How Do We Define in Pharmacology a Small Molecule?

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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