Effects of age and caloric restriction on mitochondrial protein oxidative damage in mice

Xiao Dong Li, Igor Rebrin, Michael J. Forster, Rajindar S. Sohal

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The hypothesis that life-span extension by caloric restriction (CR) is contingent upon the attenuation of macromolecular oxidative damage was tested in two different strains of mice: the C57BL/6, whose life span is extended by CR, and the DBA/2, in which CR has relatively minor or no impact on longevity. Mice were fed ad libitum (AL) or restricted to 40% lesser food, starting at 4 months of age. Protein damage was measured as protein-linked adducts of 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) in skeletal muscle mitochondria at 6 and 23 months of age. Protein-HNE and -MDA content increased with age in C57BL/6 mice and CR significantly attenuated these augmentations. Metalloprotease 1, NADP-dependent mitochondrial malic enzyme (isoform 2) and citrate synthase were identified by mass spectroscopy to contain HNE/MDA adducts. DBA/2 mice exhibited little effect of age or CR on protein HNE/MDA content in skeletal muscle mitochondria. In contrast, protein-HNE levels in liver mitochondria showed a significant increase with age in AL-fed mice of both strains, and CR caused significant attenuation of this damage. Overall, results indicated that the age-related increase in protein oxidative damage and its abatement by CR are genotype- and tissue-specific, and not a universal phenomenon.

Original languageEnglish
Pages (from-to)30-36
Number of pages7
JournalMechanisms of Ageing and Development
Volume133
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Food restriction
  • HNE-protein conjugates
  • Mitochondrial proteins
  • Oxidative stress
  • Protein oxidative damage

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