGE in the skin, but the value determined in the skin is highly correlated with that in other parts of the body. That is, the measurement of AGE accumulation in the skin can serve as a biomarker for disease states other than those in the skin, including cardiovascular disease and diabetes mellitus. Chronic kidney disease has also been recently shown to correlate with SAF. As I have said previously, the health of the skin is an important biomarker for the health of many other organs in the body.

Not surprisingly, an environmental factor that is likely to have a profound effects on AGE accumulation is diet. Studies have shown that breastfed infants, consuming few AGEs, had lower SAF intensities than formula-fed infants, a diet rich in AGEs. Meat consumption is also associated with higher AGEs, where lower SAF values have been observed for vegetarians in hemodialysis patients.

In addition to environmental factors, herditary factors are likely to contribute a small amount to the observed AGE phenotypes as measured by SAF.  Studies of twin and sibling pairs have implicated heredity as partly responsible for lens and skin fluorescence variations.

So what can we do? Reducing our consumption of sugars and simple carbohydrates is one obvious prophylactic measure. Another is reducing one’s consumption of meat, and eating a diet rich in vegetables. And, because environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury, restriction of dietary AGEs will suppress these effects. This is true in the skin, as well as throughout the body. Further, because metabolic state, and oxidation are important to driving the formation of AGEs, in addition to healthy lifestyle and dietary practices, one can use a course of topically applied skin care products to promote better metabolism, increased anti-oxidative capacity, and a renormalization of the extracellular matrix (ECM) in order to better prevent glycation and the formation of cross-linking and AGEs in the skin. Important to a skin care routine to prevent and remediate AGEs is the inclusion of NeoGenesis’ S²RM technology to prevent and remediate damage to the ECM and to provide a wide variety of antioxidants.