Louis is a 27-year-old assembly-line worker in Three Rivers, Michigan. He has no health problems and rarely sees a doctor. Yet for a man in his prime, Louis thinks a lot about cheating death. He researches strategies online, and he even converted to a plant-based diet after hearing from a YouTube channel called Vegan Gains that veganism could extend his life. Louis thinks the diet will buy him a few extra years, but he feels the urge to keep seeking new life-extending methods. “I’d like to live as healthily as possible for as long as possible,” he says. “And if we have therapies and practices today that will prolong our healthy life span, I believe we need to follow these therapies and practices.”
Charles is your average 50-year-old middle-class family man. He lives in the suburbs of Atlanta, works a 9-to-5 in marketing, does Brazilian jujitsu, and spends weekends watching his kid at wrestling tournaments. Except Charles has a hang-up: He worries about feeling like he’s withering, about those growing-old hallmarks like thinning hair, losing a step, and forgetting his buddy’s wife’s name. Charles is the kind of guy who’s active on antiaging Internet forums and takes fistfuls of supplements. “A few years back, when my granddad had cancer, I watched him die,” he says. Charles read up on alternative ways his granddad could attempt to extend his life, but his grandfather didn’t try them. Soon after, Charles (who asked not to use his real name) got some news that sent his hang-up into hyperdrive. “I took this 23andMe genetic test,” he says. “I found out I have a risk for Alzheimer’s.” It’s a risk that increases as your body ages.
Van is a 72-year-old who managed medical-device sales in Boston until he retired and moved to Spain. He used to run five miles and lift weights three times each per week. But in his late 60s, all that wellness stuff wasn’t working so well. “I began getting really tired in the afternoons,” says Van, who also didn’t want to give his name. “I’d be too tired at night to go out to dinner, and I also started having high blood pressure. I was feeling the effects of aging.” His attempts at flinging a kettlebell were halfhearted, and his walks around the neighborhood were getting slower. Van felt the sun was setting on the life of vitality he loved and that he was heading toward a gloomy and inevitable bedridden demise.
Each of these men found a solution to their concerns about aging at roughly the same place and time. They came across information in Reddit threads and on longevity blogs about something that people on the other end of the keyboard said could help them live better for longer. It would make Louis healthier now, as he aged, and as all of his friends saw their bodies fade. It would slash Charles’s risk of Alzheimer’s and have guys ten years younger tapping out against him in BJJ. It would kick-start Van’s training again and drop his blood biomarkers to those of someone half his age. It had the potential to be more powerful than diet and exercise. But it also had the potential to cause some problems.
It was a curious substance discovered in soil that had been scooped up on Easter Island during a 1964 Canadian research expedition. Scientists studying disease there noticed that people didn’t pick up tetanus via their feet as they would expect, and they figured the ground held some secrets. But nobody expected to find this one. The soil sat in frozen storage in a University of Montreal lab until 1969, when a researcher looked for useful compounds in it and came across a molecule that was a powerful immunosuppressant. In 1999, the FDA approved the molecule as the drug Rapamune (sirolimus), also known as rapamycin. By the mid-2000s, rapamycin was found to increase the life span of worms and yeast, and in a 2009 study, it extended the life expectancy of mice by 28 percent for males and 38 percent for females. Twenty-eight percent, plus more energy? That could translate into more than a decade of better years for humans, the Redditors and bloggers said. But there was a catch.
Rapamycin wasn’t exactly benign, nor was it something Louis, Charles, or Van could just go pick up at CVS. In high doses, rapamycin suppresses your immune system. The FDA approved it for people who’d undergone organ transplants to keep their bodies from rejecting the donated organ. The stuff could put you at risk of side effects. Roughly 5 percent of patients in clinical trials experienced them badly enough that they had to quit the drug. The FDA stamped rapamycin with a “black box” warning, its most extreme, for drugs that come with “serious or life-threatening risks”—risks like infections, pneumonia, and cancer.
