mTOR (Mechanistic Target of Rapamycin)
The molecular switch that decides between growth and longevity
Definition
mTOR (mechanistic Target of Rapamycin) is a protein kinase that acts as a central sensor of nutrients, energy, and growth factors. When mTOR is active, the cell enters 'growth and proliferation' mode: it inhibits autophagy and activates protein synthesis. When mTOR is inhibited (fasting, caloric restriction, rapamycin), the cell enters 'maintenance and repair' mode: it activates autophagy and DNA repair mechanisms. Chronic mTOR inhibition is the most reproducible intervention for extending lifespan in model organisms.
Detailed explanation
mTOR exists in two complexes: mTORC1 (regulates growth, inhibited by rapamycin) and mTORC2 (involved in glucose and lipid metabolism, harder to inhibit).
Rapamycin is the only drug that consistently extends lifespan in mice (even when administration begins at the equivalent of 60 human years, according to the NIA's ITP Study). However, chronic use in humans carries significant side effects (immunosuppression, dyslipidaemia).
Natural strategies for mTOR inhibition with a lower side-effect profile: intermittent fasting (reduces insulin and IGF-1, which activate mTOR), caloric restriction, exercise (activates AMPK, which antagonises mTOR), curcumin, resveratrol, and berberine.
The optimal balance for longevity is not fully inhibited mTOR (which would halt muscle protein synthesis) but rather pulsatile signalling: high activity post-exercise (muscle synthesis) and inhibition during rest and fasting (repair and autophagy).
Related terms
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