Sign up to receive Peter's email newsletter: https://bit.ly/4c602k2 Matt Kaeberlein is globally recognized for his research on the biology of aging and is a previous guest on The Drive. In this episode, Matt defines aging, the relationship between aging, chronic inflammation, and the immune system, and talks extensively about the most exciting molecules for extending lifespan. He discusses the current state of the literature of testing rapamycin (and rapalogs) in animals and humans, including Matt’s Dog Aging Project, and provides insights into how we can improve future trials by conceptualizing risk, choosing better endpoints, and working with regulators to approve such trials. He also examines the connection between aging and periodontal disease, biomarkers of aging, and epigenetic clocks. Finally, they explore some of the biological pathways involved in aging, including mTOR and its complexes, sirtuins, NAD, and NAD precursors. We discuss: 00:00:00 - intro 00:00:10 - The various definitions of aging 00:14:08 - The relationship between disease and the biology of aging 00:20:55 - Potential for lifespan extension when targeting diseases compared to targeting biological aging 00:31:30 - Rapamycin as a longevity agent and the challenges of targeting the biology of aging with molecules 00:38:56 - Human studies using rapalogs for enhanced immune function 00:51:22 - The role of inflammation in functional declines and diseases of aging 00:56:56 - Study showing rapalogs may improve the immune response to a vaccine 01:02:26 - Roadblocks to studying gero-protective molecules in humans 01:14:44 - Potential benefits of rapamycin for age-related diseases—periodontal, reproductive function, and more 01:24:40 - Debating the ideal length and frequency of rapamycin treatment for various indications like inflammation and longevity 01:32:38 - Biomarkers of aging and epigenetic clocks 01:41:05 - Prospects of a test that could calculate biological age 01:47:28 - The Dog Aging Project testing rapamycin in pet dogs 02:05:00 - The role of the mTOR complexes 02:16:53 - mTor inhibitor called Torin2, mitochondrial disease and other potential pathways 02:27:24 - Catalytic inhibitors, sirtuins, and NAD 02:36:47 - NAD precursors: help or hype? Show notes page: https://peterattiamd.com/mattkaeberlein2/ -------- 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 Podcasts: http://bit.ly/TheDriveGoogle