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Yeast Offers Insight Into Aging and Cancer

Older cells make more genetic mistakes, study finds

THURSDAY, Sept. 25, 2003 (HealthDayNews) --Yeast cells start making a lot of genetic mistakes as they reproduce in their old age, a finding that may help explain why the incidence of cancer in humans increases with age.

It might also someday lead to better ways of cancer prevention.

It is well known that "old age is the most powerful carcinogen," with nearly 80 percent of cancers diagnosed after age 55, and researchers have looked for molecular reasons why that is so, says study author Daniel E. Gottschling, a scientist with the Fred Hutchinson Cancer Research Center in Seattle. His report appears in the Sept. 26 issue of Science. The new observation "smells a lot like what happens in humans," he adds.

While yeast cells are a lot simpler than humans, they follow the same basic principles of reproduction, with cells dividing to produce new generations of cells that keep the organism going.

Like humans, yeast cells have a limited life span. Their life span of 30 or 35 generations of division is played out in about five days. What happens to yeast cells is the daughter cells they generate in their later years begin to have more and defects in their chromosomes, the bodies that carry genes.

That genetic instability could erode the built-in mechanisms for controlling cell growth, allowing the unlimited proliferation that is cancer, Gottschling explains.

"We've never been able to see a phenomenon in which chromosomal integrity starts breaking down with age," he says. "It happens as if a switch is thrown, like something suddenly breaking down in your car."

It is a huge step from yeast to humans, Gottschling acknowledges, but the basic principles of cellular reproduction are the same for both. In humans, reproduction happens as stem lines for various tissues keep reproducing. The thought is that older human stem cells start making the same kind of mistakes as seen in yeast.

Because of human complexity, detecting that process in our cells will be much more difficult, says David A. Sinclair, an assistant professor of pathology at Harvard Medical School, who wrote an accompanying editorial. Working with yeast "could potentially make possible rapid progress in understanding what happens in aging cells," he says.

One interesting aspect of the study is that the genetic damage occurs in daughter cells, not in the older reproducing cells, Sinclair says. "Perhaps old cells accumulate damaged proteins," he says. "Many studies have suggested that damaged proteins are the cause of aging. This study could help validate that theory."

Because yeast cells reproduce rapidly, with a new generation every two hours, the study led to sleepless nights for Michael McMurray, the graduate student who made the observations. He started with 40 "mother" yeast cell lines grown in 20 Petri dishes.

These were special yeast cells, engineered to change color when genetic instability appeared. Several strains of yeast were studied and McMurray's through-the-night observations showed the color changes appeared in every one of them at about the 25th cycle, which is late middle age for a yeast cell.

"Right now we're working like crazy to figure out how this happens, Gottschling says. "What causes the breakdown? Once we understand a little bit about the process and how genes respond, we can think about making the leap to humans."

More information

An overview of what is being done to explore the role of aging in human cancer is offered by the National Cancer Institute. Go to the American Cancer Society to learn about early detection and prevention.

SOURCES: Daniel E. Gottschling, Ph.D., scientist, Fred Hutchinson Cancer Research Center Basic Sciences Division, Seattle; David A. Sinclair, assistant professor, pathology, Harvard Medical School, Boston; Sept. 26, 2003, Science
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