Sign up to receive Peter's email newsletter: https://bit.ly/4c602k2 In this episode, Joan and Nir discuss their extensive research into rapamycin (including the category of analogs to rapamycin known as rapalogs) and metformin, respectively. Based on his work with metformin, Nir shares how he believes it could be a pro-longevity drug and the clinical trial he’s leading to test this belief. Joan discusses her work with rapalogs, their ability to suppress the immune system as well as provide immune-enhancement, and the clinical trials she has led that inform her insights. We also talk about the potential beneficial roles of both metformin and rapamycin in reducing mortality from COVID-19, reducing the risk of neurodegenerative diseases, and delaying aging as well as its related diseases. We discuss: 00:00:00 - Intro 00:03:45 - Joan’s career, interest in aging, and work with rapamycin analogs 00:15:00 - When Nir became convinced metformin could be a pro-longevity agent 00:24:15 - How metformin and rapamycin impact the hallmarks of aging and extend lifespan 00:34:15 - Enhancing the immune system with rapalogs and metformin 00:41:30 - Potential of metformin and rapamycin in reducing mortality from COVID-19 00:59:00 - Insights from Joan’s studies investigating the immune-enhancing effects of rapalogs 01:08:15 - Vaccines and treatments strategies for COVID-19, and the likelihood of long-term immunity 01:14:30 - The potential role of rapalogs and metformin in neurodegenerative disease 01:18:00 - Nir’s TAME trial—primary objectives and latest updates 01:25:45 - Potential synergistic effect when combining metformin with rapamycin 01:27:30 - Why Peter stopped taking metformin and started taking rapamycin 01:37:30 - Story from Nir’s book that demonstrates the challenge of doing good scientific studies 01:42:00 - The biology of aging—epigenetic clocks, proteomics, and Nir’s centenarian data 01:57:15 - Joan’s dream experiment to test immune-enhancing effect of RTB101 01:59:45 - Concluding thoughts on COVID-19 Show notes page: https://peterattiamd.com/joanmannick-nirbarzilai/ About: The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 30 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more. Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life). Learn more: https://peterattiamd.com/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Play: http://bit.ly/TheDriveGooglePlay