title: Effects of calorie restriction on the age-dependent accumulation of mutations in the small intestine of lacZ-transgenic mice.
abstract: To understand the effect of calorie restriction on genome maintenance systems, the age-dependent accumulation of mutations in animals maintained on high and low calorie diets was examined using lacZ-transgenic mice. Mice were fed a diet of 95 kcal/w or 65 kcal/w from 2 to 17 months of age. The mutation frequencies in the lacZ gene in epithelial tissues from the small intestine were examined at 12 and 17 months. Mutation frequencies were found to be lower in mice fed with a low calorie diet than in mice fed with a high calorie diet at the two age points. The molecular nature of the mutations was examined with DNA sequencing. It showed a predominance of transversions from G:C to T:A, and this is a typical type of mutation induced by reactive oxygen species. The fraction of this type of mutation among the different types of mutations detected was not affected by calorie restriction. The percentage of the other types of mutation was not influenced either. These results suggest that calorie restriction reduces the age-dependent accumulation of mutations by stimulating or inducing various types of DNA protection and repair systems rather than protecting cells against any specific type of DNA alteration.
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan.
authors.forename: Dongwei
authors.initials: D
authors.lastname: He
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Uehara
authors.forename: Maiko
authors.initials: M
authors.lastname: Furuya
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ikehata
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Komura
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Yi
authors.initials: Y
authors.lastname: Shang
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
authors.forename: Akira
authors.initials: A
authors.lastname: Ootsuyama
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Norimura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D007421:Intestine, Small / Q000378:metabolism*; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species