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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

Cell Reports · 2014 · ▲ 141 citations

Epigenetic alterations Deregulated nutrient-sensing Altered intercellular communication C. elegans

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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.

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Provenance

Source: OpenAlex
DOI: 10.1016/j.celrep.2014.03.056
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Fetched: 2026-09-06 MST

Cite this

APA

Simon, M., Sarkies, P., Ikegami, K., Doebley, A., Goldstein, L.D., Mitchell, J., Sakaguchi, A., Miska, E.A., & Ahmed, S. (2014). Reduced Insulin/IGF-1 Signaling Restores Germ Cell Immortality to Caenorhabditis elegans Piwi Mutants. <em>Cell Reports</em>. https://doi.org/10.1016/j.celrep.2014.03.056

Vancouver

Simon M, Sarkies P, Ikegami K, Doebley A, Goldstein LD, Mitchell J, et al. Reduced Insulin/IGF-1 Signaling Restores Germ Cell Immortality to Caenorhabditis elegans Piwi Mutants. Cell Reports. 2014. doi:10.1016/j.celrep.2014.03.056.

BibTeX

@article{matt2014Reduce, title = {Reduced Insulin/IGF-1 Signaling Restores Germ Cell Immortality to Caenorhabditis elegans Piwi Mutants}, author = {Matt Simon and Peter Sarkies and Kohta Ikegami and Anna-Lisa Doebley and Leonard D. Goldstein and Jacinth Mitchell and Aisa Sakaguchi and Eric A. Miska and Shawn Ahmed}, journal = {Cell Reports}, year = {2014}, doi = {10.1016/j.celrep.2014.03.056}, }