title: Transcriptional response to dietary restriction in Drosophila melanogaster.
abstract: Dietary restriction (DR) extends lifespan in a wide variety of organisms. Although several genes and pathways associated with this longevity response have been identified, the specific mechanism through which DR extends lifespan is not fully understood. We have recently developed a novel methodology to screen for transcriptional changes in response to acutely imposed DR upon adult Drosophila melanogaster and identified groups of genes that switch their transcriptional patterns from a normal diet pattern to a restricted diet pattern, or 'switching genes'. In this current report we extend our transcriptional data analysis with gene set enrichment analysis to generate a pathway-centered perspective. The pattern of temporal behavior in response to the diet switch is strikingly similar within and across pathways associated with mRNA processing and protein translation. Furthermore, most genes within these pathways display an initial spike in activity within 6-8h from the diet switch, followed by a coordinated, partial down-regulation after 24h. We propose this represents a stereotypical response to DR, which ultimately leads to a mild but widespread inhibition of transcriptional and translational activity. Inhibition of the protein synthesis pathway has been observed in DR in other studies and has been shown to extend lifespan in several model organisms.
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, United States.
authors.forename: Feifei
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, United States.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Gil
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Franklin
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, United States.
authors.forename: Marc
authors.initials: M
authors.lastname: Tatar
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, United States.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Helfand
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, United States; Center for Computational Molecular Biology, Brown University, Providence, RI 02912, United States. Electronic address: nicola_neretti@brown.edu.
authors.forename: Nicola
authors.initials: N
authors.lastname: Neretti
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D064688:Metabolic Flux Analysis; D053858:Metabolic Networks and Pathways; D009747:Nutritional Physiological Phenomena; D020411:Oligonucleotide Array Sequence Analysis; D011897:Random Allocation
keywords: Dietary restriction; Dietary switch; Drosophila melanogaster; Gene expression; Life span; Pathway analysis