Fighting glycation for rejuvenated skin

In our ageing society, the increasing incidence of metabolic diseases such as diabetes poses substantial problems. The rising prevalence of diabetes is attributed to obesity linked with a sugar-rich diet.   In the skin, a high presence of free sugar molecules causes glycation, a process where proteins and sugars are cross-linked to form advanced glycation end products (AGE). The formation of AGEs has a negative impact on the elasticity of the skin as cross-linked collagen and elastin fibers are stiffened. Furthermore, the yellow-brownish colour of AGEs leads to a change in skin tone towards a more yellow appearance. Additionally, AGEs lead to constant inflammatory processes which exacerbate the ageing effect of high sugar concentrations in the skin. Here we show a cosmetic approach with different testing methods to help prevent the formation of AGEs and to ameliorate the downstream effects of glycation in the skin using an extract of Ziziphus spina-christi leaves.

The prevalence of diabetes has doubled worldwide since the 1980s and continues to be on the rise.1 One of the main reasons is the increased consumption of sugar and a general unhealthy lifestyle in the industrialised world. Apart from profound clinical implications such as high blood pressure, diabetes also affects the skin. Diabetic skin parameters are similar to prematurely aged skin: loss of elasticity, dry skin, decreased microcirculation, and a yellowish skin tone. The underlying reason is a process called glycation, which is caused by free sugar molecules in the bloodstream. The blood sugar levels are especially high for diabetes patients where sugar uptake into the cells is disrupted. Notably, also during the normal ageing process, glycation takes place in the skin tissue, a process that is exacerbated by UV irradiation

During glycation, free amino groups from proteins and reducing sugars, for example glucose, are forming a covalent bond. This non-enzymatic process is an important part in the frying and bread baking process where it is responsible for the typical browning process. Due to the much lower temperatures in our bodies, the glycation process is much slower, but over many years the effects are also visible in the skin. Advanced glycation end products (AGEs) are formed as end products of the reaction between proteins and sugars. Oxidised lipids also play a role in this process and can also be crosslinked with proteins to form a covalent bond. The crosslinking of collagen and elastin leads to a stiffening of these normally elastic fibres, which reduces the skin’s elasticity. As the initial products of the glycation reaction are highly reactive and susceptible to oxidation and fragmentation, a high level of glycation will lead to collagen fragmentation in the skin. These fragments can further react with other proteins and contribute to an accelerated AGE formation. The AGEs that are formed by the glycation reaction do not just hinder normal protein activity and cellular function. AGEs bind to the AGE receptor (RAGE) that is present on the surface of many cell types, including our skin cells. This binding of AGEs to RAGE causes an inflammation response.2 AGEs also cause the formation of free radicals which lead to RAGE upregulation. This results in a vicious cycle of chronic inflammation and skin damage (Fig 1). Another hallmark of increased glycation is a yellow toned skin due to the yellow-brown colour of AGEs. It is therefore important to counteract the formation of AGEs in the skin. While glycation happens spontaneously, the removal of AGEs will require the help of an enzymatic machinery. Consequently, this machinery needs to be activated in order to recycle the AGEs already present in the skin for a rejuvenation effect.