title: A gain-of-function screen identifies wdb and lkb1 as lifespan-extending genes in Drosophila.
abstract: The insulin/insulin-like growth factor (IGF) and the target of rapamycin (TOR) signaling pathways are known to regulate lifespan in diverse organisms. However, only a limited number of genes involved in these pathways have been examined regarding their effects on lifespan. Through a gain-of-function screen in Drosophila, we found that overexpression of the wdb gene encoding a regulatory subunit of PP2A, and overexpression of the lkb1 gene encoding a serine/threonine kinase, reduced organ size and extended lifespan. Overexpression of wdb also reduced the level of phosphorylated AKT, while overexpression of lkb1 increased the level of phosphorylated AMPK and decreased the level of phosphorylated S6K. Taken together, our results suggest that wdb- and lkb1-dependent lifespan extension is mediated by downregulation of S6K, a downstream component of the insulin/IGF and TOR signaling pathways.
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Masabumi
authors.initials: M
authors.lastname: Funakoshi
authors.forename: Manabu
authors.initials: M
authors.lastname: Tsuda
authors.forename: Keigo
authors.initials: K
authors.lastname: Muramatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatsuda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D008136:Longevity / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D014921:Wings, Animal / Q000033:anatomy & histology
chemical_list: D029721:Drosophila Proteins; D011494:Protein Kinases; C523914:AMPKalpha protein, Drosophila; C495775:LKB1 protein, Drosophila; D051057:Proto-Oncogene Proteins c-akt; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases