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Am J Physiol Regul Integr Comp Physiol 292: R18-R36, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00327.2006
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INVITED REVIEW

NEW INVESTIGATOR AWARD IN REGULATORY AND INTEGRATIVE PHYSIOLOGY OF THE WATER AND ELECTROLYTE HOMEOSTASIS SECTION, 2006

An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations

Department of Integrative Physiology and Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa

Submitted 15 May 2006 ; accepted in final form 16 August 2006

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 toward 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 life span. 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 minireview 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 antiaging interventions and therapies.

oxidative damage; antioxidants; free radicals; reactive oxygen species; hyperthermia; caloric restriction

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