Sci. Aging Knowl. Environ., 1 December 2004
Paying the Price
Long-lived worms can't compete
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2004/48/nf107
Like the "gift with purchase" at the makeup counter, long life isn't free. Worms with a life-extending mutation can't hold their own against normal worms, research now reveals. Some previous findings suggested that the animals endured without paying a penalty, but the new work challenges that notion.
Conventional evolutionary wisdom holds that long life comes at a cost, such as reduced reproduction, because organisms can't optimize every biological process simultaneously (see "Aging Research Grows Up"). Yet some studies suggest that animals can persist without paying a toll. Mice with a defect in the receptor protein that heads the insulin/insulin-like growth factor-1 signaling pathway live long, are fertile, and appear healthy (see "One for All"). And blocking production of the worm version of that protein, DAF-2, early in adulthood extends life without stemming procreation, according to work done by geneticist Andrew Dillin and colleagues while he was a postdoc at the University of California, San Francisco. Those findings suggested that animals can garner long life for free (see Sonntag and Ramsey Perspective). However, molecular geneticist Gordon Lithgow of the Buck Institute for Age Research in Novato, California, and colleagues found that numbers of a different long-lived worm dwindle when pitted against normal animals (see "Get Wild"). Now, Lithgow's team has investigated whether worms with crippled DAF-2 similarly go extinct when forced to compete.
To address the question, they put 50 eggs from long-lived worms with daf-2 mutations and 50 eggs from normal worms on a culture plate and allowed them to mature. Three days later--the first day that the self-fertilizing wrigglers laid eggs--the researchers selected 100 eggs at random. They repeated the process for multiple generations. The long-lived type produced about half as many eggs as did controls, and after four generations, no daf-2 animals remained. To assess whether that reproductive difference could explain why the long-lived animals disappeared, the researchers calculated the expected proportion of each line of worm in each generation based on reproduction rates. daf-2 worms ought to fade after seven generations, they concluded. Because the creatures disappeared sooner, they harbor other, as yet unidentified, weaknesses, says Lithgow. The team also scrutinized the original data from Dillin and colleagues on worms whose DAF-2 production had been blocked starting in early adulthood. Although the animals extruded approximately the same number of eggs as did normal worms, they laid fewer eggs on their first day of adulthood. Based on that difference, Lithgow and colleagues predict that those animals would vanish after about 40 generations if they were pitted against normal ones.
"[Lithgow's] done a nice job of analyzing our data and coming up with a subtle piece that says there could be a cost," says Dillin, now at the Salk Institute for Biological Studies in La Jolla, California. But no one knows whether animals with DAF-2 blocked in adulthood would lose out, he says. The work emphasizes that "you can't get something for nothing," says ecologist Marc Tatar of Brown University in Providence, Rhode Island. Researchers should take the findings as a warning when designing antiaging interventions, says Lithgow, and be prepared to seek the hidden costs of extra life.
December 1, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150