A red-hot anti-aging strategy quietly passed its first test earlier this year after 14 volunteers took drugs meant to kill off old, toxic cells in their bodies.
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The small study in people with lung disease, reported in January, is being billed as the first attempt at “senolytics,” or employing drugs to clear people’s bodies of aged, toxic cells. Some researchers think this strategy could eventually be employed in healthy people to delay aging.
“This gives us to some extent a green light to go on to larger trials,” says James Kirkland, a Mayo Clinic professor who helped lead the trial, carried out in clinics in Texas and at Wake Forest University starting in 2016.
Patients took two pills that Kirkland and his colleagues believed could selectively get rid of aged cells: the leukemia drug dasatinib and a supplement called quercetin.
It is early days for drugs meant to slow aging, and some breathed a sigh of relief that patients in this first-of-a-kind study didn't suffer serious side-effects from the drugs. “My worry is we should not leap into this too fast, because if there’s a mistake or something we don’t understand, it could set the field back,” says Judith Campisi, a professor at the Buck Institute for Research on Aging in Novato, California.
This was a pilot trial—not even in the first phase of a three-part sequence of trials needed to win approval by the US Food and Drug Administration. So, officially, it showed nothing about aging at all.
All 14 patients suffered from a fatal, hard-to-treat lung condition called idiopathic pulmonary fibrosis, which explains why they were willing to participate in the experiment. The doctors found that nine doses of the two pills over three weeks did seem to improve patients’ ability to walk a bit farther in the same amount of time, and several other measures of well-being.
A bubble of commercial enthusiasm has been building around the idea that aging could be postponed, or its effects tempered, using drug treatments. A company called Unity Biotechnology of Brisbane, California, is developing two senolytic drugs, the first of which is in a phase 1 clinical trial for osteoarthritis—it’s being injected into people’s knees. Campisi is a cofounder of Unity, and Kirkland also holds shares in the public company, which is currently worth about half a billion dollars.
These drugs take aim at senescent cells, which have exhausted their ability to divide but remain capable of spewing out a potent mix of chemical signals. “It is thought that these cells and the substances they produce are involved in the process of aging,” says Nicolas Musi, who participated in the new study and directs the Sam and Ann Barshop Institute for Longevity and Aging Studies at the University of Texas at Austin. “The idea is that removing these cells may be beneficial to promote healthy aging and also to prevent diseases of aging.”
In idiopathic pulmonary fibrosis, senescent cells build up in the lungs. In previous tests on mice, a combination of dasatinib and quercetin, which is a plant pigment, had been shown to eliminate such cells and extend the time the animals remained healthy (although it didn’t make them live longer).
“It’s a glimmer into what may happen as we move these agents into humans,” Kirkland says. He cautions anti-aging enthusiasts from taking the pills on their own (quercetin is already available in online stores from supplement vendors with names like LifeExtension). “When we go from mice to people, that’s where we see things go wrong,” Kirkland says. “People should simply not be taking these drugs outside the context of a supervised clinical trial.”
Not everything about senescent cells is bad. The cells, and their secretions, are believed to be important during the development of embryos, in the timing of labor, and in healing wounds and forming scar tissue. “You wouldn’t ever want to administer senolytics to a pregnant woman,” Campisi says. “It’s now becoming clear that you need these secretions for certain good things to happen. When the secretions become chronic as opposed to periodic or episodic, that’s when it starts to drive pathology.”
Researchers are starting their tests in people with serious disease, but they eventually hope to explore whether senolytic agents could be given to healthy people, a bit like a semi-annual dental cleaning to remove plaque. “You reduce the burden of senescent cells, but it doesn’t have to go to zero,” Campisi imagines. “And then you get off the drugs.”
Musi says he and Kirkland and their collaborators have begun a trial in 15 more lung patients, and the team at Mayo is testing the drug combination in 20 patients with chronic kidney disease. “If we see effectiveness signals and don’t encounter really bad side effects, we’ll try to get to people with less and less life-threatening conditions,” Kirkland says. “If everything goes right.”
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