The quest for immortality, or at least delayed death, is in full swing, with billions of dollars invested in anti-aging technologies such as stem cells and gene therapy. However, there are some inexpensive and easily accessible venues for those looking to extend their lives. This includes the off-label use of generic drugs such as the diabetes drug metformin and the immune system suppressant rapamycin. Studies in mice have shown that rapamycin may extend lifespan by up to about 15%. Some preliminary data in humans indicates that rapamycin may help slow and even reverse some aspects of aging at the cellular level. However, there are also signs of potential side effects that affect the muscles and immune system.
DIY rapamycin test
Clinical trials to resolve these questions and uncertainties are expensive and time-consuming. On the other hand, many people feel that the evidence is good enough to give it a try. And they are finding doctors who will prescribe drugs for these personal longevity experiments.While researching a special feature on the science of reverse aging (scheduled for publication in next month’s spring issue of the magazine) value), I came across an effort by academic and industry researchers to see if we could learn anything from these DIY experiments with rapamycin.
The origin of this drug is exotic: the active ingredient was discovered from bacteria living in the soil of Easter Island in the Pacific Ocean. It inhibits a family of cellular enzymes called mTOR, which is the mammalian target of rapamycin. Rapamycin (and derivatives called rapalogs) is a powerful immune system suppressant when taken in large doses and is an important drug used to prevent rejection in organ transplant patients. It also has anti-cancer effects.
But researchers have long suspected that lower doses could provide beneficial effects without harming the immune system. These may include improving cellular metabolism, promoting energy-producing mitochondria, and improving the recycling of materials within cells.
Yuxin Su, a reproductive and genetics researcher at Columbia University, said, “The very convincing preclinical data that shows that rapamycin is a very powerful drug in terms of improving health and extending lifespan makes it difficult for people to understand. started taking rapamycin off-label.” “Especially people who have known risk factors for age-related diseases, such as heart disease.”
One of its biggest proponents is Dr. Alan S. Green of Queens, New York, who is studying the drug as a treatment for Alzheimer’s disease. “He started accepting it himself,” Sue says. “And he started … recommending it to his patients. So Matt and I and others collected all this data from off-label users of rapamycin.”
She’s referring to Matt Kaeberlein. He ran a lab of the same name studying aging at the University of Washington from his 2006 until his 2023, when he moved his research to the private sector and co-founded Ora Biomedical.
(Mr. Kaeberlein is also the CEO of healthcare company Optispan, and owns stakes in supplement company Novos and epigenetics startup Moonwalk Biosciences, among others. Mr. Suh is an advisor to venture capital firm LongeVC.)
“As with mice, we don’t yet know how much rapamycin actually modulates the biology of aging in humans,” Kaeberlein says. But he wants to know. “If that happens, [work the same in humans]If so, I think this is a powerful treatment, perhaps the most powerful medicine…We need to adjust the biology of aging. ”
Plan a study on health hackers
Many people take rapamycin to fight aging, but the doses are different, on different schedules, and without scientific oversight. So the challenge for Su, Kaeberlein, and the team was to collect and process data from these people in a meaningful way.
They essentially created a crowdsourced clinical trial. The research team conducted an online survey that recruited 333 adults who were using rapamycin off-label and 172 adults who had never taken rapamycin. Doses varied, but the researchers reported that 6 mg once a week was the most common in the study (taken by 101 of 229 men and 25 of 67 women).
Some clear themes emerged. Rapamycin users reported not only having less abdominal cramps and pain, muscle tension, eye pain, depression, and anxiety, but also “feeling more youthful.” Also interesting: People who became infected with COVID-19 while taking rapamycin did not report as severe symptoms as those who did not take rapamycin. And no one reported being hospitalized or suffering from long-term illness from the coronavirus.
Of course, a placebo effect may be at play here. They are the people who want the effects of medicine. And they self-report how they feel, and there are no “blind” experts to objectively assess them. However, he was not acting completely on his own. 202 men and 60 women reported taking rapamycin under medical supervision, with the most common purpose being “healthy longevity/anti-aging.”
(Apart from this study, rapamycin is also being administered at an upscale high-tech clinic called Fountain Life, which was co-founded by Xprize founder Dr. Peter Diamandis, who personally takes rapamycin. )
Not all reports were rosy. More than three times as many people (about 15%) who took rapamycin reported having a canker sore than those who did not take it. However, it is a well-known side effect of this drug.
Interestingly, none of the more feared side effects, such as harm to the immune system, were reported. (If the coronavirus reports are any guide, rapamycin may have been helpful, and at least one formal study also shows that lower doses of the drug may be good for older people’s immune systems.) ing.)
Suh points out that the longevity hackers took much lower doses of the drug than transplant patients (usually an initial dose of 6 to 15 mg, then 2 to 5 mg daily thereafter). Users also did not report muscle loss, which is another suspected downside. (Likewise, some research suggests positive effects on muscles.)
Limitations of informal research
The researchers are not claiming anything close to a clinical study here without conclusive scientific evidence of benefit or refuting theories of side effects. But they are cautiously optimistic. “I think we can say with some confidence that at the doses that people are using off-label. [there was] There are very few side effects, at least in the short term,” says Kaeberlein. “There is some evidence of some benefits.”
Based on data on rapamycin use and other observations, he believes the drug may ultimately be most helpful for people “who have a lot of chronic inflammation,” and in extreme cases, As we age, it can lead to autoimmune diseases.
But safety findings are the most immediately useful results. Dr. Hsu and his team at Columbia University recently began a formal clinical trial of rapamycin, specifically to see if it can slow the aging of the ovaries and prevent the onset of menopause. The study, known as VIBRANT, examining the benefits of rapamycin in the treatment of reproductive aging, has been studying about 15 people over three months. The DIY study helped the team determine safe levels of rapamycin to administer to young participants.
But Hsu is unsure about the future of informal research. “Appropriate randomized, double-blind clinical trials need to be conducted to assess the effectiveness of a drug and its outcomes,” she says.
Kaeberlein doesn’t disagree with this opinion, but recognizes the utility of crowdsourcing on a larger scale. “Imagine someone launching a website and saying, ‘Put your data here,'” he says.
Kaeberlein adds that in his study, participants were “consenting and went through all the processes that would normally occur as if they were in a real clinical study.” So I think if you do that, you’ll be able to collect valuable data and at least be accepted by the scientific community. ”
