抄録
Calorie restriction (CR) means a reduction of calories by 30-40% compared with animals fed ad lib without changes in essential nutrient intake and it is well known that it can reduce the pathological symptoms of aging and extend lifespan in multiple species. However, little is understood for its mechanism. Many studies have shown that genomic mutations increase with age in an organ and tissue-dependent manner. Thus, the study of the effect of CR on mutation in vivo could be an interesting challenge. Here, by using MutaTM mice harboring the lacZ reporter gene as part of a bacteriophage lambda vector, we have investigated that if the age-dependent accumulation of mutation could be affected by CR. Mice were divided into two cohorts: the control group (95kcal/week/mouse) and the CR group (65kcal/week/mouse). At 18 month, in the control group, the mutant frequencies in liver, spleen and small intestine were 14.3, 8.08 and 33.2x10-5, respectively, whereas in the CR group, they were 15.9, 9.39 and 22.6x10-5. In liver and spleen, there was no significant difference in mutant frequency between control and CR groups, while in small intestine, the mutant frequency in CR group was significantly lower than that in the control group. We also determined the spectra of mutations in small intestine. Interestingly, mutation type of G:C to T:A was high in both control and CR groups. The frequencies of the other types of mutations also showed no significant difference. The results suggest that CR suppresses all kinds of mutations in small intestine but not in liver and spleen.
