Sci. Aging Knowl. Environ., 1 September 2004
Hastening Death to Delay Aging
New approach speeds hunt for manipulations that retard fly decrepitude
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2004/35/nf81
To build a strong gymnastics squad, coaches select future superstars at a young age. Gerontologists also want to identify animals with exceptional potential, but they typically must wait until animals are old. Assessing whether genetic changes or experimental treatments prolong life means waiting for animals to die. A new strategy promises to accelerate the search by killing adolescent flies that are unlikely to live a long time. The approach might help researchers identify drugs that enhance longevity, although some scientists aren't sure whether the tactic will illuminate all aspects of aging.
Life span is the gold standard for longevity research. For organisms that don't live particularly long, such as nematodes and yeast, researchers can measure mortality in days or weeks. But experiments on other organisms are not as quick. Fruit flies survive about 3 months, for instance, and researchers must breed and track hundreds of animals to get the best data, which means considerable time and labor. Bauer and colleagues wanted to expedite the process.
Researchers had previously identified fly genes whose activity increases with age (see Tower Perspective). The authors of the new work reasoned that such genes might help key in on flies that age more slowly than normal without waiting until the end of the insects' lives. The team engineered a strain that generates a toxin when one of these biomarker genes cranks on. The scientists reckoned that the gene would switch on earlier in short-lived flies than in long-lived ones, and the short-lived insects would perish sooner. By timing the experiment carefully, they hoped to pick out long-lived animals before the critters also succumbed to the toxin.
To prove the utility of the approach, the researchers raised the engineered flies under conditions previously shown to slow aging--housing the animals at low temperature or feeding them reduced-calorie diets, for instance. In both cases, treated flies succumbed to the toxin later than did untreated ones. Similarly, two life-extending mutations and two longevity-enhancing compounds forestalled the death of toxin-bearing flies. The system allowed the researchers to discriminate between long-lived and short-lived flies in about 20 days rather than the usual 80.
"It's quite clever," says geneticist Trudy Mackay of North Carolina State University in Raleigh. "I think the major impact will be [on] drug screening."
However, the approach could be limited, cautions physiologist Arlan Richardson of the University of Texas Health Science Center in San Antonio. "You might have something that affects life span but doesn't work through this [biomarker] gene." Whether the method will improve mammalian studies is uncertain. Richardson doubts that the activity of any single mammalian gene reflects aging well enough to devise a similar strategy in such creatures: "I'm surprised it works so well in flies." But the technique might prove useful in analyzing deterioration in particular tissues or cell types, he says. If the approach fulfills its promise, it might help researchers more quickly assemble genes and chemicals that can compete against aging.
September 1, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150