New Tributary to the River of Life

The cellular fountain of youth has another wellspring. In tomorrow's Science, biologists report the discovery of a second enzyme that can slow the aging of cells. The enzyme, called tankyrase, may prove useful for extending the lives of cultured cells grown to repair burned skin and other damaged tissue. Even more tantalizing, experts say, is that inhibitors of this new enzyme may be able to stop cancer in its tracks.

Before now, researchers knew about only one enzyme, called telomerase, that could delay aging. Located at the ends of chromosomes, telomeres typically shorten with each cell division, until the end of the chromosome becomes so frayed that the cell dies. Telomerase adds back the lost DNA and keeps cancer cells, for example, forever young.

To search for new enzymes that could repair telomeres, the researchers--Susan Smith, Titia de Lange, and their colleagues at Rockefeller University in New York City--used a biochemical screen to find substances that interact with TRF1, a human protein known to bind to telomeres. Once they found tankyrase, they noticed that a section of tankyrase resembles an unusual enzyme called poly(adenosine diphosphate-ribose) polymerase (PARP), which aids in DNA repair. The team went on to show that tankyrase, like PARP, decorates itself and target proteins with chains of a molecule called ADP-ribose. Their evidence suggests tankyrase also modifies TRF1, causing it to let go of the DNA and permitting telomerase to extend the telomeres. Thus tankyrase seems to help keep cancer cells immortal.

The discovery "could open up a whole new field," says Tomas Lindahl, a biochemist with the Imperial Cancer Research Fund in London. De Lange cautions that they still need to demonstrate that what they see in their test tube studies occurs in living cells. And without knowing tankyrase's exact function, it's "too early to tell whether [the enzyme] is a good target for drug discovery," cautions telomere expert Calvin Harley of Geron Corp. in Menlo Park, California.