Reevaluation of whether a soma-to-germ-line transformation extends lifespan in Caenorhabditis elegans

Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3591-6. doi: 10.1073/pnas.1523402113. Epub 2016 Mar 14.

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.

Keywords: C. elegans; P granules; aging; daf-2; germ line.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Genes, Helminth
  • Germ-Line Mutation
  • Longevity / genetics
  • RNA Interference
  • Receptor, Insulin / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Mes-1 protein, C elegans
  • Mes-4 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin