title: Is the oxidative stress theory of aging dead?
abstract: Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates (e.g., C. elegans and Drosophila) and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited to a few studies with transgenic Drosophila that overexpress antioxidant enzymes. Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice.
authors.affiliation: Barshop Institute for Longevity and Aging Studies, Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Pérez
authors.forename: Alex
authors.initials: A
authors.lastname: Bokov
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.forename: James
authors.initials: J
authors.lastname: Mele
authors.forename: Qitao
authors.initials: Q
authors.lastname: Ran
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D002374:Catalase; D013482:Superoxide Dismutase