Every six months, Casey undergoes careful cardiac testing at a lab; she has been through extensive genetic profiling and is now enrolled in a drug trial that researchers believe could extend her life. Casey, an 11-year-old labrador-German shepherd cross who lives with her owner Kate Saunders in Massachusetts, is part of the growing effort to help dogs live better for longer, and which gerontologists hope may improve human longevity too.
Late last year, the US Food and Drug Administration (FDA) centre for veterinary medicine gave conditional approval for a drug created by San Francisco-based biotech company Loyal that could be available as a life-extending tool for large dogs by 2026.
The news from Loyal has given fresh hope to Saunders, and numerous other owners for whom extra “healthspan” (the healthy period of life) for their pets is a chance not to be missed. The new drug, LOY-001, targets a growth hormone called IGF-1 (insulin-like growth factor), the presence of which is some 28 times greater in large dogs compared with small ones. (It occurs naturally in humans too.)
Extensive research, including a 2019 study of 169,000 dogs, has shown that size is the key variable in predicting lifespan – namely, the bigger the mutt, the shorter that lifespan will be. That led Celine Halioua, Loyal’s founder and chief executive (and a self-described “big dog lover” whose rottweiler, Della, snoozes on the couch as we talk over Zoom) to target IGF-1. The breeding of dogs for size over hundreds of years “basically gave them an unintentional genetic accelerated ageing disorder,” says Halioua. Studying IGF-1, which some research has shown to be at low levels in human centenarians, was an opportunity, she says, to home in on what is “a clear unmet medical need”.
LOY-001 can successfully reduce IGF-1 levels in the blood in “a week”, according to Halioua – the question now is “how can you actually establish that there might be causation here; that high IGF-1 is accelerating ageing”. Loyal is measuring this via quality of life assessments from owners and vets (charting how comfortable the animals seem, and signs of cognitive decline such as unprompted barking) – methods that are “not perfect, but the best tools we have” – along with studies to see whether the drug has the desired effect. Early intervention is crucial, Halioua adds. “It doesn’t make sense to me that we wait until the end stages of a disease to try to start treating it.”
Other dog healthspan-extension trials are placing their focus elsewhere. The Dog Ageing Project (Dap), a collaboration between the University of Washington and Texas A&M University, has amassed more than 50,000 participants and “over 30m data points” from its canine studies, says its co-director Matt Kaeberlein. A trial (on which Casey is enrolled) is now under way exploring the effects of the drug rapamycin. It inhibits a protein called mTOR that regulates cell growth and metabolism, and has been found, at low doses, to extend laboratory animals’ lives by up to 14% when taken in older age; a 2023 paper called it “the only drug that has been consistently demonstrated to increase mammalian longevity”.
Analysis by Dap last year showed that 27% of dog owners whose pets took rapamycin noted improvements to their dog’s health and behaviour (compared with 8% who received a placebo). Kaeberlein predicts that a formulation of the drug may come to the market within two years, given its “very promising effects on heart disease and heart ageing” – in cats. “Everybody talks about dogs, but it actually might happen first in cats.”
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Yet as far as providing clues for human ageing, it is testing on dogs, as opposed to laboratory mice (or even cats) that could bridge the animal-human life extension gap, says Nir Barzilai, professor of genetics and medicine at the Albert Einstein College of Medicine in New York. “They share our environment in such a respect that their microbiota [bacteria present in a single place, such as the human digestive tract] is more similar to their owners than to other dogs.” We eat similar foods and follow a similar lifestyle, our metabolisms work in much the same way, and we suffer the same diseases, including cancer and cognitive decline. Dogs also have electronic medical records in many countries, making their – and our – health history easier to chart in close detail.
The strength of feeling people have for their pets can lead to them investing more in preserving the health of their animal than in their own wellbeing. “Dogs are going to be a platform that will be very important for us, because it will de-risk us, and without putting the dog in greater danger,” says Barzilai, who notes that dog exercise trials not only help the participants, but their owners, who must accompany them.
