The free radical theory of aging: A retrospective by its creator

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



  1. Thanks for recommending an interesting read. I was somewhat surprised to hear of Dr. Rebeca Gerschman and it seems like both she and Harman really proposed the free radical theory of aging independently in the 1950s…

    I like Gerschman’s way of putting it:
    ‘It is plausible that a
    continuous small ‘slipping’ in the defense could be a
    factor contributing to aging and death and in this
    sense one might consider that there is no threshold
    tension necessary for the appearance of the toxic
    effects of oxygen.’’

    This ties in better with how I view free radicals and aging. Not so much as a cause of aging in itself, but more of a downstream effect as a result of genetic regulation. Though, I suppose at its core, it centers on the debate if aging is purely a factor of genetic regulation, or a factor of our bodies being unable to keep up with repairs, or both.

    I bring this up more for discussion, then to propound what I consider to be solid belief…

  2. Kind of a bummer that the article is behind a Springerlink firewall, inaccessible if your library doesn’t subscribe. Naughty publishers!

  3. Closed access is always a bummer. The taxpayers pay for the research, then pay again for the researchers to pay page charges, then pay again for the researchers to buy subscriptions to read other people’s publications.

  4. The best facet of the free radical theory is that it is testable. Unfortunately, it has repeatedly lacked predictability and it thus, fail to meet the requirements of the scientific method. Large randomized controlled trials have shown that antioxidants do not reduce the risk of cancer, heart disease, strokes or aging. In fact, antioxidants can increase the incidence of cancer, heart disease, strokes and overall mortality. The free radical theory has fallen and studies attest to the low toxicity of omnipresent oxygen radicals in vivo.

  5. I’d like to share a quick brainstorm;

    What if the brain is capable of doing some sort of “system/objective check” and decide from there whether or not continuing life is the appropriate thing to do.

    We might not fully understand it yet, but humans are nothing more than a part of the cycle of time. The sole purpose for any living thing is to eventually die after completing it’s “mission”. Time/evolution might have clouded what the human’s mission is supposed to be, (everyone’s unique nowadays blabla, but we scientifically know we’ve been “simpler”) but the brain possibly still has an inert check to just “die”.

    Without a doubt the human “thought capabilities” is the most advanced of any life-form on the planet. And that might allow us to bend the checklist here and there.

    I’m probably stretching it by saying comas are a state where the brain either “missfires” and decides to “half die”.

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