Still, the forums had links to legit research and showed lots of buzz in the ranks of influential biohackers like Tim Ferriss and physicians like Peter Attia, M.D., who’ve had MIT researchers and University of Chicago doctors appear on their podcasts talking about the drug’s potentially age--bending benefits. Doctors generally won’t openly prescribe rapamycin for longevity. Van got lucky and found someone who did. But Louis and Charles, like many people who want something today, went looking around the web.
We talked to many men like Louis, Charles, and Van for this story. They range in age from 27 to 76, and their opinions on the drug go from “probably helpful but no better than exercise” to “easily the most important drug ever discovered by mankind and should be a key topic of discussion in the upcoming presidential election cycle.” They are manual laborers, academics, medical doctors, entrepreneurs, and everything in between. There are hundreds, perhaps thousands, of these men quietly experimenting with rapamycin across the country. And if these guys are right, they could be like the lucky rodents in the research, walking around with improved brain health, heart health, and vitality while the rest of us surrender to mortality. Or they could be killing themselves slowly. It’s too soon to tell.
The Mystery of Aging
scientists still don’t know what actually causes aging. Maybe it’s that your cells stop dividing, or that your telomeres shorten, or that you exhaust your stem cells, or that your DNA becomes damaged and stops repairing itself, or a combination of all those processes. Or maybe it’s none of them. All we can do to live longer and better for now is treat aging’s symptoms. So that’s what the antiaging community until this point has been stuck with trying to do.
It’s a history of whack-a-huckster. In the 1800s, the treatments were patent medicines like Clark Stanley’s Snake Oil Liniment and Hamlin’s Wizard Oil. In the 1920s, antiaging doctors charged $750 to $2,000 for life-extending gland transplants. Medical boards in the late ’30s intervened to cut down on these quack treatments. But in the ’90s, boomers brought the quack back. This generation was hitting middle age and, having grown up in the turbulent ’60s, was willing to question the establishment—in this case, the medical establishment—and turn to self-help. Boomers began popping questionable OTC supplements and getting HGH injections, all in the hope of extra life. In 2002, when the antiaging market hit $43 billion, a group of 51 scientists in the field published a statement in Scientific American decrying the burgeoning, built-on-almost-nothing business of antiaging medicines. No one really cared. Just five years later, the market was expected to reach $64 billion.
Which is about the time Silicon Valley stepped in with big data, big science, and big money to, of course, “disrupt” death. Larry Page, Peter Thiel, Jeff Bezos, and other tech billionaires have since funneled billions into life--extension companies such as Calico and the Methuselah Foundation. (See “Death Disrupters,” page 111.) Much of the new research is founded on an antiaging discovery that occurred all the way back in 1935. It was then that researchers at Cornell found that rats that spent their lives in a state of caloric restriction lived longer.
Eventually, this finding would be connected to that life--extending compound in the Easter Island soil through the microscope of David Sabatini, Ph.D., M.D. Dr. Sabatini didn’t set out to get mixed up in this odd world of antiaging, but in 1992, peering down at a sample he was analyzing one day as a student at Johns Hopkins Medical School, he discovered a protein, now called mTOR (short for mammalian target of rapamycin), that would eventually form a link between the way rapamycin might extend life and the way caloric restriction does. He had discovered the mTOR cellular--signaling pathway that answers to rapamycin. The drug just might act on the very causes of aging.
Dr. Sabatini, now a professor of biology at the Whitehead Institute and MIT, explains the mTOR pathway like this: Pretend your body is an old house. Your oldest cells have all sorts of problems and are implicated in your house falling apart. “You couldn’t fully renovate the old house by bringing in only a plumber, or only an electrician, or a roofer, or a drywall guy,” says Dr. Sabatini. “You’d need to hire a general contractor, who would hire all those specialists who would then come fix all those problems that needed to be fixed.” The mTOR pathway is like the general contractor, signaling to your body to demolish parts of its old cells and replace them with newer, healthier ones.
Dr. Sabatini thinks rapamycin essentially tricks the body into thinking that it’s in a state of calorie deprivation, which is what causes the contractor to call in all the guys for renovation work. The cellular workers consume your oldest, weakest cell parts, even parts of senescent cells. These are cells that no longer divide and are thought to spur aging and maybe even drive cancer. Which is to say that rapamycin could give you all the benefits of fasting without the ravenous downsides. In addition to the studies on rapamycin in yeast, worms, flies, and mice, in 2014 scientists began work on dogs; it found that those on the drug showed signs of younger hearts and a reversal of age-related cardiac issues.
While this was going on, Mikhail Blagosklonny, Ph.D., M.D., a prolific researcher on aging at the Roswell Park Comprehensive Cancer Center in Buffalo, began writing about his theories on rapamycin in medical journals. He noted its antiaging promise in 2008 and hypothesized that a lower dose than transplant patients take might bring on benefits without side effects. On Christmas Eve in 2014, a study conducted by researchers at Novartis and Stanford and published in Science Translational Medicine confirmed Dr. Blagosklonny’s theory. Older people taking the drug for six weeks didn’t see their immunity decrease—it actually increased in groups that took as little as 0.5mg a day or 5mg a week. Adult transplant patients typically take a 2mg dose every day.
Today, more than 2,000 clinical trials studying rapamycin are under way around the globe, nearly 1,000 of them in the United States, and even the director of the NIH has blogged about its potential benefits. All of which means rapamycin checks a lot of boxes in the description of a trend that’s about to explode: wellness gurus talking it up, credible researchers giving it ink, and enough unknowns to interpret the research in any way that works with your world-view. But the science, as science does, is proceeding slowly and carefully and may never find answers. Because the drug is already generic, drug companies aren’t interested, and antiaging enthusiasts are going ahead and taking it, sometimes with severe consequences.
Deciding to pop the pill
in the world of rapamycin for antiaging, guys find ways to get the drug. Louis and Charles searched the forums—not the somewhat moderated ones, like Reddit’s, but forums Charles would “rather not mention, just to protect them, you know?” Charles found a post with a link to an obscure, unregulated pharmacy in India that was willing to ship anyone rapamycin, no prescription needed. Louis got his from a supplier he won’t disclose.
Van located the one doctor in the U.S. who would prescribe the drug. His name is Alan Green, M.D., and he treats patients out of his home in Bayside, Queens. Because you have to visit him in person, Van flew to LaGuardia Airport, took a cab to Bayside, and wound up in Dr. Green’s office.
With these antiaging meds, there are the sketchy, we-don’t-know-the-effects-yet prescriptions—the ones you get from Dr. Green—and then there are the sketchy sketchy ones from overseas pharmacies and underground suppliers. Many foreign pills are fine, but some aren’t. The bad ones can be counterfeit, contaminated, tainted, or otherwise unsafe. They can make you sick, lead to dangerous interactions with other medicines you take, and even kill you. In Charles’s and Louis’s eyes, the bigger risk was doing nothing. They each asked for a shipment of rapamycin; Charles got a four-month supply for $100, and Louis got two years’ worth for about $200.
Van’s prescription came from Dr. Green, who takes the drug himself. The doctor—five-foot-ten and 175 pounds when he started, with a rim of white hair around his tan head—says the decision to take it was easy. He had just turned 72, and “everything was going to shit. It was clear that I was going downhill fast,” says the now-76-year-old. “I would get winded easily and wasn’t moving as well. I knew I wouldn’t be alive much longer if I kept deteriorating at this rate.” He came upon Dr. Blagosklonny’s work and wrote himself a prescription for 6mg once a week. “I didn’t have anything to lose,” he says. “The first thing I noticed is that it became easy to lose weight. I was losing two pounds a week. I also had a marked increase in energy and wasn’t getting winded as easily.”
Dr. Green continued his treatment for a whole year with nothing but upsides. “So I decided, ‘Well, I’ll make this available to other people,’ ” he says. “The FDA’s black-box warning is an excellent warning—as it applies for use for organ transplants.” At the doses for antiaging? Not so much, says Dr. Green. It’s not illegal for him to prescribe the medication. “Once the FDA approves a drug, health care providers generally may prescribe it for an unapproved use when they judge that it is medically appropriate for their patient,” explains Jeremy Kahn, a spokesman for the FDA. Overall, one in five prescriptions today is doled out for off-label use, like the blood--pressure drug Inderal being used for performance anxiety or the antidepressant Zoloft for premature ejaculation.
