Cellular Aging Free Radical Hypothesis

The free radical hypothesis of aging states that free radicals in the cell damage cell macromolecules and lead to senescence and, eventually, to cell death (44-46). Free radicals are molecules that contain unpaired and reactive electrons. Various kinds of free radicals are present in the cell and come from either endogenous or exogenous sources (45). There are two major kinds of free radicals (Table 4). One is the extensively studied reactive oxygen species (ROS), which are metabolites of molecular oxygen (O2) and are the predominant species of free radicals (46,47). Examples of ROS include weakly active superoxide radical (O2), weakly reactive nonradical hydrogen peroxide (H2O2), and highly reactive hydroxyl radical (OH). These ROS can be generated and reduced to stable water through sequential reactions of oxygen with electrons (e-) and protons.

The other type of free radicals is reactive nitrogen species (RNS) (Table 4). Nitric oxide (NO) is a major RNS, which is not reactive with nonradical molecules but reactive with many other free radicals such as the superoxide radical (48). NO can react with an organic-free radical and form stable nonradicals that can essentially terminate free radical chain reactions. Additionally, NO can react with superoxide radicals to produce

TABLE 4 Biologic Oxidants and Oxidation Catalysts

Name

Structure

Oxygen activation

Superoxide radical

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