Modulation of metallothionein-1 isoform on mice survival Marco Malavolta, Andrea Basso, Francesco Piacenza, Laura Costarelli, Robertina Giacconi, Eugenio Mocchegiani Ctr. Nutrition and Ageing, POR-INRCA, Ancona, Italy The role of MTs in aging and longevity is not completely understood. Several studies have brought evidence that these proteins could represent a basic defense system against oxidative damage. Their positive role in longevity and health span has been recently shown in cardiac specific transgenic mice. However, observational studies in humans have also leaded to the hypothesis that MTs might display a potential antagonistic pleiotropic role that could be affected by nutritional zinc. In order to further insight on these aspects, we set up to study the longevity of old and very old MT-1 overexpressing mice and their respective controls (C57 BL6 mice). Both strains were fed a standard diet or a diet supplemented with zinc in drinking water. Our results show that MT-1 transgenic mice have mean and maximum lifespan higher than their respective controls thus confirming that these proteins might constitute a family of important gerontogenes. Zn supplementation display different effects on longevity of MT-1 overexpressing mice and C57 BL6 controls. This study poses the basis for future intervention based on gene therapy with MTs to enhance longevity and health span of laboratory mice.