The free radical theory of aging (FRTA) was first advanced by Denham Harman more than 50 years ago. The theory proceeds logically from a small number of straightforward assumptions, based on observations from radiation biology. From the Science of Aging Timeline:

Harman’s logic proceeds from three observations: (1) irradiation causes premature aging; (2) irradiation creates oxygen radicals, which may mediate its effects; and (3) cells produce oxygen radicals under normal conditions. From these premises, he theorized that aging could be caused by endogenously generated oxygen radicals.

Over a half-century, the FRTA has evolved substantially (eventually focusing on the mitochondria as a major source of the initially postulated endogenous radicals), and has lately been the subject of several reviews evaluating its explanatory power and extent of current acceptance.

A unique perspective on the FRTA’s history has recently been provided by none other than its initiator, Denham Harman, who is retired but still intellectually active. From his review:

Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009

Aging is the progressive accumulation in an organism of diverse, deleterious changes with time that increase the chance of disease and death. The basic chemical process underlying aging was first advanced by the free radical theory of aging (FRTA) in 1954: the reaction of active free radicals, normally produced in the organisms, with cellular constituents initiates the changes associated with aging. The involvement of free radicals in aging is related to their key role in the origin and evolution of life. The initial low acceptance of the FRTA by the scientific community, its slow growth, manifested by meetings and occasional papers based on the theory, prompted this account of the intermittent growth of acceptance of the theory over the past nearly 55 years.

It’s a very personal account, starting with the educational experiences that Harman credits with putting him in the right place at the right time, continuing with a description of the origins of the theory, and paying a great deal of attention to the “fits-and-starts” advancement of the theory toward broad acceptance (though not without effort and extensive modification). Pieces like these, in which the originator of a hugely influential theory provides their individual perspective on the consequences of their work, are rare indeed — hence this is a must-read for students and practitioners of biogerontology.

ResearchBlogging.orgHarman, D. (2009). Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009 Biogerontology DOI: 10.1007/s10522-009-9234-2