It may not sound as appetizing as aquavit, but telomerase--an enzyme discovered only a decade ago in a single-celled protozoan--may well be the elixir of youth. This chemical acts in immortal cancer cells, sperm and ovum to repair telomeres, the strands of DNA that tie up the ends of chromosomes. And now it seems that activating telomerase in sundry other cells grants them a longer lease on life as well.

The finding, which was published in the January 16 issue of Science, finally proves what was a highly controversial model linking telomeres to cellular aging. More important, it opens up new avenues for research into diseases that occur when cells grow old, including macular degeneration in the eye and atherosclerosis, and those that arise when cells don't age at all, such as cancer.

The connection between telomeres and aging first emerged in 1986, when Howard Cooke of the Medical Research Council in Edinburgh noticed that the telomeres in reproductive cells were longer than those in shorter-lived somatic cells--the sort found in skin, muscle and nerve tissues. Knowing that telomeres shortened each time a cell divided, he speculated that somatic cells might not make telomerase. If somatic cells could not repair telomeres, he reasoned, their telomeres would continually shrink.

In addition, Cooke suggested that ever-shortening telomeres, like sands passing through an hourglass, might count out a cell's days. After a certain number of cell divisions, the telomeres would be so short as to somehow prevent the cell from further proliferation--putting it in a state called senescence. In other words, he proposed that telomere length offered a clock for telling a cell's longevity.

Image: SOUTHWESTERN MEDICAL CENTER LIVING PROOF. Cells treated to produce active telomerase continue to divide vigorously (bottom), whereas normal cells of the same age have lost their vigor (top).

The idea got a lot of attention--and attacks. Cooke himself wrote a paper in 1990 showing that mice having extraordinarily long telomeres did not live for an extraordinarily long time. And last year, M. A. Blasco of Cold Spring Harbor Laboratory discovered that even when mice were genetically engineered so that they could not manufacture telomerase, the animals still, on occasion, developed malignancies. Either some other mechanism had protected the telomeres in these murine tumor cells against erosion or shortened telomeres did not suppress tumor growth in mice as it was suspected they did in humans.

Now, it is clear the latter is likely the case. In a salvo of papers published over the past few months, researchers have shown that the telomerase gene can be activated in human cells--and that it does extend cell life. The initial development was a report in the August 15, 1997, issue of Science that a group headed by Nobelist Thomas Cech of the University of Colorado at Boulder and colleagues at Geron Corporation, a biotechnology company specializing in aging research in Menlo Park, Calif., had isolated the human gene for a catalytic protein called telomerase reverse transcriptase (hTRT).

Although the gene for telomerase is present in all cells, hTRT is present only in immortal cells, where it serves to fuse the repeating sequences of DNA to the chromosomes, thereby lengthening the telomeres. Proof that introduction of the hTRT gene into mortal cells would cause them to produce active telomerase was offered in the December 1, 1997, issue of Nature Genetics by the Geron group, this time in a collaboration with researchers from the University of Texas Southwestern Medical Center in Dallas.

But does lengthening the telomeres actually prolong the life of human cells? Groups from Southwestern Medical Center and Geron proved just that in the recent Science article. By introducing the hTRT gene, they caused three different kinds of cells--retinal pigment epithelial cells, foreskin fibroblasts and vascular endothelial cells--to resume telomerase activity.

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