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Enzyme treatment could lengthen cell life

PALO ALTO, Calif., Nov. 18 (UPI) -- Scientists reported Monday they might have found a new way to extend a cell's lifespan -- by using ordinary biochemicals to elongate its chromosomes.

Although it is too early to say whether this might help reverse human aging, experts think the findings could help treat cancers that fail to die or provide organs to the hundreds of thousands of patients awaiting transplants worldwide annually.

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"If you can make cells live longer in a test tube, there's also the possibility of growing tissue for transplantation. That could also get away from the problems around stem cell research," senior researcher Eric Kool, a biological chemist at Stanford University, told United Press International. "Right now it's only a dream, but I actually don't think we're that far away."

Each time a cell replicates its DNA, each chromosome loses a few of the building blocks, known as bases, from its ends. To preserve this genetic information, an enzyme known as telomerase adds thousands of copies of a six-base-long sequence onto each telomere, or chromosome end.

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Most cells stop making telomerase early in development. Telomeres therefore shrink with age, dictating the maximum number of times a cell can divide.

"Human telomeres in a new born infant are roughly 15,000 bases long. When they reach 3,000 or 5,000 bases, that's when cells switch off and die," Kool said. "Depending on the kind of cells, some might divide once a day, while some might divide once every few months."

Telomerase switches back on in cancer cells, making them immortal, one reason why they are so deadly and so hard to kill. Knowing more about telomeres therefore could help tackle cancer as well as aging. "In the long run, we hope it's possible to make telomeres longer in living cells and thus make the cells live longer," Kool said.

Little is known about how telomeres fold or form because it is difficult extracting high levels of functional purified telomerase from cells. Kool and his team have now avoided this problem altogether by creating a telomerase mimic. As they describe in this week's Proceedings of the National Academy of Sciences, they already have used their system in test tubes to elongate chromosomes extracted from human kidney cells.

First, the researches bind a tiny circle of DNA onto the ends of chromosomes. This circle contains the code for the six-base sequence making up telomeres. Then, the scientists expose the chromosomes to a readily available DNA duplicating enzyme known as DNA polymerase. The biochemical uses the DNA circle as a template to manufacture thousands of copies of the six-base sequence.

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For reasons currently unclear, this new system builds telomeres at least 10 times faster than telomerase does. So far the investigators are routinely elongating telomeres by 15,000 bases. They are now testing their technique on human bone marrow in test tubes to see whether it works in cells.

Biochemist David Corey of the University of Texas in Dallas found the work exciting.

"I'd love to collaborate with Dr. Kool on it to try and make the technique work inside cells. It'd be a rewarding challenge," he said. "Increasing the lifetime of cells would have many therapeutic applications, particularly in techniques that require stem cells to be grown for transplantation. This may also be a first step towards reversal of aging at the level of a whole organism or organ, but it is too early to do more than speculate."

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(Reported by Charles Q. Choi, UPI Science News, in New York)

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