Rapamycin: Could a simple pill add years to your life? 

“I’m interested in changing the curve of my life. For most people, as they get older, their health starts to fail. Their quality of life isn’t ideal. I believe it’s possible to change the trajectory of the last decades of one’s life.”

Based in Kentucky, Samson, a violinist who taught at the University of Louisville, tells the Irish Examiner that he’s interested in increasing his health span: the number of years he stays healthy. 

He has been taking Rapamycin for the past five years, a drug popular in the US for promoting longevity and anti-ageing.

“I see Rapamycin as a second-level intervention,” says Samson, whose first intervention is exercise. 

He’s convinced his weekly 5mg dose of Rapamycin puts him ahead of peers who also exercise. 

“I go to a gym frequented by a lot of people my age. And I’m just more limber. I’m more awake in my mental capacity. I don’t think it’s conceivable I’d be like that without Rapamycin.”

Rapamycin is FDA-approved for kidney-transplant rejection, cardiac stent use, and the treatment of patients with lymphangioleiomyomatosis (LAM), a rare, progressive condition that causes cysts to form in the lungs, kidneys, and lymphatic system.

A prescription-only medicine, in Ireland Rapamycin is sold under the brand name Rapamune. 

Here, it is authorised by the European Medicines Agency for kidney-transplant patients and for people with sporadic lymphangioleiomyomatosis.

However, the HPRA (Health Products Regulatory Authority) says there are “certain clinical situations” when ‘off-label’ use of a medicine “may be judged in the best interests of the patient, on the basis of available evidence, and such decisions rest with the registered healthcare professional”. 

Off-label use of authorised medicines is outside the HPRA remit.

Matt Kaeberlein, an affiliate professor at the University of Washington and a former director at the Healthy Aging and Longevity Research Institute, was a researcher on a paper published last year on off-label use of Rapamycin. 

“Several physicians are now prescribing Rapamycin off-label as a preventative therapy to maintain health span,” the paper reported.

“I think Rapamycin is currently the best candidate drug we have that has likely benefits for ageing,” Kaeberlein says, and he outlines the ramifications of Rapamycin, an inexpensive drug, now being off-patent. 

“Pharmaceutical companies don’t want to invest in [costly] trials, though there’s a lot of data to say we should for age-related diseases.”

Bacteria discovery

Rapamycin was collected by scientists in the 1960s from Easter Island, a remote tropical island also called Rapa Nui. 

“They [found] several strains of unique bacteria that were unknown to science,” says Robert Lufkin, a physician and professor at USC Keck School of Medicine in California. 

“One of the bacteria secreted a compound that had unusual health and biological properties never seen before…. Rapamycin.”

Lufkin’s focus is the applied science of longevity and he takes Rapamycin.

“I’ve never felt better. However, I’m doing many new lifestyle changes and it’s difficult to attribute the benefits to any one intervention,” he says.

Lufkin, author of Lies I Taught in Medical School: How Conventional Medicine Is Making You Sicker and What You Can Do to Save Your Own Life, says Rapamycin acts on a molecule called mTOR, a protein present in almost all animal cells, from yeast to human beings. mTOR, says Lufkin, is “arguably the single most important signalling protein in all of biology”.

When TOR senses the presence of nutrients, it tells the cell to grow. It also turns up inflammation.

“If no nutrients are detected, mTOR switches the other way. It turns off cell growth, it turns off inflammation, and it turns up a repair system called autophagy.”

Lufkin points to what he calls “one of the most exciting theories of longevity and ageing”: That, at its most basic, ageing is driven by mTOR over-activation.

“mTOR is turned on too much, there’s too much cell growth and cell proliferation, too much inflammation.” Rapamycin can target this over-activity, says Lufkin. It works on mTOR and “specifically turns mTOR down”.

Dr Brad Stanfield is about to start recruiting patients for a trial looking at how Rapamycin affects human muscle performance. 

A New Zealand-based GP, Stanfeld says that if mTOR is over-activated, it blocks the separate process of autophagy; basically, a cell-clearance process.

“Think of it like our muscles hoarding all these old, damaged proteins and components. By using Rapamycin intermittently, we switch off mTOR and allow autophagy to happen, so that our muscles can clear away these old, damaged components.”

Excitement around Rapamycin’s anti-ageing potential has come from animal studies that have repeatedly shown benefits for a wide range of age-related diseases across multiple species. Studies have reported increased lifespan in laboratory organisms, including yeast, worms, and mice.

Lufkin and other longevity medics believe if we can change certain disease processes, we can increase lifespan. And, of course, health span.

Rapamycin has shown numerous health-span benefits in rodents, including lower cancer incidence, improved cognitive, kidney and intestinal function, preservation of tendons, preservation of ovarian function, and protection against hearing loss.

“Over and over again, when Rapamycin is tested in mice, it extends lifespan by over 20%,” says Stanfield, who believes that it’s vital to determine if Rapamycin can offer these benefits to humans.

‘Very promising’

Rose Anne Kenny is regius professor of medicine at Trinity College Dublin, where she heads up the ageing research programme. 

She is cautiously positive about Rapamycin. 

“Of all the supplements [for anti-ageing], that one shows most promise. But it has side effects and it hasn’t been approved by the FDA. It’s used in oncology treatment, and the way it works in oncology is very similar to the way it’s anticipated to work in slowing down ageing.

“It looks very, very promising, but we need clinical trials to weigh up the benefits and the side effects. And is it going to have an effect on ageing more than getting good sleep and reducing stress?” asks Kenny, author of Age Proof—The New Science of Living a Longer and Healthier Life, who, on the morning we speak, went for a cold-water swim in the Forty Foot.

