“Most good science comes only after a massive amount of failure.”
– David M. Sabatini
This episode was a blast.
It was a tropical exploration of biology, life extension, and all good things. This included a lot of Carménère wine and good old-fashioned ball busting.
I was joined by:
Peter Attia, MD (@peterattiamd), who rejoins the show (catch his last appearance here). He is a former ultra-endurance athlete (e.g., swimming 25-mile races), compulsive self-experimenter, and one of the most fascinating human beings I know. He is one of my go-to doctors for anything performance- or longevity-related. Peter earned his MD from Stanford University and holds a BSc in mechanical engineering and applied mathematics from Queen’s University in Kingston, Ontario. He did his residency in general surgery at the Johns Hopkins Hospital, and conducted research at the National Cancer Institute under Dr. Steven Rosenberg, where Peter focused on the role of regulatory T cells in cancer regression and other immune-based therapies for cancer.
David M. Sabatini, M.D., Ph.D. (@DMSabatini) of MIT’s Whitehead Institute for Biomedical Research. David is on a short list for the Nobel Prize for his work in elucidating the role of rapamycin and mTOR.
Navdeep S. Chandel, Ph.D., the David W. Cugell Professor of Medicine and Cell Biology at the Feinberg School of Medicine, Northwestern University. Nav established his lab there to further the understanding of how mitochondria work as signaling organelles to regulate physiology and pathology. He is also the author of Navigating Metabolism.
Perhaps you’ve heard of people in Silicon Valley taking metformin, rapamycin, and supplements for longevity. In this conversation, we dig into the real science, what current evidence supports (or doesn’t), and other important matters like how to staple properly, which fonts reasonable people use, and why Borat is a genius. Enjoy!
Listen to it on iTunes.
Stream by clicking here.
Download as an MP3 by right-clicking here and choosing “save as.”
Want to hear another episode with Peter Attia? — Listen to his first appearance on the podcast. In this episode, we discuss optimizing blood testing, training for ultra-endurance sports, consuming synthetic ketones, using metabolic chambers, extending longevity by avoiding certain types of exercise, and much more (stream below or right-click here to download):
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QUESTION(S) OF THE DAY: What was your favorite quote or lesson from this episode? Please let me know in the comments.
Scroll below for links and show notes…
Selected Links from the Episode
Connect with Peter Attia: Twitter | The Eating Academy
Connect with David M. Sabatini: Twitter | Sabatini Lab
Connect with Navdeep S. Chandel: Chandel Lab
Dr. Peter Attia on Life-Extension, Drinking Jet Fuel, Ultra-Endurance, Human Foie Gras, and More (Peter’s last appearance on this show)
The 1994 discovery of mTOR (mechanistic target of rapamycin) — at the time called RAFT1
An MIT Interview with David Sabatini
Easter Island, National Geographic
A Rogue Doctor Saved a Potential Miracle Drug by Storing Samples in His Home After Being Told to Throw Them Away by Kevin Loria, Business Insider
Navigating Metabolism by Navdeep Chandel
I Am Birdman, Hear Me Roar by Bucky McMahon, Men’s Journal
Rapalogs and mTOR Inhibitors as Anti-aging Therapeutics
Rapamycin Intervention Trial in Pet Dogs
The Dueling Banjos scene from Deliverance
Novartis Working on ‘Fountain of Youth’ Drug by Jim Algar, Tech Times
Regulation of mTORC1 by Amino Acids
2016 Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy
mTOR Signaling in Growth Control and Disease in Cell
Metformin: Uses, Dosage, Side Effects
Effect of Metformin on Breast Cancer Metabolism
Antioxidants: Beyond the Hype, Harvard School of Public Health
Miami Freestyle: 13 Best Acts of All Time by Jacob Katel, Miami New Times
Narcos
All About The Human Genome Project
“Correlation does not imply causation.”
LaTeX – A document preparation system
Fonts mentioned: Times New Roman, Myriad Pro Condensed, Helvetica, Verdana, and Comic Sans
The Helvetica documentary
Five Vision Myths, American Academy of Ophthalmology
Basis by Elysium
Easter Island: Secret Caves And Tunnels by Brien Foerster
Borat – Horse is Like a Man
Siddhartha by Hermann Hesse
Lincoln: A Novel (The American Chronicle Series) by Gore Vidal
Burr: A Novel by Gore Vidal
The Satanic Verses: A Novel by Salman Rushdie
Wathan Funeral Home’s Text and Drive billboard
The Monkey Puzzle Tree
Understanding Altruism, Psychology Today
George Costanza Does the Opposite
EQ vs. IQ
The Mythical Man-Month: Essays on Software Engineering by Frederick P. Brooks, Jr.
