title: Lifespan extension by dietary restriction is not linked to protection against somatic DNA damage in Drosophila melanogaster.
abstract: Dietary restriction (DR) has been shown to robustly extend lifespan in multiple species tested so far. The pro-longevity effect of DR is often ascribed to an increase in cellular defense against somatic damage, most notably damage by reactive oxygen species (ROS), considered a major cause of aging. Especially irreversible damage to DNA, the carrier of genetic information, is considered a critical causal factor in aging. Using a recently developed transgenic Drosophila melanogaster model system harboring a lacZ-plasmid construct that can be recovered in E. coli, spontaneous DNA mutation frequency in flies under DR and ad libitum conditions are measured. Three different DR conditions, imposed by manipulating levels of different types of yeast sources, were tested in females and males of two lacZ reporter gene lines. Feeding with the ROS producer paraquat at 1 mM resulted in a rapid accumulation of somatic mutations, indicating that the frequency of mutations at the lacZ locus is a reliable marker for increased oxidative stress. However, none of the DR conditions altered the accumulation of spontaneous mutations with age. These results suggest that the beneficial effects of DR are unlikely to be linked to protection against oxidative somatic DNA damage.
authors.affiliation: Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Edman
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Garcia
authors.forename: Rita A
authors.initials: RA
authors.lastname: Busuttil
authors.forename: Dylan
authors.initials: D
authors.lastname: Sorensen
authors.forename: Martha
authors.initials: M
authors.lastname: Lundell
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kapahi
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
mesh_terms: D000818:Animals; D004249:DNA Damage; D004032:Diet; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D005260:Female; D017930:Genes, Reporter; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D008297:Male; D009154:Mutation; D010269:Paraquat / Q000633:toxicity
chemical_list: D010269:Paraquat