A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants


Unlike the soma, which ages during the lifespan of multicellular organisms, the germ line traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation towards reproduction at the expense of cellular senescence. Here we show that Caenorhabditis elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germ line. Decreased insulin-like signalling causes the somatic misexpression of the germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. The forkhead boxO1A (FOXO) transcription factor DAF-16, the major transcriptional effector of insulin-like signalling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also causes somatic misexpression of PGL-1. These results indicate that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival.

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Figure 1: Mutations in the insulin/IGF-like signalling pathway cause soma-to-germline transformation.
Figure 2: DAF-16 regulates the expression of pie-1.
Figure 3: The somatic misexpression of germline-specific genes in insulin-like signalling mutants contributes to their increased longevity.
Figure 4: The cytosolic chaperonin complex regulates the expression of PGL-1 in somatic cells.
Figure 5: Model for the regulation of germline gene expression in the soma by C. elegans longevity regulators.


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Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health National Center for Research Resources. We thank A. Conery, H. Gabel, J. Melo, E. O’Rourke, D. Simon, A. Soukas and M. Wang for reagents, discussion and reading of the manuscript; G. Seydoux and members of the Ruvkun, Ausubel and Kaplan laboratories for discussion; S. Strome for the pie-1p::gfp::pgl-1 strain and C. Mello for monoclonal antisera against PGL-1, S. S. Lee, S. Ercan and the Kingston laboratory for technical advice on ChIP. This work was supported by grants from the National Institutes of Health and the National Institute on Aging F32-AG026207 to S.P.C. and R01-AG016636 to G.R. and the European Molecular Biology Organization and the Human Frontier Science Program to C.G.R.

Author Contributions S.P.C. and G.R. conceived and designed the experiments. S.P.C., X.W. and C.G.R. performed the experiments. S.P.C. and G.R. wrote the manuscript.

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Correspondence to Gary Ruvkun.

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Curran, S., Wu, X., Riedel, C. et al. A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants. Nature 459, 1079–1084 (2009). https://doi.org/10.1038/nature08106

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