The story, as usually occurs in science, sounded so interesting. Cells have a molecular clock that determines how lengthy they stay. In case you can simply cease the clock, cells can stay 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 tip of chromosomes — the lengthy twisted strings of DNA carrying the cells’ genes. The caps on chromosomes, referred to as telomeres, are chains of quick, repeated segments of DNA. Each time a cell divides, its telomeres get just a little shorter, till lastly they get so quick that the cell dies.
“Brief telomeres had been regarded as unhealthy — individuals with untimely growing old syndromes had quick telomeres — so, by analogy, lengthy telomeres had been regarded as good,” mentioned Dr. Mary Armanios, professor of oncology at Johns Hopkins College Faculty of Drugs and director of the Telomere Heart on the medical college’s Sidney Kimmel Complete Most cancers Heart. “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 Drugs, with outcomes of a research that Dr. Armanios led, exhibits that the telomere story is not any exception. Whereas quick 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 referred to as 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 the invention of an enzyme concerned in making telomeres and who was not concerned within the research, mentioned it was a “lovely paper” that went past correlations to point out a direct hyperlink between lengthy telomeres and illness. She added that the analysis “enlightens this entire trade-off.”
For Dr. Armanios, it’s the fruits 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 type of a ticking clock, figuring out how lengthy they must stay.
Quickly, telomeres had been hailed as a secret to growing old — firms marketed that they may inform your organic age by measuring the size of your telomeres. Others mentioned that you would prolong your life by preserving your telomeres with dietary supplements.
However Dr. Armanios and different researchers had seen that telomere lengths appeared constrained to a slim vary, indicating there’s a value to pay for very lengthy or very quick telomeres.
Inhabitants 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 conventional telomere spectrum.
These with shorter than common telomeres appeared to have an elevated danger of immune system issues and quite a lot of degenerative illnesses, 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,” mentioned Dr. Benjamin Ebert, chairman of medical oncology on the Dana-Farber Most cancers Institute. “And mice don’t stay 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 mentioned.
She suspected, she mentioned, that “you simply can’t elongate telomeres with out a value,” and started in search of 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 can lead to lengthy telomeres. It was recognized 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.
Additionally they had tumors, starting from benign, like goiters and uterine fibroids, to malignant, like these from melanoma and blood cancers. Through 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 contributors 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 mentioned, “there’s actually not a lot I can do at this level,” as a result of there isn’t any approach to forestall extra tumors from growing.
The results of lengthy telomeres on individuals like Ms. Brown make good sense, mentioned Dr. Norman Sharpless, professor of most cancers coverage and innovation on the College of North Carolina Faculty of Drugs and a former director of the Nationwide Most cancers Institute.
“It’s not that lengthy telomeres make cells develop,” he mentioned. “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 usually. The longer they’re dividing within the physique, the extra time they must accumulate random mutations, a few of which immediate tumor progress.
That’s very true in blood, the place cells are continuously being produced. POT1 mutations in a few of these blood cells can provide them time to build up different mutations that give them a selective benefit in progress. 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 had been at elevated danger for blood most cancers, that CHIP itself was inflicting most cancers.
As a substitute, Dr. Armanios mentioned, it’s that lengthy telomeres are each creating CHIP and, independently, giving cells time to develop cancer-causing mutations.
“Getting older biology is much more difficult than we’d hoped,” Dr. Sharpless mentioned.
Or, as Dr. Blackburn noticed: Lengthy telomeres aren’t the key to everlasting youth.
“There isn’t any free lunch,” she mentioned.