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Seeking the fountain of youth in the cells of a worm

By Jesus Castillo

Scientists at the Salk Institute for Biological Studies are on a painstaking search to understand the processes within cells that cause cancer and that lead to diseases of aging. These modern-day Ponce de Leons are not searching the swamps of Florida. However, they are looking inside the cells of roundworms - C. elegans, to be precise. It turns out that the peculiar chromosome ends of C. elegans could have important implications for cancer treatment and aging research.

Though scientists officially issued the press release proclaiming some positive results from their work on March 11, Jan Karlseder, Ph.D., one of the scientists currently working on the project, said that the original discovery was made three years ago.

“Every time you discover something really novel, the discovery often takes a very short time,” Karlseder said. “But to show that you are actually correct and haven’t made an error, that takes a long time. Before you publish a new concept, you have to make damn sure that it wasn’t just an experimental error.”

Karlseder’s work focuses on the study of telomere structures, which serve as caps that protect both ends of a chromosome. Each time a cell divides, the telomeres get shorter and shorter. When telomeres become too short, chromosomes begin to accidentally fuse with each other and the cell eventually dies. This process is closely linked to aging.

The key feature of cancerous cells is just the opposite - they have mechanisms that elongate their telomeres indefinitely.

“Cancer cells are immortal cells,” Karlseder explained. “There are two ways in which they elongate their telomeres. One is through the release of an enzyme called telomerase.”

Telomerase is a reverse transcriptase which adds a DNA sequence to the end strands of a chromosome’s telomere segments.

“The other is a process called recombination,” said Karlseder, “in which a short telomere finds a long one and takes a piece of it to make itself longer.”

But applying a cancer cell’s methods to prolonging the lifespan of a normal cell remains an unrealistic possibility.

“Every time you mess with an aging pathway, you run the risk of activating a cancer pathway,” Karlseder said. “Aging and cancer are two flipsides of the same coin. It’s very difficult to divide the two pathways apart.”

As for treating cancer, scientists do not yet understand what regulates the telomerase and recombination pathways enough to learn how to suppress both of them. Here, the discovery of the roundworm’s distinctive telomere structures comes into play.

“What we found in the roundworm is that one side of the chromosome regulates the telomerase pathways and the other side seems to regulate this recombination pathway,” Karlseder said. “This allows us to look at those pathways completely independently of each other for the first time, and we might be able to find regulators.”

But despite three years of research, Salk scientists hesitate to make predictions about how much and how quickly the study of C. elegans will yield practical results that will advance cancer treatment and the fight against aging.

“Some people predicted 10 years ago that in 10 years we would solve the cancer problem, and they were completely wrong,” Karlseder said. “No biologist will give you an exact time, because it’s impossible to tell.”

As for the aging question, Karlseder said that today’s scientific community should concern itself not with finding the secret to immortality but rather a way to combat age-related diseases.

The place to look for those profound answers appears to be inside the wriggling bodies of some very unglamorous worms.