title: Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila.
abstract: A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila. Starting with a gene centric analysis comparing the changes in common between DR and two DR related molecular genetic life span extending manipulations, Sir2 and p53, lead to a molecular confirmation of Sir2 and p53's similarity with DR and the identification of a small set of commonly regulated genes. One of the identified upregulated genes, takeout, known to be involved in feeding and starvation behavior, and to have sequence homology with Juvenile Hormone (JH) binding protein, was shown to directly extend life span when specifically overexpressed. Here we show that a pathway centric approach can be used to identify shared physiological pathways between DR and Sir2, p53 and resveratrol life span extending interventions. The set of physiological pathways in common among these life span extending interventions provides an initial step toward defining molecular genetic and physiological changes important in life span extension. The large overlap in shared pathways between DR, Sir2, p53 and resveratrol provide strong molecular evidence supporting the genetic studies linking these specific life span extending interventions.
authors.affiliation: Institute for Brain and Neural Systems, and Department of Physics, Brown University, Providence, RI, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Antosh
authors.forename: Rachel
authors.initials: R
authors.lastname: Whitaker
authors.forename: Adam
authors.initials: A
authors.lastname: Kroll
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hosier
authors.forename: Chengyi
authors.initials: C
authors.lastname: Chang
authors.forename: Johannes
authors.initials: J
authors.lastname: Bauer
authors.forename: Leon
authors.initials: L
authors.lastname: Cooper
authors.forename: Nicola
authors.initials: N
authors.lastname: Neretti
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Helfand
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D019295:Computational Biology; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D007605:Juvenile Hormones / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000235:genetics; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D007605:Juvenile Hormones; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; C447899:Sirt2 protein, Drosophila; D037761:Sirtuins; D006655:Histone Deacetylases; D000077185:Resveratrol