title: Reevaluation of whether a soma-to-germ-line transformation extends lifespan in Caenorhabditis elegans.
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.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064.
authors.forename: Andrew Kekūpa'a
authors.initials: AK
authors.lastname: Knutson
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rechtsteiner
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064 sstrome@ucsc.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Strome
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth; D018095:Germ-Line Mutation; D008136:Longevity / Q000235:genetics; D034622:RNA Interference; D011972:Receptor, Insulin / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; C415743:Mes-1 protein, C elegans; C449639:Mes-4 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin
keywords: C. elegans; P granules; aging; daf-2; germ line