Link Between Long Telomeres and Long Life Is a Tall Tale, Study Finds

The story, as typically occurs in science, sounded so interesting. Cells have a molecular clock that determines how lengthy they reside. If you possibly can simply cease the clock, cells can reside indefinitely. And the identical ought to go for individuals, who’re, in any case, made out of cells. Stop the cell clocks and you may stay youthful.

The clocks come within the type of caps on the tip of chromosomes — the lengthy twisted strings of DNA carrying the cells’ genes. The caps on chromosomes, known as telomeres, are chains of brief, repeated segments of DNA. Every time a cell divides, its telomeres get just a little shorter, till lastly they get so brief that the cell dies.

“Short telomeres were thought to be bad — people with premature aging syndromes had short telomeres — so, by analogy, long telomeres were thought to be good,” mentioned Dr. Mary Armanios, professor of oncology at Johns Hopkins University School of Medicine and director of the Telomere Center on the medical college’s Sidney Kimmel Comprehensive Cancer Center. “And the longer the better.”

But, in fact, nothing in biology is so easy. And a paper revealed Thursday within the New England Journal of Medicine, with outcomes of a research that Dr. Armanios led, exhibits that the telomere story isn’t any exception. While brief telomeres do result in well being issues, lengthy telomeres result in well being issues of their very own. Far from extending life, lengthy telomeres seem to trigger most cancers and a blood dysfunction often called CHIP, a situation that will increase the chance of blood cancers and coronary heart illness.

Dr. Elizabeth Blackburn, an emerita professor on the University of California, San Francisco, who shared a Nobel Prize for her discovery of telomeres and who was not concerned within the research, mentioned it was a “beautiful paper” that went past correlations to point out a direct hyperlink between lengthy telomeres and illness. She added that the analysis “enlightens this whole trade-off.”

For Dr. Armanios, it’s the fruits of labor she started 20 years in the past.

When scientists began learning telomeres, they noticed that younger individuals had longer ones than older individuals. When cells are grown within the lab, their telomeres act as form of a ticking clock, figuring out how lengthy they should reside.

Soon, telomeres have been hailed as a secret to getting older — firms marketed that they might inform your organic age by measuring the size of your telomeres. Others mentioned that you possibly can prolong your life by preserving your telomeres with dietary supplements.

But Dr. Armanios and different researchers had observed that telomere lengths appeared constrained to a slim vary, indicating there’s a value to pay for very lengthy or very brief telomeres.

Population research by a number of teams appeared to help that concept. They discovered correlations — not a trigger and impact — with elevated illness dangers at both finish of the traditional telomere spectrum.

Those with shorter than common telomeres appeared to have an elevated threat of immune system issues and quite a lot of degenerative ailments, in addition to pulmonary fibrosis, a lung illness. Those with longer than common telomeres appeared to have a modestly elevated threat of most cancers.

There have been, although, some puzzlements.

“Some organisms have crazy long telomeres, like mice,” mentioned Dr. Benjamin Ebert, chairman of medical oncology on the Dana-Farber Cancer Institute. “And mice don’t live that long.”

Dr. Armanios, as a human geneticist, thought the best way to get solutions was to check people. “There are things you just can’t infer from studying cells,” she mentioned.

She suspected, she mentioned, that “you just can’t elongate telomeres without a price,” and commenced on the lookout for individuals with very lengthy telomeres to ask what that value is likely to be.

She determined to search for individuals with a standard genetic mutation, POT1, that may end up in lengthy telomeres. It was recognized to extend most cancers threat however most researchers thought it was for causes apart from lengthening telomeres.

She ended up with 17 individuals from 5 households. They ranged in age from 7 to 83 and had terribly lengthy telomeres.

They additionally had tumors, starting from benign, like goiters and uterine fibroids, to malignant, like these from melanoma and blood cancers. During the two-year research, 4 sufferers died of quite a lot of cancers.

Harriet Brown, 73, of Frederick, Md., is without doubt one of the research individuals with very lengthy telomeres. She has had benign tumors known as paragangliomas in her neck and throat, thyroid most cancers and two melanomas. She additionally has CHIP, the blood dysfunction related to coronary heart illness and blood cancers.

She has frequent scans and exams however, she mentioned, “there is really not much I can do at this point,” as a result of there is no such thing as a approach to forestall extra tumors from creating.

The results of lengthy telomeres on individuals like Ms. Brown make excellent sense, mentioned Dr. Norman Sharpless, professor of most cancers coverage and innovation on the University of North Carolina School of Medicine and a former director of the National Cancer Institute.

“It’s not that long telomeres make cells grow,” he mentioned. “It’s that they don’t have the brakes to make them stop growing.” And as a result of the telomeres of individuals with POT1 mutations don’t develop shorter with every cell division, the cells dangle round, dividing repeatedly. The longer they’re dividing within the physique, the extra time they should accumulate random mutations, a few of which immediate tumor progress.

That’s very true in blood, the place cells are consistently being produced. POT1 mutations in a few of these blood cells may give them time to build up different mutations that give them a selective benefit in progress. Soon a few of these mutated blood cells just about take over an individual’s bone marrow. The result’s CHIP.

That is a brand new view of CHIP. The thought had been that as a result of individuals with CHIP have been at elevated threat for blood most cancers, that CHIP itself was inflicting most cancers.

Instead, Dr. Armanios mentioned, it’s that lengthy telomeres are each creating CHIP and, independently, giving cells time to develop cancer-causing mutations.

“Aging biology is a lot more complicated than we’d hoped,” Dr. Sharpless mentioned.

Or, as Dr. Blackburn noticed: Long telomeres will not be the key to everlasting youth.

“There is no free lunch,” she mentioned.