Dietary restriction in rats and mice: a meta-analysis and review of the evidence for genotype-dependent effects on lifespan.

Laboratory survival experiments have shown that dietary restriction (DR) can increase median and maximum lifespan. This paper provides a meta-analysis of laboratory experiments that have evaluated the effects of DR on lifespan in rats and mice (1934-present). In rats, DR increased median lifespan by 14-45% in half of all experiments, but in mice the effects of DR have been much weaker (4-27%). The least favorable effects of DR on lifespan have been observed among inbred rather than non-inbred mouse strains. In fact, some inbred mouse strains do not necessarily live longer with DR, including DBA/2 male mice and several strains from the ILSXISS recombinant inbred panel. Shortening of lifespan with DR has also been observed and confirmed for ILSXISS strain 114. Importantly, all rodent studies may be biased by the effects of laboratory breeding, since one study has shown that median lifespan is not improved by DR in wild-derived mice. These findings suggest that the set of genetic backgrounds studied in rodent DR experiments should be diversified. This will broaden the scope of genotypes studied in aging research, but may also be critical for translation of findings from rodents to historically outbred and genetically heterogeneous primate species. Copyright Â