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The "longevity Gene ": Mass Media v. Scientific Writing"

STRUCTURE OF CDK2-CYCLIN A WITH PHA-404611(permission pending)

In recent years, researchers began to unlock the secret of some of the mechanisms that may prolong lives. One such mechanism is calorie restriction. By reducing the amount the food intake of animals such as worms, yeasts, and mice, researchers had increased their life spans significantly. How does dietary- restriction induced longevity work? What are the genes involved? Is there a gene that plays a key role for dietary restriction induced longevity? The following scientific article from Nature provides some insights into these questions.

Science Article from Nature: "PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans"

Contextual information: what prompted researchers to do the experiment

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A group of researchers from The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory investigated previous research on the aging process and found that the insulin/IGF-1 signaling pathway (IIS) is an important regulator for longevity in worms, flies and mice. They wanted to know if IIS also regulates diet-restriction-induced longevity. However, they learned from previous papers that the extended longevity of all known ISS mutants is completely dependent on a forkhead-like transcription factor called DAF-16 and DAF-16 is dispensable for diet-restriction-induced longevity. They also found out that smk-1 which regulates the longevity function of DAF-16 is essential for diet-restriction-induced longevity even though DAF-16 is not the key player.With this information, the group hypothesized that under conditions of low food intake, smk-1 could interact with forkhead-like transcription factors other than DAF-16.

Methodology: what methods researchers used to find out the fork-head like gene

Researchers systematically inactivated each of the fifteen forkhead-like genes found in the C.elegans genome to examine their function in dietary-restriction-induced longevity. They discovered that the RNAi of pha-4 completely suppressed the long lifespan of eat- 2 mutants. They also designed a non-genetic model experiment to see if the absence of pha-4 suppressed dietary restriction in worms. By controlling the bacteria concentration fed to worms in culture, they noticed that wild type worms were short-lived under high and extremely low bacteria concentrations but live significantly longer under conditions of optimal food intake. In contrast, the pha-4 mutants were all short-lived under different bacteria concentrations.

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Since pha-4 played an important role during embryo development in the morphogenesis of the pharynx, the group tested whether the early development function of pha-4 can be separated from its role in diet restriction during adulthood by only deactivating pha-4 genes long after the early development. The diet-restriction-induced longevity was suppressed and they concluded that the role of pha-4 indevelopment and longevity is separable. By using the semi-quantitative PCR with reverse transcription and quantitative real-time RT_PCR, researchers found that expression of pha-4 was increased by more than 80% under conditions of low food intake.

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Moreover, the group over-expressed pha-4 in wild type worms under normal feeding conditions to see if they could extend longevity. The fount out that the longevity of the wild type animals only increased slightly. However, when they over-expressed pha-4 in DAF-16 mutant strain, the life span of the mutants were significantly increased. They provided two explanations for this result. One is the competition of pha-4 and DAF-16 and the other is the partially redundant role of pha-4 and DAF-16.

The author from the USA TODAY started the article by asserting that “Scientist have identified the first gene essential to extending the lives of animals on low-calorie diets, raising the prospects of longevity pill.” Then the author continued to explain the term “caloric restriction” and its life-extension potential. The author spent another paragraph to talk about the difficulty of practicing dietary restriction and how the discovery of the PHA-4 gene brought hope to people who would love to “ skip starvation and still live longer.” After quoting other biologists for their response to this discovery, the author ended the article by noting that “If similar experiments work in mice, a final step would be to try boosting the activity of the mammalian version of the gene, called Foxa1, in people”.

After reading the USA TODAY article, an inquisitive reader might wonder: " How does this discovery connect to previous discoveries? How did the researchers find out PHA-4 gene? Does PHA-4 gene have other functions? " etc.

The author did mention in one paragraph that though other genes have been found to be important for diet restriction but the “the presence or absence of PHA-4 in worms was the make-or-break factor.” However, in the original paper from Nature, researchers stated that smk-1 was also essential for diet-restriction-induced longevity.

The USA TODAY article also omitted a lot of other experiments done on PHA-4 such as the experiments designed to understand whether the early development function of pha-4 can be separated from its role in diet restriction during adulthood or whether overexpressing PHA-4 in worms under normal feeding conditions can prolong their life span.

Compared with scientific article from Nature, The USA TODAY article neither conveyed any contextual information nor explained the methods and reasoning involved. Instead, the USA TODAY article focused on the potential implications of the discovery of the PHA-4 gene.

References

1) Siler H. Panowski1, Suzanne Wolff1, Hugo Aguilaniu1,2, Jenni Durieux1 & Andrew Dillin1,2007, Nature 47, 550-555, "PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans",<http://www.nature.com/nature/journal/v447/n7144/full/nature05837.html> accessed 2008, Sep 16.

2) Dan Vergano, 2007, May 3, "Longevity gene linked to low-calorie diets", USA TODAY, <http://www.usatoday.com/news/health/2007-05-02-longevity-gene_n.htm> accessed 2008, Sep 16.

3)Kua, E, Reder M, and Grossel MJ. 2004. Science in the news: A study of reporting genomics. Public Understanding of Science 13(309-322). . Accessed 2008 Setp. 15.

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