Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals

Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12920-5. doi: 10.1073/pnas.231472998. Epub 2001 Oct 23.


Oxidation of proteins by reactive oxygen species is associated with aging, oxidative stress, and many diseases. Although free and protein-bound methionine residues are particularly sensitive to oxidation to methionine sulfoxide derivatives, these oxidations are readily repaired by the action of methionine sulfoxide reductase (MsrA). To gain a better understanding of the biological roles of MsrA in metabolism, we have created a strain of mouse that lacks the MsrA gene. Compared with the wild type, this mutant: (i) exhibits enhanced sensitivity to oxidative stress (exposure to 100% oxygen); (ii) has a shorter lifespan under both normal and hyperoxic conditions; (iii) develops an atypical (tip-toe) walking pattern after 6 months of age; (iv) accumulates higher tissue levels of oxidized protein (carbonyl derivatives) under oxidative stress; and (v) is less able to up-regulate expression of thioredoxin reductase under oxidative stress. It thus seems that MsrA may play an important role in aging and neurological disorders.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Cell Line
  • Gene Targeting
  • Life Expectancy
  • Methionine / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Oxidative Stress
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Oxidoreductases Acting on Sulfur Group Donors


  • Antioxidants
  • Methionine
  • Oxidoreductases
  • Oxidoreductases Acting on Sulfur Group Donors
  • sulfoxide reductase