The Search for a Pill That Can Help Dogs—and Humans—Live Longer

Bocce, a chihuahua-dachshund mix with brown eyes and a long lost friend, is greeted by celine Halioua in a crouch. She exclaimed, "Oh my gosh, you're so beautiful!" Light and urine can be seen through the open windows of the upstairs room where the two met. A group of elderly dogs, none taller than a knee cap, are sleeping on linoleum or blankets. Bocce rests his head in Halioua's lap.

A tragedy of human-canine relations is that a 10-year-old dog such as Bocce is older than a 28-year-old person such as Halioua. One of the lucky ones is bocce. The lifespan of a dog is related to body size. In the animal kingdom, elephants easily outlive mice, which in turn outlive mosquitoes. An Irish wolfhound can live up to seven or eight years, while a Great Danes can live up to fifteen years.

Halioua is hoping that the startup with her name on it can start to fix the bug in the wolf bioengineering project. She founded and leads a company that is developing drugs to prolong the lifespan of dogs. She has raised close to $60 million and has two drugs in the works. She wants to have the first commercial drug that states on the label that it prolongs lifespan for any species. Halioua sees it as a starting point to create similar drugs for humans.

Today's most far-out ideas for preventing death, such as freezing people for eventual revival, and reincarnating them digitally, sound like technological fairy tales. Life extension in lab animals is already happening, with studies increasing lifespans of worms, flies, and mice. Aging is not yet recognized as a condition that can be treated by regulators.

Halioua, a fast talker who speaks in a confident mix of Silicon Valley and biotech jargon, believes that starting with dogs puts her on the best path to the firstaging treatments for people. Only about 90 percent of new drugs fail in clinical trials. It won't take decades to know if a pill increases longevity because the animals' shorter lives mean it won't take that long to find out. The lifespan and lifestyle of a pet dog are more humanlike than a lab mouse's is, so Halioua argues she'll be in a good position to jump from pups to people.

She has been enamored with dogs since she was a child in suburban Texas. Loyal has worked with the staff at Muttville to recruit owners and their dogs into two studies of aging.

Halioua can see how Muttville would care for a more diverse crowd if Loyal's drugs worked. The age of dogs in that world would be from 10 to 12 or 14.

Life has never been better for dogs who have a home. Multispecies families are created when pet parents invest more money and emotion in their pets than ever before. It would appear that a drug to prolong their time together is easy to sell. Dogs should deliver more years to humans. You can't ask a friend for more.

At the University of Texas at Austin, she was majoring in neuroscience. She got a position at a prestigious independent stem cell lab after looking at an ad for summer internships in a department newsletter. She didn't know that the internship's sponsor was a Silicon Valley-based nonprofit that wanted to help build the industry that will cure the diseases of aging. The scientific mastermind was a computer scientist who was turning into an old man. He was a high-profile voice in a part of biology that was not fully established.

In 1993, a team of UC San Francisco scientists showed that disabling a single gene could double the lifespan of a worm. The title of the group's report in a nematode newsletter drew a provocative analogy to humans: "Imagine Being 140" A new field dedicated to wresting control of the biological mechanisms of aging was created by the study.

Researchers tracked down genes that were linked to longevity. Some of the same mechanisms they identified in worms could be used in flies and mice. Evidence began to show that aging wasn't just inevitable. It was a biological process that might one day be hacked. Some wild animals have a long life span. One of the longest-lived mammals is the bowhead whale. Naked mole rats and some tortoises are resistant to age related diseases.

De Grey was annoyed by society's indifference to the idea of slowing or reversing aging in humans, but he was inspired by the science. In 2003 he drew interest to his cause by celebrating a dwarf mouse known as GHR-KO 11C, who died at Southern Illinois University a week short of his fifth birthday. The first payouts from the Methuselah Mouse Prize went to the creator of 11C. When speaking about 11C, de Grey took the opportunity to promote a program he had drawn up called Strategies for engineered negligible senescence that he claimed could eventually defeat aging, allowing a person who was 50 in 2030.

In 2005, 28 distinguished researchers wrote a paper declaring de Grey's strategies to be a farrago in "the realm of fantasy rather than science." Their target continued to win media attention and make headway with tech industry freethinkers despite this. He received over 3 million dollars from Peter Thiel. The SENS Research Foundation was founded by de Grey in 2009.

The foundation provided small grants to researchers around the world and had labs of its own in Mountain View. A new generation of scientists was supposed to be created by the summer fellowship program.

Halioua had a summer in California that made her think more about aging than most teens. She looked through a microscope at cells from patients who had died from aggressive brain tumors, which, as with most forms of cancer, becomes more likely with age as changes accumulate in a person's genes. She returned to a room she had rented from an elderly veteran with a goofy smile and a hill- running habit. A vet befriended a nervous intern and invited her to go on dates with him. It was her first time talking to an older person. Halioua says that he helped her realize that she will be old someday.

Halioua met de Grey at the annual conference of the SENS Research Foundation in San Francisco at the end of the summer. The crowd mixed respected academic scientists with tech investors, a science adviser to Obama's secretary of state, and other people who hoped to see de Grey's most far-out predictions come true.

The idea that aging could be treated like a disease was gaining traction among Silicon Valley's richest men. When Larry Page turned 40, he announced that his company was backing a new venture that would work on aging treatments. The creator of the long-lived worms was hired by it. The US National Institutes of Health, the world's largest public backer of medical research, created a "geroscience" initiative to investigate how the aging process contributed to chronic diseases, such as Alzheimer's and cancer.

Studies in lab animals show that certain drugs can extend lifespan and stave off age related diseases, a glimpse of what people might one day enjoy. Some of them appeared to do so by boosting cellular signals that ramp up when food is not available. Rapamycin is a drug that humans take when they receive an organ donation. Steven Austad, codirector of the aging research center at the University of Alabama at Birmingham, said that it could extend the lives of mice by up to 25 percent. It was worth seriously investigating how aging might be treated in humans, even though Austad was a coauthor on the 2005 paper.

She rented the same room from her old friend for her second internship. He died from Pancreatic Cancer. He was struggling to pay his health insurance premiums even though he was still running. Halioua overpaid her rent so that he could get extra cash.

De Grey argued that it was necessary to devote more scientific effort to slowing or stopping the processes underlying cancer and other age related diseases. Halioua said it made sense. I knew I was going to live here for the rest of my life. She impressed a researcher with her presentation at the end of the summer season. She accepted when he asked her to join him in the UK as a graduate student. Her landlord passed away that fall. She moved to England with a new purpose.

Halioua loved Oxford. Her thesis looked at how health systems might cover treatments that only lasted a short time. She had a part-time job that was supported by the foundation. Her life began to fall apart.

Halioua and her supervisor had a falling out. He forced her to do work for a company he worked for and restricted who she could talk to. Halioua didn't name her supervisor. He didn't reply to the request.

She was not comfortable with the spirit of de Grey. The foundation had a lot of glamour for her. Rich and distinguished men were encouraged to donate to the war on aging at the formal dinners. She thought she was only being invited because she was cute. Also smart, but they didn't care about that. She said de Grey plied her with alcohol and told her that she had a duty to have sex with donors. De Grey denied making the statements after Halioua went public.

Halioua was looking for a way out. She says that she snapped because of what her professors did. It made me want to create my own sphere of influence. One of the few prominent women in the small circles is Laura Deming. After receiving a fellowship from Peter Thiel, Deming dropped out of MIT at the age of 14 and now runs a venture capital fund in San Francisco that invests in aging-related startups. She is working on technology to freeze organs without damaging them. Halioua was introduced to De Grey by him, and now she is looking for an internship.

The interviewer was arranged by Deming. It was very intense. I asked her a question about Markov models, a math trick to analyze processes that change over time, and she was determined to figure it out, even though she didn't have the exact answer. That was great. The internship was only two weeks, but for Halioua it was enough to be a refuge. She went to California in the beginning of the year.

The WeWork in the Tenderloin is located in a San Francisco neighborhood that is also rife with human misery and crime. It wasn't safe to leave the office at night in Oxford or Austin. It felt like working in venture capital wasn't familiar. At Oxford, graduate students and researchers leave the lab at 5 pm and go home or to the pub. Emails were lengthy and formal. Entrepreneurs and investors in San Francisco spent hours over dinner debating their ideas about the future.

Halioua received a job offer at the end of her internship. She was able to accept and complete her PhD at the same time. The arrangement worked for a while, but relations with her supervisor deteriorated and she filed a formal complaint. Halioua found her department's investigation to be slow even though he left the university. The head of her former department said that all complaints will be considered carefully and rigorously. She had panic attacks while she was waiting for the official assessment. She says that she feels like she's crazy. Everybody tells you that you are being sensitive or misinterpreting what someone says to you. She left Oxford for good after working for Deming for a while.

