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Am J Physiol Regul Integr Comp Physiol (August 17, 2006). doi:10.1152/ajpregu.00327.2006
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Submitted on May 15, 2006
Accepted on August 16, 2006

An Integrated View of Oxidative Stress in Aging: Basic Mechanisms, Functional Effects and Pathological Considerations

Kevin C. Kregel1* and Hannah J Zhang1

1 Departments of Integrative Physiology and Radiation Oncology, University of Iowa, Iowa City, Iowa, United States

* To whom correspondence should be addressed. E-mail: kevin-kregel{at}uiowa.edu.

Aging is an inherently complex process that is manifested within an organism at genetic, molecular, cellular, organ and system levels. Although the fundamental mechanisms are still poorly understood, a growing body of evidence points towards reactive oxygen species (ROS) as one of the primary determinants of aging. The "oxidative stress theory" holds that a progressive and irreversible accumulation of oxidative damage caused by ROS impacts on critical aspects of the aging process and contributes to impaired physiological function, increased incidence of disease, and a reduction in lifespan. While compelling correlative data have been generated to support the oxidative stress theory, a direct cause-and-effect relationship between the accumulation of oxidatively mediated damage and aging has not been strongly established. The goal of this mini-review is to broadly describe mechanisms of in vivo ROS generation, examine the potential impact of ROS and oxidative damage on cellular function, and evaluate how these responses change with aging in physiologically relevant situations. In addition, the mounting genetic evidence that links oxidative stress to aging is discussed, as well as the potential challenges and benefits associated with the development of anti-aging interventions and therapies.




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