The story, as typically occurs in science, sounded so interesting. Cells have a molecular clock that determines how lengthy they dwell. If you may simply cease the clock, cells can dwell indefinitely. And the identical ought to go for individuals, who’re, in any case, comprised 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 a little shorter, till lastly they get so brief that the cell dies.
“Short telomeres have been regarded as unhealthy — individuals with untimely getting old syndromes had brief telomeres — so, by analogy, lengthy telomeres have been regarded as good,” mentioned Dr. Mary Armanios, professor of oncology at Johns Hopkins University School of Medicine and director of the Telomere Center on the medical faculty’s Sidney Kimmel Comprehensive Cancer Center. “And the longer the higher.”
But, after all, nothing in biology is so easy. And a paper revealed Thursday within the New England Journal of Medicine, with outcomes of a examine that Dr. Armanios led, exhibits that the telomere story is not 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 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 University of California, San Francisco, who shared a Nobel Prize for her discovery of telomeres and who was not concerned within the examine, mentioned it was a “stunning paper” that went past correlations to indicate a direct hyperlink between lengthy telomeres and illness. She added that the analysis “enlightens this complete trade-off.”
For Dr. Armanios, it’s the fruits of labor she began 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 kind of a ticking clock, figuring out how lengthy they should dwell.
Soon, telomeres have been hailed as a secret to getting old — corporations marketed that they may inform your organic age by measuring the size of your telomeres. Others mentioned that you would lengthen your life by preserving your telomeres with dietary supplements.
But Dr. Armanios and different researchers had observed that telomere lengths appeared constrained to a slender vary, indicating there’s a worth 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 conventional telomere spectrum.
Those with shorter than common telomeres appeared to have an elevated danger of immune system issues and a number of degenerative illnesses, in addition to pulmonary fibrosis, a lung illness. Those with longer than common telomeres appeared to have a modestly elevated danger of most cancers.
There have been, although, some puzzles.
“Some organisms have loopy lengthy telomeres, like mice,” mentioned Dr. Benjamin Ebert, chairman of medical oncology on the Dana-Farber Cancer Institute. “And mice do not dwell that lengthy.”
Dr. Armanios, as a human geneticist, thought the best way to get solutions was to check people. “There are belongings you simply cannot infer from learning cells,” she mentioned.
She suspected, she mentioned, that “you simply cannot elongate telomeres with out a worth,” and started searching for individuals with very lengthy telomeres to ask what that worth is likely to be.
She determined to search for individuals with a frequent 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 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 examine, 4 sufferers died of a number of cancers.
Harriet Brown, 73, of Frederick, Md., is among the examine 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’s actually not a lot I can do at this level,” as a result of there isn’t any technique to forestall extra tumors from creating.
The results of lengthy telomeres on individuals like Ms. Brown makes good 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 lengthy telomeres make cells develop,” he mentioned. “It’s that they do not have the brakes to make them cease rising.” And as a result of the telomeres of individuals with POT1 mutations don’t develop shorter with every cell division, the cells grasp 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 development.
That’s very true in blood, the place cells are always 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 development. Soon a few of these mutated blood cells just about take over a individual’s bone marrow. The result’s CHIP.
That is 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.
Instead, Dr. Armanios mentioned, it is that lengthy telomeres are each creating CHIP and, independently, giving cells time to develop cancer-causing mutations.
“Aging biology is a lot extra sophisticated than we might hoped,” Dr. Sharpless mentioned.
Or, as Dr. Blackburn noticed: Long telomeres will not be the key to everlasting youth.
“There is not any free lunch,” she mentioned.