Halioua didn't know much about venture capital or Silicon Valley, but she did know how to network. She began to send out news of pharma deals, photos of San Francisco beaches, and her appreciation of Musk. She helped bring about investments in two companies that aim to fight diseases of aging by modifying a patient's genes. The news that Oxford had upheld most of her complaints came almost a year after she had filed them.

A dense, roughly 50-page memo on the investment potential of the biochemical pathway Cynthia Kenyon had used to double the lifespan of worms emerged from Halioua's own company. In many species, including humans, it involves a hormone that adjusts an animal's growth and metabolism. The lifespans of flies, worms, and mice could be extended by tinkering with this pathway.

The literature didn't seem to have a lot of clues for how to turn this knowledge into a drug. Although the pathway was implicated in certain eye diseases unrelated to aging, Halioua wasn't excited about working on them.

Halioua was drunk on a camping trip when a factoid came back to her. The trip was organized by the founders of a trucking startup. She made a joke around the campfire that she knew how to extend the lifespan of a dog because it was implicated in dog body size.

Herquip became part of the collective consciousness of Silicon Valley. One investor mentioned Halioua's idea to a founder he knew, who in turn gave it to a venture capitalist. The first cloned dog, an Afghan named Snuppy, was created by scientists in South Korea. When he met Halioua for coffee in San Francisco, he realized she had a solution to the problem of a dog not living long enough.

Funding for the year was $5.1 million. She sent all of her investors a thank you note. Her company's formative months, and first hires, took place via a number of online platforms. Scientists, veterinarians, and an expert in getting new animal drugs past the FDA were hired.

She painted a mural of a giant German shepherd in Loyal's office and ordered shirts that said "Save the dogs, save the world." She adopted a dog named Wolfie, who she said was Loyal's chief Evangelist. She said her bad experiences at Oxford influenced her management style. She tries to convince her workers that her boss is telling the truth when she talks about her goals or beliefs. She says that even if you don't trust her, you still know she's right.

Halioua's new science team helped refine her original idea. The compound they believed could be given to young dogs to delay their aging process was found by them. They discovered a second compound that could be used to target processes that cause cognitive decline in older dogs.

Halioua noticed some patterns in her interactions with other people. She tried to get women to invest, but it was hard because there weren't many to ask. When she met with investors who were men, some would try to convert a business meeting into a date, and others would explain science to her that she knew inside out. Her time at Oxford lowered her expectations of those with more power and prestige than her.

She didn't feel the same. She had left her PhD in part due to unhappiness with a harassment investigation, but she was still able to convince people that she was serious. She tried to learn the industry's jargon by listening to hundreds of Silicon Valley podcasts. She said in the post that she was a grump who had the money she needed to build her company.

Halioua wrote a post about her Oxford PhD supervisor in the spring of 2021. She said that one of the worst experiences of her life taught her to be skeptical of social power. Two years have passed since I left. She wrote that she is not broken but still feels the cracks. My preconceived notions of how the world works were shattered by his abuse.

The burden of Halioua's experience with de Grey still weighed on her. She had known de Grey for a long time and had experienced an uncomfortable experience with him. De Grey was asked to introduce her to someone days before her 18th birthday. He said in his reply that he wanted to have sex with Deming. I have a fairly adventurous love life, and I am not coy in talking about it, but I have always taken care to avoid talking about it with someone so young as you. I could treat you as an equal on every other level, that's what it felt like. Maybe those days are behind us. De Grey said the email was an error in judgement.

In June 2021, the two of them heard that de Grey might be helping another girl. The two women decided to report their experiences to the foundation in order to protect this girl and other people. The organization put de Grey on leave while they investigated the allegations. The nonprofit promoted de Grey's posts on social media in the weeks after.

The two of them decided to go public because they were worried that the nonprofit was too conflicted to investigate itself. Two women posted detailed statements to their websites at the same time. A round of media coverage about the allegations, as well as denials from de Grey, followed the spread of word.

The board of the SENS Research Foundation decided to separate from de Grey immediately after learning that he had tried to undermine the investigation by sending emails to a participant. The law firm of the foundation upheld the accounts of the two people. According to De Grey, the women were tricked by people trying to get him out of his nonprofit and that he has never said anything to them.

