Is the oxidative stress theory of aging dead?

Viviana I. Pérez, Alex Bokov, Holly Van Remmen, James Mele, Qitao Ran, Yuji Ikeno, Arlan Richardson

Research output: Contribution to journalReview articlepeer-review

431 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1005-1014
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number10
DOIs
StatePublished - Oct 1 2009

Keywords

  • Antioxidant defense
  • Knockout mice
  • Longevity
  • Oxidative damage
  • Oxidative stress
  • Transgenic mice

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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