The story, as usually occurs in science, sounded so interesting. Cells have a molecular clock that determines how lengthy they stay. If you may simply cease the clock, cells can stay indefinitely. And the identical ought to go for individuals, who’re, in spite of everything, made out of cells. Stop 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, known as telomeres, are chains of quick, repeated segments of DNA. Every time a cell divides, its telomeres get a little shorter, till lastly they get so quick that the cell dies.
“Short telomeres had been regarded as dangerous — individuals with untimely ageing syndromes had quick telomeres — so, by analogy, lengthy telomeres had been regarded as good,” stated 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 higher.”
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 quick 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, stated 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 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 should stay.
Soon, telomeres had been hailed as a secret to ageing — firms 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.
But Dr. Armanios and different researchers had seen that telomere lengths appeared constrained to a slender vary, indicating there’s a worth to pay for very lengthy or very quick 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 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 threat of most cancers.
There had been, although, some puzzles.
“Some organisms have loopy lengthy telomeres, like mice,” stated Dr. Benjamin Ebert, chairman of medical oncology on the Dana-Farber Cancer Institute. “And mice do not stay that lengthy.”
Dr. Armanios, as a human geneticist, thought the way in which to get solutions was to check people. “There are stuff you simply cannot infer from finding out cells,” she stated.
She suspected, she stated, that “you simply cannot elongate telomeres with out a worth,” and started in search of individuals with very lengthy telomeres to ask what that worth may be.
She determined to search for individuals with a frequent genetic mutation, POT1, that may end up in lengthy telomeres. It was identified 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 a number of cancers.
Harriet Brown, 73, of Frederick, Md., is likely 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 stated, “there’s actually not a lot I can do at this level,” as a result of there isn’t any option to stop extra tumors from creating.
The results of lengthy telomeres on individuals like Ms. Brown makes good sense, stated 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 stated. “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 commonly. 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 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 had been at elevated threat for blood most cancers, that CHIP itself was inflicting most cancers.
Instead, Dr. Armanios stated, 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 difficult than we would hoped,” Dr. Sharpless stated.
Or, as Dr. Blackburn noticed: Long telomeres are usually not the key to everlasting youth.
“There isn’t any free lunch,” she stated.