Glycation Lorna Bowes examines the concept of glycation and reviews the evidence behind various topical ingredients shown to inhibit accumulation of Advanced Glycation Endpoints (AGEs) As we, aesthetic practitioners, cosmetic dermatologists and cosmetic scientists, learn more about the ageing process, we uncover new and improved ways to target the many signs and symptoms of ageing skin. Sometimes, these new understandings pave the way for new ingredients, and at other times we discover that existing proven technologies have actions previously not described or fully understood. Glycation and AGEs There are many processes implicated in ageing, however one generating increased interest in both general and aesthetic medicine is glycation. AGEs, or Advanced Glycation End products, is the name given to the irreversible damage caused to proteins by sugar molecules, i.e. glycation. This is a negative process that is not exclusive to the skin, but is found throughout the body where proteins are present. Glycation differs from glycosylation, as glycosylation is a normal process in which sugars are combined with protein in a site-specific, enzyme-mediated process that is essential for molecular function. Glycation, however, is an abnormal process; a non-enzymatic joining of a sugar with a protein that impairs molecular function and causes irreversible damage to proteins in the skin, as well as other organs. The more we understand AGEs, the more interest there is in finding the perfect AGE inhibitor. AGEs are not only relevant in aesthetics; exogenous AGEs are formed when sugars are cooked in combination with proteins and fats. This is seen by the food industry as a very positive reaction as they are able to use this to create a cooked effect. For example, by adding sugar to food before cooking, the glycation process creates the non-enzymatic browning reaction, which improves the appearance of the food and is important for flavour.1 The food industry terminology for this is ‘caramelisation’, first described by Louis-Camille Maillard, a French chemist in 1912, and hence known as the Maillard reaction, a non-enzymatic browning process.3
Glycation before using maltobionic acid
Treatment Focus Glycation
Glycation has been widely studied in relation to diabetes, with results from multiple medical studies1 showing that not only is there a link between obesity and the onset of diabetes, but that there is a correlation between the quantity of food cooked at high temperature and the development of type 2 diabetes and related cardiovascular disease. Researchers have looked for possible links between increased AGEs and a reduction in the body’s natural defense against insulin resistance. It is this research which led to new research being undertaken focusing on the skin ageing effects of glycation. How are AGEs formed in the skin? The Maillard reaction occurs irreversibly in the skin, causing protein crosslinking, which leads to yellow colouring and a sallow appearance.2 The production of AGEs in skin is a slow three-step chemical process; the longer the biological half-life of a protein, the stronger the effect of glycation on the protein. Collagen is a triple helical structure of protein, mostly glycine, proline and hydroxyproline, which is essential for the structure of the Extra Cellular Matrix (ECM) in the skin. Collagen has a significant halflife in the dermis and is thus highly susceptible to the damage potential of AGEs. In the presence of heat, the primary amino acid component of the collagen triple helix is ‘grabbed’ by a sugar (glucose) yielding glycation intermediates known as Schiff bases (step 1), which in turn are oxidised and either disseminate or form a further intermediate known as an Amadori product (step 2). Finally in step 3, lasting several weeks, irreversible oxidative crosslinks are formed by the Amadori products and AGEs are ultimately formed causing slow deterioration of structural tissue.3,4,5 The damaged collagen is less susceptible to normal catabolism and therefore AGEs accumulate in the skin, as described above in the Maillard reaction. Additionally, with around 30% of the sugars and AGEs that we eat ending up in the skin, accumulation of AGEs is compounded. In addition, UV exposure, pollution and smoking add to the production of AGEs. Likewise, increased accumulations of AGEs are seen in certain diseases such as diabetes.6,7 Cosmetic Appearance of AGEs AGEs accumulate in the upper dermis and this causes the yellowing of skin known as sallowness. Due to the effect of the crosslinking of the collagen and damage to the elastin in the skin, the skin becomes brittle and inflexible, wrinkles develop and the loss of elasticity leads to stiffness of the skin. The dermal processes involve the mid dermis as well as the upper dermis, creating an immediate challenge to formulators as the processes that active ingredients are required to affect are protected by the skin barrier function.
Anti-glycation results after using maltobionic acid
Aesthetics | January 2015
Anti-glycating Ingredients To create an anti-glycating effect, scientists have studied a selection of inhibitors. For example, aspirin blocks glycation by acetylating lysine residues; there are protein competitors that work by inhibiting sugars, such as aldose and ketose, which prevent a Maillard reaction in the presence of proteins. This is in fact one of the 45
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