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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / antagonists & inhibitors
  • Argonaute Proteins / genetics*
  • Argonaute Proteins / metabolism
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Forkhead Transcription Factors
  • Germ Cells / cytology
  • Germ Cells / metabolism*
  • Insulin / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Oxidoreductases, N-Demethylating / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptor, Insulin / deficiency
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism


  • Argonaute Proteins
  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • PRG-1 protein, C elegans
  • RNA, Small Interfering
  • Transcription Factors
  • daf-16 protein, C elegans
  • Insulin-Like Growth Factor I
  • Oxidoreductases, N-Demethylating
  • DAF-2 protein, C elegans
  • Receptor, Insulin