Joan Mannick on Rapamycin Longevity Series | Turning down mTOR to young levels may be good for aging

Dr Joan Mannick is one of the world’s leading rapamycin and mTOR researchers in the longevity field. Joan has a background in academic medicine and is currently CEO at her own company Tornado Therapeutics where they focus on developing the next generation of mTOR inhibitors. One of the company goals is to create a mTOR inhibitor which is better than Rapamycin. Throughout the years Joan has made important discoveries in humans when it comes to finding a connection between mTOR inhibition and improvement of the aging immune system. In this podcast we are going to talk about her research, drug development, mTOR, rapamycin, rapalogs and other interesting longevity topics. 00:00 Intro 01:59 Longevity interest and research 03:40 How Joan's longevity career started 06:24 What is mTOR and what makes it unique 08:55 Mechanisms underlying the effects of mTOR 10:56 How translatable is the effects of mTOR to humans 12:43 mTOR inhibition and it's upstream pathways 14:02 What is Rapamycin and how it was discovered 15:21 The weak points of Rapamycin 16:35 mTOR contains of mTORC1 and mTORC2 17:28 What is a rapalog 18:31 Detect early signs of mTORC2 inhibition 19:40 Tornado Therapeutics and it's portfolio of rapalogs 23:13 Joan proposed a courage trial to the board 27:07 Animal data show Rapamycin may improve the immune system 28:09 Designing the dosing protocol for phase 1 trial 29:26 The phase 1 trial and it's results 32:50 Aged immune system may drive aging 35:12 A good immune system may prevent cancer 36:05 Influenza and the aging immune system 38:29 The phase 2a trial and mTOR inhibition in elderly 39:32 The phase 2b and 3 trial 40:28 Antiviral genes are upregulated 42:26 Catalytic mTOR inhibitor RTB101 43:05 The phase 3 trial did not meet the primary endpoint 46:02 Pilot trial to decrease the severity 46:59 Dose protocol of Everolimus and RTB101 49:37 Safety profile between Everolimus and RTB101 52:10 Vaccines and/or mTOR inhibitor 54:51 Dosing protocol to improve the antiviral response 56:44 Taking a break or continue taking mTOR inhibitor during a common cold 57:49 Immune system biomarkers 59:24 Sarcopenia and mTOR inhibition 1:01:50 Leading candidate in Tornado Therapeutics portfolio 1:03:19 Safety profile of the rapalog TOR101 1:06:13 Next step for TOR101 1:08:25 Rhinovirus trial with TOR101 1:08:56 When will a mTOR inhibitor be FDA approved for longevity 1:10:28 Lifespan studies with TOR101 1:11:49 Joan's own personal approach to mTOR inhibitors 1:13:33 Most promising longevity interventions 1:15:30 Autophagy and mTOR inhibitors 1:16:40 Big challenges in the longevity field 1:19:20 What the field really needs 1:20:48 Contact information Links - Tornado Therapeutics https://www.tornado-tx.com - Joan's LinkedIn https://www.linkedin.com/in/joan-mannick-8089a614 - Joan’s research publications https://pubmed.ncbi.nlm.nih.gov/?term=Mannick+JB - Big thanks to TimePie for the research help for this episode https://www.youtube.com/@timepie7959 Rapamycin resources - Rapamycin Longevity Lab https://masteronething.com - Rapamycin.news https://www.rapamycin.news - Rapamycin Facebook group https://www.facebook.com/groups/rapamycin - Rapamycin Reddit group https://www.reddit.com/r/Rapamycin Connect with Krister on: Twitter: https://twitter.com/KristerKauppi Instagram: https://www.instagram.com/longevity.lifestyle.hacker Disclaimer: The podcast is for general information and educational purposes only and is not medical advice for you or others. The use of information and materials linked to the podcast is at the users own risk. Always consult your physician with anything you do regarding your health or medical condition.