Advanced Glycation End Products (AGEs): Emerging Mediators of Skin Aging Paraskevi Gkogkolou and Markus Böhm Contents Introduction ............................................ 1 A Brief Biochemistry of AGEs ....................... 2 Receptors of AGEs .................................... 3 Detection of AGEs in Aged Skin ..................... 4 Cellular and Noncellular Targets of AGEs Within the Skin ............................................. 4 Extracellular Matrix Proteins ........................... 5 Intracellular Proteins .................................... 5 Growth Factors and Growth Factor Receptors ......... 5 Cutaneous Cell Types Responding to AGEs ........... 5 AGEs and ROS ........................................ 6 Anti-AGEs Strategies as a Perspective Against Skin Aging ............................................... 7 Conclusion ............................................. 9 References .............................................. 9 Abstract Advanced glycation end products (AGEs) derive from nonenzymatic reactions between reducing sugars and proteins, lipids or nucleic acids. In this chapter, we highlight the role of AGEs as an emerging class of mediators of skin aging. After a short section on the biochemistry and biology of AGEs we will put these mole- cules into the context of skin aging. Evidence will be provided that: (1) AGEs are detectable in skin, (2) that they accumulate over time in aged skin, and (3) that they act via diverse mecha- nisms (receptor and nonreceptor-mediated) on various cellular and noncellular targets of the skin. Special emphasis will be devoted to the connections between AGEs and reactive oxy- gen species, the latter established players of cutaneous aging. Finally, current and future strategies are described by which the impact of AGEs on skin aging may be counteracted. Introduction Advanced glycation end products (AGEs) derive from nonenzymatic reactions between reducing sugars, such as glucose and proteins, lipids or nucleic acids. This process is called glycation [1] and is distinguished from glycosylation, which is an enzymatic procedure. Glycation was first described by Maillard in 1912 [2] but its role in food browning during thermal processing was disclosed by Hodge only 50 years later [3]. P. Gkogkolou • M. Böhm (*) Department of Dermatology, Laboratory for Neuroendocrinology of the Skin and Interdisciplinary Endocrinology, University of M€ unster, M€ unster, Germany e-mail: paraskevi.gkogkolou@ukmuenster.de; bohmm@uni-muenster.de # Springer-Verlag Berlin Heidelberg 2015 M.A. Farage et al. (eds.), Textbook of Aging Skin, DOI 10.1007/978-3-642-27814-3_137-1 1