The Drive with Peter Attia — David Sabatini

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On: Rapamycin and the discovery of mTOR — the nexus of aging and longevity?

Episode: 9

Date: August 2018

Key Subjects:

  • mTOR (mammalian target of rapamycin) (see mTOR write-up)
    • Central regulator of metabolism and physiology.
    • Regulating many cellular processes (cell growth, proliferation, protein synthesis, autophagy).
  • Rapamycin inhibits the activation of mTOR.
    • Initially used as immunosuppressant (in high doses).
    • In lower doses, rapamycin may have additional benefits, including extension of life span and prevention of cancer development, neurodegenerative diseases.
  • Unclear why rapamycin extends lifespan;
  • mTOR particularly useful and efficient target to modulate, since it is involved in many different cell pathways (one stop shop).
  • mTOR is activated by many substrates, including glucose, insulin, amino acids.
    • Amino acids are a particularly potent in activating mTOR (leucine, arginine, methionine).
  • For life extension, methionine restriction may work the same as caloric restriction in inhibiting mTOR (and thereby IGF-1).
  • Speculation: mTOR signaling gets higher with age (not good); mTOR signaling is high in early life (good) but fails to decrease with age (bad).

Key Takeaways:

  • Explore measuring levels of certain amino acids – leucine, arginine, methionine.
  • The same trait that is adaptive for survival early in life may become a threat to survival later in life. 

Worth Listening:

  • 7/10



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