Glutathione metabolism in long-living Ames dwarf mice

Ames dwarf mice live significantly longer than their wild type siblings and exhibit elevated antioxidative defenses and reduced oxidative damage. This study was conducted to determine the levels of components of glutathione (GSH) synthesis, degradation and utilization in dwarf and wild type mice. Glutamate-cysteine ligase protein levels were significantly elevated in dwarf liver at 3 and 24 months of age and muscle tissue at all ages examined. In kidney, activity of γ-glutamyltranspeptidase (GGT) was decreased 42, 30 and 33% in 3, 12 and 24-month-old dwarf mice compared to wild type mice (P<0.0001). In contrast, GSH-S-transferase (GST) activity was markedly elevated (85, 113 and 53%) in kidneys of 3, 12 and 24-month-old dwarf mice (P<0.0001). GGT activity was higher in hearts of young dwarf and wild type mice while GST activity tended to be greater in dwarf mice. Similar to liver and kidney, brain GGT activity was also lower in dwarf mice (P<0.0001). Results of these experiments coupled with previous data provide a mechanism to partially explain the enhanced resistance to oxidative insult and conceivably, the extended longevity of dwarf mice.