Pinkston-Gosse and Kenyon follow a C. elegans-ortholog of FOXO transcription factors, DAF-16, to phenotypes of manipulated lifespans and cancer susceptability. The pathway stems from the respective ortholog of insulin/insulin-like growth factor 1 (IGF-1) receptors, and FOXO transcription factors turn on genes involved in p53-dependent apoptosis, cell cycle arrest, and cellular stress resistance.
So, when DAF-16 is turned off in C. elegans, some genes stop being expressed, and tissues become less stable. That this entire biochemical pathway is conserved, from worms to mammals, is of central importance, and helps to explain the oft-observed correlation between age and incidence rates of cancer.
Pinkston-Gosse and Kenyon took these findings a step further, identifying 29 DAF-16/FOXO-regulated genes that act in the insulin/IGF-1 pathway to influence C. elegans tumor growth, using siRNA’s. Some of these genes are required for the entire effect of this pathway, but none appear to be required for the entire effect on cell division. This suggested to Pinkston-Gosse and Kenyon that these 29 gene products act in a synergistic or cumulative manner, each contributing some capacity to tumor suppression and/or longevity.
The FOXO/DAF-16 pathway is not the only connection between aging and cancer, however. Telomerase is another strong candidate. Are they connected? Probably, at least indirectly.
Brunet A. Aging and cancer: killing two birds with one worm. Nature Genetics 39:1306-1307 (2007) doi:10.1038/ng1107-1306
Pinkston-Gosse J, Kenyon C. DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans. Nature Genetics 39:1403-1409 (2007) doi:10.1038/ng.2007.1
Recently we wrote an article about widespread cell culture contamination and how to detect it. This follow-up article will provide practical tips on avoiding cross-contamination in the first place. Be Cautious While Working The first way of cross-contaminating cultures is by accidentally mixing two cultures together, which may lead to an unintended co-culture or the displacement […]
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