Such research has encouraged the notion that if telomerase is essential in allowing tumor cells to divide and flourish, a compound that blocks telomerase could potentially halt or even reverse cancer’s progress. And because restricting the enzyme should have little impact on normal adult cells—as most of them need so little telomerase—this approach might have fewer side effects than other anticancer drugs.

One potential stumbling block for telomerase interference is that it might work too slowly. But Blackburn’s research group is finding that’s not a problem. “It’s as if the tumor cells were junkies, addicted to telomerase, and they go through cold-turkey withdrawal,” she says. “So in theory, the strategy of depleting their telomerase makes sense, though we are still a long way from using this approach to cure cancer.” The first candidate compounds are in preclinical or early clinical testing.

But just as it has become increasingly clear that too much telomerase promotes cancer, scientists have also discovered that too little telomerase activity in normal cells can allow other maladies of aging to develop. And one disease, a rare genetic disorder called dyskeratosis congenita, has turned out to be a perfect medium for studying the connections among telomere length, telomerase activity and aging.

Dyskeratosis congenita causes such anomalies as hyperpigmentation, prematurely gray hair and, worse, bone marrow failure; patients eventually die when their infection-fighting cells can no longer replenish themselves and their immune systems collapse. Each generation succumbs earlier, with more severe symptoms. “We see grandparents present symptoms of the disease at age 65, parents at 40 and the latest generation at 9,” Greider says.

Telomere researchers have long been fascinated by dyskeratosis congenita because even the youngest patients have abnormally short telomeres—and unusually low levels of telomerase. People with the disease all have a defective gene, inherited from one parent, that doesn’t produce any telomerase. As a result, those who are afflicted have only half the normal amount of telomerase in their cells.

In 2001, Greider and her collaborators were conducting experiments with a telomerase-deficient mouse they had developed to understand the relationship between telomerase levels, telomere length and cancer when she read a new study that identified the missing gene in dyskeratosis congenita. It happened that this gene was the same one Greider had knocked out in the mice for her cancer studies, and she decided to adapt the mice to study the genetic disorder. She crossed telomerase-deficient mice with normal ones, breeding them so that after seven generations, all the offspring had extremely short telomeres but only half had reduced levels of telomerase. If it were lack of the enzyme rather than prematurely shortened telomeres that caused dyskeratosis congenita, only half those mice would have had the disease.

But instead, they all developed the same spectrum of symptoms seen in dyskeratosis congenita. “It was really startling,” Greider says. “It told us it’s the short telomeres, rather than the amount of telomerase, that causes this disease.”

It turns out that two other diseases, aplastic anemia and pulmonary fibrosis, have the same root cause—the same defective telomerase gene that somehow ages cells throughout the body. “It’s what a physician sees first that drives the diagnosis,” Greider says. “If the symptoms first show up in skin irregularities, the diagnosis is dyskeratosis. If a patient’s immune system fails because the immune cells that fight infections go into senescence, it’s aplastic anemia. If the symptoms first affect the lungs, then it’s pulmonary fibrosis.”