We are all descendents of an unbroken line of cell divisions, dating back to the last common ancestor of all life on Earth. At some point, long after our lineage had acquired features like nuclei and mitochondria, a less distant ancestor stumbled on a major innovation: it grew a body, bringing with it the advantages of cell and tissue specialization.

For many multicellular organisms, this specialization included a distinction between the mortal cells (the “soma”) and the potentially immortal cells (the “germ line”) that are capable of participating in the creation of new organisms. When you look at us, most of what you see is soma — the germ line is safely tucked away in the gonad, which is (usually) itself tucked away someplace safe.

But both the germ line and soma are made of cells. How is it that the soma is mortal while the germ line is, for practical purposes, immortal?

The disposable soma theory of aging begins from the premise that an organism has access to a finite amount of resources (broadly, energy and matter), and that it must distribute these resources in a way that maximizes reproductive fitness. First dibs goes to the germ line (without which it doesn’t matter, in a fitness sense, what becomes of the rest of the organism) and the rest gets divided among the cells of the soma.

For the moment, all we really need to take away from this model is that the germ line and soma are maintained in different ways, either in quality or extent. The germ line is doing something differently than the soma, the upshot of which is that the germ line is immortal. (A strict interpreter of the theory would presume that this “something” is resource-intensive, so that it wouldn’t be possible to apply the strategy to the soma. It’s also possible, however, that it’s simply inconsistent with optimal somatic functions — e.g., that making a muscle the best muscle it can be requires that myocytes not partake of the germ line strategy for immortality, for some structural reason that has nothing to do with resource allocation per se.)

One oh-wow corollary of this model is that if somatic cells could be made more like germ line cells, they would live longer. This prediction has a deliciously outrageous quality — yet is so simple that upon first hearing it, I reached for the nearest journal with the intention of rolling it up and smacking myself repeatedly on the forehead. Fortunately, there was a copy of Nature handy.

To be honest, it didn’t really happen that way. That copy of Nature contained the very article that introduced me to this concept: Curran et al. have shown that in long-lived mutants of the worm C. elegans, somatic tissues start acting like germ line cells:

A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants

Unlike the soma, which ages during the lifespan of multicellular organisms, the germ line traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation towards reproduction at the expense of cellular senescence. Here we show that Caenorhabditis elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germ line. Decreased insulin-like signalling causes the somatic misexpression of the germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. The forkhead boxO1A (FOXO) transcription factor DAF-16, the major transcriptional effector of insulin-like signalling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also causes somatic misexpression of PGL-1. These results indicate that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival.

Just to be clear: the somatic tissues of the long-lived mutants had not actually transformed into germ line cells as such, nor were the mutant worms festooned with extra gonads (though admittedly, that would be totally awesome). Rather, the somatic tissues exhibited gene expression patterns ordinarily found only in the germ line.

On the correlation vs. causation issue: The authors showed, using RNAi knockdowns, that the germ line-restricted genes were required for the longevity enhancement due to the mutation in daf-2 (worm insulin/IGF). There’s a bit of a wrinkle: in wildtype animals, blocking these same genes actually resulted in an increase in lifespan. How to explain that? The proffered rationale is that in the wildtype, germ line-restricted genes are only present in the germ line. Knocking them down has no effect on somatic tissue, but might reduce the activity of germ line cells; it’s been known for some time that ablating part of the gonad has life-extending consequences in wildtype animals.

The critical observation, in any case, is that the germ line genes are turned on in daf-2 mutants, and this activation is necessary in order for daf-2 mutation to extend lifespan.

Next questions, in rough order of difficulty:

  1. Does the soma-to-germ line transition occur in other long-lived mutants, or in calorie restricted animals?
  2. By what mechanisms are the germ line-restricted genes extending the somatic lifespan?
  3. Will this finding generalize to other metazoans?
  4. Do the germ line genes expressed in daf-2 soma contribute to germ line immortality?

ResearchBlogging.orgCurran, S., Wu, X., Riedel, C., & Ruvkun, G. (2009). A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants Nature DOI: 10.1038/nature08106