Advanced glycation end products: Key players in skin aging?

Abstract

Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. They have been etiologically implicated in numerous diabetes- and age-related diseases. Strategies inhibiting AGE accumulation and signaling seem to possess a therapeutic potential in these pathologies. However, still little is known on the precise role of AGEs during skin aging. In this review the existing literature on AGEs and skin aging will be reviewed. In addition, existing and potential anti-AGE strategies that may be beneficial on skin aging will be discussed.

Keywords: AGEs; RAGE; advanced glycation end products; photoaging; skin aging.

Figure 1. Schematic presentation of the Maillard reaction. Reactive carbonyl groups of a reducing sugar react with neutrophilic free amino groups of proteins to form a reversible Schiff base. Through rearrangement a more stable Amadori product is formed. Dependent on the nature of these early glycation end products, protein adducts or protein crosslinks are formed.

Figure 2. Effects of AGEs on skin. AGEs are formed intracellularly and extracellularly. They can react with proteins, lipids and nucleic acids in almost all skin cells as well as on intracellular or extracellular proteins. Through alteration of the physicochemical properties of dermal proteins, decreased cell proliferation, increased apoptosis and senescence, induction of oxidative stress and proinflammatory mediators as well as other pathways, AGEs contribute to the overall picture of skin aging. Triangles represent AGEs. Abbreviations: jak/stat, januskinase/signal transducers and activators of transcription; MCP-1, monocyte chemotactic protein-1; all other abbreviations are already explained in the text.