James Kirkland started his career in 1982 as a geriatrician, treating aging patients. But he found himself dissatisfied with what he could offer them.
“I got tired of prescribing wheelchairs, walkers and incontinence devices,” recalls Kirkland, now at the Mayo Clinic in Rochester, Minnesota. He knew that aging is considered the biggest risk factor for chronic illness, but he was frustrated by his inability to do anything about it. So Kirkland went back to school to learn the skills he’d need to tackle aging head-on, earning a PhD in biochemistry at the University of Toronto. Today, he and his colleague Tamara Tchkonia, a molecular biologist at the Mayo Clinic, are leaders in a growing movement to halt chronic disease by protecting brains and bodies from the biological fallout of aging.
If these researchers are successful, they’ll have no shortage of customers: People are living longer, and the number of Americans age 65 and older is expected to double, to 80 million, by 2040. While researchers like Kirkland don’t expect to extend lifespan, they hope to lengthen “health span,” the time that a person lives free of disease.
One of their targets is decrepit cells that build up in tissues as people age. These “senescent” cells have reached a point — due to damage, stress or just time — when they stop dividing, but don’t die. While senescent cells typically make up only a small fraction of the overall cell population, they accounted for up to 36 percent of cells in some organs in aging mice, one study showed. And they don’t just sit there quietly. Senescent cells can release a slew of compounds that create a toxic, inflamed environment that primes tissues for chronic illness. Senescent cells have been linked to diabetes, stroke, osteoporosis and several other conditions of aging.
These noxious cells, along with the idea that getting rid of them could mitigate chronic illnesses and the discomforts of aging, are getting serious attention. The US National Institutes of Health is investing $125 million in a new research effort, called SenNet, that aims to identify and map senescent cells in the human body as well as in mice over the natural lifespan. And the National Institute on Aging has put up more than $3 million over four years for the Translational Geroscience Network multicenter team led by Kirkland that is running preliminary clinical trials of potential antiaging treatments. Drugs that kill senescent cells — called senolytics — are among the top candidates. Small-scale trials of these are already underway in people with conditions including Alzheimer’s, osteoarthritis and kidney disease.
“It’s an emerging and incredibly exciting, and maybe even game-changing, area,” says John Varga, chief of rheumatology at the University of Michigan Medical School in Ann Arbor, who isn’t part of the TGN.
But he and others sound a note of caution as well, and some scientists think the field’s potential has been overblown. “There’s a lot of hype,” says Varga. “I do have, I would say, a very healthy skepticism.” He warns his patients of the many unknowns and tells them that trying senolytic supplementation on their own could be dangerous.
Researchers are still untangling the biology of senescent cells, not only in aging animals but in younger ones too — even in embryos, where the aging out of certain cells is crucial for proper development. So far, evidence that destroying senescent cells helps to improve health span mostly comes from laboratory mice. Only a couple of preliminary human trials have been completed, with hints of promise but far from blockbuster results.
Even so, Kirkland and Tchkonia speculate that senolytics might eventually help not only with aging but also with conditions suffered by younger people due to injury or medical treatments such as chemotherapy. “There may be applications all over the place,” muses Kirkland.
