Alzheimer's Disease

Life extension in humans is around the corner

Researchers at the University of Colorado at Boulder have found that microscopic worms called C. elegans can live longer despite cellular defects, a discovery that can provide scientists with a deeper understanding as to how the human body ages, and how genetic mutations that cause inherited diseases may be limited or reversed.

Washington, October 2 : Researchers at the University of Colorado at Boulder have found that microscopic worms called C. elegans can live longer despite cellular defects, a discovery that can provide scientists with a deeper understanding as to how the human body ages, and how genetic mutations that cause inherited diseases may be limited or reversed.

Shane Rea of CU-Boulder's Institute for Behavioral Genetics has revealed that during an experiment, his team manipulated the metabolic state of genetically engineered lab worms, and discovered a window of high-efficiency cellular processing that enabled the worms to slow their rate of aging.

He said that the findings of his team raised hopes that soon such gene therapies might be developed as reverse or lessen the effects of mitochondrial diseases, the largest family of human genetic diseases.

He further said that his study's results might also find applications in treating disease linked to mitochondrial dysfunction such as Huntington's, Parkinson's and Alzheimer's.

"We appear to have found a window where life is able to preserve itself even better than when operating in the absence of any cellular defects. It's a metabolic state where cells are probably getting close to the best they can be for long life and good health," said Rea.

During the study, the researchers used RNA interference (RNAi) technology to produce worms with varying levels of mitochondrial dysfunction. They wanted to determine 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.

It was found that long life occurred in worms only when energy production by their mitochondria was 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.

According to him, the study indicates that the worms' cells receive signals from their nuclei as DNA problems are sensed and not from their disrupted mitochondrial power sources, as previously thought.

Rea believes that the signal-sending nuclei order cells to shut down DNA replication, and allow them time to fix problems and create an environment that copes better with DNA damage and stress.

"It is only in this window that survival is enhanced. Once you move too far outside, then, like human cells, worm cells also die. 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," Rea said.

He and his colleagues are now planning to build on these findings with biochemistry and genetics to discover what controls this pro-longevity mode, and how humans can reduce oxidative stress that causes cellular damage.

"Life extension in humans is around the corner. There is no doubt about it," Rea said.

The study, co-authored by CU-Boulder worm researcher Thomas E. Johnson and the University of Rome's Natascia Ventura, has been published in the Public Library of Science journal PLoS Biology.

ANI