‘Zombie cells’ may play big role in aging
Call them zombie cells — they refuse to die.
Scientists actually call these senescent cells. They start out normal but then encounter a stress, such as damage to their DNA or a viral infection. At that point, a cell can choose to die or basically enter a state of suspended animation (hence the popular term “zombie cell”).
The problem is that senescent cells, though they no longer replicate, still release chemicals and proteins that can harm nearby normal cells. That’s where the trouble starts.
As these cells and their proteins build up in your body, studies suggest, they promote aging and the conditions that come with it, such as osteoporosis and Alzheimer’s disease.
Researchers are studying drugs that can kill these cells and possibly treat the problems they bring.
Basically, the goal is to fight aging itself, which hopefully will delay the appearance of age-related disease and disabilities as a group, according to geriatrics specialist Dr. James Kirkland of the Mayo Clinic in Rochester, Minnesota. That’s in contrast to playing a “whack-a-mole game” of treating one disease only to see another spring up, he said.
Promising studies in mice
The research has been done chiefly in mice, where drugs that eliminate senescent cells — known as senolytics — have been shown to improve an impressive list of conditions, such as cataracts, diabetes, osteoporosis, Alzheimer’s disease, enlargement of the heart, kidney problems, clogged arteries and age-related loss of muscle.
Mouse studies have also shown a more direct tie between senescent cells and aging. When drugs targeting those cells were given to aged mice, the animals showed better walking speed, grip strength and endurance on a treadmill.
Even when the treatment was applied to very old mice, the equivalent of people ages 75 to 90, it extended lifespan by an average of 36 percent.
Researchers have also shown that transplanting senescent cells into young mice basically made them act older: their maximum walking speed slowed down, and their muscle strength and endurance decreased. Tests showed the implanted cells converted other cells to zombie status.
Will drugs work in people?
Earlier this year, the first test of senolytics in people was published by Kirkland and his colleagues, and provided some tantalizing results.
It involved 14 patients with idiopathic pulmonary fibrosis, a generally fatal disease that scars the lining of the lungs. Risk rises with age, and the lungs of patients show evidence of senescent cells.
In the preliminary experiment, after three weeks of treatment, patients improved on some measures of physical fitness, like walking speed. Other measures, however, did not show improvement.
Still, the results were encouraging and “it really raises enthusiasm to proceed with the more rigorous studies,” said Dr. Gregory Cosgrove, chief medical officer of the Pulmonary Fibrosis Foundation, who played no role in the study.
The field of zombie cells is still young. But Kirkland estimates at least a dozen companies have formed or have launched efforts to pursue treatments. He holds shares in one.
Apart from age-related diseases, senolytic drugs might be useful for treating premature aging among cancer survivors that brings on the early appearance of some diseases, said Laura Niedernhofer of the University of Minnesota.
Don’t try this at home
Some of these drugs have been approved for other uses or are even sold as supplements. But Niedernhofer and Kirkland stress that people should not try them on their own, nor should doctors prescribe them for the uses now under study, because more research has to be done first.
Niedernhofer said the best drugs may be yet to come. The goal is not to prevent stressed cells from turning into zombies, she said, because they may become cancerous instead. The aim is to trigger death of cells that have already transformed, or to limit the harm they do.
And what about giving senolytic drugs to healthy people who want to ward off aging? That’s possible but a long way off, after studies have established that the drugs are safe enough, she said. On the other hand, “we may not get there,” Kirkland said.
In any case, experts are impressed by the research so far. “I think this is very exciting,” said Dr. George Kuchel of the University of Connecticut Center on Aging in Farmington. The results from animal studies are “very spectacular. It’s very compelling data.”
Nir Barzilai, a researcher of aging at the Albert Einstein College of Medicine in New York, said he believes targeting senescent cells will play a role in the overall effort to delay, stop and maybe reverse aging.
So much research suggests they promote aging that “we know that it should be true,” he said.