#118 – Lloyd Klickstein, M.D., Ph.D.: Rapamycin, mTOR inhibition, and the biology of aging

Sign up to receive Peter's email newsletter: https://bit.ly/4c602k2 Original release date: 7/6/20 Lloyd Klickstein is the Chief Science Officer at resTORbio, a biopharmaceutical company that develops medications to target the biology of aging. In this episode, Lloyd discusses his company’s clinical application of rapamycin and its derivatives. He also elucidates details of his 2014 paper—a paper that greatly influenced Peter’s perspective of rapamycin in the context of longevity. Peter and Lloyd go on to discuss the dose-dependent effect of rapamycin on immune function and compare rapamycin, fasting, and caloric restriction. We discuss: 00:00:00 - Intro 00:06:15 - His background and decision to leave academia for translational medicine 00:10:30 - Translational medicine—bridging the gap between basic science and clinical medicine 00:18:00 - What prompted Lloyd to focus on mTOR inhibition? 00:21:30 - Defining mTOR, TORC1, and TORC2, and the consequences of inhibiting them with rapamycin 00:42:15 - Dose-dependent impact of rapamycin on immune function, mTOR inhibition, and toxicity 00:53:00 - Lloyd’s 2014 experiment—mTOR inhibition improves immune function in the elderly 01:13:00 - Insights into autophagy, antigen presentation, and the pleiotropic benefits of a rapalog, and how it compares to fasting 01:18:45 - Lloyd’s 2018 experiment—TORC1 inhibition enhances immune function and reduces infections in the elderly 01:29:00 - Creation of resTORbio, subsequent studies, and takeaways about dosing, TORC2 inhibition, and tissue selectivity 01:40:00 - Comparing the longevity effect of rapamycin, fasting, and caloric restriction 01:47:00 - Excitement around RTB101—resTORbio’s mTOR inhibiting molecule 01:56:15 - Identifying rapalogs selective for TORC1 02:00:00 - Treating depression with ketamine, an activator of mTOR 02:03:30 - Epigenetic clocks, rapalogs, and metformin Show notes page: https://peterattiamd.com/lloydklickstein/ 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