Oxidative stress in aging human skin

Abstract

Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis.

Figure 1

Schematic of the interplay between different ROS sources and the anti-oxidative systems in the skin. All ROS sources discussed in this manuscript are exemplified in black letters: cytochrome c oxidase, ETC (electron transport chain), iron ions, xanthine oxidase, peroxisomal oxidases, lipoxygenases, cytochrome P450, cyclooxygenases, NADPH oxidases, UV-radiation, xenobiotics and several chromophores that lead to ROS. Examples of anti-oxidative systems are given in blue letters: vitamin C and E, GSH (glutathione), GSH peroxidases, uric acid, beta-carotene, the SPRR2 (small proline rich repeat) family, SOD (superoxide dismutase), CoQ10 (coenzyme Q) and ferritin. Generally it has to be stated that only the SPRR2 proteins are specific for the epidermis, but the concentration of most anti-oxidants is much higher in the epidermis than in the dermis. Possible outcomes of oxidative damage to the cells (damage to DNA, proteins and lipids) are shown on the left-hand side of the figure. (M) stands for mitochondria, (ER) for endoplasmic reticulum, (N) for nucleus and (G) for Golgi apparatus.