(Cold water, she says, benefits a range of systems involved in the ageing process. “Noradrenaline, a critical neurotransmitter, rises fourfold on cold water exposure, and it’s released in brain areas that control emotions, concentration and memory).

Kaeberlein estimates that the number of off-label users of Rapamycin for health-span reasons in the US is more than 10,000. “I doubt it’s over 50,000 yet, but now there are a couple of telehealth Rapamycin providers, it’s possible,” he says.

A Rapamycin user himself, he first took it for adhesive capsulitis (frozen shoulder). “It was extremely painful. I couldn’t sleep, or throw a ball with my son. My doctor said there was nothing I could do, just get back to physical training and it’d probably go away in a year,” says the 53-year-old.

“I realised this was a chronic inflammatory condition of the shoulder capsule. I knew Rapamycin was very potent at knocking down inflammation in animal studies, and that it was pretty safe in the doses people were taking [5-6mg a week].”

Within two weeks of taking it, he saw a decline in pain and improvement in mobility. “By the end of 12 weeks, I was 95% back to my full range of motion. For me, it was pretty convincing that, at least for some, Rapamycin can have a big benefit for quality of life.”

Kaeberlein, who is also CEO of Optispan, takes Rapamycin in cycles of 12 weeks and breaks for six to eight months.

“I haven’t noticed anything profound [since that first time], but then I haven’t had any severe issues. I do a lot of resistance training. I gradually get more aches and pains in my joints when I lift weights.

“At the point where it’s bothering me, I take Rapamycin. My perception is the aches and pains go down.”

With a background in molecular biology, Daniel Tawfik is co-founder of Healthspan, which aims to “provide medication that can increase health-span”. He had seen a “real disconnect” between what is happening in the clinical community and the research community. “Research showing positive effects of [some] drugs isn’t making it in to the clinical frontline.”

When his wife’s cancer relapsed, she had a stem-cell transplant and was prescribed Rapamycin.

Intrigued by Rapamycin’s recalibration of mTOR over-activity back to normal levels — and that it seemed from research to be “a deterrent against the progression of age-related diseases” — Tawfik says: “It gives us a foundation to say there’s something here.”

Most of Healthspan’s 3,000 patients are on Rapamycin for longevity and health-span.

Tawfik’s telehealth service, costing $105 monthly, aims to make a drug like Rapamycin available and assure safety by measuring patient progress. “All patients get blood work done at the beginning, and we notify them every four to six weeks to get further blood work done.

“On an individual level, we’re ensuring there’s no immune suppression. It’s very rare we see [it]. Sometimes there can be [metabolic] effects: elevated lipids or glucose. Monitoring allows us to fine-tune the dosage.”

Tawfik says 50% of clients report no benefits from Rapamycin. “They don’t experience any monumental shift.”

But he adds: “In their blood work, we may be seeing major indicators of good metabolic health, indicating someone’s in a healthy state and going in the right direction.” 

And feedback from patients with systemic inflammation or “some inflammatory issue” is very positive. “If they have some condition that’s clearly related to mTOR over-activity, which elevates inflammatory signalling — osteoarthritis, psoriasis — these patients tell us they feel better. Rapamycin is solving an active issue for them.”

Tawfik, 39, has been taking Rapamycin for almost four years. “Not to feel better specifically, but to slow down the cellular dysfunction that accelerates ageing.”

Healthspan doesn’t prescribe to 15-20% of clients, and Tawfik cautions that no-one should take Rapamycin “like an aspirin”: You need to be monitored under medical supervision.

Kaeberlein says it’s too early to say how Rapamycin’s anti-ageing promise will play out.

“There may be gradual build-up of momentum, where we begin to see [much more] mainstream use of it, rather than just for transplant patients. There’s a growing population of people using it off-label and under supervision. What happens may depend on the data from those individuals.”

Whatever else, Kaeberlein believes it’s time to change how we approach health.

“Historically, we’ve approached it from the lens of disease. Our healthcare system is a reactive disease-care system. We need to change the paradigm and work on keeping people healthy. Targeting the biology of ageing needs to be part of that toolkit.”

Rapamycin may become a valuable element of that toolkit for millions worldwide.

We just don’t know yet.

Research on potential ‘anti-ageing’ drug

A paper published in 2023 that evaluated off-label Rapamycin use to promote healthspan in 333 adults found general quality-of-life improvement after starting the drug. 

Three out of four reported improvements in health, happiness, brain function, feelings of youthfulness, confidence, calmness, anxiety, and generalised aches and pains. 

“Greater than fivefold more Rapamycin users agreed [with the statement] that ‘family/friends have commented that I look good’ than disagreed’,” the paper reported.

On side effects, the study found that the only significantly more prevalent side effect, compared to 172 non-Rapamycin users, was mouth sores. 

“[This] makes sense, given that mouth sores are the most common side effect seen at high doses in organ transplant patients. Potentially more interesting is the significant improvements in pain, depression, and anxiety, as well as reduced risk of severe or long covid,” says Professor Matt Kaeberlein.

Researchers acknowledged the study is small and that care must be taken “not to over-interpret the data”.

More research in the pipeline:

New Zealand-based researcher Dr Brad Stanfield is starting a trial to see if Rapamycin can slow or reverse age-related muscle function decline.

“We lose about one per cent of our strength per year from the age of 40 – that decline accelerates from age 60. Overall, it’s hoped that by using Rapamycin intermittently, we can restore the mTOR balance and improve muscle strength.”

Dentist Jonathan An, based at the University of Washington School of Dentistry, is about to enrol the first participants in a trial examining the potential benefit of Rapamycin for periodontal disease. 

“Given the correlation between periodontal disease and other age-related conditions — Alzheimer’s disease, cardiovascular disease and diabetes — treating periodontal disease in older adults could have broader positive effects on age-related health globally,” An tells the Irish Examiner.