ARE LONG TELOMERES THE FOUNTAIN OF YOUTH? Telomeres are structures made from DNA sequences and proteins at the ends of our chromosomes. Telomeres cap and protect the chromosome end, like the end of a shoelace. Many believed that those achieving a very long life had very long telomeres. Did we get it wrong?

A new study shows that the longer a person’s telomere, the greater the risk of cancer and other disorders. We may need to rethink a popular hypothesis about genes and vitality.

“It is not true that people stop pursuing dreams because they grow old, they grow old because they stop pursuing dreams.”
― Gabriel García Márquez

What are Telomeres?

Telomeres are repetitive sequences of DNA located at the ends of chromosomes in eukaryotic cells. They protect by preventing the loss or damage of important genetic information during cell division.

The structure of telomeres consists of a region of repetitive nucleotide sequences, typically TTAGGG in humans, which is repeated thousands of times. These repetitive sequences are not involved in coding for proteins or other genetic information but play a crucial role in maintaining chromosome stability.

Telomeres function as a protective cap, similar to the plastic tips at the ends of shoelaces. During DNA replication, the enzyme responsible for copying DNA, DNA polymerase, cannot fully replicate the ends of linear chromosomes. As a result, a small portion of the telomere is lost with each round of replication. This phenomenon is known as the “end replication problem.”

Without telomeres, chromosomes would progressively lose genetic material and become shorter with each cell division. This process could lead to the loss of essential genes and genomic instability. Telomeres act as a buffer zone, preventing the erosion of genetic information within the chromosomes.

In addition to their protective role, telomeres also play a role in cellular aging and senescence. With each cell division, telomeres shorten, eventually reaching a critically short length. At this point, cells may enter a state of senescence or undergo programmed cell death, known as apoptosis. Telomere shortening is a hallmark of aging and is linked to age-related diseases.

The enzyme telomerase can partially compensate for the loss of telomere length by adding repetitive sequences to the ends of chromosomes. Telomerase is active in stem cells, germ cells, and some cancer cells, allowing them to maintain their telomere length and proliferative capacity.

Understanding telomeres and their role in cellular function and aging has significant implications for areas such as cancer research, regenerative medicine, and the biology of aging.

Rethinking Telomeres and Senescence

The story has always appealed to me: Cells have a ticking molecular clock, such that when the clock runs down, our lives end. Stop the clock, and we might achieve cellular and organism immortality. Voila! Keeping telomeres long becomes a fountain of youth.

My wife’s paternal grandparents lived into their 100s (and her maternal grandparents well into their 90s), and I always thought they must have been born with particularly long telomeres.

It seems so logical. The telomeres get shorter each time a cell divides. Finally, the DNA caps become so short that the cell dies (and we do too).

The fact that individuals who age prematurely have short telomeres indirectly supports the notion that long telomeres are good. Longer telomeres, longer life.

Moreover, young people tend to have longer telomeres than older individuals. Finally, in the laboratory, telomeres serve as a “ticking clock,” determining how long cells survive.

When cells are grown in the lab, their telomeres act like a ticking clock, determining how long they have to live.

I mean, suspense and twists are almost impossible these days. — Danny Boyle

You probably knew a plot twist was coming. A New England Journal of Medicine paper published this May 4, 2023, in the New England Journal of Medicine, a research team reported the following discovery:

While short telomeres cause health problems, long telomeres create a separate set of health issues. Far from extending life, long telomeres appear to cause cancer and a blood disorder (known as CHIP) that elevates blood cancer and heart disease risk.

Mary Armanios, M.D., and the research team observed that telomere lengths are constrained to a narrow range; there appears to be a price we pay for very short or very long telomeres.

We should not be entirely surprised: Population studies by several research groups report a correlation with elevated disease risks at either end of the normal telomere spectrum: Shorter than average telomeres are associated with an increased risk of immune system problems, degenerative diseases, and lung fibrosis (scarring).

Here’s what Dr. Amanios and colleagues did: They searched for individuals with a common mutation (POT1) that can lead to long telomeres. It also increases cancer risk, but researchers thought it was for reasons separate from telomere lengthening.

The team found 17 people from five families aged seven to 83. All had extraordinarily long telomeres. They also had tumors, benign (for example, uterine fibroids and goiter, the latter a thyroid condition) and malignant (including melanoma and blood cancers).

During the two-year study, four patients died from various types of cancers. Their cells did not appear to have the normal stop signs for cell division that more normal ones do.

Because the telomeres do not shorten for those with POT1 mutations, the cells hang around longer in the body, allowing time to have random mutations. Some of these changes initiate tumor growth.

Telomeres – brakes on cell growth and division

Speaking to the New York Times, Dr. Benjamin Ebert, chairman of medical oncology at Harvard’s Dana-Farber Cancer Institute: “Some organisms have crazy long telomeres, like mice. And mice don’t live that long.”

Some medicines aim to lengthen telomeres, but the approach may need to be revised. Telomeres are brakes on cell growth and infinite division. I will continue to slow my telomere shortening by getting physical activity, eating well, and practicing mindfulness activities such as meditation (Vinyasa flow yoga almost left me permanently on the floor at class’ end).