Expression of the methionine sulfoxide reductase lost during evolution extends Drosophila lifespan in a methionine-dependent manner

Sci Rep. 2018 Jan 17;8(1):1010. doi: 10.1038/s41598-017-15090-5.


Accumulation of oxidized amino acids, including methionine, has been implicated in aging. The ability to reduce one of the products of methionine oxidation, free methionine-R-sulfoxide (Met-R-SO), is widespread in microorganisms, but during evolution this function, conferred by the enzyme fRMsr, was lost in metazoa. We examined whether restoration of the fRMsr function in an animal can alleviate the consequences of methionine oxidation. Ectopic expression of yeast fRMsr supported the ability of Drosophila to catalyze free Met-R-SO reduction without affecting fecundity, food consumption, and response to starvation. fRMsr expression also increased resistance to oxidative stress. Moreover, it extended lifespan of flies in a methionine-dependent manner. Thus, expression of an oxidoreductase lost during evolution can enhance metabolic and redox functions and lead to an increase in lifespan in an animal model. More broadly, our study exposes the potential of a combination of genetic and nutritional strategies in lifespan control.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Animals
  • Biological Evolution
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics*
  • Eating / physiology
  • Fertility / physiology
  • Gene Expression
  • Longevity / drug effects
  • Longevity / genetics*
  • Methionine / analogs & derivatives*
  • Methionine / metabolism*
  • Methionine / pharmacology
  • Methionine Sulfoxide Reductases / genetics*
  • Methionine Sulfoxide Reductases / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Paraquat / pharmacology
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Starvation / enzymology
  • Starvation / genetics
  • Transgenes


  • Saccharomyces cerevisiae Proteins
  • Methionine
  • Methionine Sulfoxide Reductases
  • Paraquat
  • methionine sulfoxide