An Attack on Aging

By Christine Gorman

It sounds like something from the Twilight Zone or The X-Files. Working to unlock the secrets of life and death, the heroes in this tale develop a powerful enzyme with the potential to rejuvenate the human body's aging tissues. But this is no sci-fi fantasy. It is an experiment sponsored by the National Institute on Aging and the Geron biotech company of Menlo Park, Calif., and a report on the research appeared in last week's issue of the prestigious journal Science. Not surprisingly, when word of the study first hit Wall Street, Geron's share price jumped 40%, to close at 14 3/8, and press bulletins heralded the newly discovered "fountain of youth."

But don't cancel your life-insurance policy just yet. While the new work suggests a way to prolong life, scientists are a long way from making it a reality--and it may be too risky to be useful. The study proves something that researchers already suspected: each of the 1 trillion cells in the human body contains its own biological clock, which tells the cell when to stop growing and start dying. It might be possible to stop that clock. But would it be prudent? Many biologists think the cell's planned obsolescence is an all-important safeguard against the development of cancer.

Scientists have long theorized that a cell's biological clock lies in its telomeres, little bits of DNA that coat the tips of the chromosomes and, much like the plastic cuffs on shoelaces, prevent the strands from unraveling. Every time a cell splits in two, the telomeres shorten, until finally, after about 40 to 90 divisions, they are reduced to stubs. Because any further divisions would fray the chromosomes, the cells settle into a twilight stage and eventually die. Only an enzyme called telomerase, first discovered in 1984, can repair the damaged telomeres. However, most human cells, with the exception of reproductive cells, stop making the compound during fetal development.

Fast-forward to last summer, when three different groups of researchers cloned a gene that makes it possible to reactivate telomerase in human-tissue samples. The race was on to see who could make cells live longer than they normally do. Researchers from Geron and the University of Texas Southwestern Medical Center at Dallas infected normal cells with a virus that had been genetically engineered to switch telomerase on. In every case the cells' telomeres lengthened instead of shortening, while the cells stayed healthy and continued to divide. "When we submitted the paper, we were at 20 generations past the usual limit," says Jerry Shay, a cell biologist at Southwestern. "Now we're at 40, with no end in sight."

There's quite a difference, however, between getting a few cells to live longer and increasing even a single human life-span. Doctors are already familiar with cells that live indefinitely: they're called cancer cells. Apparently one reason tumors expand aggressively is that their cells are full of telomerase. So, unless scientists carefully control cell division, activating human telomerase may not prolong life but just create cancers.

Even if the fountain-of-youth business doesn't pan out, however, knowing how to activate telomerase may help Geron discover how to deactivate the compound in cancer cells. That could lead to an effective anticancer drug. It wouldn't be the key to eternal life, but it might be a valuable weapon against one of life's worst scourges.