Brain Health,
Smart Drugs,
45 MINS

#134: Rapamycin: The Real Deal Anti-Aging Pill?

June 24, 2016

Quick, name something that can extend your lifespan.  Diet?  Exercise?  A multivitamin?

Bet you didn’t think of a compound derived from a soil bacterium (Streptomyces hygroscopicus) found on Easter Island:  Rapamycin (named after the island’s native name — Rapa Nui).

In Episode 134, Jesse talks to Dr. Matt Kaeberlein, Professor of Pathology at the University of Washington, about the anti-aging and longevity implications of rapamycin — for everything from yeast to dogs to humans.

Important Disclaimer:  it’s far too early to tell healthy humans to start taking rapamycin.  The current research is very promising, but there’s a big difference between mice and humans.

Current Uses of Rapamycin

Rapamycin is currently FDA approved, just not for anything longevity-related.  The two primary uses of rapamycin are as:

  1. An immunosuppressant:  Rapamycin was first approved by the FDA for human use to prevent organ transplant rejection.  At low doses, rapamycin slows the rate of cell division, and at high doses it stops cell division.  Immune cells are one type of cell that rapidly divide.  This is great for people getting organ transplants.
  2. A cancer treatment:  Cancer cells are another type of cells that grow fast, and rapamycin slows their growth.  Derivatives of rapamycin are being used as treatments for kidney, lung, and breast cancers.

Possible Future Uses of Rapamycin

In studies on yeast, C. elegans, fruit flies, and mice, rapamycin has shown some pretty fantastic results in extending life and delaying or preventing the onset of age-related diseases, like Alzheimer’s, cardiac disease, and cancer.

The most exciting research so far has been a major study showing that rapamycin extends the lifespans of mice by 9% for males and 15% for females.

graph showing increased longevity for mice treated with rapamycin

Source:  Bloomberg

Particularly promising is exactly how rapamycin increases lifespan.  It inhibits TOR (target of rapamycin) pathways, known as mTOR pathways in mammals.  TOR is a protein that plays a key role in regulating growth and metabolism.

When TOR pathways are active, cells grow and divide; when they’re inhibited, cells switch into survival mode, becoming stress resistant and triggering autophagy (recycling of old cellular components).  It’s the inhibition of TOR pathways that leads to longevity.

Don’t start popping rapamycin just yet though.  We don’t have enough data to be confident that this effect on mice will apply to people.  It seems likely that humans will derive some longevity benefit from rapamycin, since other benefits seen in mice have also been seen in humans, but there may be a difference in magnitude of the benefit.

It’s a Dog’s (Long) Life

While human trials still need to be conducted, Dr. Kaeberlein has started studying the effects of rapamycin on dogs.  Looking at larger dogs (since they age faster than small dogs) that are at least 6 years old with no pre-existing medical conditions, Dr. Kaeberlein has completed the first phase of the trial, to make sure there were no serious side effects and to confirm preliminary benefits.

Middle-aged mice hearts start functioning like much younger hearts after just 10 weeks of rapamycin treatment, so the goal was to see if these initial benefits would be observed in dogs as well.

The good news:  compared to placebo, 10 weeks of rapamycin did improve heart function of healthy older dogs.  The next step is now to extend the study for the next five years to observe any effects on aging and longevity.

Rapamycin Links

Show Notes
  • 00:00:26

    Our first dog-themed episode

  • 00:02:03

    This Week in Neuroscience: Prenatal fruit consumption boosts babies' cognitive development

  • 00:05:11

    The audience interaction section

  • 00:07:45

    Intro to Dr. Matt Kaeberlein and The Dog Aging Project

  • 00:09:19

    The discovery of Rapamycin and its mechanism of action

  • 00:10:58

    Rapamycin as an immune suppressant

  • 00:11:54

    Dr. Kaeberlein's first interest in aging and Rapamycin

  • 00:12:48

    Unbiased geneteic screening

  • 00:14:17

    Target of Rapamycin (TOR)

  • 00:17:31

    How do studies in animals translate to projected results in humans?

