On: Rapamycin and the discovery of mTOR — the nexus of aging and longevity?
Date: August 2018
- 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;
- May have something to do with autophagy (decreased mTOR upregulates autophagy). (see also “The Drive with Peter Attia — Matt Kaeberlein“)
- Cycling of cell death and subsequent rebuild / recovery.
- 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).
- 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.