Worms Help Researchers with the Mystery of Aging in Humans

From the University of Colorado at Boulder comes research that has given them some insight into one day being able to limit or even reverse genetic mutations that cause many inherited diseases and the answer came from tiny microscopic worms that are used for scientific research.

They had known that the worms are living longer lives in spite of having cellular defects. When the researchers manipulated the metabolic state of the lab worms, called C. elegans, who had been genetically engineered, they found a window of high efficiency cellular processing that gave the worms the ability to slow down the rate at which they were aging.

The researchers hope that one day their discovery might lead to the creation of gene therapies that would reverse or lessen the effects of the largest group of genetic disease in humans called mitochondrial diseases. These are the diseases that affect the mitochondria, which is the power source in the cells, such as Huntington's, Parkinson's and Alzheimer's.

For close to ten years, there have been experiments done with RNA interface, RNAi, technology for the purpose of reducing the gene expression for the purpose of getting a better understanding on human disease. This technique is a very effective way to silence specific DNA in living organisms.

The team used the RNAi method to produce worms that had different levels of mitochondrial dysfunction. Their hope was that they would be able to solve a mystery that had been puzzling researchers for years. The wanted to see why worms that are called Mit mutants live longer in spite of having cellular defects that would have killed off similar human cells.

What they found was a window in time where life has the ability ro preserve itself better than it can when it is without any cellular defects. It is a metabolic state in which the cells are thought to being the best they can be for long life as well as good health.

They came to the conclusion that long life happens in the worms only when the energy that is produced by the mitochondria is reduces to very discrete levels. They figure that if they can tweak the cells into that very tight little window in time when they are highly efficient, they may be able to increase the life span and health span in both the sick and the healthy.

It seems that the worm's cells get signals from their nuclei as it senses problems with DNA. Previously, it was thought that the signals came from their disrupted mitochondrial power sources. The signals that the nuclei send out order the DNA to stop replicating, giving them the time they need to fix the problem and create an environment in which they can better cope with the damage to the DNA and the resulting stress.

It is only in this window in time when there is the chance of survival. If you move too far outside, then the worm cells will die, just like the human ones. They think that what happens is a shift in the metabolism in the way it protects the DNA and that long life is linked to controlling cell division.

They equate this system to the hunker down mode that animals in stress, such as during the periods of famine and danger when they basically shut down their whole system. Then when the conditions improve, they procreate again to be able to ensure that the species survives.

They hope to be able to build upon the finding with further biochemistry and genetics testing so that they can determine exactly what control the pro longevity mode and how a human might be able to reduce the oxidative stress that is the cause of cell damage.

The lead study author is Shane Rea of CU-Boulder's Institute for Behavioral Genetics and the co authors are
Professor Thomas E. Johnson and the University of Rome's Natascia Ventura.

The project was funded by grants from the National Institutes of Health and other agencies.

Source: University of Colorado http://www.colorado.edu/