As is often the case in science, the story was very fascinating. Cells have a molecular clock that determines their lifespan. If we can stop the clock, cells can continue to live indefinitely. After all, so are humans, who are made up of cells. Stopping the cellular clock keeps you young.
Clocks are in the form of caps at the ends of chromosomes. This is a long, twisted strand of DNA that carries the cell’s genes. Caps on chromosomes called telomeres are chains of short, repetitive segments of DNA. Every time a cell divides, its telomeres get a little shorter, until eventually the cell dies.
“Short telomeres were thought to be bad — people with progeria syndrome had short telomeres — and by analogy, long telomeres were thought to be good.” Of the telomere center: “And the longer, the better.”
But of course, nothing in biology is that simple. and, paper The results of a study led by Dr. Armanios, published Thursday in the New England Journal of Medicine, show that the telomere story is no exception. Short telomeres cause health problems, but long telomeres cause their own health problems. Far from prolonging life, long telomeres seem to cause him a blood disorder known as CHIP, a condition that increases the risk of cancer, blood cancers and heart disease.
Dr. Elizabeth Blackburn, professor emeritus at the University of California, San Francisco, who won the Nobel Prize for discovering the enzymes involved in making telomeres, was not involved in the study, but called it a “great paper.” I’m here. Beyond correlation, we have shown a direct link between long telomeres and disease. She added that the study “enlightens this whole trade-off.”
For Dr. Armanios, this is the culmination of research she began 20 years ago.
When scientists began studying telomeres, they observed that young people have longer telomeres than older people. When cells are grown in the laboratory, telomeres act like ticking clocks and determine lifespan.
Soon, telomeres were hailed as the secret to aging.Companies touted that measuring telomere length could tell you your biological age. He said that by doing so, you can extend your life.
But Dr. Armanios and other researchers noticed Its telomere length appears to be restricted to a narrow range, indicating that very long or very short telomeres come at a price.
population the study Several groups appeared to support the idea. They found a correlation between increased disease risk at both ends of the normal telomere spectrum, rather than cause and effect.
People with shorter than average telomeres Growing risk These include immune system problems, various degenerative diseases, and pulmonary fibrosis, a disease of the lungs. Those with longer than average telomeres appeared to have a slightly higher risk of cancer.
There were some confusions, though.
“Some organisms, like mice, have very long telomeres. “And mice don’t live that long.”
Dr. Armanios, a human geneticist, believed that the way to get answers was to study humans. “There are things you can’t infer from cell studies,” she said.
“You can’t lengthen telomeres without a price,” she thought, so she started looking for people with very long telomeres and asking how much it would cost.
She decided to look for people with the common genetic mutation, POT1, which results in longer telomeres. It was known to increase cancer risk, but most researchers thought it was for reasons other than telomere lengthening.
She ended up going from 5 families to 17 people. They ranged in age from 7 to 83 years and had very long telomeres.
In addition, there were various tumors, from benign such as goiter and uterine fibroids to malignant such as melanoma and blood cancer. Four patients died from various cancers during the two-year study.
Harriet Brown, 73, of Frederick, Maryland, is one of the study participants who has very long telomeres. She has a benign tumor called a paraganglioma on her neck and throat, thyroid cancer and two melanomas. She also has CHIP, a blood disorder related to heart disease and blood cancers.
She has frequent scans and tests, but “there’s not much we can do at this point,” she said.
Dr. Norman Sharpless, professor of cancer policy and innovation at the University of North Carolina School of Medicine and former director of the National Cancer Institute, said the impact of long telomeres on people like Mr. Brown makes perfect sense.
“Long telomeres don’t make cells grow,” he said. “It just means they don’t have the brakes to stop growth.” Also, telomeres in people with POT1 mutations don’t shorten with each cell division, so the cells dangle and divide regularly. . The longer it divides in the body, the longer it takes to accumulate random mutations, some of which promote tumor growth.
This is especially true for blood, where cells are constantly being produced. Her POT1 mutation in some of these blood cells gives them time to accumulate other mutations, giving them a selective advantage in proliferation. Soon, some of these mutated blood cells almost take over a person’s bone marrow. The result is CHIP.
That’s the new look at CHIP. Because people with CHIP have an increased risk of blood cancers, CHIP itself was thought to cause cancer.
Instead, long telomeres create CHIP, giving the cell time to independently develop cancer-causing mutations, Dr. Armanios said.
“The biology of aging is much more complex than we would have liked,” said Dr. Sharpless.
Or, as Dr. Blackburn observed, long telomeres are not the secret to eternal youth.
“No free lunch,” she said.