Revisiting the Free Radical Theory of Aging

Thoughts on the impact of better technology on free radical theory: "The role of oxidative stress in aging proposed by the free radical theory has been the focus of investigations for more than fifty years. The results of a large number of these investigations provide support for this theory. However, numerous recent findings point to the existence of unexpected complexity in the relationships between oxidative stress and aging. This complexity is highlighted by the discovery [that] a key element of oxidative stress defenses in the model organism budding yeast, shortens lifespan in concert with enhanced resistance to oxidative stress. In addition to the implications of this finding for understanding aging, identification of this mutation by massively parallel sequencing of whole genomes emphasizes the enormous utility of next-generation sequencing technologies as investigative tools that will likely revolutionize genetics. ... In some cases, the apparent disconnect between experimental results and predictions of the free radical theory regarding connections between oxidative stress and lifespan is related to hormesis effects that elevate oxidative and other stress defenses in response to low levels of oxidative stress. ... The more transparently clear lesson here is that not all forms of oxidative stress are equivalent in their effects on aging. This isn't surprising in the context of the multitude of pathways that respond to different forms of oxidative stress and the numerous mechanisms by which oxidants can modify different macromolecular targets. Whatever the explanation, [research findings] emphasize the enormous complexity of relationships between oxidative stress and aging."

Link: http://www.impactaging.com/papers/v2/n8/full/100188.html

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