Reactive oxygen species and protein oxidation in aging: a look back, a look ahead

The existence of free radicals, as chemical entities, was inferred 100 years ago but not universally accepted for some 30-40 years. The existence and importance of free radicals in biological systems was not recognized until the mid 1950s, by a small number of visionary scientists who can be credited with founding the field of reactive oxygen biochemistry. For most of the remaining 20th century, reactive oxygen species (ROS) were considered a type of biochemical "rusting agent" that caused stochastic tissue damage and disease. As we enter the 21st century, reactive oxygen biochemistry is maturing as a discipline and establishing its importance among the biomedical sciences. It is now recognized that virtually every disease state involves some degree of oxidative stress. Moreover, we are now beginning to recognize that ROS are produced in a well-regulated manner to help maintain homeostasis on the cellular level in normal, healthy tissue. This review summarizes the history of reactive oxygen biochemistry, outlining major paradigm shifts that the field has undergone and continues to experience. The contributions of Earl Stadtman to the recent history of the field (1980-present) are especially highlighted. The role of ROS in signal transduction is presented in some detail as central to the latest paradigm shift. Emerging technologies, particularly proteomic technologies, are discussed that will facilitate further evolution in the field of reactive oxygen biochemistry.