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The Iron Age

By Ada S. Polla May 2006 issue of Skin Inc. magazine

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Iron often is recognized in the context of anemia, or iron deprivation. The various ways of ensuring appropriate iron intake have been thoroughly discussed, whether through diet or the use of daily supplements.
      However, there is a dark side to iron—namely, excess iron, which is discussed less frequently. Excess iron is a component of a variety of diseases, such as those involving cardiovascular, brain or muscle health. These all have an oxidative component and involve premature skin aging. The consequences of iron in the skin and its implication in aging are covered in this article.

Reactive oxygen species
      Reactive oxygen species (ROS) are oxygen-derived reactive molecules. Some contain an unpaired electron and, because of this, are in a highly excited atomic state; these are known as free radicals. Others, such as hydrogen peroxide, do not. ROS are derived from molecular oxygen (O2), which is crucial to human survival. O2 is metabolized via successive reductions to the hydroxyl radical (.OH). These reactions are catalyzed by a series of antioxidant enzymes—including superoxide dismutase (SOD), glutathione peroxidase and catalase—and by the availability of the cofactors of these enzymes, such as selenium. At basal levels, ROS are involved in cellular metabolism, cell proliferation and, most importantly, in antibacterial and immune defenses. At unbalanced, high levels, however, ROS become toxic and play key roles in inflammation, cancer, cardiovascular diseases and skin aging.
      ROS contributes significantly not only to skin aging, but also to more general aging processes throughout the body through the induction of oxidative injuries. These injuries damage almost all cellular and extracellular components, including proteins (intracellular and extracellular), lipids (lipid peroxidation), DNA (strand breaks and cross-links) and mitochondria (uncoupling of oxidative phosphorylation).

The link between iron and ROS
      The ROS theory of aging is based on the existence of an equilibrium—or the lack of one—between aggressive oxidants and defensive/protective antioxidants. It also is based on the evidence that many age-related diseases are caused by increased production or exposure to oxidants and subsequent oxidative injury.
      Iron, like oxygen, is indispensable for cell metabolism and overall good health. However, it also plays a major role in oxidative stress through the nonenzymatic Haber Weiss1 and Fenton2 reactions, producing the highly toxic .OH radical. Thus, the highly reactive .OH is produced whenever and wherever iron is available for the Haber Weiss/Fenton reactions. In the skin, these reactions are stimulated by sun exposure. It has been shown that ultraviolet (UV) exposure enhances the production of ROS, as well as the release of free iron, which induces further ROS. This is a deleterious vicious cycle. In the skin, excess iron combined with UV radiation plays a pro-oxidant role by promoting the production of the highly toxic .OH and further accelerating skin aging.

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