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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #140535

Title: ALTERED METHIONINE METABOLISM IN LONG LIVING AMES DWARF MICE

Author
item Uthus, Eric
item BROWN-BORG, HOLLY

Submitted to: Experimental Gerontology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2003
Publication Date: 5/1/2003
Citation: Uthus, E.O., Brown-Borg, H.M. 2003. Altered methionine metabolism in long living Ames dwarf mice. Experimental Gerontology 38:491-498.

Interpretive Summary: Ames dwarf mice live up to 64% longer than their normal siblings. The reason for their increased lifespan is not known. These mice, however, are deficient in growth hormone, prolactin, and thyroid-stimulating hormone. These hormones can affect various processes including the metabolism of certain amino acids (obtained from dietary protein) including methionine. Also, we previously reported that the dwarf mice exhibit enzyme activities and levels that combat oxidative stress more efficiently than normal mice. 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 and wild type (normal) mice. The activity of several enzymes that are important in the metabolism of methionine was increased up to 200%. 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.

Technical Abstract: 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 normal mice. And, 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.