Key insights:
- The FDA has issued its first indication that regulatory approval for aging therapies in dogs is possible.
- Promising new therapies are challenging the idea that the short life span of many large dog breeds is inevitable. Research has revealed that some breeds die early due to an accelerated aging disorder stemming from hundreds of years of intensive breeding.
- By targeting these large dogs’ high levels of the growth hormone IGF-1, aging therapies could help give a dog a greater number of healthy middle years.
- All the research now being done on dogs could have implications for longevity research in humans.
In the animal kingdom, size often directly correlates with lifespan. Small mammals like mice may live a few years, while elephants can reach 60 and whales, 100. In dogs, we see the inverse: the larger the dog, the shorter the expected lifespan. At the extremes, a Chihuahua may live 18 years, while a Great Dane only eight. In fact, dogs are one of the only species where we see such a stark difference in life expectancy within the same species.
A new understanding of canine longevity
I founded Loyal in late 2019 around the core idea that the short lifespan of big dogs is not inherent, but instead an unintended consequence of historical inbreeding for size. The genes that turn a small puppy into a large lovable Dane or calm, affectionate mastiff also seem to drive them to post-skeletal maturity faster than their smaller companions. In effect, their short lifespans are a type of accelerated aging disorder created by hundreds of years of intensive breeding.
One of the core insights driving our research relates to the growth hormone IGF-1. Large and giant breed dogs have levels up to 28 times higher than those of smaller dogs. This small protein circulates in the blood, binding to cells and, among other things, drives cellular nutrient use and growth. As a result, the tiny puppy grows rapidly into the large Dane. However, once the dog is fully grown, high IGF-1 levels turn pathological, making the dog more vulnerable to disease, reducing their quality of life, and ultimately shortening their lifespan.
IGF-1 is one of the most well-studied longevity pathways. In studies with roundworms and mice, reducing IGF-1 extends healthy lifespans; increasing IGF-1 shortens them. This has been replicated dozens of times, and there is even genetic data suggesting a similar mechanism in humans.
“today’s most promising lifespan-extension therapies — ours and those of other groups — target the increase of an animal’s healthy years”
I decided to develop a drug to target this pathway because this was the starkest example of aging I had observed. High IGF-1 robs large dogs of up to eight years of life, as compared to their smaller companions. I believed this was fixable. I also hoped that by developing a drug to benefit large dogs, we could help create a new regulatory pathway — one that would allow other lifespan-extending drugs for dogs, and eventually humans, to be developed.
Extending a dog’s healthy middle years
Last month, we achieved a crucial milestone in bringing this product to veterinarians and dog owners: efficacy package approval. Specifically, the FDA (yes, the FDA regulates dog drugs!) let us know that our canine compound LOY-001, which reduces IGF-1 in large dogs, had met one of the agency’s three requirements for conditional approval. Based on our study with 451 dogs, the agency indicated that LOY-001 has a “reasonable expectation of effectiveness” for extending a dog’s lifespan. This step represents a significant landmark in longevity research. For the first time, the FDA has signaled formal confidence that a drug can be developed and approved to slow down aging.
But what does this really mean? Aging technologies are often associated with immortality or pie-in-the-sky ambitions to bend the laws of biology. To be clear, our goal isn’t to create 50-year-old dogs. We also don’t want to extend a dog’s last years when its health and quality of life are dramatically diminished. Instead, today’s most promising lifespan-extension therapies — ours and those of other groups — target the increase of an animal’s “healthy years.” By reducing IGF-1, we expect that LOY-001 will slow down the abnormal aging process of large dogs, delaying the onset of progressive and debilitating diseases and expanding those good middle years.
“For the first time, the FDA has signaled formal confidence that a drug can be developed and approved to slow down aging.”
Our next steps are to prove that this medicine is safe for dogs and that we can manufacture it reliably. If these hurdles are cleared, we expect that by 2026, vets could give their canine patients that are at least 7 years old and 40 pounds an injection every three to six months that will help keep them healthy longer. Based on our research, we think this could extend the lives of these dogs by at least one year, a meaningful portion of their time on Earth. Eventually, we expect to be able to generate additional data that will allow dogs to receive doses at younger ages.
A step toward research on human aging
We’re hardly the only ones working on what once seemed like science fiction. The FDA’s preliminary acceptance will benefit the broad field of longevity science, enhancing its overall credibility and bolstering the work of other companies and researchers targeting additional drivers of longevity in dogs — and in humans.
In fact, the work being done in dogs will not only serve our furry friends but function as a bridge to new insights about human aging. Although scientists frequently use mice as a model for humans, dogs are actually much more similar to us, both genetically and physiologically. They suffer from many of the same age-related diseases we do, from blindness and arthritis to cancer, dementia, and Parkinson’s.
I’m excited about what canine research can teach us about human potential. I see momentum building for lifespan-extension research and therapies that may one day help us also prolong our healthy middle years. Although these future medicines could boost our average lifespans by a few years, their most tantalizing benefits will be in how they change the way we think about the arc of our lives. Today, much of our physical and mental decline — muscle mass and strength, bone density, balance, energy levels — starts in our 50s. What if those processes didn’t start until our 60s or 70s? The implications for how people see their lives and how society functions are fascinating. After all, if people are mentally sharp, energetic, and largely disease-free into their 70s, changing careers or having kids at 40 or 50 is no big deal.
We’re obviously a long way off from 70 being the new 50, but everything we do in dogs today is teaching us about human aging. Our canine companions already give us so much. This may be one of their most important gifts.
