by Telomeres are the “caps” that protect the ends of DNA strands from being damaged by a cell. They consist of regions of repeated DNA sequences combined with specific proteins at the ends of chromosomes – the tightly wound structures of DNA and proteins inside cells. Telomeres play a role in how quickly cells age, but exactly how is not entirely clear.
Organisms without circular chromosomes—including humans, other animals, plants, and even unicellular protists—have telomeres. Telomeres act as barriers, preventing DNA from being degraded and damaged.
If our cells didn’t have telomeres, cellular machinery would “chew away the ends of chromosomes and into essential genes,” said Jan Karlseder (opens in a new tab), professor at the Salk Institute for Biological Studies in California and director of the Glenn Center for Biology of Aging Research at the Salk Institute. The cell can also attach the end of one chromosome to the end of another, which he said would be “a catastrophic event” for a cell.
“Since our chromosomes are linear pieces of DNA, a structure called the telomere has evolved that protects the natural ends of the chromosomes from being recognized as DNA damage,” Karlseder told LiveScience.
Each time a cell divides, part of the repetitive sequence in a telomere is lost. When telomeres become too short to function efficiently, a cell either dies or stops dividing. So, because most cells cannot regenerate their telomeres, they shorten as people age. The rate at which telomeres shorten has also been associated with rates of aging.
Jan Karlseder received his doctorate from the Institute for Molecular Biology in Austria and completed postdocs at both the Center for Applied Genetics (Austria) and Rockefeller University. He is currently a professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and holder of The Donald and Darlene Shiley Chair.
What is the function of telomeres?
In humans and all vertebrates, telomeres repeat the nucleotide sequences TTAGGG – two thymine, one adenine and three guanine molecules. Nucleotides are the molecules that make up the sequence of DNA. In humans, this sequence can be repeated up to approx. 3000 times, but the number of repetitions varies for different species. At the end of a telomere, there is a kind of “knot” called a T-loop, which is maintained by a specific protein structure called a shelterin complex. The T-loop and shelterin make it harder for the cell to destroy DNA at the end of a chromosome, while the repeated sequences provide layers of genetic code that the cell can destroy without disrupting the DNA it needs to function.
In most cells, telomeres shorten over time as the cell destroys more of their genetic code. However, some cells, such as stem cells, which generate the body’s many types of specialized cells, and germ cells, which form eggs and sperm, can use an enzyme called telomerase to regenerate their telomeres. Some research indicates that there may be ways to slightly increase telomere length in other types of cells.
Telomeres and aging
Most cells cannot regenerate their telomeres, causing them to shorten over the lifespan of both a cell and an organism. “Telomere shortening really puts a lifespan on our cells by limiting the number of population doublings or proliferation cells can undergo,” Karlseder said.
Since biologist Elizabeth Blackburn’s Nobel Prize-winning work (opens in a new tab) revealing the nature of telomeres and the existence of the enzyme telomerase, many studies have supported a link between biological age, telomere length, general health and mortality.
A study from 2003 in the journal The Lancet (opens in a new tab) found that in a sample of apparently healthy people over 60 that researchers followed over time, people with shorter telomeres had higher mortality from both heart disease and infectious diseases. In 2013, the first study (opens in a new tab) of its kind found that lifestyle changes in exercise, diet, stress management and social support were associated with increased telomere length in a small group of men with low-risk prostate cancer. A review from 2022 (opens in a new tab) found that regular moderate to vigorous physical activity appeared to help preserve telomere length. The frequency of telomere shortening has been linked to longevity in a number of organisms. A 2019 study in the journal Proceedings of the National Academy of Sciences (opens in a new tab) found that while a general measurement of an organism’s telomere length had no correlation with lifespan, the faster an organism’s telomeres decreased in length, the shorter their lifespan.
“The exact causes of aging are still not understood, and it is unclear why some species live less than 1 (day), while others can live more than 400 (years),” the study’s striking opening reads. Telomeres may help shed light on this long-standing mystery.
A study from 2021 in the journal GeroScience (opens in a new tab) suggests that the consequences of telomere length may affect how old a person looks. Researchers examined survey results from over 400,000 participants in the UK Biobank, a large database of health information from people living in the UK. They found that people who had genetic predictors of longer telomere length were more likely to say that people tended to think they looked younger than their age.
Telomeres and cancer
An important way telomeres are linked to health is through cancer risk. When telomeres become very short, DNA that is copied during cell division is more likely to be damaged, which can increase cancer risk.
Another way a telomere error can lead to cancer is if the telomerase enzyme becomes active in cells where it shouldn’t be.
“Pretty much every single cancer cell has found mechanisms to maintain telomeres and overcome the telomere shortening pathway,” Karlseder said. “And that’s what keeps cancer cells immortal.”
The body tries to prevent cancer by preventing cells with excessively short telomeres from dividing, which is called senescence.
Karlseder, along with a team of Salk Institute researchers, completed a study published in 2023 in the journal Nature (opens in a new tab), showing how telomeres can trigger cell death: They talk to a cell’s mitochondria, its energy supplier, to cause lethal inflammation during crisis, initiating programmed cell death in response to critically short telomeres. The process sheds light on how telomeres help prevent cells from becoming cancerous.
Although a little research (opens in a new tab) suggests that protecting or even regenerating telomeres could extend lifespan, Karlseder said the risk of causing cancer makes this difficult.
“I would very much caution against the approaches that simply lengthen telomeres,” he said. “We know that it will lead to cancer, and not necessarily to a long life.”
Instead of trying to extend lifespan and reverse aging, he said, researchers should be more focused on extending the “health span” — how long people spend in good health.
One of the purposes of the aging process “is really to prevent cancer occurrence,” Karlseder said. “We should welcome aging as a cancer-suppressing mechanism.”
