Ames dwarf mice are mutant mice that live about 50% longer than their normal siblings^,, because they carry a 'longevity' gene, Prop1^df, and in some phenotypic respects they resemble normal mice whose lifespan has been extended by restricted food intake^,,. Here we investigate whether these factors influence lifespan by similar or independent mechanisms, by deliberately reducing the number of calories consumed by Ames dwarf mice. We show that calorie restriction confers a further lifespan increase in the dwarfs, indicating that the two factors may act through different pathways.