SEATTLE — Ever since last summer, when Lynn Gemmell’s dog was inducted into the trial of a drug that has been shown to significantly lengthen the lives of laboratory mice, she has been the object of intense scrutiny among dog park regulars.
To those who insist that Bela, 8, has turned back into a puppy — “Look how fast she’s getting that ball!” — Gemmell has tried to turn a deaf ear. Bela, a border collie/Australian shepherd mix, may have been given a placebo, for one thing.
For another, the drug, rapamycin, which improved the heart health and appeared to delay the onset of some diseases in older mice, may not work the same magic in dogs. There is also a chance it could do more harm than good. “This is just to look for side effects in dogs,” Gemmell told Bela’s many well-wishers.
Technically that is true. But the trial also represents a new frontier in testing a proposition for improving human health: Rather than seeking treatments for the individual maladies that come with age, we might do better to target the biology that underlies aging itself.
While the diseases that now kill most people in developed nations — heart disease, stroke, Alzheimer’s, diabetes, cancer — have different immediate causes, age is the major risk factor for all of them. That means that even breakthroughs in these areas, no matter how vital to individuals, would yield on average four or five more years of life, epidemiologists say, and some of them likely shadowed by illness.
Different strategy
A drug that slows aging, the logic goes, might instead serve to delay the onset of several major diseases at once. A handful of drugs tested by federally funded laboratories in recent years appear to extend the healthy life span of mice, with rapamycin, approved by the Food and Drug Administration to treat organ transplant patients and some types of cancer, so far proving the most effective.
In a 2014 study by the drug company Novartis, the drug appeared to bolster the immune system in older patients. And the early results in aging dogs suggest that rapamycin is helping them, too, said Matt Kaeberlein, a biology of aging researcher at the University of Washington who is running the study with a colleague, Daniel Promislow.
But scientists who champion the study of aging’s basic biology — they call it “geroscience” — say their field has received short shrift from the biomedical establishment. And it was not lost on the University of Washington researchers that exposing dog lovers to the idea that aging could be delayed might generate popular support in addition to new data.
“Many of us in the biology-of-aging field feel like it is underfunded relative to the potential impact on human health this could have,” said Kaeberlein, who helped pay for the study with funds he received from the university for turning down a competing job offer. “If the average pet owner sees there’s a way to significantly delay aging in their pet, maybe it will begin to impact policy decisions.”
Is life span unbending?
Most of us harbor the intuition that we age because our bodies, like our cars, our furniture and our patience, just wear out. But the best argument that life span is not hard-wired, biologists say, has long been evident: Living things age at significantly different rates.
“The squirrels in my neighborhood have a 25-year life span, but they look like rats that live two years,” said Gary Ruvkun, a pioneer in aging biology at Harvard Medical School. “If you look at what nature has selected for and allowed, it suggests that you might be able to get your hands on the various levers that change things.”
That aspiration gained traction in the 1990s and 2000s, when scientists, armed with new tools of molecular biology, homed in on the complex cellular pathways that regulate life span in many species. By removing genes that produced certain proteins, or adding genes that produced others, researchers found they could significantly extend the lives of simple laboratory organisms.
Since genes cannot be so easily manipulated in humans, it was significant in 2006 when Kaeberlein and others demonstrated that rapamycin, the drug now being tested in dogs, suppressed one of the crucial proteins in yeast, resulting in a longer life span without removing a gene. The protein is known to be involved in cell growth. But just how its suppression works to extend life is still unclear, raising questions about potential unknown downsides.
Aging in mouse and dog years
Dogs age faster than humans, and bigger dogs age faster than smaller dogs. The 40 dogs that participated in the rapamycin trial, which just concluded its pilot run in Seattle, had to be at least 6 years old and weigh at least 40 pounds.
Like Gemmell’s Bela, whose cholesterol was high, many of them were showing signs of aging: loose skin, graying muzzles, a stiffness in the joints. So were some of their owners.
“How are you going to be sure people are going to be giving this to their dog rather than taking it themselves?” Gemmell, 58, joked with Kaeberlein on her first visit to the veterinary clinic, where Bela was given a checkup before the 10 weeks that she would be given the drug.
More than 1,500 dog owners applied to participate in the trial of rapamycin, which has its roots in a series of studies in mice, the first of which was published in 2009. Made by a type of soil bacteria, rapamycin has extended the life spans of yeast, flies and worms by about 25 percent.
But in what proved to be a fortunate accident, the researchers who set out to test it in mice had trouble formulating it for easy consumption. As a result, the mice were 20 months old — the equivalent of about 60 human years — when the trial began. That the longest-lived mice survived about 12 percent longer than the control groups was the first indication that the drug could be given later in life and still be effective.
Last month, Kaeberlein reported at a scientific meeting that no significant side effects had been observed in the dogs, even at the highest of three doses. The researchers would like to enroll 450 dogs for a more comprehensive five-year study but do not yet have the money to do it.
Even if the study provided positive results on all fronts, a human trial would carry risks.
Kaeberlein, for one, said they would be worth it.
“I would argue we should be willing to tolerate some level of risk if the payoff is 20 to 30 percent increase in healthy longevity,” he said. “If we don’t do anything, we know what the outcome is going to be. You’re going to get sick and you’re going to die.”