In 1984, Greider and Blackburn discovered the enzyme telomerase and worked out how it rebuilds telomeres by adding back repetitive blocks of DNA sequences to the tip,
essentially extending the zipper’s foot. Normally telomerase is most active early in life, keeping telomeres in good repair while cells divide furiously to keep up with growth and development. By adulthood, most tissues need their cells to divide only occasionally, and so the cells need infinitesimal amounts of telomerase. As a rule, only reproductive cells—eggs and sperm—and stem cells, which can replenish lost cells, must maintain significant levels of the enzyme.

The exceptions to this rule are such tissues as skin, intestinal lining and bone marrow. In these, there’s rapid turnover and constant need to replenish cells damaged by ultraviolet radiation, wounds, digestive acids and infections. These self-replenishing tissues must have telomerase throughout adulthood, though at much lower levels than in early development.

With age, though, telomerase cannot keep up with the demands of cell division. There’s less of the enzyme just when aging cells may need more. So telomeres become shorter, germ cells lose their fertility, and stem cells lose their capacity for self-renewal. That’s the start of what Blackburn describes as a “Dr. Jekyll and Mr. Hyde” role for telomerase in the life of both the cell and the organism.

Every time a cell divides—copying its DNA and sending one copy to each daughter cell—it risks making a mistake in replicating one or more of the 3 billion “letters,” or chemical base pairs, in the chromosomes. Some copying errors—mutations—may change the significance of a gene. Meanwhile, the wear and tear of daily living, from sunlight, infections, cigarette smoke and other toxins, further damages DNA and introduces more mutations.

During what is usually a gradual process that accelerates as we age, these mutations make genes oncogenic, or cancer promoting. When that happens, cells normally sense the danger and activate the cell-death program apoptosis to prevent the cell from becoming malignant. Occasionally, though, the mutations help the cell override apoptosis and continue dividing.

But cancer prevention is so important to an organism that it has other checkpoints, including telomere shortening, that may stem the destruction. Cancerous cells divide at a faster-than-normal pace, and their telomeres rapidly become too short to protect the chromosome. That usually sends the cells into senescence, which puts the brakes on cancer.

For cancer to continue developing, cells must bypass the telomere-shortening roadblock; the most common way to do that is to rev up telomerase activity. Blackburn notes that while telomere shortening may act to suppress tumors in early cancer stages, once that protection fails, telomerase may play an oncogenic role. Studies in cell cultures and mouse models have largely substantiated this theory, and there’s growing evidence that it also works that way in human tumors.