title: takeout-dependent longevity is associated with altered Juvenile Hormone signaling.
abstract: In order to understand the molecular mechanisms of longevity regulation, we recently performed a screen designed to enrich for genes common to several longevity interventions. Using this approach, we identified the Drosophila melanogaster gene takeout. takeout is upregulated in a variety of long-lived flies, and extends life span when overexpressed. Here, we investigate the mechanisms of takeout-dependent longevity. takeout overexpression specifically in the fat body is sufficient to increase fly longevity and is additive to the longevity effects of Dietary Restriction. takeout long-lived flies do not show phenotypes often associated with increased longevity, such as enhanced stress resistance or major metabolic abnormalities. However, males exhibit greatly diminished courtship behavior, leading to a reduction in fertility. Interestingly, takeout contains a binding domain for Juvenile Hormone, a fly hormone that plays a role in the regulation of developmental transitions. Importantly, the longevity and courtship phenotypes of takeout overexpressing flies are reversed by treatment with the Juvenile Hormone analog methoprene. These data suggest that takeout is a key player in the tradeoff-switch between fertility and longevity. takeout may control fertility via modulation of courtship behavior. This regulation may occur through Juvenile Hormone binding to takeout and a subsequent reduction in Juvenile Hormone signaling activity.
authors.affiliation: Department of Biological Sciences, Southern Methodist University, 6501 Airline Drive, 238-DLS, Dallas, TX 75275, USA.
authors.forename: Khalil H
authors.initials: KH
authors.lastname: Chamseddin
authors.forename: Sabina Q
authors.initials: SQ
authors.lastname: Khan
authors.forename: Mai L H
authors.initials: ML
authors.lastname: Nguyen
authors.forename: Michael
authors.initials: M
authors.lastname: Antosh
authors.forename: Siti Nur Sarah
authors.initials: SN
authors.lastname: Morris
authors.forename: Santharam
authors.initials: S
authors.lastname: Kolli
authors.forename: Nicola
authors.initials: N
authors.lastname: Neretti
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Helfand
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Bauer
mesh_terms: D000375:Aging; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D005298:Fertility; D007605:Juvenile Hormones / Q000378:metabolism*; D008136:Longevity; D008297:Male; D010641:Phenotype; D012737:Sex Factors; D012726:Sexual Behavior, Animal; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
chemical_list: D029721:Drosophila Proteins; D007605:Juvenile Hormones; C411066:TO protein, Drosophila