Longevity of insulin receptor substrate1 null mice is not associated with increased basal antioxidant protection or reduced oxidative damage

Melissa M. Page, Dominic J. Withers, Colin Selman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Insulin receptor substrate-1 null (Irs1 (-/-)) mice are long lived and importantly they also demonstrate increased resistance to several age-related pathologies compared to wild type (WT) controls. Currently, the molecular mechanisms that underlie lifespan extension in long-lived mice are unclear although protection against oxidative damage may be important. Here, we determined both the activities of several intracellular antioxidants and levels of oxidative damage in brain, skeletal muscle, and liver of Irs1 (-/-) and WT mice at 80, 450, and 700 days of age, predicting that long-lived Irs1 (-/-) mice would be protected against oxidative damage. We measured activities of both intracellular superoxide dismutases (SOD); cytosolic (CuZnSOD) and mitochondrial (MnSOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT), and reduced glutathione (GHS). Of these, only hepatic CAT was significantly altered (increased) in Irs1 (-/-) mice. In addition, the levels of protein oxidation (protein carbonyl content) and lipid peroxidation (4-hydroxynonenal) were unaltered in Irs1 (-/-) mice, although the hepatic GSH/GSSG ratio, indicating an oxidized environment, was significantly lower in long-lived Irs1 (-/-) mice. Overall, our results do not support the premise that lifespan extension in Irs1 (-/-) mice is associated with greater tissue antioxidant protection or reduced oxidative damage.
Original languageEnglish
Pages (from-to)647-658
Number of pages12
JournalAge
Volume35
Issue number3
Early online date29 Feb 2012
DOIs
Publication statusPublished - Jun 2013

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Insulin Receptor
Antioxidants
Catalase
Glutathione
Liver
Insulin Receptor Substrate Proteins
Glutathione Disulfide
Glutathione Reductase
Peroxides
Lipid Peroxidation
Superoxide Dismutase
Skeletal Muscle
Proteins
Pathology
Brain

Keywords

  • insulin receptor substrate-1
  • Irs1
  • lifespan
  • antioxidant enzymes
  • oxidative damage
  • ageing

Cite this

Longevity of insulin receptor substrate1 null mice is not associated with increased basal antioxidant protection or reduced oxidative damage. / Page, Melissa M.; Withers, Dominic J.; Selman, Colin.

In: Age, Vol. 35, No. 3, 06.2013, p. 647-658.

Research output: Contribution to journalArticle

Page, Melissa M. ; Withers, Dominic J. ; Selman, Colin. / Longevity of insulin receptor substrate1 null mice is not associated with increased basal antioxidant protection or reduced oxidative damage. In: Age. 2013 ; Vol. 35, No. 3. pp. 647-658.
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