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Published Online: 21 January 2014

The Free Radical Theory of Aging Is Dead. Long Live the Damage Theory!

Publication: Antioxidants & Redox Signaling
Volume 20, Issue Number 4


The free radical theory of aging posits that aging is caused by accumulation of damage inflicted by reactive oxygen species (ROS). Although this concept has been very useful in defining the contribution of oxidative damage to the aging process, an increasing number of studies contradict it. The idea that oxidative damage represents only one of many causes of aging also has limitations, as it does not explain causal relationships and inevitability of damage accumulation. Here, it is discussed that infidelity, heterogeneity, and imperfectness of each and every biological process may be responsible for the inevitable accumulation of by-products and other damage forms. Although ROS are prototypical by-products, their contribution to aging is governed by the metabolic organization of the cell, its protective systems, and genotype. These factors are controlled by natural selection and, like dietary and genetic interventions that extend lifespan, change the composition of cumulative damage and the rates of accumulation of its various forms. Oxidative damage, like other specific damage types viewed in isolation or in combination, does not represent the cause of aging. Instead, biological imperfectness, which leads to inevitable accumulation of damage in the form of mildly deleterious molecular species, may help define the true root of aging. Free radical and other specialized damage theories served their purpose in the understanding of the aging process, but in the current form they limit further progress in this area. Antioxid. Redox Signal. 20, 727–731.

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Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 20Issue Number 4February 1, 2014
Pages: 727 - 731
PubMed: 24159899


Published in print: February 1, 2014
Published online: 21 January 2014
Published ahead of print: 4 December 2013
Published ahead of production: 28 October 2013
Accepted: 26 October 2013
Revision received: 26 October 2013
Received: 2 February 2013


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Vadim N. Gladyshev
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.


Address correspondence to:Prof. Vadim N. GladyshevDivision of GeneticsDepartment of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston, MA 02115E-mail: [email protected]

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