SummaryA diet deficient in the amino acid methionine has previously been shown to extend lifespan in several stocks of inbred rats. We report here that a methionine-deficient (Meth-R) diet also increases maximal lifespan in (BALB/ cJ × × × × C57BL/6 J)F1 mice. Compared with controls, Meth-R mice have significantly lower levels of serum IGF-I, insulin, glucose and thyroid hormone. Meth-R mice also have higher levels of liver mRNA for MIF (macrophage migration inhibition factor), known to be higher in several other mouse models of extended longevity. Meth-R mice are significantly slower to develop lens turbidity and to show age-related changes in T-cell subsets. They are also dramatically more resistant to oxidative liver cell injury induced by injection of toxic doses of acetaminophen. The spectrum of terminal illnesses in the Meth-R group is similar to that seen in control mice. Studies of the cellular and molecular biology of methionine-deprived mice may, in parallel to studies of calorie-restricted mice, provide insights into the way in which nutritional factors modulate longevity and late-life illnesses.

Founder effects, together with access to unoccupied ecological niches, may allow rodent populations on isolated islands to evolve constellations of life-history traits that distinguish them from their mainland relatives, for example in body size, litter size, and longevity. In particular, low intrinsic mortality risks on islands with reduced predator numbers and not subject to harsh winter climates may in principle support the development of stocks with extended longevity. Conversely, the conditions under which laboratory rodents are typically bred are thought to select for genotypes that produce large, rapidly maturing races with high early reproductive rates but diminished longevity. To test these ideas, and to generate new mouse stocks suitable for genetic and molecular analysis of the processes that time life-history events, we have developed speci®c pathogen-free stocks from mice trapped from three distinct populations: the U.S. mainland (Idaho) and the tropical Paci®c islands Majuro and Pohnpei. Mice from all three locations were found to be shorter and lighter, to have smaller litters, and to have higher faecal corticosterone levels than mice of a genetically heterogeneous stock derived from four common laboratory inbred strains. Among the wild-derived stocks, mice from Pohnpei and Majuro were signi®cantly lighter and shorter than Idahoderived animals, even in populations kept from birth under identical housing conditions. Litter size and reproductive success rates did not differ signi®cantly among the three wild-derived stocks. Although further work will be needed to see if, as predicted, the wild-derived stocks differ from one another and from laboratory mice in longevity, these stocks provide useful tools for genetic dissection of factors that regulate body size and reproductive success.

Founder effects, together with access to unoccupied ecological niches, may allow rodent populations on isolated islands to evolve constellations of life-history traits that distinguish them from their mainland relatives, for example in body size, litter size, and longevity. In particular, low intrinsic mortality risks on islands with reduced predator numbers and not subject to harsh winter climates may in principle support the development of stocks with extended longevity. Conversely, the conditions under which laboratory rodents are typically bred are thought to select for genotypes that produce large, rapidly maturing races with high early reproductive rates but diminished longevity. To test these ideas, and to generate new mouse stocks suitable for genetic and molecular analysis of the processes that time life-history events, we have developed speci®c pathogen-free stocks from mice trapped from three distinct populations: the U.S. mainland (Idaho) and the tropical Paci®c islands Majuro and Pohnpei. Mice from all three locations were found to be shorter and lighter, to have smaller litters, and to have higher faecal corticosterone levels than mice of a genetically heterogeneous stock derived from four common laboratory inbred strains. Among the wild-derived stocks, mice from Pohnpei and Majuro were signi®cantly lighter and shorter than Idahoderived animals, even in populations kept from birth under identical housing conditions. Litter size and reproductive success rates did not differ signi®cantly among the three wild-derived stocks. Although further work will be needed to see if, as predicted, the wild-derived stocks differ from one another and from laboratory mice in longevity, these stocks provide useful tools for genetic dissection of factors that regulate body size and reproductive success.