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In a late January episode of his popular interview podcast The Joe Rogan Experience, Rogan asked his guest, the Harvard geneticist and human longevity specialist David Sinclair, a simple question: “Do you feel incredibly fortunate to be living in this century?”
Sinclair had spent the prior 45 minutes of the interview detailing his work discovering and testing molecules that could extend human lifespan. That’s high-level life science, and Sinclair is good at it—he runs a lab at Harvard Medical School dedicated to understanding why we age and how to reverse it. But what sets Sinclair apart from many of his colleagues—and why he found himself on Rogan’s podcast, which often features scientists and thinkers in the field of what might loosely be described as human optimization—is his willingness to test his work on himself.
“I am not going to let anyone try technology until I’ve tried it first,” Sinclair has said. Beyond eating healthily and practicing intermittent fasting, he takes daily anti-aging supplements like 0.5 grams of resveratrol mixed into homemade yogurt in the morning and metformin—a prescription drug for diabetes that also is believed to have aging-related benefits—each night.
“Thirty years ago when I started talking about this, I was considered crazy for even working in this area of biology.”
As for Rogan’s question, Sinclair said he feels fortunate “every day” to be living in this century, but added this: “I would love to live in the next century because it’s going to be even cooler.”
Statements like this have long caused many of Sinclair’s peers to believe he’s, in a word, nuts. For years, Sinclair was one of only a handful of scientists studying the aging process at the cellular level, with the goal of discovering therapies that could allow humans to live longer and healthier. Longevity research had a touch of the alchemical about it, one that overpromised and underdelivered—which is why it was long ignored by most serious scientists.
“Thirty years ago when I started talking about this, I was considered crazy for even working in this area of biology,” Sinclair says. “It was really considered a backwater science.”
Today the field of longevity science—while still a playground for transhumanists and biohackers—includes some of the world’s most renowned researchers. Tech billionaires are supporting biotech companies researching the secrets of aging, like the Google-backed Calico and Jeff Bezos-backed Unity Biotechnology. Research into expanding the human lifespan is no longer automatically dismissed as charlatanry—with a few exceptions—and it is most definitely big business: The global anti-aging market was worth $42.5 billion in 2018 and is estimated to reach $55 billion by 2023. And David Sinclair is at the forefront of the movement.
His latest act is Life Biosciences, a longevity company he founded in 2017 with Tristan Edwards, a former equities trader at Goldman Sachs. The two worked in self-described “stealth mode” between 2016 and 2018 to complete a land grab of “the best intellectual property and people [in the field] we could find across the planet,” according to Sinclair. Life Biosciences is now a holding company of six subsidiary startups focused on developing medicines to combat the human aging process.
What sets Sinclair’s approach apart is his aim as much as his methods. Rather than create new treatments for some of the leading causes of death—like cancer or heart disease—the six companies under Life Biosciences are tackling the underlying causes of aging in the body, like stem cell exhaustion, metabolism, chromosomal instability, and cellular senescence, which is what happens when cells stop functioning normally. Sinclair is trying to convince the medical community and health regulators that aging itself isn’t just a natural biological byproduct of the passage of time, but a medical condition—one that can be treated, just like any other medical condition.
Sinclair and others in the longevity field argue that as we age, our bodies undergo changes at the cellular level that put us at a higher risk for disease. Rather than treating those diseases one by one, a successful longevity therapy would instead treat the underlying causes of aging itself. Doing so successfully would reduce the amount of time the body spends in the decline caused by aging, which would delay disease and, as a result, extend human lifespan. It’s not about living forever—yet. It’s about living healthier for longer, extending what Life Biosciences calls “healthspan.” The company wants to develop drugs that allow people to age without actually getting old.
“We are trying to change the view of the world about aging from something that is considered a natural course of life to something that we can find interventions for,” says Sinclair.
“A true intervention for aging will dwarf any other current public health intervention to date in terms of impact.”
It’s a lofty goal. It’s also potentially a very lucrative one. On March 4, the former chief scientific officer of PepsiCo, Inc., Mehmood Khan, announced that he would be retiring from the $170 billion food, snack, and beverage company and would become the CEO of Life Biosciences. Khan, an endocrinologist, told Bloomberg that he’d followed advances in the field of aging biology for years and knew some of the field’s leading scientists. “Historically, aging has been looked at as a normal consequence of life, and as medical professionals, we have not looked at aging as a disease process,” he said. “What makes [Life Biosciences] different is we are looking at all aspects of the known pathways of aging. Nothing is off the table.”
A company that successfully produces a therapy to slow, stop, or reverse aging first will “become extraordinary wealthy overnight,” says S. Jay Olshansky, a professor who specializes in aging at the School of Public Health at the University of Illinois at Chicago and is not involved with Life Biosciences. “Some of these proposed therapies will be legitimate, some of them not. But a true intervention for aging will dwarf any other current public health intervention to date in terms of impact.”
Life Biosciences, which is still private, closed a Series B financing round of $50 million in January. WeWork founder and CEO Adam Neumann is a founding investor and also sits on the company board. But only recently has Life Biosciences spoken publicly about its plans for the future, and in February, OneZero visited its 24,000-square-foot lab in the biotech hub of Cambridge, Massachusetts.
Inside the entrance of the Life Biosciences laboratory hangs a blown-up image of a photograph of the Wright brothers’ first flight in North Carolina, in 1903. It’s not there because Sinclair has a particular interest in aviation history. Rather, he likes to make an analogy between the discovery of flight and the grand ambitions of the longevity research taking place at his lab.
Before the Wright brothers flew for the first time, the idea that humans would achieve flight was largely science fiction. “After the Wright brothers flew, it was obvious and a whole new industry emerged, and the world was never the same,” Sinclair says. “The aging field is similar to 1903. We know we can glide, and we are strapping on the motors to see how far we can fly.”
Sinclair is still a full-time professor at Harvard Medical School, where he runs the Sinclair Lab, which focuses on the biology of aging. During his career, he’s made several major aging-related discoveries, including identifying a cause of aging in yeast while he was a postdoctoral researcher at MIT. He’s focused much of his research on sirtuins, a class of enzymes that control the body’s natural defenses against disease and aging itself. He has co-founded multiple biotech companies around this research, though none at the scale of Life Biosciences.
The idea to launch Life Biosciences began during a 2016 phone call between Sinclair and Edwards. Both men are from Australia—Sinclair has lived and worked in the U.S. since the mid-1990s, but Edwards was living in Brisbane at the time. After 20 years as a trader and hedge fund manager, Edwards says he was burned out. Aging research had always been a personal area of interest, and he decided he wanted to start a company around the subject.
Sinclair was the logical person to call. In 2008, a pharmaceutical company founded by Sinclair called Sirtris Pharmaceuticals was sold to GlaxoSmithKline (GSK) for $720 million. The company’s aim was to make drugs that activate the sirtuins Sinclair had long studied. GSK’s move was a major signal that aging research could earn investment from Big Pharma—though GSK ultimately shuttered the company facility five years later and absorbed its staff. “We decided to do this because the research at Sirtris exploring the biology of sirtuins has been highly successful and now requires the resources and expertise available from our broader drug discovery organization,” a GlaxoSmithKline spokesperson told media at the time. Kaiser Health News, however, has reported that the company’s results were “underwhelming.”
Nonetheless, Edwards was immediately taken by Sinclair’s ideas during their initial call. “While we were talking, I was looking at flights to Boston from Australia,” he says. Edwards asked Sinclair if he was available to meet in person the following day at 11 a.m., and Edwards booked a flight on the spot.
“I hang up and get my passport,” says Edwards. “I didn’t pack a bag or anything.”
Today Life Biosciences has slightly over 100 employees, including many PhD-level researchers. While all the startups are based in part in Boston, a couple are also co-located in Barcelona and Sydney. Each daughter company has lab staff members who work full-time out of the Cambridge laboratory. The marching orders for the six daughter companies are to both independently and collaboratively target eight biological pathways of aging. Spotlight Biosciences, for instance, is a company spun out of Sinclair’s lab at Harvard. The team developed a platform that allows researchers to scan samples of tissue, plasma, urine and more to identify thousands of new small proteins and genes that were missed in the genome-mapping projects of the early 2000s, and which might now be relevant for treating aging and other human diseases.
“Most people just imagine how hard it is living in your eighties and nineties. They can’t imagine adding 30 or 40 years to that. It sounds horrific to them.”
Senolytic Therapeutics, which is based in both Boston and Barcelona, is focused on finding ways to get rid of so-called “zombie” senescent cells. When the body’s cells stop working, they die and are replaced by new cells. Senescent cells are cells that should be dead but are instead building up in the body, causing inflammation that could eventually lead to cancer, as well as tissue degradation. Removing these cells from the body with drugs is believed to help treat aging-related disease.
Animal Biosciences is focused on finding drug and supplement targets for dogs, cats, and horses. But the company’s approach also offers an opportunity to explore molecules that might one day be used in humans as well. Edwards says there are molecules available today that show age-related efficacy in animals but “we can’t sell in humans yet because the FDA [approval] process is five to seven years, and for good reason. But we can sell in animals very quickly… That’s interesting because it brings revenue forward, but it’s more interesting because it gives us a huge amount of animal data that we can use for our human trials.”
Edwards also views Animal Biosciences as an easier way to inform the public about what anti-aging drugs can do—and what they don’t do. “I think bringing longevity medicines through our pets is a very good way to socialize this huge change that’s coming through to the medical system,” he says.
Making longevity science both comprehensible and acceptable to the public hasn’t been easy. Even with the bold-name hires, the major-league investors, and promises to protect our four-legged friends, Life Biosciences faces a major obstacle: Surveys show that most people say they would not undergo medical treatments to slow the aging process and live to 120 or more. It’s not hard to understand why. Those respondents likely had grandparents and parents who lived long lives, but spent many of those final years in pain, propped up by ever-more expensive and invasive medical care.
“There’s a lot of confusion,” says Edwards. “Most people just imagine how hard it is living in your eighties and nineties. They can’t imagine adding 30 or 40 years to that. It sounds horrific to them.”
But Edwards says the future they imagine at Life Biosciences is one where those added years are spent healthy and active. “That sounds fantastic to me,” he says.
While dreams of a cure for aging have existed since Herodotus’s first writings of the fountain of youth, longevity research is a relatively modern area in science. In the 1930s, researchers began to suspect that there might be a cellular-level driver to aging. As the writer Seth Mnookin has reported, Cornell scientists discovered that rats kept on calorically restricted diets lived significantly longer than their well-fed peers. But it wasn’t until the late 1980s that the first genes associated with aging were discovered. Scientists identified genetic mutations that caused tiny roundworms called C. elegans to live longer. A few years later, researchers at MIT identified genes in yeast linked to longer lifespan—genes that are also present in humans. “That was a surprise because we thought that aging was too complicated to be controlled by single genes,” says Sinclair, who was part of this research.
Those genetic insights legitimized the research of scientists in the longevity field. Modifying the aging process in both microscopic worms and humans proved far more complex than simply editing out a genetic mutation, however. “At the beginning, we thought it would be simple—a clock!—but we’ve now found about 550 genes in the worm that modulate life span,” Gordon Lithgow, a leading C. elegans researcher, told the New Yorker in 2017. “And I suspect that half of the 20,000 genes in the worm’s genome are somehow involved.”
Even so, research into aging has since gathered momentum—and funding. Some of Sinclair’s own discoveries related to sirtuins have moved the field forward dramatically. He discovered that a compound called resveratrol—which is found in the skin of grapes—could activate sirtuins and intervene in aging. (It’s the same compound that Sinclair now takes himself, though it hasn’t been approved as an anti-aging drug.) “It was the first molecule that could mimic the [anti-aging] effects of diet and exercise [in the body],” he says.
Today many scientists who study aging will tell you that people are still looking at longevity in the wrong way. Sinclair is in the camp of researchers who want aging to be accepted as a disease that can be treated in the same way as high blood pressure—not something that can be cured, exactly, but something that can be managed far better than it is today, in a way that benefits overall health and forestalls death. “We haven’t really made a concerted effort, as a society or as a species, to get at the root cause of aging, largely because we didn’t think it was possible until recently,” says Sinclair. “But that’s rapidly changing.”
The likelihood for diseases like cancer and Alzheimer’s increases as the human body ages. These diseases are much more common among people in their sixties and beyond than people in their twenties and thirties. Thanks to medical advances like vaccines, antibiotics, and improved hygiene, people in richer nations are now routinely living into their eighties. But that also means more people are living with disease, sometimes for years, at the end of their lives.
“If all we were doing was stretching out the period of sickness, then none of this would be worth it,” says Sinclair. “But we feel confident that we will not just extend lifespan but compress that period of decline and sickness.” A 2013 paper published in the journal Health Affairs projects that delaying aging could add 2.2 years to life expectancy, most of which would be spent in good health, and would have an economic value of $7.1 trillion over the next 50 years, thanks in part to reduced health care costs. And in doing so, the longevity field could solve a problem that modern medicine itself created.
“We’ve created our own nightmare where people live longer but not better.”
Life expectancy at the turn of the 20th century in developed countries was between 45 and 50, with about 22% of all people born in 1900 dying before their 10th birthday, largely due to infectious diseases. As Olshansky outlines in an October 2018 paper published in the journal Journal of the American Medical Association, thanks to public health gains, 96% of infants born in developed countries today will live to 50 or older and 84% will live past 65. “The 30-year increase in life expectancy at birth in the past 100 years is one of humanity’s greatest achievements,” he writes. But public health was ill-prepared to deal with the much greater incidences of diseases that come with so many people living into old age. In the U.S alone one in every four deaths is from cancer and an estimated 5.7 million Americans are living with Alzheimer’s disease.