Dr. Green created a website laying out the research and began hearing from people who’d found him online. “I figured I’d see a few patients a month,” he says. His phone started ringing far more than that. “I think I was Dr. Green’s second patient,” says Van. The doctor ran Van through a handful of questions about his health history, why he was interested in rapamycin, and what he hoped to get from it. Then he did some basic blood testing, Van says, and wrote him a prescription. Van filled the Rx, dumped six of the aspirin-sized 1mg pills into his hand, and popped them into his mouth. He flew back to Boston, and at home he’d take that same 6mg dose once weekly. “My blood work quickly became that of someone 20 to 30 years younger,” he says.
Seeing Dr. Green isn’t cheap. You’ll have to travel, and he charges $350 for an initial visit and $100 to $200 for follow--ups. Your insurance won’t cover the meds, which cost $75 to $150 a month. Dr. Green now sees about three patients a week, and “many are doctors, Ph.D.s, and executives,” he says. But that doesn’t help guys like Charles and Louis.
They received the rapamycin pills a couple weeks after placing their orders. Charles added a 5mg dose in with all the other supplements he takes and washed the mix downwith water. Louis did the same with a 7mg dose. Both guys take their pills once a week. “I dropped 10 or 15 pounds in the three months I’ve been taking it,” says Charles, who admits he has also been eating better. “I feel less sore, like I’m taking Advil. I was going to quit jujitsu a couple years ago because of my joint pains, and now I’m rolling with 25-year-olds. My hair also seems a lot thicker.” Louis has been on and off it for almost a year; he says he can’t tell if less joint pain and an improved mood are direct results or merely coincidental. He had some mouth sores, indications of a compromised immune system, but they didn’t rattle him—he thought they, too, might just be a coincidence.
Concerns about infections and worse are one reason more doctors aren’t prescribing rapamycin. Dr. Green says bacterial infections happen in about 5 percent of patients. “I’ve had a few skin and soft-tissue infections, which I treated with antibiotics,” he says, and he emphasizes that the infections can get bad quickly without antibiotic treatment. “I have two patients who’ve developed pneumonia and required hospital treatment. In both cases, they’d delayed a few days to a week or more in starting antibiotics.”
“I think [prescribing rapamycin] is bordering on unethical,” says Dr. Sabatini, who does not take the drug. “I think we’re far away from knowing that there are no downsides to long-term use.” Dr. Attia, the influential 46-year-old physician focused on longevity, says he won’t prescribe it to other people either—at least not yet. “I take rapamycin myself, so on some level I’ve decided it’s a smart option,” he says. “But I haven’t prescribed it to any patients, except one, who is himself a scientist studying rapamycin. And I think that speaks to my desire to better understand the risks, not only of taking too much but also of not taking enough.” We’ll likely never be able to study directly whether rapamycin really helps humans live longer, says Dr. Attia. It’s too time-consuming and too expensive to do a study like that well. “We’ll have to rely on some combination of proxies,” he says, and scientists are discussing the development of such tests to analyze what kinds of markers could really pin down what’s happening with the drug.
Yet Louis, Charles, and Van aren’t waiting for science to catch up. They’ve been on the stuff for as long as two years and don’t plan on stopping. Maybe the three of them, the rest of Dr. Green’s patients, and the untold numbers finagling rapamycin off the Internet will be among the 95 percent of people who see no negative side effects. That’s assuming the pills they get are legit. And maybe they’ll end up outliving us all. Or maybe they’ll find an unknown, unforeseen consequence. Medicine can be a gamble. Some medications sat on shelves for decades before doctors realized they came with harmful long-term side effects and had to be pulled. The painkiller Vioxx, for example, was linked to 27,000 heart attacks and strokes after it was FDA approved, and the acne drug Accutane dramatically increased the risk of miscarriage and severe birth defects in women taking it during pregnancy. Many later sued its maker.
Not that any of those cases will influence the decisions of the antiagers we spoke to. “I don’t know if it’ll make me live longer, but hopefully I can head off dementia,” says Charles. “And I feel good, man. So why not?”
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