Dietary restriction attenuates the accelerated aging phenotype of Sod1 -/- mice

Yiqiang Zhang, Yuji Ikeno, Alex Bokov, Jon Gelfond, Carlos Jaramillo, Hong Mei Zhang, Yuhong Liu, Wenbo Qi, Gene Hubbard, Arlan Richardson, Holly Van Remmen

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Dietary restriction is a powerful aging intervention that extends the life span of diverse biological species ranging from yeast to invertebrates to mammals, and it has been argued that the antiaging action of dietary restriction occurs through reduced oxidative stress/damage. Using Sod1-/- mice, which have previously been shown to have increased levels of oxidative stress associated with a shorter life span and a high incidence of neoplasia, we were able to test directly the ability of dietary restriction to reverse an aging phenotype due to increased oxidative stress/damage. We found that dietary restriction increased the life span of Sod1-/- mice 30%, returning it to that of wild-type, control mice fed ad libitum. Oxidative damage in Sod1-/- mice was markedly reduced by dietary restriction, as indicated by a reduction in liver and brain F2-isoprostanes, a marker of lipid peroxidation. Analysis of end of life pathology showed that dietary restriction significantly reduced the overall incidence of pathological lesions in the Sod1-/- mice fed the dietary-restricted diet compared to Sod1-/- mice fed ad libitum, including the incidence of lymphoma (27 vs 5%) and overall liver pathology. In addition to reduced incidence of overall and liver-specific pathology, the burden and severity of both neoplastic and nonneoplastic lesions was also significantly reduced in the Sod1-/- mice fed the dietary-restricted diet. These data demonstrate that dietary restriction can significantly attenuate the accelerated aging phenotype observed in Sod1-/- mice that arises from increased oxidative stress/damage.

Original languageEnglish (US)
Pages (from-to)300-306
Number of pages7
JournalFree Radical Biology and Medicine
Volume60
DOIs
StatePublished - Jul 2013

Keywords

  • Aging oxidative stress
  • Cu/ZnSOD
  • Dietary restriction
  • Free radicals

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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