THE FREE-RADICAL THEORY OF AGING MATURES

The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly attracting the interest of the mainstream of biological re search. From its origins in radiation biology, through a decade or so of dormancy and two decades of steady phenomenological research, it ha s attracted an increasing number of scientists from an expanding circl e of fields. During the past decade, several lines of evidence have co nvinced a number of scientists that oxidants play an important role in aging. (For the sake of simplicity, we use the term oxidant to refer to all ''reactive oxygen species,'' including O-2-(L) ., H2O2 and . OH , even though the former often acts as a reductant and produces oxidan ts indirectly.) The pace and scope of research in the last few years h ave been particularly impressive and diverse. The only disadvantage of the current intellectual ferment is the difficulty in digesting the l iterature. Therefore, we have systematically reviewed the status of th e free radical theory, by categorizing the literature in terms of the various types of experiments that have been performed. These include p henomenological measurements of age-associated oxidative stress, inter species comparisons, dietary restriction, the manipulation of metaboli c activity and oxygen tension, treatment with dietary and pharmacologi cal antioxidants, in vitro senescence, classical and population geneti cs, molecular genetics, transgenic organisms, the study of human disea ses of aging, epidemiological studies, and the ongoing elucidation of the role of active oxygen in biology.