Worm study challenges prevailing theory of aging

Washington, July 25 : A new study of worms suggests that aging may be part of the genetic plan, not the result of wear-and-tear on the body.

The finding contradicts a commonly held theory and gives hope that science eventually may find a way to stop or reverse the aging process.

"We were really surprised," said Stuart Kim, PhD, professor of developmental biology and of genetics, who is the senior author of the research.

Kim and colleagues examined the regulation of aging in C. elegans, a millimeter-long nematode worm whose simple body and small number of genes make it a useful tool for biologists.

The worms age rapidly: their maximum life span is about two weeks.

Comparing young worms to old worms, researchers discovered age-related shifts in levels of three transcription factors, the molecular switches that turn genes on and off.

These shifts trigger genetic pathways that transform young worms into geezers.

"Our data just didn't fit the current model of damage accumulation, and so we had to consider the alternative model of developmental drift," Kim said.

For the study, researchers used microarrays - silicon chips that detect changes in gene expression - to hunt for genes that were turned on differently in young and old worms.

They found hundreds of age-regulated genes switched on and off by a single transcription factor called elt-3, which becomes more abundant with age. Two other transcription factors that regulate elt-3 also changed with age.

To see whether these signal molecules were part of a wear-and-tear aging mechanism, the researchers exposed worms to stresses thought to cause aging, such as heat, free-radical oxidation, radiation and disease.

However, none of the stressors affected the genes that make the worms get old.

So it looked as though worm aging wasn't a storm of chemical damage.

Instead, Kim said, key regulatory pathways optimized for youth have drifted off track in older animals.

Natural selection can't fix problems that arise late in the animals' life spans, so the genetic pathways for aging become entrenched by mistake.

Kim's team refers to this slide as "developmental drift."

"We found a normal developmental program that works in young animals, but becomes unbalanced as the worm gets older. It accounts for the lion's share of molecular differences between young and old worms," he said.

Kim can't say for sure whether the same process of drift happens in humans, but said scientists can begin searching for this new aging mechanism now that it has been discovered in a model organism.

And he said developmental drift makes a lot of sense as a reason why creatures get old.

The study will appear in the July 24 issue of the journal Cell.

ANI