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Cell Rep. 2014 May 8;7(3):762-73. doi: 10.1016/j.celrep.2014.03.056. Epub 2014 Apr 24.

Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants.

Author information

1
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
2
The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
3
Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
4
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
5
The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: eam29@cam.ac.uk.
6
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: shawn@med.unc.edu.

Abstract

Defects in the Piwi/piRNA pathway lead to transposon desilencing and immediate sterility in many organisms. We found that the C. elegans Piwi mutant prg-1 became sterile after growth for many generations. This phenotype did not occur for RNAi mutants with strong transposon-silencing defects and was separable from the role of PRG-1 in transgene silencing. Brief periods of starvation extended the transgenerational lifespan of prg-1 mutants by stimulating the DAF-16/FOXO longevity transcription factor. Constitutive activation of DAF-16 via reduced daf-2 insulin/IGF-1 signaling immortalized prg-1 strains via RNAi proteins and histone H3 lysine 4 demethylases. In late-generation prg-1 mutants, desilencing of repetitive segments of the genome occurred, and silencing of repetitive loci was restored in prg-1; daf-2 mutants. This study reveals an unexpected interface between aging and transgenerational maintenance of germ cells, where somatic longevity is coupled to a genome-silencing pathway that promotes germ cell immortality in parallel to the Piwi/piRNA system.

PMID:
24767993
PMCID:
PMC4049074
DOI:
10.1016/j.celrep.2014.03.056
[Indexed for MEDLINE]
Free PMC Article
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