Some scientists consider rapamycin one of the most promising candidates for a human longevity drug. More than a few people take it off the label for this purpose. Kaeberlein said he would like them to send him information about his health. He also takes a low-dose rapamycin pill weekly, in intermittent 10-week cycles, and is beginning to monitor the effects on his blood biomarkers and epigenome.
The drug triggers some of the same molecular and metabolic actions as extreme calorie restriction, which has consistently increased lifespan in laboratory studies. Kaeberlein believes that rapamycin may also regulate inflammation, a major factor in age-related diseases.
But self-experimentation and crowdsourced anecdotes will prove nothing, and rapamycin is off-patent, so the pharmaceutical industry has little incentive to fund a large clinical trial. “There’s no money to be made, or at least not as much money as if it were a new drug,” says Kaeberlein.
Their double-blind, placebo-controlled study involves healthy seven-year-olds, so a significant gain in life extension would become apparent within three years. Depending on their findings, they could shell out money for clinical trials or consign rapamycin to the long list of drugs that initially raised hopes for a breakthrough in longevity but failed.
Andrei Gudkov believes that there are too many variables in pet homes to provide clean scientific data. So he and his colleagues in Vaika’s study recruited 102 former sled dogs, ages eight to 11, from across the United States to live out their golden years in a Cornell College of Veterinary Medicine kennel under tightly controlled conditions, with ample room to run and play. .
Scientists scrupulously monitor adult life changes—dogs do treadmill tests, cognitive tasks, and problem-solving activities like figuring out how to get around a fence. The scientists also tested two drugs for their antiaging potential: lamivudine, an FDA-approved treatment for HIV and hepatitis B, and entolimod. A recombinant protein developed to counteract the effects of radiation poisoning, entolimod is also being evaluated at the Mayo Clinic as an immune system booster in people age 65 and older.
Meanwhile, a San Francisco startup with the reverent canine name of Loyal is testing a soluble implant that delivers a drug designed to slow aging in large breeds, which age faster and die younger than small dogs. Also in the works: a tasty pill for older dogs of all but the smallest breeds, codenamed LOY-002. Like rapamycin, it emulates the biological effects of caloric restriction.
“While we are developing these canine longevity drugs and giving them something that parents cherish, at least from the emails I get, we really want to, we are also learning something about how to help people live longer, healthier lives,” says Celine Halioua, founder and CEO of Loyal. “Honestly, the most important thing Loyal can do is prove that aging should be a class of drugs… that there is a way to develop a drug for this mechanism.”
The DNA Cure
Ace’s mother, Gabby, developed mitral valve disease before him. The leaky valve causes blood to flow back into the upper left chamber of the heart instead of moving to the lower chamber. At age 12, Gabby was part of the first pack of dogs to receive the gene therapy that Ace would later receive. Its treatment arose from experiments led by Noah Davidson, then a postdoctoral researcher in the laboratory of Harvard biologist George Church.
Davidson knew that gene expression – the process by which information stored in DNA is translated into molecules that control how cells function – can go wrong as we age. He believed that properly regulating gene expression, which means turning some genes on and others off, was the key to slowing down aging and eliminating the many diseases that accompany it.
He and his colleagues zeroed in on three genes known to promote healthy aging and longer life in genetically engineered mice. He theorized that an extra copy of any one of these genes, or perhaps all of them, would have broad health benefits in normal mice. The team created one therapy from each gene and tested them in mice, one therapy at a time and in cocktails of two and three genes. In a 2019 paper in PNAS, scientists reported that a single dose of a two-gene combination mitigated four age-related diseases: type 2 diabetes, obesity, heart failure, and kidney failure.
Rejuvenate Bio, co-founded by Church, Davidson and Daniel Oliver, quickly moved into testing on dogs. The study, focused on assessing the safety of the therapy, is not limited to Cavalier King Charles Spaniels. But a passionate and well-organized community of breed owners, most of whom will own a dog with mitral valve disease, released the judgment. “This is a big deal in the Cavalier world,” says Stephanie Abraham.
In early 2020, Abraham drove Gabby to the Cummings School of Veterinary Medicine at Tufts University in Massachusetts, an hour from his home. The dog received an intravenous infusion in the hind leg. Despite all the amazing science and painstaking research that went into creating the therapy, the IV drip took less than 15 minutes. “There was no pain or crying,” says Abraham. Ace went through the infusion two years later.
Rejuvenate Bio has not announced the results, but it has partnered with an animal health company and plans to seek FDA approval for canine gene therapy. The startup also plans to recode the gene cocktail for human use and test it for two diseases: arrhythmogenic right ventricular cardiomyopathy, which destroys part of the heart’s muscular wall and increases the risk of irregular heartbeats and sudden death; and familial partial lipodystrophy, an abnormal fat storage disorder that leads to diabetes, liver enlargement, and other health problems in adulthood.
Gabby and Ace have had no discernible complications or side effects from the therapy, and Abraham is encouraged by blood tests for a hormone that indicates how well the heart is pumping blood and can signal incipient heart failure. Gabby’s levels have improved; Ace’s are stable. The trickster shows no signs of keeping his paws off the pole.
For information about the Dog Aging Project and the rapamycin trial, visit the website. You can nominate your canine companion to participate. The project is recruiting dogs of all shapes, sizes and breeds.