How Telomeres Work


Telomeres (in white) cap the ends of human chromosomes, protecting the genetic information from damage.
Telomeres (in white) cap the ends of human chromosomes, protecting the genetic information from damage.
Image courtesy the ­Human Genome Program

­The 1982 science fiction classic "Blade Runner" pulses with dystopian ponderings about the human condition -- plus it's highly quotable. There's hardly a Rutger Hauer line in the film that hasn't been sampled by a DJ or used as a MySpace headline. In one scene, Hauer's character -- an artificial human with a mere four-year life span -- confronts the scientist who created him. He makes a very human demand: "I want more life."

As a race, we spend a great deal of time fleeing from our own mortality. After all, the will to survive is essential to our genetic mission to propagate the species. In our more ambitious moments, we even dare dream of immortality. "The Epic of Gilgamesh," the oldest-known written text, explored this topic more than four millennia ago. Why do we die? What if we could live forever?

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­While the philosophic aspects of these questions will likely remain a matter of discussion for ages to come, modern science has made startling headway in the study of telomeres. Discovered in 1938 by gen­eticist Hermann J. Müller, telomeres (Greek for "end part") are essentially protective caps composed of short DNA sequences on the tips of chromosomes. The chromosomes they protect, in turn, contain the DNA that determines our entire biologic profile [source: Huaire]. Geneticist Elizabeth Blackburn compared them to the little plastic caps on the ends of your shoelaces. Without them, the laces begin to unravel.

Each time a cell divides, however, the telomeres become shorter. If they grow too short, they reach the Hayflick limit, the point at which they can no longer protect the chromosomes from damage. In this, they sound less like the ends of shoelaces and more like a lit candle. Even now, your telomeres may grow shorter with each cell division, burning down ever closer to the point of guttering out.

­We fear the­ inevitable­ darkness -- ponder its immeasurable depths. Might telomere research hold the key to not only staving off death, but defeating it?

The Incredible Shrinking Telomere

That mole may be more than a mere beauty mark -- it might indicate a long life. A 2007 dermatology study conducted at King's College London indicates that people with more moles often have longer telomeres.
That mole may be more than a mere beauty mark -- it might indicate a long life. A 2007 dermatology study conducted at King's College London indicates that people with more moles often have longer telomeres.
Gianfranco Calcagno/FilmMagic/­Getty Images

­The biblical characters of Adam, Noah and Methuselah all enjoyed life spans of more than 900 years. Rutger Hauer's replicant character in "Blade Runner," Roy Batty, barely made it to his fourth birthday. Today, the modern human enjoys a life expectancy of a little less than 80 years in some parts of the developed world [source: NCHS].

No matter how fundamental your beliefs or fantastical your science fiction fandom, you probably know better than to apply too much hard science to any of those examples. Nevertheless, based on what we know about genetics, we can make a couple of scientific guesses as to why Noah and friends lived so long.

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On one hand, Noah might have been born with rather long telomeres, while Batty drew the proverbial shortest straw. In reality, some people are born with longer telomeres than others. Since telomeres shorten with each cell division, it pays to start out ahead. Once you approach the Hayflick limit, the cellular effects of old age begin to set in due to cell death and damage. The situation may even begin to go south beforehand.

Geneticists at the University of Utah found that test subjects with shorter telomeres were eight times more likely to die from disease and three times more likely to die from a heart attack [source: Biever]. Harvard Medical School epidemiologists also discovered that women with shorter-than-average telomeres are 12 times more likely to develop precursors to dementia [source: Scientific American Mind].

Another possibility is that Noah's and Batty's telomeres simply shortened at different rates. Telomeres don't shrink significantly in healthy humans for decades due to an enzyme called telomerase, which partially repairs and lengthens them after each shortening.

Telomerase appears most frequently in stem cells, as well as in cells that divide frequently (such as those that take part in immune functions). Telomerase production goes mostly dormant in most adult cells, but certain factors can increase production. A study conducted by California's Preventive Medicine Research Institute saw telomerase production boosted by 29 percent in 24 patients who switched from a sedentary lifestyle to one defined by exercise, healthy diet and stress management. Was Noah a health nut? Was Batty just stressed out?

­As you might imagine, telomerase has attracted a great deal of interest. If this precious enzyme can stave off telomere shortening, then can't it also allow us to prevent death -- or even reverse the effects of ageing?

Telomeres and Cancer

When Dolly the cloned sheep died at the premature age of 6, scientists discovered unusually short telomeres in her cells.
When Dolly the cloned sheep died at the premature age of 6, scientists discovered unusually short telomeres in her cells.
Stephen Ferry/Getty Images News/­Getty Images

­If we've learned nothing else from legend and fantasy, it's that quests for immortality generally don't turn out the way we hope. Whether it's a matter of mad science or dark sorcery, living forever often comes with its share of complications.

So far, studies suggest that more telomerase production can result in longer life and increased immune function. In theory, proper tinkering could prevent ageing or even turn back the clock, effectively creating cells that never reach the Hayflick limit. However, immortal cells are hardly a fountain of youth. For instance, sea birds known as Leach's storm petrel actually experience telomere growth as they grow older -- an unexplained anomaly in the animal kingdom [source: Yeoman]. The species certainly enjoys a long life for a small bird (up to 36 years), yet they still die.

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On the human front, at least one human being possessed immortal cells -- and they were found in a tumor. In 1951, Henrietta Lacks went in for a routine biopsy in Baltimore, Md. While a portion of her tumor cells went to a lab for diagnosis, another was sent, without her authorization, to researchers at Johns Hopkins University Medical School [source: Highfield]. Lacks died of cervical cancer in 1951, but her cells live on in laboratories around the world. Called HeLa cells, they divide indefinitely. Before this discovery, cells used in laboratories always carried a shelf life linked to telomere shortening.

Why were these immortal cells found in a fatal tumor? While telomerase production decreases almost entirely in healthy adult cells, it increases in cancerous cells. In fact, 90 percent of human tumors exhibit more telomerase activity. Remember, cancer is essentially uncontrolled cellular replication. As older cells are most likely to turn cancerous, telomere shrinkage may have actually evolved as a means to repress tumor growth [source: Biever].

As you might expect, these facts complicate the notion of boosting telomerase production to stop ageing. In fact, some scientists propose decreasing telomerase production as a means of fighting cancer. In 2009, researchers at Stanford University School of Medicine pinpointed a protein called TCAB1 that controls the movement of telomerase. By blocking its expression in cancer cells, doctors may be able to let nature take its course on these out-of-control cells.

Scientifically speaking, there's a lot riding on telomere research, from ageing and cancer prevention to the future of cloning. Scientists all over the world continue to advance their research, even as their own telomeres steadily wear away.

Explore the links on the next page to learn even more about genetics.

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More Great Links

Sources

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