Reduced Insulin/IGF-1 Signaling Restores Germ Cell Immortality to Caenorhabditis elegans Piwi Mutants

Matt Simon; Peter Sarkies; Kohta Ikegami; Anna-Lisa Doebley; Leonard D. Goldstein; Jacinth Mitchell; Aisa Sakaguchi; Eric A. Miska; Shawn Ahmed

doi:10.1016/j.celrep.2014.03.056

Cell Reports (May 2014)

Reduced Insulin/IGF-1 Signaling Restores Germ Cell Immortality to Caenorhabditis elegans Piwi Mutants

Matt Simon,
Peter Sarkies,
Kohta Ikegami,
Anna-Lisa Doebley,
Leonard D. Goldstein,
Jacinth Mitchell,
Aisa Sakaguchi,
Eric A. Miska,
Shawn Ahmed

Affiliations

Matt Simon: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA
Peter Sarkies: The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
Kohta Ikegami: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA
Anna-Lisa Doebley: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA
Leonard D. Goldstein: The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
Jacinth Mitchell: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA
Aisa Sakaguchi: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA
Eric A. Miska: The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
Shawn Ahmed: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA

DOI: https://doi.org/10.1016/j.celrep.2014.03.056
Journal volume & issue: Vol. 7, no. 3
pp. 762 – 773

Abstract

Read online

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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal