Altered methionine metabolism in long living Ames dwarf mice

Ames dwarf mice (df/df) are deficient in growth hormone, prolactin, and thyroid-stimulating hormone and live significantly longer than their normal siblings. In the current study, we found that the hormone deficiencies affect methionine metabolism. We previously reported that the dwarf mice exhibit enzyme activities and levels that combat oxidative stress more efficiently than those of normal mice. Moreover, methionine or metabolites of methionine are involved in antioxidative processes. Thus, we performed an experiment that compared various parameters of methionine metabolism between 18-month old male dwarf (N=6) and wild type (N=5) mice. The specific activity of liver methionine adenosyltransferase (MAT) was significantly elevated (205%, p<0.0001) in the dwarf mice, as were cystathionine synthase (50%, p<0.01), cystathionase (83%, p<0.001), and glycine N-methyltransferase (GNMT, 91%, p<0.001) activities. Even though the activities of MAT and GNMT were elevated, the concentration of liver S-adenosylmethionine was decreased (24%, p<0.001) and S-adenosylhomocysteine increased (113%, p<0.001) in the dwarf mice. These data indicate that dwarf mice, compared to wild type mice, have a markedly different metabolism of methionine. Altered methionine metabolism may partially explain earlier reports indicating less oxidative damage to proteins in dwarf mice. Taken together, the data suggest that methionine metabolism may play a role in oxidative defense in the dwarf mouse and should be studied as a potential mechanism of extended lifespan.