How Long Do I Have, Doc?: Protein foretells life span of genetically identical nematodes

Star Trek fans know that the unnamed crewman will usually die before the episode's first commercial. In real life, however, even doctors can't make such accurate predictions about a person's remaining time. But researchers might achieve the feat for nematodes, according to a new study suggesting that a worm's output of a stress-fighting protein forecasts its life span. The work might eventually allow scientists to devise tests to estimate human longevity.

It might seem obvious that a marathon runner will outlast a hard-partying rock star, but chance plays a huge role in longevity, complicating life-span predictions. For instance, among genetically identical nematodes, some worms endure up to 50 times longer than others. To gauge an individual's survival prospects, researchers have sought biomarkers, or indicators of aging rate (see "Will We Find Biomarkers of Aging?"). However, years of searching haven't turned up any reliable measures. Geneticist Thomas Johnson of the University of Colorado, Boulder, and colleagues decided to investigate whether quantities of heat shock proteins--molecules that shelter other proteins when temperatures rise--portend persistence. Long-lived mutant worms pump out extra quantities of the proteins, suggesting that they help prolong survival.

To minimize the inherited and environmental differences that might alter aging, the researchers reared genetically identical worms in standard cultures. The team wanted to gauge production of a particular heat shock protein, so they modified the creatures to carry a DNA snippet containing the on-off switch for the protein hooked to a gene that encodes a glowing molecule. The more heat shock protein the worms crafted, the brighter they shone. Measurements showed that the worms that were the gaudiest on the first day of adulthood ended up living the longest. For example, nematodes that fashioned the most heat shock protein could expect to live another 15 days, but those making the smallest quantities could count on only seven more. That finding suggests that the amount of heat shock protein the worms manufacture early in adult life foretells their longevity. The researchers don't think that the heat shock protein itself stretches life, says Johnson, because cranking up its production adds only about a day to a worm's existence. Instead, the protein reflects a worm's health and ability to endure adversity, he says. Some worms last longer because, by chance, they are tougher.

The work is significant because it probes "a question that a lot of other people are getting interested in: What determines the differences between individuals?" says molecular geneticist Gordon Lithgow of the Buck Institute for Age Research in Novato, California. Although the results are preliminary, they could one day help researchers identify human biomarkers, he says. One mystery is what causes the life-span inequalities, says Johnson. When the scientists tested the worms' offspring, they found that the differences in heat shock protein output weren't passed on. That finding indicates that chance events early in a worm's life, rather than inherited disparities in quantities of the proteins, help determine future survival. How these events translate into longevity isn't clear, Johnson says. Further investigation might reveal what accounts for some worms' healthy glow.