Master One Thing - Rapamycin Longevity Series Joan Mannick on Rapamycin Longevity Series | Turning down mTOR to young levels may be good for aging
Jan 17, 2024
Joan Mannick, physician-scientist and CEO of Tornado Therapeutics known for pioneering human mTOR/rapamycin studies. She discusses mTOR biology and its role in aging. Short-course, low-dose strategies to tune TORC1 without immunosuppression. Designing human trials that measure immune responses and translating rapalogs into safer, TORC1-selective drugs.
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mTOR Acts As The Nutrient Switch For Aging
- mTOR links nutrient availability to growth and protective fasting pathways.
- In aging mTOR becomes hyperactive and fails to switch off, so turning it down to youthful levels restores autophagy, lowers inflammation, and improves cellular cleanup.
How The First Human mTOR Vaccine Trial Was Born
- Joan proposed a short human trial testing whether an mTOR inhibitor could improve aged immune response to flu vaccine.
- Novartis greenlit a six-week dosing, two-week break then flu vaccination to get a quick go/no-go signal for aging biology in humans.
Partial mTOR Inhibition Improves Vaccine Response
- Low or intermittent mTOR inhibition improved flu vaccine antibody responses in people 65+.
- Doses predicted to inhibit mTOR ~40–80% were tested; moderate inhibition helped but the 80% inhibition dose did not.