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.germ line | aging | C. elegans | daf-2 | P granules G erm and soma are the two most fundamentally different cell types found in multicellular organisms (1). Germ cells are totipotent and constitute the only immortal lineage, capable of generating entire new organisms generation after generation, whereas somatic cells differentiate into specialized cell types and are mortal, senescing and dying each generation. Maintaining the proper identity of these cell types is essential for propagation of species, and molecular barriers at both the transcriptional and translational levels have evolved to ensure the germ-soma distinction (1). Removal of these barriers in germ cells can lead to both expression of somatic factors and sterility (2-4), whereas removal of these barriers in somatic cells is associated with reentry into the cell cycle and cancer (5, 6). Despite these barriers, it is unknown whether some cell types can tolerate partial fate switching and perhaps adopt traits of other cell types to benefit the organism.An attractive possibility is that acquisition of a germ-cell program by the somatic body can capture some of the immortality of the germ lineage and extend lifespan (7,8). Indeed, a study in Caenorhabditis elegans supports that possibility (9). In C. elegans, inhibition of the insulin-like signaling pathway by a mutation in daf-2 doubles lifespan through activation of the FOXO transcription factor DAF-16...

The inducible response of the nematodeCaenorhabditis elegansto members of its natural microbiome across development and adult life

“…Moreover, data sets related to the GATA transcription factor gene elt-2 (RNAi (Schieber and Chandel, 2014), ChIP-Seq targets (Mann et al, 2016)) or the E-box transcription factor gene hlh-30 (study on S. aureus (Visvikis et al, 2014) and hlh-30 mutant (Grove et al, 2009)) were also enriched, suggesting an involvement of these transcription factors in the nematode's response to the microbiome. Additional overrepresented gene sets relate to C. elegans dietary responses, for example gene sets related to the insulin-like pathway (daf-2 (Knutson et al, 2016) anddaf-16 (McElwee et al, 2004)), fasting (Lee et al, 2014, 1), and starvation (Mueller et al, 2014). We further found an enrichment of the worm's response to the previously studied food bacterium Comamonas DA1877 .…”

Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons

“…DEPS-1 positively regulates the RNAi factor rde-4/dsRBD , and many DEPS-1- and ADAR-ERI-regulated retrotransposons are also regulated by the RNAi factors mut-2/TENT and rde-4/dsRBD (Supplemental Figure 4B). Similarly, in pgl-1 mutants that are also defective in P granules (26), retrotransposons are desilenced (Figure 4F).…”

Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons

“…S4B). Similarly, in pgl-1 mutants that are also defective in P granules (30), retrotransposons are desilenced ( Fig. 4F).…”