View episode show notes here: https://bit.ly/36CzHME Become a member to receive exclusive content: https://bit.ly/3k03Sk6 Sign up to receive Peter's email newsletter: https://bit.ly/4c602k2 Nir Barzilai, Director of the Institute for Aging Research at the Albert Einstein College of Medicine, is back for his third appearance on The Drive. In this episode, Nir divulges insights into lifespan and healthspan through the lens of his extensive research on centenarians as well as the latest from the TAME trial (Targeting/Taming Aging with Metformin), a multi-center study investigating the concept that the multi-morbidities of aging can be delayed in humans. He discusses common gene variants found in centenarians, important pathways for longevity, and ultimately what we can learn from centenarians about extending lifespan while also trying to improve healthspan. Additionally, Nir goes into depth on metformin as a longevity tool for humans, including studies with positive and negative results. He discusses the impact metformin can have on exercise for both strength training and cardiovascular training, as well as future research facilitated by data from the TAME Trial. He also touches on epigenetic clocks and concludes with his take on the usefulness of NAD precursors as a potential gero-protective agent. We discuss: 0:00:00 - Intro 0:00:08 - Insights from genetic studies of centenarians and twins 0:11:13 - Genes with protective variants that aid longevity 0:22:23 - The relationship between growth hormone and IGF-1 0:35:37 - Use of growth hormone as a longevity tool 0:44:29 - Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP 0:50:04 - The correlation between high TSH and longevity 0:56:30 - Important pathways for longevity 1:04:38 - Insights from centenarian studies, nature vs. nurture, and more 1:14:56 - The contraction of morbidity that comes with improved healthspan 1:20:56 - Defining healthspan 1:26:14 - Unique perspectives and positive attitudes of centenarians 1:33:32 - Lessons to take away from centenarians 1:38:48 - Metformin overview: history, studies, and potential for gero-protection 1:50:07 - The TAME trial (Targeting Aging with Metformin) 1:59:29 - The challenge of studying metformin in animals models 2:07:27 - How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics 2:14:54 - The search for biomarkers to identify who can benefit from treatment 2:26:29 - The impact of metformin on exercise, and finding the right indication for the use of metformin 2:39:36 - Are NAD precursors geroprotective? -------- 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 40 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://bit.ly/3EIgCWa 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