Telomeres: What are they, and how do they impact aging?
Telomeres are sections of DNA that are found at the ends of chromosomes and seem to play a role in aging.
Telomeres are the "caps" that protect the ends of DNA strands from being destroyed by a cell. They are made up of areas 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 fast cells age, though exactly how isn't totally clear.
Organisms without circular chromosomes — including humans, other animals, plants and even single-celled protists — have telomeres. Telomeres act as barriers, preventing DNA from being degraded and corrupted.
If our cells did not have telomeres, cellular machinery "would chew away the ends of the chromosomes and into essential genes," said Jan Karlseder, a professor at the Salk Institute for Biological Studies in California and the director of the Glenn Center for Biology of Aging Research at the Salk Institute. The cell might also attach the end of one chromosome to the end of another, which he said would be "a disastrous 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 Live Science.
Each time a cell divides, some part of the repeating sequence in a telomere is lost. When telomeres become too short to function effectively, a cell either dies or stops dividing. So because most cells cannot regenerate their telomeres, they become shorter as people age. The rate at which telomeres shorten has also been associated with rates of aging.
Jan Karlseder received his PhD 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 repeat up to about 3,000 times, but the number of repeats 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 more difficult 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 interfering with the DNA it needs to function.
In most cells, telomeres get shorter 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 germline cells, which form eggs and sperm — can use an enzyme called telomerase to regenerate their telomeres. Some research indicates that there might be ways to increase telomere length slightly in other types of cells.
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Telomeres and aging
Most cells cannot regenerate their telomeres, causing them to become shorter over the lifetime of both a cell and an organism. "Telomere shortening really sets a life span 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 uncovering the nature of telomeres and the existence of the enzyme telomerase, many studies have supported a link between biological age, telomere length, overall health and mortality.
A 2003 study in the journal The Lancet found that in a sample of apparently healthy people over age 60 who researchers followed over time, people with shorter telomeres had higher rates of mortality from both heart disease and infectious diseases. In 2013, the first study 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 2022 review found that regular moderate to vigorous physical activity appeared to help preserve telomere length. The rate of telomere shortening has been tied to life span in a variety of organisms. A 2019 study in the journal Proceedings of the National Academy of Sciences found that while a general measurement of an organism's telomere length didn't have any correlation with life span, the more quickly an organism's telomeres decreased in length, the shorter their life span was.
"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]," reads the study's striking opening. Telomeres could help shed light on this long-standing mystery.
A 2021 study in the journal GeroScience posits that the consequences of telomere length could impact 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 United Kingdom. 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
A major way telomeres are linked to health is through cancer risk. When telomeres become very short, DNA copied during cell division is more likely to be corrupted, which can increase cancer risk.
Another way a telomere malfunction could 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 the telomeres and overcome the telomere shortening pathway," Karlseder said. "And that is what keeps cancer cells immortal."
The body tries to thwart cancer by preventing cells with overly 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, showing how telomeres can trigger cell death: They talk to a cell's mitochondria, its energy provider, to cause deadly inflammation during crisis, the initiation of programmed cell death in response to critically short telomeres. The process sheds light on how telomeres help prevent cells from becoming cancerous.
Though some research suggests that protecting, or even regenerating, telomeres could extend life span, Karlseder said the risk of causing cancer makes this dicey.
“I would very much caution against the approaches that simply elongate telomeres,” he said. “We know that will lead to cancer, and not necessarily to a long lifespan.”
Rather than trying to extend life span and reverse aging, he said, researchers should be more focused on extending "health span" — the amount of time they spend in good health.
One of the purposes of the aging process “really is to prevent cancer occurrence," Karlseder said. "We should welcome aging as a cancer suppressive mechanism."
Rebecca Sohn is a freelance science writer. She writes about a variety of science, health and environmental topics, and is particularly interested in how science impacts people's lives. She has been an intern at CalMatters and STAT, as well as a science fellow at Mashable. Rebecca, a native of the Boston area, studied English literature and minored in music at Skidmore College in Upstate New York and later studied science journalism at New York University.