Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors

Abstract

Our skin is an organ with the largest contact area between the human body and the external environment. Skin aging is affected directly by both endogenous factors and exogenous factors (e.g., UV exposure). Skin saccharification, a non-enzymatic reaction between proteins, e.g., dermal collagen and naturally occurring reducing sugars, is one of the basic root causes of endogenous skin aging. During the reaction, a series of complicated glycation products produced at different reaction stages and pathways are usually collectively referred to as advanced glycation end products (AGEs). AGEs cause cellular dysfunction through the modification of intracellular molecules and accumulate in tissues with aging. AGEs are also associated with a variety of age-related diseases, such as diabetes, cardiovascular disease, renal failure (uremia), and Alzheimer’s disease. AGEs accumulate in the skin with age and are amplified through exogenous factors, e.g., ultraviolet radiation, resulting in wrinkles, loss of elasticity, dull yellowing, and other skin problems. This article focuses on the damage mechanism of glucose and its glycation products on the skin by summarizing the biochemical characteristics, compositions, as well as processes of the production and elimination of AGEs. One of the important parts of this article would be to summarize the current AGEs inhibitors to gain insight into the anti-glycation mechanism of the skin and the development of promising natural products with anti-glycation effects.

N‐acetyl‐L‐hydroxyproline – A potent skin anti‐ageing active preventing advanced glycation end‐product formation in vitro and ex vivo

“…AGEs are classified according to their crosslinking structure and fluorescence characteristics [2]. Pentosidine, one of the most prevalent cutaneous AGEs, for instance, belongs to the AGE subset showing fluorescent properties.…”

“…The group of advanced glycation end-products (AGEs) is characterized by a wide range of heterogeneous molecules generated by a non-enzymatic reaction between reducing sugars such as glucose and free amino groups of proteins, lipids or nucleic acids [1,2]. By irreversibly reacting with amino groups of proteins or peptides, AGEs can create compounds of high molecular weight [3,4].…”

“…In the course of these glycation processes, a physiologically relevant amount of reactive oxygen species (ROSs) is generated. Using a different mechanism, AGEs can also exert actions by binding to receptors for advanced glycation end-products (RAGE) initiating additional oxidative stress and increased inflammation [2,5].…”

“…Generation and accumulation of AGEs in the skin are widely believed to be a crucial cause of human skin ageing. AGEs influence all layers of the skin, leading to impairment of skin function, cutaneous inflammation, formation of wrinkles, loss of elasticity and a yellowish skin appearance [1,2,12,13].…”

“…Glycation can damage both extracellular and intracellular proteins (e.g., vimentin), and especially long-lived dermal proteins (e.g., collagen, elastin) are considered as major targets for glycation [2]. The resulting crosslinked proteins and/or protein adducts are very difficult to degrade.…”