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CU-Boulder worm study sheds light on human aging, inherited diseases
Date:10/1/2007

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For nearly a decade, scientists have experimented with RNA interference, or RNAi, technology to reduce gene expression with an eye toward learning more about human disease, Rea said. The technique is an effective way to silence specific pieces of DNA -- the genetic material that makes up the basic building blocks of life -- in living organisms, he said.

Rea and his team used RNAi to produce worms with varying levels of mitochondrial dysfunction with the hope of solving a mystery that has baffled scientists for years. They wanted to know why the genetically engineered worms, known as "Mit mutants," lived longer despite cellular defects that would have caused similarly damaged human cells to become diseased or die off in the lab.

The team concluded that long life occurs in worms only when energy production by their mitochondria is reduced to very discrete levels. "By tweaking cells into that tight little window of high efficiency, we may be able to increase the life span and health span of both sick and healthy people," Rea said.

The research suggests that the worms' cells receive signals from their nuclei as DNA problems are sensed and not, as previously thought, from their disrupted mitochondrial power sources. The signal-sending nuclei order cells to shut down DNA replication, allowing them time to fix problems and create an environment that copes better with DNA damage and stress, researchers believe.

"It is only in this window that survival is enhanced. Once you move too far outside, then, like human cells, worm cells also die," Rea said. "We think there's a whole shift in the metabolism and the way it protects DNA. We show very clearly in our work that long life is intimately linked with the control of cell division."

The process appears to mimic the "hunker down" survival mode that stressed animals adopt during times of famine and danger. When conditions improve, the animals procreate again to en
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Contact: Shane Rea
srea@colorado.edu
303-492-2505
University of Colorado at Boulder
Source:Eurekalert

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