Halioua was certain that she had done the right thing and that her career was not in danger. She didn't have time to think about the uproar. In August her team announced that the National Institute on Aging would collaborate with Loyal to test two of the company's compounds to extend the lifespan of mice. She turned 27 in three weeks. She disclosed that Loyal had raised an additional $27 million. Women made up half of her new investors.

The scientific muscles needed to upend conventional wisdom about aging began to be flexed by Halioua and her team. They collected data from over 500 dogs who were brought to a vet clinic for a health assessment. For a second study, they recruited some 2,000 owners to receive Loyal- branded doggy DNA sample kits that they could use to understand the markers of aging. Dog lovers on social media immediately picked up the scent and both studies filled up fast. She says she has nothing against cats, but that they are less appealing because of their long lives, dislike of medicine, and lack of humanlike qualities. Halioua says they are like littlebiological aliens.

Loyal is preparing for the trials of its products. Halioua isn't giving away a lot of information about Loyal's drugs, but she does say that both medicines have performed well when given to lab dogs One of the reasons for owners to have an animal euthanized is to delay the start of age related diseases such as dementia. Halioua says it uses pathways that are used in restriction of calories. She expects to launch a full clinical trial next year in order to win regulatory approval for the drug. The second drug may affect the cellular processes that are believed to condemn the largest dog breeds to short lives.

The FDA sign-off on the study designs will be the first thing the company tries to get. The agency would be supporting the idea that drugs can be tested and proven to increase longevity. To hit a whole suite of ailments by tackling aging at its root is what that is.

To navigate the scientific and regulatory hurdles, human longevity startups have taken to focusing on drugs that are effective enough to get first approved as a conventional treatment for a single disease, and they hold broad antiaging effects. The hope is that once the drug is benefiting patients, data will pile up that proves its preventive powers.

James Peyer, the CEO and co-founder of antiaging startup Cambrian Biopharma, has raised more than $150 million. Establishing a rich portfolio of potential drugs for humans helped win investors over, according to him. He admits his two-step approach isn't the only way to go, and it's possible that Halioua could have hit on a quicker way to get an antiaging drug for humans. She can focus on the drugs' antiaging properties right from the beginning, one of the reasons she is so brilliant. The company could be well positioned to jump species if the mechanisms that Halioua's team discovers align with human biology.

There are other outfits trying to understand dog longevity. The Dog Aging Project, led by the University of Washington and Texas A&M College of Veterinary Medicine and Biomedical Sciences, has completed two small studies in which owners were given rapamycin or placebo pills. According to Matt Kaeberlein, a University of Washington professor who is codirector of the project and an adviser to Loyal, people who gave their dogs the drug reported that they became more active. He hopes to get firm proof of rapamycin's effectiveness in a larger trial of about 600 dogs.

Some aging mechanisms are shared across the animal kingdom according to Kaeberlein, who studied life-extending genes and treatments in yeast, worms, and mice. He says that he is certain that something will affect lifespan and health span in dogs. He doesn't want to say if he gives rapamycin to his dog, Dobby, an 11-year-old German shepherd. Kaeberlein believes that the drug helped resolve an attack of frozen shoulder, a condition in which the joint becomes stiff and painful.

Like other veterans of academic aging science, Kaeberlein has levelheaded excitement but also impatience when it comes to the future of aging treatments. Evidence shows that it is possible to slow down the aging process in animals. Would you like that pill to exist? The director of the Institute of Aging at Albert Einstein College of Medicine says that scientists should be given time and money to figure it out.

According to Barzilai, we need to start making progress with drugs that won't make us live 150 years but will make us healthier for a long time. He has been trying to get funding for a human clinical trial to investigate if a common diabetes drug can delay aging. Longer-lived and more active dogs could have other effects on humans, such as more support for aging research and more active owners.

Halioua was sitting on an easy chair in Loyal's San Francisco office and argued that Loyal could break the psychological barriers holding back the war on aging. "Many people don't know that we've extended lifespan in mice many times, and even if they do, it's a mouse." She says that a proof of concept that is more persuasive and lovable is what would kick the field into a higher gear.

She wants people to see aging science not as a realm of weird ideas and thinker but as a branch of pharma. Silicon Valley entrepreneurs are known for creating products that cause jaws to drop. Halioua may make her greatest mark by killing hype rather than creating it, which will transform the idea that drugs can extend life into an everyday comfort.

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