Maintenance of the germ-soma distinction ensures proper cellular identity and function. A 2009 study reported that long-lived daf-2 mutants of C. elegans ectopically express a germline program in their somatic cells, including mRNAs for the P-granule factors PGL-1 and PGL-3 (Curran et al. Nature 459: 1079-1084, 2009). Importantly, knock-down of several germline factors via RNAi in adult daf-2 worms resulted in a slight decrease in those worms' lifespan, suggesting that those proteins confer some lifespan extension to daf-2 mutants. Our lab's interest in germline development, regulators of the germ-soma distinction, and the possibility that some of the immortality of germ cells can be harnessed to extend somatic lifespan led us to explore and extend the daf-2 findings. Our results have shown that somatic expression of a germline program does not extend lifespan in C. elegans: 1) We do not detect ectopic expression of P-granule proteins in daf-2 worms, as assayed by immunostaining for PGL proteins and by expression of a PGL-1::GFP transgene under the control of the pgl-1 promoter. 2) Simultaneous depletion of 4 constitutive components of P granules (PGL-1, PGL-3, GLH-1, and GLH-4) from daf-2 mutants did not decrease lifespan but instead slightly extended lifespan. 3) Expressing a PGL-1::GFP fusion protein in the intestine of wild-type worms did not alter lifespan. 4) Six synMuv mutants that ectopically express germline proteins in their somatic cells at 24oC are not long-lived compared to wild type. We also tested the effect of loss of the master germline chromatin regulator MES-4 on the lifespan of daf-2 worms. Compared to daf-2 single mutants, fertile daf-2; mes-4 double mutants had the same lifespan, while sterile daf-2; mes-4 double mutants were dramatically longer-lived. We attribute this hyper-increased longevity to the synergistic effects of reduced insulin-like signaling and absence of a germline. Taken together, our results show that extreme extension of lifespan can be accomplished by combining loss of DAF-2 with absence of germ cells, and that somatic expression of germline proteins does not extend lifespan, arguing against the appealing possibility that expression of a germline progam in somatic cells can provide the somatic body with partial "germline immortality.".

Affiliation:
- Department of Molecular, Cell, and Developmental Biology, UC Santa Cruz, Santa Cruz, CA 95064