#09 - David Sabatini, M.D., Ph.D.: rapamycin and the discovery of mTOR — the nexus of aging and longevity?

The Peter Attia Drive

Peter Attia, MD

Health & Fitness, Medicine, Fitness

4.7 • 7.3K Ratings

🗓️ 13 August 2018

⏱️ 71 minutes

🔗️ Recording | iTunes | RSS

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Summary

In this episode, my good friend David Sabatini delves into his extensive work with the mechanistic target of rapamycin—better known as mTOR—and rapamycin. The compound rapamycin is the only known pharmacological agent to extend lifespan all the way from yeast to mammals—across a billion years of evolution. David, a professor of biology and a member of the Whitehead Institute at MIT, shares his remarkable journey and discovery of mTOR in mammalian cells and its central role in nutrient sensing and longevity. Fasting, rapamycin, mTOR, autophagy, gedankenexperiments: having this conversation with David is like being the proverbial kid in the world’s greatest candy store.

We discuss:

mTOR and David’s student years [4:30];
Rapamycin and the discovery of mTOR [8:15];
The connection between rapamycin, mTOR, and longevity [30:30];
mTOR as the cell’s general contractor [34:45];
The effect of glucose, insulin, and amino acids on mTORC1 [42:50];
Methionine sensing and restriction [49:45];
An intermittent approach to rapamycin [54:30];
Rapamycin’s effects on cancer, cardiovascular disease, and neurodegeneration [57:00];
Gedankenexperiment: couch potatoes on rapamycin vs perfectly behaved humans [1:03:15];
David’s dream experiment with no resource constraints [1:07:00]; and
More.

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Transcript

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0:00.0	Hey everyone, welcome to the Peter Atia Drive. I'm your host, Peter Atia.
0:10.0	The drive is a result of my hunger for optimizing performance, health, longevity, critical thinking,
0:15.7	along with a few other obsessions along the way. I've spent the last several years working
0:19.6	with some of the most successful top performing individuals in the world, and this podcast
0:23.8	is my attempt to synthesize what I've learned along the way to help you live a higher quality
0:28.3	more fulfilling life. If you enjoy this podcast, you can find more information on today's
0:32.5	episode and other topics at peteratiamd.com.
0:41.7	In this podcast, I'll be speaking with my close friend and amazing scientist, David Sabatini.
0:46.7	David's a professor of biology, a member of the Whitehead Institute at MIT. He's also an
0:51.1	investigator at the Howard Hughes Medical Institute and a senior member of the Broad Institute,
0:55.1	along with a bunch of other accolades that would take too long to get into here.
0:59.5	This podcast was actually recorded initially as part of an interview series I was doing for
1:04.1	research around my book. This was recorded in August of 2017. Maybe at some point,
1:09.4	we'll even just put the video up as this was actually done as a video interview.
1:12.7	David, along with a number of his amazing postdocs, and certainly some of those will probably
1:17.5	make their way into the podcast as well. In this episode, we talk about his amazing journey
1:22.4	in science and the work and stuff that he's done around MTOR and RAPA MISON. If you've been
1:28.5	following the blog and or paying attention to stuff that I'm interested in, you'll know that
1:32.5	MTOR and RAPA MISON sit kind of at the heart of it. Now, about four years ago, David and I were
1:37.8	having lunch one day. It was kind of the first time that he ever really told me the full story of
1:43.6	his work as a graduate student at Hopkins, where he was part of the MDPD program.
1:48.4	And I was just, you know, I remember sitting there taking notes on a napkin and thinking, God,
	...

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