The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: a systematic review

Abstract

Lay SummaryOur skin is the body’s first line of defense. It is the barrier that protects us from chemical and biological threats such as viruses, bacteria or corrosive liquids. It is the sensor that allows us to detect physical threats like extreme temperatures, pressure and pain. And when these preventative measures fail, the skin has yet another property: the ability to heal.Skin changes visibly with age, most notably with the appearance of wrinkles. However, there is more to ageing than meets the eye; invisible alterations cause the decline of various functions of the skin, such as wound healing and scar formation. An array of non-conclusive research has been done in this field. One theory that has gained traction during the last decade is the Advanced Glycation End products (AGEs) theory. The theory states that AGEs play an important role in skin aging, wound healing and the effectiveness of different therapeutic options. Their presence supposedly indicates a diminished ability for wound healing and scar formation.AGEs are proteins to which sugar molecule is bound. The sugar molecule inhibits the original protein from functioning properly. As skin contains many proteins like collagen, the formation of these AGEs could be a viable explanation for the diminished functioning with ageing. In this review, we investigated whether the accumulation of AGEs affects wound healing and scar formation.Normal scar formation results in a thin scar. However, it may happen that scarring results in thick, large, painful and itchy scars. We investigated whether people with a high AGE content in their skin, like diabetics and elderly, have difficulties forming aesthetically pleasing scars. Secondly, we investigated which therapies reduce the AGE content and, if so, whether these therapies can improve wound healing and scarring. This literature study involved research in scientific databases with qualitative analysis of 14 articles after a three-staged selection process with the use of set criteria.We found the different ways in which AGEs affect skin properties and wound healing. Collagen, one of the most important proteins in the skin, is affected by these AGEs. Once a sugar binds to it, the collagen strings becomes thinner and shorter, and the different collagen proteins cross-link with each other in an unstructured way. The result of these alterations is a reduced elasticity, i.e. the skin becomes stiffer. The scar will be thinner and the time for wounds to close is longer. We also found strategies to diminish the AGE content, including dietary AGE restriction and Metformin, a drug used in diabetes.We can conclude that there is proof of AGEs playing an important role in skin ageing, wound healing and the effectiveness of different therapeutic options. However, more research is required to conclude the exact role of AGEs in scar formation and scar therapy.