Physiological Reviews

The Free Radical Theory of Aging Matures



Beckman, Kenneth B., and Bruce N. Ames. The Free Radical Theory of Aging Matures. Physiol. Rev. 78: 547–581, 1998. — The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly attracting the interest of the mainstream of biological research. From its origins in radiation biology, through a decade or so of dormancy and two decades of steady phenomenological research, it has attracted an increasing number of scientists from an expanding circle of fields. During the past decade, several lines of evidence have convinced 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⋅, H2O2 , and ⋅OH, even though the former often acts as a reductant and produces oxidants indirectly.) The pace and scope of research in the last few years have been particularly impressive and diverse. The only disadvantage of the current intellectual ferment is the difficulty in digesting the literature. Therefore, we have systematically reviewed the status of the free radical theory, by categorizing the literature in terms of the various types of experiments that have been performed. These include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, the manipulation of metabolic activity and oxygen tension, treatment with dietary and pharmacological antioxidants, in vitro senescence, classical and population genetics, molecular genetics, transgenic organisms, the study of human diseases of aging, epidemiological studies, and the ongoing elucidation of the role of active oxygen in biology.


  • B. N. Ames was supported by National Cancer Institute Outstanding Investigator Grant CA39910 and National Institute of Environmental Health Sciences Grant ES-01896.

  • In writing a review on as broad a topic as the free radical theory, we have been forced to limit both the content and the number of references cited. Although we have done our best to include recent work, omissions were inevitable. We apologize to all authors whose work we have not managed to include and direct readers to other recent reviews for material we have left out.

  • Address for reprint requests: K. B. Beckman, Dept. of Molecular and Cell Biology, 401 Barker Hall, Univ. of California, Berkeley, CA 94720-3202.

View Full Text