“We believe that modern medicine is a good start to human health,” says Sinclair. “It’s been successful in extending our lives, but we’ve reached a point where we’re not keeping people healthier in their old age.”
According to Sinclair, that’s partly because currently available drugs are developed to target what he describes as “symptoms of aging,” which include diseases like cancer and heart disease. Even with the availability of new treatments like statins, which lower cholesterol levels, heart disease remains the leading cause of death for Americans. While rates of cancer deaths are dropping year by year, the number of new cases and deaths is rising, due to a population that is both bigger and older; (46 million Americans are 65 or older now, a number projected to more than double by 2060). “We’re missing an opportunity to address the actual causes of these diseases,” says Sinclair. “We’ve created our own nightmare where people live longer but not better. It’s costing society and families a great deal of angst and money keeping people around who are unproductive and not really with us anymore. It’s the living dead.”
Another challenge for Life Biosciences is the fact that the U.S. Food and Drug Administration, the federal agency responsible for drug approval, does not appear to view aging as a medical condition. Any therapies that come through Life Biosciences will at least initially need to be approved to treat diseases, rather than treat aging on its own.
“People are skeptical that you can change both a person’s healthspan and their life span,” says Dr. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine and a medical adviser for Life Biosciences. “They think you will live longer with disease, but that’s not what we are saying. We are saying, ‘aging drives disease, and if you end aging, you end disease.’”
Not everyone agrees. In a 2017 editorial in the journal Advances in Gerontology, two researchers at the University of Chicago—Leonid A. Gavrilov and Natalia Gavrilova—argued that “aging is too broad a concept to be reduced to a single, specific pathology.”
“In our view, aging differs from disease in the same way that cause differs from effect,” they write. “Aging is the cause of many age-related diseases. Correspondingly, these age-related diseases are a consequence of aging. Thus, it is an oversimplification to recognize aging as a disease (as to equate cause and effect).”
Many longevity researchers—including Sinclair, Barzilai, and Olshansky—are hopeful that regulators will come to agree with them anyway. Conversations with regulators around the idea of building a framework for aging drugs to be assessed and approved have been productive, says Olshansky, who met with the FDA a few years ago. “We were expecting resistance. Not only did we not get resistance, but the FDA was great and helpful.”
There are also questions around which therapies for longer living are legitimate areas of research versus which ones are expensive and questionable marketing for life extension. While Life Biosciences plans to develop drugs that are taken through the federal approval process—rather than supplements that do not require clinical trials—there are a number of companies already selling pills marketed for anti-aging perks, including the kinds of supplements Sinclair takes personally. You can even get transfusions of blood plasma from young people, on the medically questionable grounds that it can rejuvenate the body. (The FDA recently recommended against such procedures).
Olshansky says there is longevity research and there are anti-aging supplements and “there’s a huge chasm between the two.” While longevity scientists may themselves be interested in living past 100, the distinction is really about living healthier for longer and not just reaching the centenarian milestone. “Maybe maximum lifespan will be 125, [or] maybe it will be 110, but I am honestly not interested in that,” he says.
But consumers may not easily understand that distinction. There are pills sold online today that claim to interfere with the aging process. And even though aging researchers—including Sinclair—may try them, support them, or sit on supplement companies’ advisory boards, supplements do not need to prove the same effectiveness that drugs do. A drug that targets aging pathways in the body and is approved by the federal government would signal the first real treatment for extending lifespan, but any such drug is likely many years away.
“If it were possible to safely slow aging, the positive consequences for human health would likely be substantial,” says Jeffrey Flier, a Harvard professor and former Harvard Medical School dean. “But it’s a very difficult problem, both scientifically and practically from the perspective of drug development. The end points—normal aging and death—take a very long time to be reached… Given the interest in achieving the goal, people are sometimes tempted to exaggerate how close they are. Buyer beware.”
While he may not approve of some of the therapies Sinclair takes on his personal time—“Nobody, especially scientists, should be taking any of these supplements until they are proven safe and efficacious”—Olshansky says Life Biosciences appears to be taking steps beyond the incremental.
“I approve of what David Sinclair is doing,” he says. “This kind of aging science not only makes sense but it’s the only pathway forward, and we need to pursue it aggressively.”
In the meantime, Sinclair is confident Life Biosciences will produce tangible results to convince more people, especially regulators, that drugs for aging are feasible—and that his company will discover them. “I can’t speak on behalf of everybody, but my hope is that within our lifetimes, we will see that doctors are able to prescribe medicines as a preventive measure against the diseases of aging,” he says.
The idea of picking up a prescription for a drug that stalls aging at the local pharmacy still feels like science fiction, but it’s a goal many longevity scientists believe we’ll achieve this century. And if they can do so, David Sinclair won’t be the only person who just might live to see the next one.