Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants.
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.
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.
Matt
M
Simon
The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Peter
P
Sarkies
Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Kohta
K
Ikegami
Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Anna-Lisa
AL
Doebley
The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Leonard D
LD
Goldstein
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.
Jacinth
J
Mitchell
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Aisa
A
Sakaguchi
The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: eam29@cam.ac.uk.
Eric A
EA
Miska
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.
Shawn
S
Ahmed
D000818:Animals; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D060565:Argonaute Proteins; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; C530363:PRG-1 protein, C elegans; D034741:RNA, Small Interfering; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D010089:Oxidoreductases, N-Demethylating; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin