Is there any truth to anti-aging schemes?

On a Thursday evening in late January, the faithful gather. They trickle into the Church of Perpetual Life, about an hour’s drive north of Miami, until a throng of around 100 people cram around tables lining the first-floor hall of this renovated house of worship. Along one wall is a display of reading material: pamphlets on heart disease, flyers itemizing the additives in Cheez-Its and their detrimental health effects, a handbill about the Ms. Senior Florida pageant. On the other side of the room, there’s a snack buffet with beans, broccoli, carrots, cubed cheese, sliced meats, and olives. It’s easy to pick out the regulars, who mingle clutching biology textbooks or readily shaking hands. Many of them pause to greet the diminutive man who is their host: Bill Faloon. Clean-shaven and youthfully slim in a dark suit, with jet-black hair and a formidably bridged nose, he is the church’s founder. Just yesterday, he laid out its gospel to me, saying, “We’re talking about immortality.” His followers, he says, are “people trying to live as long as possible, maybe even forever.” At 63, Faloon is old enough to remember when such talk labeled you a kook or charlatan. In the late 1970s, he co-founded the Life Extension Foundation, a nonprofit promoting the notion that people don’t need to die—and later started a business to sell them the supplements and lab tests to help make that dream real. Nowadays he also distributes a magazine to 300,000 people nationwide and invites speakers to monthly gatherings at the church, billed as a science-based, nondenominational meeting place where supporters learn about the latest developments in the battle against aging. Their faith is in human technologies that might one day end involuntary death. After an hour of mixing, we all head to the second-­floor nave and fill the pews for the evening’s event. Several rows back sits a beer scientist. Next to me, two women in dresses and heels. At the front, an elderly gentleman with hearing aids. Tonight’s speaker is Aubrey de Grey, a biomedical gerontologist and chief science officer of SENS Research Foundation, a Mountain View, California, outfit that studies regenerative medicines that might cure diseases associated with old age. De Grey’s startup reflects the rush of Big Tech money into this arena as the U.S. population ages. Baby boomers are retiring, and the Census Bureau estimates older people will outnumber children by 2035. Google launched Calico in 2013 to solve the challenges of aging and associated illnesses. Two years later, Facebook founder Mark Zuckerberg and his wife, Priscilla Chan, started the $3 billion Chan Zuckerberg Science program, whose lofty goals include curing all disease. And Amazon founder Jeff Bezos and PayPal co-founder Peter Thiel invested in Unity Biotechnology, launched in 2016 to develop therapies for age-related ailments.

Today, it’s also easy to locate university-affiliated labs at places such as Harvard and Stanford investigating their own interventions in the process of growing old. Since the National Institutes of Health established its Institute on Aging division in 1974, scientists have dedicated more and more resources to the challenge. Over the past dozen years, the NIA’s budget has doubled to more than $2 billion.

Faloon predates them all. These days, the several ­hundred people who regularly attend events at the church are personal validation for Faloon, who thinks that anyone his age and younger, given the proper physiological tweaking, could live to a healthy age of 130. The hope is that, by then, new solutions will make death truly optional. Yet no amount of self-tinkering can assure him and his followers that day will ever come.

Faloon was 8 years old and living in ­Pittsburgh when his mother told him that dying was a part of life. The concept didn’t sit well with him. “I was determined to find a way to conquer death,” he says. As a teenager, he became fascinated by the nascent and dubious field of cryonics—freezing the body upon death in hopes that a future technology can reanimate it. After high school, Faloon ­studied mortuary science so he could cryopreserve people. To this day, he is a licensed funeral director and embalmer. In the early ’70s, at age 19, he moved to South Florida and soon fell in with folks equally fascinated by cryonics. At a get-together of local enthusiasts, he met Saul Kent, a fellow believer, and in 1977, the two founded what would eventually become the Life Extension Foundation. A few years later, the two men formed a business—the Life Extension Buyers Club—to sell supplements. The problem was that they were also helping their members obtain medications that were not approved in the U.S. In 1987, federal agents kicked in their doors, seizing their products. In 1991, the U.S. government indicted them for helping to distribute unapproved drugs and pharmaceuticals without a prescription.

“We were promoting all kinds of ways to slow aging that nowadays are recognized but hadn’t made it into the mainstream yet,” Faloon says. For instance, metformin. Approved for prescription in England in 1958 and in Canada in 1972, the drug increases insulin sensitivity, improving the body’s ability to process sugars. This effect on glucose metabolism is the main reason metformin is now commonly used in the U.S. to treat type 2 diabetes, but the Food and Drug Administration didn’t approve it until 1994. Studies since then show that diabetics on the medication generally live longer and appear to get cancer as much as 40 percent less than diabetics on other medications.

Back in the ’80s, Faloon considered what he’d read about metformin enough for him to recommend it to buyers. But science isn’t so quick to repurpose a drug. First, a randomized controlled trial has to show results . This year, one such test, called Targeting Aging with Metformin, or TAME, should get underway. It is the only FDA-sponsored study to look at whether a specific drug can slow aging.

FDA approval is predicated on outcomes. If you want permission to sell a new kind of pharmaceutical for lowering cholesterol, you will first need to show that it decreases a person’s risk of developing heart disease. That it took the regulatory agency this many decades even to consider greenlighting an anti-aging drug speaks to how complex a challenge it is to untangle the process of growing old.

Aging begins at the cellular level. But it took a long time to figure that out. For much of the 20th century, biologists thought that cells were immortal. That changed in the 1960s, when microbiologist Leonard Hayflick discovered that some human cells divide 40 to 60 times before stopping at what we now call the Hayflick Limit. That division is important. It’s what helps your body grow, or repair damage (like after you cut your finger ), or fend off attack (like when your immune system defends against a virus).

Since then, researchers have discovered that even cells that keep dividing age, and they become inefficient at basic functions such as repairing DNA and recycling proteins, lipids, and other key molecules. Unable to ­maintain themselves, they accumulate damage, which impedes their ability to function normally or repair bodily tissues. Think of a car that falls into disrepair until one day, it just won’t start. Our senses diminish, our skin goes slack, our joints creak, our muscles atrophy, and eventually the diseases associated with our older years creep in to finish us off: stroke, Alzheimer’s, pulmonary fibrosis, diabetes, heart disease, cancer.

Faloon was determined to use the Life Extension ­Foundation to search for alternatives. He persisted even while under indictment; the foundation and buyers club remained legally free to market and sell supplements. Federal prosecutors, struggling to find testifying witnesses, ended up dropping all charges by 1996.

In 2013, he and Kent took their mission a step ­further, spending $880,000 to buy a building and open the Church of Perpetual Life. At first attendance was low, but now the venue is regularly packed. The place attracts medical doctors and laypeople alike. For several hours each month, they swap the latest information, take in what visiting researchers have to say, and, afterward, enjoy a catered meal together (January’s menu offered chicken, salmon, and tilapia).

“The idea is to bring people together and talk about a lot of ideas,” says Faloon. “It’s a real attempt to persuade more of the public that dying is not a good thing.”

Forever Family

In 2013, the academic journal Cell published a paper called “The Hallmarks of Aging,” which identified nine factors. Some contribute to the decline of young cells, while ­others play a role in driving the ­pathologies that lead to our demise. The report also highlighted several experimental therapies that have yielded encouraging results so far.

Most of the approaches that are mentioned in the paper fit into particular buckets: drugs that regulate metabolic pathways related to aging; tactics for killing off cells that have hit their division limit; restorative treatments to supply missing stem cells, which divide to repair tissues and organs. Researchers had previously tested all of the remedies in rodents.

“We don’t know for sure that the same tricks we use in laboratory animals will work in people, but probably some of them will,” says Matt Kaeberlein, a pathology professor at the University of Washington Medical Center in Seattle. Metformin and rapamycin are two drugs with promising implications. In mice and rat trials, both ­extended life span. Some of Kaeberlein’s work shows that rapamycin, typically delivered as an immunosuppressant following organ transplants in humans, mimics the effects of caloric restriction. Eating less puts strain on the body, and might alert cells that it’s time to halt division and focus on repair and stress resistance, both of which could contribute to longevity. Rapamycin might create the same effect without requiring you to skip a meal.

Nir Barzilai likes metformin because it is safe. ­Diabetics have used metformin, a modified version of a plant compound, for decades. Barzilai is director of the Institute for Aging Research at New York’s Albert ­Einstein College of Medicine, the lead sponsor of the five-year TAME trial that will soon enroll 3,000 ­participants between ages 65 and 80. He believes that the drug does more to alleviate damage in an aging cell than it does for improving glucose metabolism.

“People with diabetes on metformin have 17 ­percent less mortality than people without diabetes, even though they are more obese and more sick to begin with,” ­Barzilai says of the drug’s effect. “So metformin is really about aging much more than diabetes.”

The Cell paper highlighted other ways to disrupt the aging process. If these units of living matter become inefficient as they age and divide, couldn’t we just replace them? In the case of stem cells, yes.

“What’s the key to being able to turn a 1950 ­Chevrolet into a useful operating tool?” asks surgeon-turned-­biomedical pioneer Bob Hariri. “It’s all about ­replacement parts, right? Look at what happens to people who get stem-cell transplants for bone-marrow reconstitution. If the donor is younger than the recipient, quite often the biology of that recipient improves.”

Hariri is a co-founder of Human Longevity Inc., a ­Silicon Valley venture using supercomputers to search for genes related to human aging. But he’s better known for his research into stem-cell therapies, first as CEO of Celgene Cellular Therapeutics, and now as founder of Celularity, a startup that launched this year. Its plan: Harvest stem cells from human placentas and inject them into older people. Hariri believes the usually frail organ systems of older individuals will improve because they will, in effect, be composed of younger cells.

Another strategy is to try to clear senescent cells—older ones that stop dividing—from the body. Research shows that some of these old-timers produce chemical signals that interfere with the functions of healthy cells. They can also cause symptoms such as inflammation, and help bring on fatal age-associated diseases.

Killing those rogues is a new focus among researchers. A team at the Mayo Clinic’s Kogod Center on Aging recently managed to destroy senescent cells in mice using a new class of medications called senolytic agents. As reported this past summer in Nature Communications, other testing on human cells in culture showed that seno­lytic drugs targeted senescent cells while leaving other types alone. A clinical trial to test the drugs in humans with chronic kidney disease is underway.

“We’ve got approval to start trials, and some are just beginning, but they’re in people who’ve got serious illnesses directly tied to cellular senescence,” says Kogod Center director James Kirkland. He adds that they need to see what happens before moving on to healthier populations.

Across all these potential aging interventions, there is one common denominator, and that is their fallibility. The medical community doesn’t know what slows or reverses the process in humans, let alone what might cause harm. For that reason, Kirkland and his peers caution against the kind of self-experimentation Faloon practices.

“We’re playing with a new treatment paradigm,” Kirkland says of their research. “I’ve been around long enough to know there are going to be unpredictable things that happen as we get into people.”

Faloon believes he faces a bigger risk from waiting than from being his own guinea pig. “I’m afraid that with aging research, some of the people don’t have a sufficient sense of urgency,” he says. He continually incorporates different interventions into his life-extension regimen. He restricts his calories to some 1,200 a day, about half what the average man consumes. He also ingests more than 50 medications daily, including metformin and Life Extension’s own concoctions of nutraceuticals with names like Cell Regenerator and LongevityAI. “Anything that might work, I am doing,” he says. Most recently, Faloon underwent a series of infusions of NAD+ molecules, which David Sinclair, co-director of the Glenn Center for the Biology of Aging at Harvard Medical School, has called “the closest we’ve gotten to a fountain of youth.” The molecules help regulate cellular aging but diminish over time. In studies, older mice given NAD+ molecule precursors look and act younger. Because he’s impatient for clinical trials to yield ­conclusive results, Faloon gives about $5 million a year in profits from the buyers club to underwrite medical research. So far, the data from two recent studies on NAD+ and rapamycin that he backed are unpublished. “If we don’t accelerate all these different projects, I’m not going to make it,” Faloon says.

But there’s a reason that science is slow. Most researchers will say that aging, if not an outright mystery, remains a cross between a jigsaw puzzle and an ­aggravating game of Whac-A-Mole. They warn that meddling with nature can carry unforeseen consequences. For instance, one experimental strategy, which deploys the enzyme telomerase to renew old cells, might encourage premalignant cells to turn cancerous.

“People look at aging as something that is very simple,” says Michael Fossel, a former professor of the biology of aging at Grand Valley State University in Michigan. “They pick their favorite parameter, and then they push it. Can we reverse aging in people in clinical trials? Nobody knows yet.”

Most current studies have a more circumscribed ­objective, which is to ameliorate the diseases that occur in our senior years. Take, for example, the TAME trial. According to lead scientist Barzilai, the FDA will ­consider metformin a sufficient anti-aging drug if it can delay ­age-­related diseases for two years.

In other words, radical life extension—the notion of immortality that the Church of Perpetual Life promotes—is not the goal. Pushing back the onset of major maladies so we live a little longer and die a little healthier is. For the Silicon Valley companies and barons of Big Tech assisting this effort, there’s clearly a business imperative. “Anything that extends life and maintains health is the biggest potential business in the history of mankind,” Celularity’s Hariri says. Another researcher, Kris Verburgh, a professor at Silicon ­Valley-based think tank Singularity University, aptly points out in his book The Longevity Code, “If there is one thing ­multimillionaires dislike, it is having to die.”

But aging research can’t promise them—or Bill ­Faloon—​anything. “Gerontology is science, and immortalism is religion,” says rapamycin researcher ­Kaeberlein. “It’s based on the faith that human technology will get to the point where you can actually live forever. But there’s no scientific basis for that at all.”

In science, time outs the truth. For Faloon, time will ­always be the enemy. Undaunted, he keeps cryonics as an insurance policy for himself, his wife, and his two sons. Don’t wait for the mainstream, he tells his followers. Come to church. Celebrate. Rejoice. And live.

This article was originally published in the Summer 2018 Life/Death issue of Popular Science.