The Good, the Bad, and the Ugly of ROS: New Insights on Aging and Aging-Related Diseases from Eukaryotic and Prokaryotic Model Organisms

Figure 1

The sources and cellular responses to reactive oxygen species (ROS). Oxidants are generated as a result of normal intracellular metabolism in mitochondria and peroxisomes, as well as from a variety of cytosolic enzyme systems. In addition, a number of external agents can trigger ROS production. A sophisticated enzymatic and nonenzymatic antioxidant defense system including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) counteracts and regulates overall ROS levels to maintain physiological homeostasis. Lowering ROS levels below the homeostatic set point may interrupt the physiological role of oxidants in cellular proliferation and host defense. Similarly, increased ROS may also be detrimental and lead to cell death or to an acceleration in aging and age-related diseases. Traditionally, the impairment caused by increased ROS is thought to result from random damage to proteins, lipids, and DNA. In addition to these effects, a rise in ROS levels may also constitute a stress signal that activates specific redox-sensitive signaling pathways. Once activated, these diverse signaling pathways may have either damaging or potentially protective functions. Reproduced with permission from T. Finkel and N.J. Holbrook: Oxidants, oxidative stress and the biology of aging. Nature, vol. 408, no. 6809, pp.239-247, 2000.