In this insightful episode, host Buck Joffrey sits down with Dr. Joan Mannick—a leading physician-scientist and biotech entrepreneur—to explore how targeting the mTOR pathway may unlock new frontiers in longevity and immune health. With experience spanning Harvard, biotech startups, and clinical trials, Dr. Mannick offers a rare blend of scientific rigor and translational vision.

Key Points:

This episode underscores the transformative potential of mTOR-targeted therapies—not only for living longer but for ageing better. The work of Dr. Joan Mannick and her team is steadily turning the science of ageing into practical medicine.

• What is mTOR and Why It Matters: Dr. Mannick explains mTOR (mechanistic Target Of Rapamycin) as a key nutrient-sensing protein that governs growth and cellular repair. While essential for development, chronic overactivation of mTOR with age may accelerate aging—suggesting that inhibiting it could slow down age-related decline.
• The Power of Selective Inhibition: mTOR has two complexes—TORC1 and TORC2. Inhibiting TORC1 appears to promote longevity and immune function, while inhibiting TORC2 may cause harmful side effects like insulin resistance. Mannick’s current company, Tornado Therapeutics, is developing next-gen inhibitors that selectively target TORC1 for safer long-term use.
• From ICU to Immune Resilience: Inspired by a groundbreaking paper by Cynthia Kenyon, Mannick shifted from treating critically ill patients to exploring how organisms might live far longer than expected. This led to her pioneering clinical trials showing that low-dose mTOR inhibitors can enhance immune responses in older adults, even improving their response to flu vaccines.
• Longevity, Muscle, and mTOR Balance: While mTOR supports muscle growth, excessive activation in aging bodies can impair cellular repair. Surprisingly, mTOR inhibition in older animals not only preserved function but improved muscle health—highlighting the nuanced role of dose, age, and tissue specificity.
• Lessons from Clinical Trials: Her team’s trials with RTB101 (a TORC1-selective compound) aimed to reduce respiratory infections in older adults. Although one Phase 3 trial failed due to flawed endpoints, the work revealed promising antiviral gene activation. The next frontier? Safer, more targeted drugs with broad applications across age-related diseases.