text: Methionine sulfoxide (MetO), the oxidized form of the amino acid methionine (Met), increases with age in body tissues, which is believed by some to contribute to biological ageing. Oxidation of methionine residues in tissue proteins can cause them to misfold or otherwise render them dysfunctional. Uniquely, the methionine sulfoxide reductase (Msr) group of enzymes act with thioredoxin to catalyze the enzymatic reduction and repair of oxidized methionine residues. Moreover, levels of methionine sulfoxide reductase A (MsrA) decline in aging tissues in mice and in association with age-related disease in humans. There is thus a rationale for thinking that by maintaining the structure, increased levels or activity of MsrA might retard the rate of aging.
  Indeed, transgenic Drosophila (fruit flies) that overexpress methionine sulfoxide reductase show extended lifespan. However, the effects of MsrA overexpression in mice were ambiguous. MsrA is found in both the cytosol and the energy-producing mitochondria, where most of the bodys endogenous free radicals are produced. Transgenically increasing the levels of MsrA in either the cytosol or the mitochondria had no significant effect on lifespan assessed by most standard statistical tests, and may possibly have led to early deaths in the cytosol-specific mice, although the survival curves appeared to suggest a slight increase in maximum (90%) survivorship, as did analysis using Boschloos Exact test, a binomial test designed to test greater extreme variation.
  The oxidation of methionine serves as a switch that deactivates certain protein activities such as E.coli ribosomal protein, L12.  Proteins with great amount of methionine residues tend to exist within the lipid bilayer as methionine is one of the most hydrophobic amino acids. Those methionine residues that are exposed to the aqueous exterior thus are vulnerable to oxidation.  The oxidized residues tend to be arrayed around the active site and may guard access to this site by reactive oxygen species. Once oxidized, the MetO residues are reduced back to methionine by the enzyme methionine sulfoxide reductase. Thus, an oxidation–reduction cycle occurs in which exposed methionine residues are oxidized (e.g., by HO) to methionine sulfoxide residues, which are subsequently reduced.
  Methionine(protein)+ HO→ Methionine Sulfoxide(protein)+ HO
  Methionine Sulfoxide(protein)+ NADPH+H→ Methionine(protein)+ NADP+HO