Which of the following is associated with aging?

Free radicals are chemical species with a single unpaired electron in an outer orbital. Such chemical states are extremely unstable, and free radicals readily react with inorganic and organic chemicals; when generated in cells, they avidly attack nucleic acids as well as a variety of cel- lular proteins and lipids. In addition, free radicals initiate reactions in which molecules that react with free radicals are themselves conveed into other types of free radicals, thereby propagating the chain of damage. Reactive oxygen species (ROS) are a type of oxygen- derived free radical whose role in cell injury is well estab- lished. Cell injury in many circumstances involves damage by free radicals; these situations include ischemia- reperfusion (discussed later on), chemical and radiation injury, toxicity from oxygen and other gases, cellular aging, microbial killing by phagocytic cells, and tissue injury caused by inflammatory cells. There are different types of ROS, and they are produced by two major pathways (Fig. 1-18). * ROS are produced normally in small amounts in all cells during the reduction-oxidation (redox) reactions that occur during mitochondrial respiration and energy genera- tion. In this process, molecular oxygen is sequentially reduced in mitochondria by the addition of four elec- trons to generate water. This reaction is imperfect, however, and small amounts of highly reactive but sho-lived toxic intermediates are generated when oxygen is only paially reduced. These intermediates include superoxide (O2 * ), which is conveed to hydro- gen peroxide (H2O2) spontaneously and by the action of the enzyme superoxide dismutase. H2O2 is more stable than O2 * and can cross biologic membranes. In the pres- ence of metals, such as Fe2+ , H2O2 is conveed to the highly reactive hydroxyl radical * OH by the Fenton reaction. Ref Robbins 9/e p26