View show notes here: https://bit.ly/4bwwZVe Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer’s disease. Disclosure: Peter is an investor in Jocasta Neuroscience, a company working to develop klotho as a therapy for people with Alzheimer’s disease. We discuss: 0:00:00 - Intro 0:01:19 - Dena’s fascination with aging and how she came to study klotho 0:11:00 - Biological properties of klotho: production, regulation, decline with age, and factors influencing its levels 0:23:08 - Potential benefits of klotho on brain health 0:36:18 - The relationship between soluble klotho protein, platelet factors, and cognitive enhancement 0:52:31 - The role of platelet factor 4 (PF4) and it’s interaction with GluN2B in mediating cognitive enhancement 1:02:52 - Benefits of klotho observed in a mouse model of Parkinson’s disease 1:11:22 - Benefits of klotho observed in a mouse model of Alzheimer’s disease 1:17:18 - Promising results of klotho in primate models, and the importance of finding an appropriate therapeutic dose before moving to human trials 1:39:34 - Speculating why a single klotho injection has such long-lasting effects 1:42:45 - Potential cognitive benefits of klotho in humans, the impact of the KL-VS genetic variant on klotho levels, and the need for human trials to confirm these effects 1:50:10 - The interaction between the KL-VS genetic variant and APOE4 and how it impacts risk of Alzheimer’s disease 2:05:26 - The significance of klotho levels: studies linking lower levels to increased mortality and the broader implications for organ health and disease prevention 2:11:48 - Measuring klotho levels and determining an individual’s KL-VS status 2:18:32 - The promising potential of klotho for Alzheimer’s disease treatment, and the importance of philanthropy for funding research -------- About: The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, and all that goes into that from physical to cognitive to emotional health. With over 90 million episodes downloaded, it features topics including exercise, nutritional biochemistry, cardiovascular disease, Alzheimer’s disease, cancer, mental health, and much more. Peter Attia is the founder of Early Medical, a medical practice that applies the principles of Medicine 3.0 to patients with the goal of lengthening their lifespan and simultaneously improving their healthspan. Learn more: https://peterattiamd.com 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 Disclaimer: This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit my website where I keep an up-to-date and active list of such companies. For a full list of our registered and unregistered trademarks, trade names, and service marks, please review our Terms of Use: https://peterattiamd.com/terms-of-use/