Youthful Restraint
Authors: Davenport R. John 
Published: August 2003

SINGAPORE
--Driving 70 kilometers per hour on the freeway annoys other motorists, but it adds to a car's life. Similarly, putting the brakes on cellular energy production helps animals persist, a hypothesis of aging posits. Research presented at the Asia Pacific Conference and Exhibition on Anti-Ageing Medicine 2002, held here from 23 to 26 June, suggests that restricting mileage on a biological energy generator early in life can prolong a worm's life. Some scientists say that the study throws a spanner in the hypothesis's works, but others argue that the worms aren't gaining meaningful life, they're just living in slow motion.

The rate-of-living hypothesis says that the higher an animal's metabolic rate, the shorter its life, because toxic byproducts build up (see
"The Two Faces of Oxygen"
). Several observations support the idea; for example, some mutations that reduce energy production let worms live longer, and keeping flies at low temperature, which slows chemical reactions, grants them extra time. As an antiaging strategy for humans, however, the idea holds little promise, because people wouldn't want to spend their extra years hibernating.

New results hint that
Caenorhabditis elegans
with reduced metabolism only during their youth reap life-extending benefits in adulthood. Ao-Lin "Allen" Hsu and colleagues at the University of California, San Francisco, used short pieces of RNA to turn off
C. elegans
genes one by one. To get the RNA molecules into the worms, the researchers grew the animals on petri plates, each coated with bacteria carrying RNA molecules that target a different gene. The worms gulped the bacteria, including the small RNA molecules. After 24 days, most control worms had died, but worms on some test plates survived. This method enabled the researchers to identify four genes that influence longevity, each of which produces a different component of protein machines that help turn food into energy. The worms carried lower concentrations of the high-energy molecule ATP than did controls, indicating that thwarting the genes slowed metabolism.

Then Hsu and colleagues probed whether the timing of gene inactivation influenced longevity. They grew one set of worms on bacteria with interfering RNA only after the animals had reached adulthood; they exposed another group to the engineered bacteria during larval stages and allowed the genes to turn back on once the worms had matured. Animals with the genes shut down during adulthood died when controls did, but those with genes turned off only as larvae kept wriggling. The results suggest that slowing metabolism during larval development dictates adult life-span, although the mechanism is unclear. Longevity didn't depend on the amount of time that energy production slowed, so the life-extending manipulation runs counter to the rate-of-living theory, the scientists reason.

"It is elegant genetic work," says evolutionary biologist Michael Rose of the University of California, Irvine. The tenacious worms, however, move, defecate, and reproduce more slowly than do normal worms, and he suggests that the animals are not acquiring quality time. Nevertheless, the study hints that slowing your engine while young can have far-reaching effects.

--R. John Davenport

Further Reading

Asia Pacific Conference and Exhibition on Anti-Ageing Medicine 2002
http://www.antiaging2002.org/index.shtml