Study questions life extension mechanism in roundworms

(Phys.org)—It's strange to think that there was a time when molecular cell biology was considered by professionals of other scientific specialties as disreputable or laughable. But the motivation for much cellular biology research around the mid-20th century was the search for the mechanisms of aging and the means to alter them—for centuries, people have been understandably frustrated by the indignities of aging and the burden of mortality, and the search for a "fountain of youth" was universally regarded as a foolish and hopeless endeavor.

It was only across decades of slow progress that the field was established as a fundamental source of health and medical science. (Watson and Crick certainly gave the field a boost with the discovery of DNA in 1953.) Now the discipline has exerted a sweeping and transformative effect across multiple fields including agriculture, food production and safety, pharmaceutical science, toxicology, human fertility, and biotechnology.

The mechanisms of cellular aging and longevity are slowly clarifying, and one of the avenues of interest is the distinction between germ cells and somatic cells in multicellular organisms. Germ cells give rise to gametes in sexually reproductive organisms. They are the only kind of cells that divide by meiosis as well as mitosis and are often called "immortal" because they are capable of generating entire new organisms across generations, while normal somatic cells differentiate into other cell types and are mortal, senescing and dying each generation.

Some researchers hope to capture germ cell programming and apply it to the somatic cells to prolong lifespan or even prevent death at the cellular level, and scientists seek examples of this dynamic in existing life forms. A study of daf-2 mutant Caenorhabditis elegans worms in 2009 suggested that they experience longer lifespans due to germ cell factors in their somatic cells. However, a new study questioning that result has found exactly the opposite: that expression of certain germ-line factors in the worms' somatic cells is actually detrimental to their health and results in a reduction of lifespan.

In the current study, published in the Proceedings of the National Academy of Sciences, researchers expressed puzzlement at the findings of the 2009 study. They write, "In our reevaluation of the Curran et al. findings, we took precautions to control for genetic background effects, which have been shown to influence lifespan, and we addressed key questions using multiple approaches... We found that daf-2 mutants do not detectably express germ-line proteins or transcripts in their somatic cells." They also note that lifespan analyses revealed that the worms don't use P granules or a particular master germ-line chromatin regulator to extend their lifespans.

The paper draws the obvious conclusion that the factors and molecular mechanisms responsible for germ-line immortality are not yet clearly understood. They write, "Future research will likely reveal how germ-line proteins influence these unique characteristics at the transcriptome and proteome levels. As the functions of various germ-line factors become clearer, a better understanding of the effects of misexpressing those factors in the soma will become clearer, as well."

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