  • 00:20:27

    Extending healthspan

  • 00:21:24

    The Dog Aging Project

  • 00:25:07

    Purebred and mixed-breed dogs and life expectancy

  • 00:26:10

    How close are dogs to humans on an evolutionary tree?

  • 00:29:36

    Because of the huge variation in breeds and living conditions, what sample size will produce significant results?

  • 00:31:52

    Sign your dog up for the study at www.DogAgingProject.com

  • 00:33:02

    Rapamycin as an anti-aging compound in humans

  • 00:36:57

    What is an acceptable risk profile for an anti-aging drug?

  • 00:39:42

    Ruthless Listener-Retention Gimmick: 6 medical conditions that dogs can sniff out

PS:  You’ll find other ways to live longer and better in our weekly Brain Breakfast email.

Read Full Transcript
Show Notes
  • 00:00:26

    Our first dog-themed episode

  • 00:02:03

    This Week in Neuroscience: Prenatal fruit consumption boosts babies' cognitive development

  • 00:05:11

    The audience interaction section

  • 00:07:45

    Intro to Dr. Matt Kaeberlein and The Dog Aging Project

  • 00:09:19

    The discovery of Rapamycin and its mechanism of action

  • 00:10:58

    Rapamycin as an immune suppressant

  • 00:11:54

    Dr. Kaeberlein's first interest in aging and Rapamycin

  • 00:12:48

    Unbiased geneteic screening

  • 00:14:17

    Target of Rapamycin (TOR)

  • 00:17:31

    How do studies in animals translate to projected results in humans?

  • 00:20:27

    Extending healthspan

  • 00:21:24

    The Dog Aging Project

  • 00:25:07

    Purebred and mixed-breed dogs and life expectancy

  • 00:26:10

    How close are dogs to humans on an evolutionary tree?

  • 00:29:36

    Because of the huge variation in breeds and living conditions, what sample size will produce significant results?

  • 00:31:52

    Sign your dog up for the study at www.DogAgingProject.com

  • 00:33:02

    Rapamycin as an anti-aging compound in humans

  • 00:36:57

    What is an acceptable risk profile for an anti-aging drug?

  • 00:39:42

    Ruthless Listener-Retention Gimmick: 6 medical conditions that dogs can sniff out

3 comments

  1. Kimberly Fretz says:

    Hello Jesse, I wanted to let you know that the knowledge that you present on this podcast has had a profound impact on my life! As a woman in my mid 50’s, discovering many of the supplements that you discuss on your show has recharged my aging brain and opened up a new world of possibilities for me me!! Energized and engaged again!! Thank you!!

    1. Jesse Lawler says:

      Love to hear that, Kimberly! Thank you. 🙂

  2. ben says:

    For more of the history of rapamycin, and how it mimics fasting, there was a great episode of the Tim Ferriss podcast (“Life Extension Pilgrimage”) where David Sabatini, Peter Attia, and Navdeep Chandel) talk about it in-depth. Apparently, the researcher (Suren Sehgal) that saved the Easter Island bacteria that makes the rapamycin compound, was able to temporarily halt his metastatic colon cancer with it!

    However, despite the potential upside (longevity/cancer-prevention), and few downsides (mouth sores, decreased insulin sensitivity etc) of taking intermittent rapamycin, many researchers that study it (David Sabatini, Valter Longo,etc ) still aren’t in favor of supplementing with it! Equally strange is if rapamycin acts as an immune suppressant for organ transplants, how can it also be used for helping the elderly that have a poor responding immune system? Or how can something that’s produced by bacteria, be anti-bacterial/fungal!

    Would have also loved to hear more about mTORC1 and mTORC2, and how affecting the former yields the anti-aging function, whereas tinkering with the latter affects sugar metabolism. Or the science why GABA is often taken with rapamycin.

Leave a Reply

Scroll to top