Kaeberlein says there could be other crossover areas for human and canine healthspan extension. These include urolithin A – “a natural product that activates a process called autophagy [when cells remove unnecessary or damaging components] and, particularly, what’s called mitophagy [removal of mitochondria, the powerhouses of cells that release energy, to improve mitochondrial function] during ageing” – and parabiosis, where older mice are given the blood of younger mice, which is shown to lengthen their lives by 6-9%.
He also suggests the targeting of the metabolic pathways using AMP-activated protein kinase, an enzyme that regulates cell metabolism, and metformin, used as a diabetes drug in the UK, which human longevity researchers believe is a vital tool in cutting age-related disease.
There are 12 broadly agreed upon hallmarks of human ageing, including genomic instability (accumulated genetic damage), cellular senescence (when cells can no longer grow and divide), stem cell exhaustion (where they struggle to renew, leaving organs unable to recover from damage) and chronic inflammation.
Currently the most tried and tested means of tackling several of these at once is – as ever – a good diet and exercise. A 2022 study published in the British Journal of Sports Medicine concluded that “adhering to both quality diet and sufficient physical activity is important for optimally reducing the risk of mortality from all causes”, with the greatest risk reduction among those who practised both. “Living longer is a side-effect of living healthier,” Barzilai says.
Still, in a post-Ozempic world, the idea of a medical fix to our problems has become all the more compelling – even if there are “conflicting opinions” over what that might look like, says Cathy Slack, a research scientist studying ageing at the University of Warwick. While LOY-001 has triggered plenty of buzz where dog ageing is concerned, “IGF-1 levels in the blood provide us with a useful biomarker of human ageing in certain contexts, [but] it doesn’t tell us the whole picture”.
There is also the matter of how widely individual ageing varies, according to Slack, posing “a considerable hurdle in devising universal interventions. Everyone will age differently, reflecting not only individual genetic differences but how our genetics, environments and experiences interact.” Wealth, she adds, might prove a more compelling marker of life expectancy than our DNA.
Barzilai says that drugs to help us live longer are in the works – but that more momentum is needed to pressure governments into approving them faster. “We need the public to say: ‘What’s going on? Why is it so difficult for [authorities] to understand that we want to stay healthy and not get diseases?’ This is what the field is promising. And the reason it’s not delivering is more on the [challenges of] regulation than of lack of evidence.”
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The UK Health Security Agency’s 2018 health profile for England report concluded that “although we are living longer than decades ago, we are not necessarily living healthier lives”. The number of years lived in poor health rose from 15.7 to 16.2 for men and from 18.6 to 19.3 for women within a two-year period. The over-65 age group will account for a quarter of the UK population by 2043, according to projections; numbers of over-85s, who now cost the NHS an average of £7,000 per person a year, will double.
“We cannot afford not to do it,” Barzilai says of the mission to develop longevity drugs. “It’s good for the individual to be healthy and it’s good for the economy to be healthy. For people to say longevity is a dream, or it’s expensive, is absolutely ridiculous.”
The more attention these drugs get, though, the more so-called “longevity influencers” are looking to cash in. They have become social media magnets (for humans now, but perhaps soon for dogs), making a veritable fortune pushing supplements without scientific backing to their millions of online followers and creating “a lot of noise” for consumers unsure how to separate the wheat from the chaff, according to Barzilai. Though most are harmless (and do not require regulatory approval because of being billed as health supplements, rather than medication), the effects when they are combined could be more damaging than we realise.
If “you buy all those things… you’re more likely to get sick than to get healthy,” Barzilai warns, as “we cannot assume that everything is additive, or synergistic. Some of them are antagonistic.”
It will take more clinical trials and regulatory will to bring longevity medication to shelves, but in the meantime, Barzilai says that dogs will play a key part in establishing “confidence with drugs that we are not ready for using [on] humans”. Many owners agree, and hope enrolling their pooches proves a win-win game.
“Extending dogs’ quality of life is a great goal and we might learn something about factors that help other species, including humans,” Saunders says. “I think we all want to help those we love live healthier and happier lives, whether you walk on two feet or four.”
