As a doctor and as a student of longevity science, I combine the tried and true with promising emerging therapies. I’m hugely invested in essentials like quality sleep, fresh whole foods, everyday movement, resistance training, stress reduction. And I embrace additional approaches like intermittent fasting, targeted supplements, hormone replacement therapy and peptides. But one thing I’m not doing just yet is rapamycin, even though it's talked about quite a bit. I probably get asked about it more than any other longevity-related drug.

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Over the past few years, rapamycin has garnered a tremendous amount of buzz, frequently showing up on podcasts, blog posts, scientific papers, and online forums. Some outlets treat it like the most promising anti-aging intervention mankind has ever seen while others view it’s ‘next big thing-ness’ as a dangerous overreach. I fall somewhere in the middle: fascinated by the science, cautious about the risks, and not yet persuaded that the current evidence is strong enough to justify all-purpose “off-label” use. 

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All that said, rapamycin still has plenty of potential as a longevity therapy so I wanted to share with you the basics of why scientists are investigating it, what the research tells us, what we still don’t know, and why lifestyle still matters more than the pharmaceuticals in the anti-aging space – at least for now! What to know about rapamycin? Here’s a topline:

A minor miracle by way of Easter Island. 

Rapamycin was first discovered in the 1970s  in soil bacteria from Easter Island (also known as Rapa Nui). Over time, it was developed into a drug and approved by the FDA as an immunosuppressant called sirolimus, mainly used to suppress the immune system in people who had received organ transplants, helping to prevent the body from attacking a new kidney, liver, or heart.

Rapamycin’s aging and anti-aging connection.

As with a handful of other pharmaceuticals, rapamycin’s not one-trick-pony, but may provide unexpected or unintended benefits that reach far beyond what it was originally designed to do, and with rapamycin, longevity may be the ‘side-effect.’ 

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What makes rapamycin so intriguing to longevity researchers actually has nothing to do with transplants and everything to do with how it interacts with a biological pathway called mTOR (or “Mechanistic Target of Rapamycin,”) – a protein that acts like a master switch for growth and metabolism in the body. 

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When mTOR activity is high, cells are in growth mode. They constantly divide, making use of nutrients to make new proteins and build new tissue. When mTOR activity is lower, cells shift more toward maintenance and repair. It’s that balance between growth and repair that turns out to be central to aging. While some mTOR activity is essential -- kids need to grow and adults need to maintain muscle – we want to turn down the mTOR dial as we age to reduce inflammation and the tamp down the build-up of metabolic waste, key drivers of unhealthy aging. And, in theory, rapamycin, in much lower doses than organ transplant patients receive, might help us do just that. 

Rapamycin, autophagy, and “cellular cleanup” – oh my!

One of the main ways dialing down mTOR seems to help is by allowing the body’s built-in cleanup systems to switch back on. Taken together, this combination — less constant growth signaling, more cellular cleanup, and lower oxidative stress — is what makes rapamycin such a fascinating tool for aging research. But it’s important to remember that most of this evidence still comes from animals and lab models. Whether these same benefits translate safely to long-term use in healthy humans remains one of the biggest open questions in longevity science. Of course, as with most things in biology, the story gets a bit more complicated when you look under the hood...

Your mTOR isn’t just one switch – there’s also mTORC1 and mTORC2.

OK, so here’s where it gets a little tricky: mTOR doesn’t operate as a simple, single on-off switch. It works through at least two major complexes in the body, usually referred to as mTORC1 and mTORC2. Researchers describe mTORC1 and mTORC2 as responding to different cues and controlling overlapping-but-not-identical jobs in cells and tissues.

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For example, mTORC1 is sensitive to nutrients, particularly amino acids like leucine and to insulin and glucose. It promotes protein synthesis and cell growth. And mTORC2, in contrast, plays a role in metabolism, insulin sensitivity, and muscle maintenance.

