title: The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling.
abstract: In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Yamawaki
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Berman
authors.forename: Monika
authors.initials: M
authors.lastname: Suchanek-Kavipurapu
authors.forename: Mark
authors.initials: M
authors.lastname: McCormick
authors.forename: Marta Maria
authors.initials: MM
authors.lastname: Gaglia
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kenyon
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002782:Cholestenes / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D006066:Gonads / Q000166:cytology / Q000502:physiology; D008024:Ligands; D008136:Longevity / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction; D013256:Steroids / Q000494:pharmacology
chemical_list: D029742:Caenorhabditis elegans Proteins; D002782:Cholestenes; C410905:DAF-12 protein, C elegans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids; C533800:dafachronic acid
references.citation: Curr Biol. 2009 May 12;19(9):715-22
references.pmid: 19375320
references.citation: Cell. 2006 Mar 10;124(5):1055-68
references.pmid: 16530050
references.citation: Genes Dev. 2000 Jun 15;14(12):1512-27
references.pmid: 10859169
references.citation: Development. 2002 Jan;129(1):221-31
references.pmid: 11782415
references.citation: Nature. 1999 May 27;399(6734):362-6
references.pmid: 10360574
references.citation: FASEB J. 1999 Aug;13(11):1385-93
references.pmid: 10428762
references.citation: Nature. 1993 Dec 2;366(6454):461-4
references.pmid: 8247153
references.citation: Science. 2003 Oct 24;302(5645):611
references.pmid: 14576426
references.citation: Biochem J. 2000 Jul 15;349(Pt 2):629-34
references.pmid: 10880363
references.citation: Genetics. 1974 May;77(1):71-94
references.pmid: 4366476
references.citation: Science. 2008 Nov 7;322(5903):957-60
references.pmid: 18988854
references.citation: Science. 2002 Jan 18;295(5554):502-5
references.pmid: 11799246
references.citation: Aging Cell. 2003 Jun;2(3):185-90
references.pmid: 12882411
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6368-73
references.pmid: 18434551
references.citation: Cold Spring Harb Symp Quant Biol. 2003;68:159-69
references.pmid: 15338614
references.citation: PLoS Genet. 2009 Sep;5(9):e1000639
references.pmid: 19749979
references.citation: Nat Genet. 2006 Feb;38(2):251-7
references.pmid: 16380712
references.citation: Cell. 2006 Mar 24;124(6):1209-23
references.pmid: 16529801
references.citation: Dev Cell. 2006 Apr;10(4):473-82
references.pmid: 16563875
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5014-9
references.pmid: 17360327
references.citation: Development. 2004 Apr;131(8):1777-86
references.pmid: 15084462
references.citation: Biochim Biophys Acta. 2000 Nov 15;1494(1-2):104-16
references.pmid: 11072073
references.citation: BMC Mol Biol. 2008 Jan 22;9:9
references.pmid: 18211699
references.citation: Nat Genet. 2001 Jun;28(2):139-45
references.pmid: 11381260
references.citation: Genetics. 2008 Jan;178(1):513-26
references.pmid: 18202391
references.citation: Cell. 1987 Nov 20;51(4):589-99
references.pmid: 3677168
references.citation: Dev Cell. 2001 Dec;1(6):841-51
references.pmid: 11740945
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13496-501
references.pmid: 16157872
references.citation: Cell. 2003 Nov 14;115(4):489-502
references.pmid: 14622602