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Scientists Extend Life Of Human Cell

WEDNESDAY, JAN. 14, 1998

Striking new evidence that life span may be stretchable is coming from experiments in which human cells were engineered to stay young and vigorous far longer than usual, scientists reported Tuesday.

The researchers, from Texas and California, said the discovery offers a potential target for cancer therapy because one hallmark of tumors is that cells accumulate, somehow making themselves immortal and failing to die.

The experiments extended the cells’ life span by inserting a gene that makes an enzyme, telomerase, which prevents a natural erosional process that normally kills cells after they have divided 50 or 100 times.

“We have found that cellular aging can be bypassed,” said Dr. Jerry Shay, at the University of Texas Medical Center in Dallas. During the study, the cell’s lifetime was extended through at least 20 more cycles of cell division without obvious harm.

“The expression of telomerase in normal human cells should extend their lifespan indefinitely,” Shay added, and the cells that have been immortalized appear to be young and vigorous.

It has long been known that most normal cells - except those germline cells reserved for making sperm and eggs - have a finite lifetime, going into senescence and dying after a maximum number of division cycles.

More recent evidence shows this process is based, at least in part, on specialized bits of DNA, called telomeres, which sit at the ends of chromosomes. Telomeres may keep the DNA from disintegrating.

Research has also shown, however, that telomeres are vulnerable; each gets whittled away slightly in each round of cell division. After enough whittling, telomeres get so short they can’t function, the cell stops growing, and it dies. This process, senescence, is a possible explanation for aging.

Under special circumstances, however - as in cancer cells and in germline cells - telomeres are kept long and healthy by this special enzyme, telomerase. The gene that makes telomerase is naturally “on” in germline cells, and abnormally “on” in cancer cells. In both cases, the cells live longer.

The new experiments - by Shay in collaboration with Andrea Bodnar and her colleagues at Geron Corp., in Menlo Park, Calif. - offer strong support for the telomere/telomerase idea. The experiment was outlined in the journal Science.

Although the idea of extending the human life span with engineered telomerase genes is distant, scientists already are seeking ways to control telomerase to fight cancer. If the immortality of cancer cells can be erased, then the growth of tumors may be stopped.

xxxx TAKING STOCK The report is to be published in the journal Science on Friday. It was released prematurely on Tuesday by a Washington aging research organization, causing a dramatic rise in the stock price of Geron Corp., a California biotech research company that collaborated with the Texas researchers and which holds rights to some of the findings. Trading of Geron stock on the Nasdaq stock exchange was briefly halted after it soared 24 percent. After trading resumed, the stock continued to climb, closing the day at $14.375, up more than 43 percent. Nearly 4 million shares were traded. Its daily average is about 140,000.

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