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Edited by Judith Kimble, University of Wisconsin–Madison, Madison, WI, and approved February 9, 2016 (received for review November 25, 2015)
Significance
Understanding the genetic mechanisms that control lifespan is essential for the development of regenerative therapies that seek to reverse the aging process. In the nematode Caenorhabditis elegans, long-lived mutants that are defective in insulin signaling up-regulate a number of stress response genes to promote survival. A study published in 2009 reported that these long-lived mutants also express in their somatic cells factors that are normally restricted to germ cells and that these mutants rely on germ-line factors for some of their lifespan extension. Our studies call these findings into question and instead suggest that expression of certain germ-line factors in the somatic cells of worms is detrimental to the health of worms and reduces lifespan.
Abstract
The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germ-line traits in somatic cells, to try to confer some of the germ lineage’s immortality on the somatic body. Notably, a study in Caenorhabditis elegans suggested that expression of germ-line genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2’s long lifespan. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knockdown of individual P-granule and other germ-line genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germ-line program to daf-2’s long lifespan and also tested whether other mutants known to express germ-line genes in their somatic cells are long-lived. Our key findings are as follows. (i) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. (ii) Whole-genome transcript profiling of animals lacking a germ line revealed that germ-line transcripts are not up-regulated in the soma of daf-2 worms compared with the soma of control worms. (iii) Simultaneous removal of multiple P-granule proteins or the entire germ-line program from daf-2 worms did not reduce their lifespan. (iv) Several mutants that robustly express a broad spectrum of germ-line genes in their somatic cells are not long-lived. Together, our findings argue against the hypothesis that acquisition of a germ-cell program in somatic cells increases lifespan and contributes to daf-2’s long lifespan.
Footnotes
- ↵1To whom correspondence should be addressed. Email: sstrome{at}ucsc.edu.
Author contributions: A.K.K. and S.S. designed research; A.K.K. performed research; A.R. performed the RNA-seq bioinformatic analysis; and A.K.K. and S.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The transcriptome profiling data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE76946).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1523402113/-/DCSupplemental.
- aDepartment of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064
Edited by Judith Kimble, University of Wisconsin–Madison, Madison, WI, and approved February 9, 2016 (received for review November 25, 2015)
Significance
Understanding the genetic mechanisms that control lifespan is essential for the development of regenerative therapies that seek to reverse the aging process. In the nematode Caenorhabditis elegans, long-lived mutants that are defective in insulin signaling up-regulate a number of stress response genes to promote survival. A study published in 2009 reported that these long-lived mutants also express in their somatic cells factors that are normally restricted to germ cells and that these mutants rely on germ-line factors for some of their lifespan extension. Our studies call these findings into question and instead suggest that expression of certain germ-line factors in the somatic cells of worms is detrimental to the health of worms and reduces lifespan.
Abstract
The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germ-line traits in somatic cells, to try to confer some of the germ lineage’s immortality on the somatic body. Notably, a study in Caenorhabditis elegans suggested that expression of germ-line genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2’s long lifespan. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knockdown of individual P-granule and other germ-line genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germ-line program to daf-2’s long lifespan and also tested whether other mutants known to express germ-line genes in their somatic cells are long-lived. Our key findings are as follows. (i) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. (ii) Whole-genome transcript profiling of animals lacking a germ line revealed that germ-line transcripts are not up-regulated in the soma of daf-2 worms compared with the soma of control worms. (iii) Simultaneous removal of multiple P-granule proteins or the entire germ-line program from daf-2 worms did not reduce their lifespan. (iv) Several mutants that robustly express a broad spectrum of germ-line genes in their somatic cells are not long-lived. Together, our findings argue against the hypothesis that acquisition of a germ-cell program in somatic cells increases lifespan and contributes to daf-2’s long lifespan.
- germ line
- aging
- C. elegans
- daf-2
- P granules
Footnotes
- ↵1To whom correspondence should be addressed. Email: sstrome{at}ucsc.edu.
Author contributions: A.K.K. and S.S. designed research; A.K.K. performed research; A.R. performed the RNA-seq bioinformatic analysis; and A.K.K. and S.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The transcriptome profiling data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE76946).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1523402113/-/DCSupplemental.
Germ features in soma do not extend lifespan
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