A picture of the plaque commemorating the discovery of rapamycin
Show Notes
Nav introduces David and explains why we’re on Easter Island. [08:47]
David introduces Nav and his work in the study of mitochondria. [10:48]
Peter talks about how he’s connected to Nav and David and elaborates more on how our trip to Easter Island came about. [12:30]
The connection between Easter Island (aka Rapa Nui) and rapamycin — and how one of the most important discoveries of medical science was almost lost. [14:37]
David details his connection with rapamycin and what research was like with early, limited samples. [19:27]
Why metabolism research is the key to treating a long list of diseases. [22:58]
mTOR’s role in metabolism. [28:56]
Potential applications of rapamycin. [31:58]
Why rapamycin longevity studies in mice may be inaccurate — and how new dog trials may give us better data. [33:04]
Lifespan vs. healthspan. [36:40]
What is the logic behind intermittent dosing of rapamycin? [42:43]
Does intermittent dosing of rapamycin mimic fasting? [47:55]
Are there downsides to going from a fasted state back to a fed state? [49:19]
What is the difference between rapamycin and metformin? [50:23]
Do any of the guests use metformin — why or why not? [1:03:52]
Would having an expected lifespan of more than a hundred years make Nav less effective? [1:06:29]
Why Nav does not take metformin, and why David does not take rapamycin. [1:08:44]
Thoughts on supplementing with antioxidants. [1:13:11]
Where did Nav grow up, and what prompted his pursuit of science? [1:18:57]
Parenting advice from scientists: views on confidence and conflict. [1:28:19]
Most good science comes only after a massive amount of failure. [1:38:41]
Atypical advice given to students, and what it takes to be a bad scientist. [1:40:16]
Peter’s thoughts on the importance of the right fonts, and why he’s obsessive about what might seem like nonsense to most. [1:43:27]
What are the right fonts and why? [1:47:38]
Even though David’s vision has gotten worse in the past few years, why doesn’t he wear glasses? [1:51:27]
Thoughts about Basis by Elysium. [1:52:59]
Peter explains asymmetric risk and an aversion to spelunking from trees. [1:56:44]
How might David live to be 600 if he won’t take rapamycin? [2:00:13]
Peter channels Borat. [2:04:25]
Book Nav has gifted most. [2:08:33]
Books David has gifted most. [2:10:27]
What would Nav and David’s billboards say? [2:12:38]
On a subject outside of his everyday area of expertise, what TED Talk would Nav give? [2:16:03]
Why are Nav and Dave such close friends? [2:24:21]
Have I stumbled into Dumb & Dumber meets Limitless? [2:27:30]
Peter extolls the virtues of having nuanced scientific discussions in one of the most beautiful places on the planet. [2:29:22]
The benefit of “non-potato” relationships. [2:30:36]
What advice would David give to his 30-year-old self? [2:33:45]
What advice would Nav give to his 22-year-old self? [2:37:35]
Best investment in money, time, or energy that Nav has made. [2:40:18]
As an efficient person, what are the most common mistakes Nav sees inefficient people make? [2:44:19]
How does Nav instill the importance of efficiency to his daughter? [2:46:40]
Best investment in money, time, or energy that David has made. [2:47:50]
Why Nav considers being rejected by medical school three times in 22 years a good thing. [2:51:43]
Peter tells a story about rapamycin pioneer Suren Sehgal. [2:53:08]
Closing asks, requests, suggestions, and recommendations for the listeners. [3:00:42]
People Mentioned
Julie McCoy
Suren Sehgal
Ajai Sehgal
Solomon Snyder
Homer Simpson
Matt Kaeberlein
Pablo Escobar
Borat
Antonio Banderas
Sacha Baron Cohen
Josh Waitzkin
Naval Ravikant
Gore Vidal
Abraham Lincoln
Aaron Burr
Salman Rushdie
George Costanza
Amelia Boone
Craig Thompson
O.J. Simpson