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NMR spectroscopy has uncovered the secret of eternal youth and the ability to attract sexual partners almost on a chemical whim. The results suggest that these behaviours both hinge on a novel group of pheromones. Unfortunately, before you head for the local pharmacy to stock up, these are pheromones of the lab-technician's favourite worm, the millimetre-long soil nematode Caenorhabditis elegans, so they are unfortunately very unlikely to have any effect on human behaviour or longevity. Writing in Nature, Arthur Edison of the University of Florida, Frank Schroeder of Cornell University, Jagan Srinivasan, of California Institute of Technology and their colleagues, and co-workers at the US Department of Agriculture (USDA), describe how they used a highly sensitive NMR probe to identify tiny amounts of a novel group of pheromones from C elegans, which they say act as the organism's mating signal and are also involved in effectively slowing the aging process by triggering hibernation in this species. The soil-dwelling nematode is commonly used in molecular biology laboratories as a model organism for various human conditions, including aging research partly because, despite superficial differences between ourselves and the worm, we do share much underlying biology. In one sense, the discovery of the new compounds, known as ascarosides, ties together at the molecular level two disparate life processes - sex and death. Schroeder and colleagues have found that at low levels, the pheromone signal, induces the male C. elegans to mate. However, as the nematode population grows and food becomes in increasingly short supply, the same chemical signal increases in concentration and becomes, not a molecular mating call, but a cue for the nematode to hibernate. "Even though it's the same compounds, they affect different behaviours," adds Edison's post-doctoral associate on the team Fatma Kaplan, "It's two different life traits converging." Although the work is very unlikely to lead to any anti-aging or sex-boosting products for humans it does provide new insights into the workings of the worm that may ultimately wriggle into human biomedical research or even agriculture. Amazingly, about four out of every five animals on the planet is the same type of organism as C. elegans - a nematode. Although this species is harmless to humans, other nematodes destroy crops or act as parasites, the large human intestinal parasite Ascaris lumbricoides, for instance, is also a nematode. The latest discovery about C elegans may one day be used to control more harmful worms that destroy crops and provide clues for scientists studying similar parasitic worms, explains Edison. Previously, Caltech's Paul Sternberg discovered that male C. elegans were attracted to a signal produced by the "female" (hermaphrodite form) of the species, but in 2002, the scientists were unable to identify its chemical nature. Ironically, this tiny nematode worm is one of the best-studied organisms on earth, Edison says. "The entire cell lineage of the animal is known from fertilized egg to adult animal. Every single cell division has been mapped out. But until now, its small-molecule signalling has been poorly understood. We wanted to understand how C. elegans talk to each other." The team isolated the signalling molecules secreted by the hermaphrodite form and tested them on the males. Initial tests proved the males were attracted to the secretions when the hermaphrodites were fertile. They then used NMR with a University of Florida and National High Magnetic Field Laboratory-developed NMR probe together with mass spectrometry to test the extremely small quantities of signalling molecules and to isolate the active chemicals, of which there are several, in the hermaphrodite secretions. They found that the individual chemicals have little or no effect on the worm, but work together with strong synergism to attract male worms. The collaboration with Cornell's Frank Schroeder is what led to the researcher's most significant finding, Edison says. Schroeder had recently discovered the so-called dauer pheromone. These compounds signal to the worms to enter a hibernation phase when the food supply becomes unbearably low. The collaborators determined that Schroeder's hibernation pheromone and the Florida-discovered mating pheromone were almost identical. Further tests in the worms revealed that the same pheromones involved in mating could certainly act as a dauer pheromone if they were at high enough concentrations. "It's like a bell-shaped curve," Edison explains "If the pheromone level is too low, it doesn't work. If you add more, you get a nice mating response. If it gets too high, the mating response stops and they go into hibernation mode." Piali Sengupta of Brandeis University agrees that the finding is rather significant. It also makes biological sense that one pheromone should do both jobs, since there is little point in frequent mating if there will be little food for the offspring, and if there is no chance of mating, then the worms might as well sleep. "Researchers have been trying to find C. elegans mating pheromones for a long time," he says, "This discovery opens up the field. This is just the beginning. There is going to be a lot more research coming out related to this." Related links: The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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 Schroeder and Edison
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