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Rapamycin strongly inhibits mTORC1 and, with long enough exposure, can also impact mTORC2. That distinction matters because mTORC1 and mTORC2 do not have identical effects on health or aging.

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This “two-complex” setup is one reason why people argue about rapamycin: tuning down one side of the system may create problems in the other.  

Rapamycin helps extend lifespan in different species.

With rapamycin, the animal research is quite compelling, and that has generated much of the initial excitement. Turns out, in multiple species — including yeast, worms, flies, and especially mice -- rapamycin extends lifespan. In mice, it increases both average lifespan and maximum lifespan, even when the drug is started later in life. It is one of the most reliable lifespan-extending drugs ever discovered in mammals – and that is pretty exciting stuff.

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But, as we all know, mice are not people, so we can’t yet say for sure if rapamycin will extend lifespan in humans. Given that human lifespans are much longer and our biology much more complex, side effects that might not show up in a two- or three-year mouse experiment could matter a lot over the course of 40 or 50 years in a human body. So, the smart money is on pumping the breaks a bit for now.

Telling the rapamycin story in humans. 

So, what do we actually know about rapamycin’s effects in humans, outside its well-established role in organ transplant medicine?  In lower doses, there is at least strong theoretical argument that it promotes autophagy – recycling old cell parts to make new cells – and helps the body get rid of tired “senescent” cells which spew out inflammatory pro-aging molecules. But even in these smaller doses, it can also raise blood lipids, impact glucose metabolism, delay wound healing, and cause mouth ulcers, among other unintended consequences. And, in certain contexts, long-term immune suppression can increase the risk of some cancers. What’s more, currently there’s no clinical evidence showing that rapamycin extends human lifespan or does anything to slow down rapid agers like heart disease, Alzheimer’s or cancer.  

Hurry up and wait – for a bit more evidence.

That gap between the very exciting animal data and fairly limited human data generates the controversy. On one side you’ve got those who argue that the biology is compelling enough to justify self-experimentation, albeit cautiously and with close supervision. The other side is more worried about unknown long-term consequences of prescribing the drug more broadly, in contrast to those settings where the risks are weighed against serious disease. I have to say, I’m closer to the cautious camp.

What about the on/off option? 

Some longevity advocates believe that some of the side-effect risks might be mitigated by taking rapamycin intermittently rather than continuously. The idea is that periodic doses could inhibit mTORC1 enough to trigger beneficial repair processes like autophagy without suppressing immune function for long periods or interfering too much with mTORC2. This is within the realm of possibility biologically but it’s yet to be proven safe or effective in large, long-term human trials. 

Your lifestyle choices carry a lot more anti-aging weight.

One reason I’m not willing to go out on a limb for the drug rapamycin is that many of the pathways it impacts are also strongly influenced by lifestyle. Some everyday healthy habits help shift us between “build” and “repair” modes.

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In plain terms, you can get a workable “rhythm” of signals – eat, move, rest, occasionally fast – without taking a medication that suppresses immunity. 

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When people reduce calorie intake, restrict carbohydrates, or practice intermittent or prolonged fasting, mTORC1 activity tends to go down. When people reduce intake of certain amino acids, especially branched-chain amino acids like leucine, mTORC1 signaling also decreases. That translates to less inflammation, less metabolic waste and, generally speaking, more graceful aging. 

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At the same time, physical activity, and especially resistance training, supports muscle health, insulin sensitivity, and aspects of mTORC2 function that are important for metabolism and tissue maintenance.

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The goal isn’t to simply “shut mTOR off.” The goal is balance.

Rapamycin is valuable, but still in its anti-aging infancy.

So, when people ask me about rapamycin, I tell them this: it is one of the most interesting drugs to emerge from longevity research, it has incredibly strong evidence in animals, it has real and serious risks in humans, and we do not yet know whether it helps healthy people live longer or better. Given that we currently have so many tools at our disposal to enhance healthspan, my advice is to focus on those first.