The Secret Lives of Telomerase

Telomerase has long been credited with keeping chromosomes from crumbling, a skill once thought to influence longevity. Now researchers are discovering new telomerase talents that might help keep tissues young.

Like a next-door neighbor who turns out to be a spy, a protein once thought to mete out life span is doing a few surprising things inside its cellular home. Telomerase, a cellular operative made of protein and RNA, keeps chromosome ends from shrinking each time a cell divides. Researchers used to think that this erosion could drive organismal aging. Although this idea has largely fallen out of favor, many scientists hold that corroding telomeres might hasten the demise of tissues and organs (see "Telomere Tales"). Now, a clutch of studies reveals that telomerase's talents go beyond replenishing the far reaches of our chromosomes and might include stimulating stem cells to replace tissue. The findings suggest that "telomerase has been living a secret life," says molecular biologist Elizabeth Blackburn of the University of California, San Francisco. And its covert actions might be keeping tissues youthful in an unanticipated way.

For a few years, researchers have suspected that telomerase does more than renew telomeres, the caps that protect chromosomes' ends. Cancer biologist William Hahn of the Dana-Farber Cancer Institute in Boston, for example, reported in 2003 that although certain cells show a burst of telomerase activity just before they split in two, their chromosomes still shrank. To explore what telomerase might be up to, Hahn engineered cells that could not produce the telomerase protein. He reported in the 7 June issue of the Proceedings of the National Academy of Sciences that these cells could not recover from DNA damage, suggesting that the cell requires the protein part of telomerase to fix sickly DNA. Additional experiments showed that telomerase participates in DNA repair, probably by directing other cellular proteins to do the job, Hahn says.

Another newly discovered talent has experts thinking that telomerase could contribute to tissue aging--again without exploiting its DNA-lengthening capabilities. Evidence suggests that telomerase might be involved in regulating the activity of stem cells, which maintain and replenish tissues. Cancer biologist Steven Artandi of Stanford University in California reported in August that mice with an overactive form of telomerase protein are excessively shaggy. The protein, it seems, gooses the stem cells that control the growth of new hair. And it performs this trick even in the absence of the RNA component that is required for telomerase to groom chromosome ends, suggesting that telomerase's stem-cell boosterism is independent of its ability to keep chromosomes flush. "We were very much surprised," says Artandi, adding that the protein could play an important role in keeping organs and tissues healthy.

Blackburn wonders whether overzealous telomerase might be involved in stem-cell disorders. For example, people with an illness called dyskeratosis congenita die in early middle age because the stem cells in their bone marrow give out and they can no longer generate blood and immune-system cells. These individuals produce only half the normal amount of telomerase RNA. Perhaps the RNA component normally curbs telomerase's stem-cell inciting powers, Blackburn speculates. So without enough RNA, the telomerase protein is free to wander off and titillate stem cells.

Telomerase's penchant for stimulating stem cells could also become important in fighting cancer, says Blackburn. Research suggests that cancers might be primed by overzealous stem cells. Some scientists are developing anticancer drugs that target telomerase's ability to replenish chromosome tips, an activity that helps some cancer cells survive. But perhaps the researchers will also need to knock out its new skill for supercharging stem cells, experts say. In any event, scientists have good reason to keep spying on telomerase--it might still harbor some secrets about staying youthful and disease-free.

Mary Beckman is a freelance writer in southeastern Idaho who regularly engages in covert activities to stay young and on the ball. But she can't tell you what they are.