Reevaluation of the effect of dietary restriction on different recombinant inbred lines of male and female mice.

Dietary restriction (DR) was reported to either have no effect or reduce the lifespan of the majority of the 41-recombinant inbred (RI) lines studied by Liao et al. (Aging Cell, 2010, 9, 92). In an appropriately power longevity study (n > 30 mice/group), we measured the lifespan of the four RI lines (115-RI, 97-RI, 98-RI, and 107-RI) that were reported to have the greatest decrease in lifespan when fed 40% DR. DR increased the median lifespan of female RI-115, 97-RI, and 107-RI mice and male 115-RI mice. DR had little effect (<4%) on the median lifespan of female and male 98-RI mice and male 97-RI mice and reduced the lifespan of male 107-RI mice over 20%. While our study was unable to replicate the effect of DR on the lifespan of the RI mice (except male 107-RI mice) reported by Liao et al. (Aging Cell, 2010, 9, 92), we found that the genotype of a mouse had a major impact on the effect of DR on lifespan, with the effect of DR ranging from a 50% increase to a 22% decrease in median lifespan. No correlation was observed between the changes in either body composition or glucose tolerance induced by DR and the changes observed in lifespan of the four RI lines of male and female mice. These four RI lines of mice give the research community a unique resource where investigators for the first time can study the anti-aging mechanism of DR by comparing mice in which DR increases lifespan to mice where DR has either no effect or reduces lifespan.