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What are telomeres?

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Like the rest of a chromosome, including its genes, telomeres are sequences of DNA — chains of chemical code. Like all DNA, they are made of four nucleic acid bases: G for guanine, A for adenine, T for thymine, and C for cytosine.

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Telomeres are made of repeating sequences of TTAGGG on one strand paired with AATCCC on the other strand. Thus, one section of telomere is a "repeat" made of six "base pairs."

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In white blood cells, the length of telomeres ranges from 8,000 base pairs in newborns to 3,000 base pairs in adults and as low as 1,500 in elderly people. (An entire chromosome has about 150 million base pairs.) Each time it divides, an average cell loses 30 to 200 base pairs from the ends of its telomeres.

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Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent or die.

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Telomeres do not shorten in tissues where cells do not continually divide, such as heart muscle.

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Why do chromosomes have telomeres?

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Without telomeres, the main part of the chromosome — the part with genes essential for life — would get shorter each time a cell divides. So telomeres allow cells to divide without losing genes. Cell division is necessary for growing new skin, blood, bone, and other cells.

Without telomeres, chromosome ends could fuse together and corrupt the cell's genetic blueprint, possibly causing malfunction, cancer, or cell death. Because broken DNA is dangerous, a cell has the ability to sense and repair chromosome damage. Without telomeres, the ends of chromosomes would look like broken DNA, and the cell would try to fix something that wasn't broken. That also would make them stop dividing and eventually die.

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Why do telomeres get shorter each time a cell divides?

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Before a cell can divide, it makes copies of its chromosomes so that both new cells will have identical genetic material. To be copied, a chromosome's two DNA strands must unwind and separate. An enzyme (DNA polymerase) then reads the existing strands to build two new strands. It begins the process with the help of short pieces of RNA. When each new matching strand is complete, it is a bit shorter than the original strand because of the room needed at the end for this small piece of RNA. It is like someone who paints himself into a corner and cannot paint the corner.

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Telomerase counteracts telomere shortening

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An enzyme named telomerase adds bases to the ends of telomeres. In young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, there is not enough telomerase, so the telomeres grow shorter and the cells age.

Telomerase remains active in sperm and eggs, which are passed from one generation to the next. If reproductive cells did not have telomerase to maintain the length of their telomeres, any organism with such cells would soon go extinct.

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Telomeres and aging

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Geneticist Richard Cawthon and colleagues at the University of Utah found shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

While telomere shortening has been linked to the aging process, it is not yet known whether shorter telomeres are just a sign of aging — like gray hair — or actually contribute to aging.

If telomerase makes cancer cells immortal, could it prevent normal cells from aging? Could we extend lifespan by preserving or restoring the length of telomeres with telomerase? If so, would that increase our risk of getting cancer?

Scientists are not yet sure. But they have been able to use telomerase in the lab to keep human cells dividing far beyond their normal limit, and the cells do not become cancerous.

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Some long-lived species like humans have telomeres that are much shorter than species like mice, which live only a few years. Nobody knows why. But it's evidence that telomeres alone do not dictate lifespan.

Cawthon's study found that when people are divided into two groups based on telomere length, the half with longer telomeres lives an average of five years longer than those with shorter telomeres. This study suggests that lifespan could be increased five years by increasing the length of telomeres in people with shorter ones.

People with longer telomeres still experience telomere shortening as they age. How many years might be added to our lifespan by completely stopping telomere shortening? Cawthon believes 10 years and perhaps 30 years.

After age 60, the risk of death doubles every 8 years. So a 68-year-old has twice the chance of dying within a year compared with a 60-year-old. Cawthon's study found that differences in telomere length accounted for only 4% of that difference. And while intuition tells us older people have a higher risk of death, only 6% is due purely to chronological age. When telomere length, chronological age, and gender are combined (women live longer than men), those factors account for 37% of the variation in the risk of dying over age 60.