Hyperlink Between Lengthy Telomeres and Lengthy Life Is a Tall Story, Examine Finds

The story, as usually occurs in science, sounded so interesting. Cells have a molecular clock that determines how lengthy they reside. For those who can simply cease the clock, cells can reside indefinitely. And the identical ought to go for individuals, who’re, in spite of everything, created from cells. Cease the cell clocks and you may stay youthful.

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

“Brief telomeres have been considered unhealthy — individuals with untimely getting older syndromes had brief telomeres — so, by analogy, lengthy telomeres have been considered good,” stated Dr. Mary Armanios, professor of oncology at Johns Hopkins College College of Medication and director of the Telomere Middle on the medical faculty’s Sidney Kimmel Complete Most cancers Middle. “And the longer the higher.”

However, after all, nothing in biology is so easy. And a paper revealed Thursday within the New England Journal of Medication, with outcomes of a examine that Dr. Armanios led, reveals that the telomere story isn’t any exception. Whereas brief telomeres do result in well being issues, lengthy telomeres result in well being issues of their very own. Removed 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 College of California, San Francisco, who shared a Nobel Prize for her discovery of telomeres and who was not concerned within the examine, stated it was a “lovely paper” that went past correlations to indicate a direct hyperlink between lengthy telomeres and illness. She added that the analysis “enlightens this entire trade-off.”

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

When scientists began finding out 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 need to reside.

Quickly, telomeres have been hailed as a secret to getting older — corporations marketed that they might inform your organic age by measuring the size of your telomeres. Others stated that you may lengthen your life by preserving your telomeres with dietary supplements.

However Dr. Armanios and different researchers had noticed that telomere lengths appeared constrained to a slender vary, indicating there’s a worth to pay for very lengthy or very brief telomeres.

Inhabitants studies by a number of teams appeared to assist that concept. They discovered correlations — not a trigger and impact — with elevated illness dangers at both finish of the conventional telomere spectrum.

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

There have been, although, some puzzlements.

“Some organisms have loopy lengthy telomeres, like mice,” stated Dr. Benjamin Ebert, chairman of medical oncology on the Dana-Farber Most cancers Institute. “And mice don’t reside that lengthy.”

Dr. Armanios, as a human geneticist, thought the best way to get solutions was to check people. “There are stuff you simply can’t infer from finding out cells,” she stated.

She suspected, she stated, that “you simply can’t elongate telomeres with out a worth,” and commenced in search of individuals with very lengthy telomeres to ask what that worth is perhaps.

She determined to search for individuals with a typical genetic mutation, POT1, that can lead to lengthy telomeres. It was identified to extend most cancers danger however most researchers thought it was for causes aside 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.

In addition they had tumors, starting from benign, like goiters and uterine fibroids, to malignant, like these from melanoma and blood cancers. Through the two-year examine, 4 sufferers died of quite a lot of cancers.

Harriet Brown, 73, of Frederick, Md., is without doubt one of the examine members with very lengthy telomeres. She has had benign tumors referred to 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 stated, “there’s actually not a lot I can do at this level,” as a result of there isn’t a technique to stop extra tumors from creating.

The results of lengthy telomeres on individuals like Ms. Brown make good sense, stated Dr. Norman Sharpless, professor of most cancers coverage and innovation on the College of North Carolina College of Medication and a former director of the Nationwide Most cancers Institute.

“It’s not that lengthy telomeres make cells develop,” he stated. “It’s that they don’t have the brakes to make them cease rising.” And since the telomeres of individuals with POT1 mutations don’t develop shorter with every cell division, the cells grasp round, dividing often. The longer they’re dividing within the physique, the extra time they need to accumulate random mutations, a few of which immediate tumor development.

That’s very true in blood, the place cells are continuously 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 development. Quickly a few of these mutated blood cells just about take over an individual’s bone marrow. The result’s CHIP.

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

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

“Growing older biology is much more difficult than we’d hoped,” Dr. Sharpless stated.

Or, as Dr. Blackburn noticed: Lengthy telomeres are usually not the key to everlasting youth.

“There isn’t a free lunch,” she stated.