mTOR (Mechanistic Target of Rapamycin)

What it is

mTOR (mechanistic target of rapamycin) is a serine/threonine kinase that sits in two distinct complexes:

• mTORC1 — growth, anabolism, protein synthesis. Sensitive to acute rapamycin.
• mTORC2 — cytoskeleton, AKT activation, insulin sensitivity. Less sensitive acutely; chronic rapamycin can inhibit it indirectly.

Why it matters in aging

Reduced mTOR signalling is the most reproducible mammalian lifespan extension. Mice with reduced mTORC1 activity (genetic or pharmacological) live longer. Centenarian cohorts show signatures of preserved mTOR regulation. Excess mTORC1 activation drives age-related metabolic disease, cancer, and sarcopenia.

Inputs

• Amino acids (especially leucine) via the Rag GTPases.
• Insulin / growth factors via PI3K-AKT.
• Energy state via AMPK (inhibitory).
• Oxygen via REDD1.

Outputs

• Protein synthesis (S6K1, 4E-BP1).
• Lipid synthesis (SREBP).
• Autophagy suppression (ULK1).
• Mitochondrial biogenesis.

What inhibits it

Rapamycin is the canonical pharmaceutical. Caloric restriction, intermittent fasting, exercise, and metformin all reduce mTOR tone via different inputs.

Related entries

Deregulated nutrient-sensing, AMPK, Sirtuins, Disabled macroautophagy.