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359 ‒ How metabolic and immune system dysfunction drive the aging process, NAD, aging clocks, & more

Eric Verdin is a physician-scientist & the CEO of the Buck Institute for Research on Aging. In this episode, Eric traces his scientific journey from studying viruses to leading aging research at the Buck Institute, offering insights into how aging impairs immune & nervous system function—including thymic shrinkage, chronic inflammation, & reduced vaccine response—& how these changes impact lifespan. He explores the metabolic underpinnings of aging, such as oxidative stress & insulin & IGF-1 signaling, & he discusses practical tools like zone 2 cardio, ketogenic diets, & GLP-1 drugs. The conversation also covers declining NAD levels with age, the roles of NAD-consuming enzymes such as sirtuins & CD38, & what current NAD-boosting strategies can & can’t accomplish. Eric weighs in on promising longevity interventions including rapamycin, growth hormone for thymic regeneration, & anti-inflammatory therapies, the promise & limitations of current biological age tests, & the potential of combining epigenetic, proteomic, & organ-specific metrics with wearables to guide personalized longevity care. View show notes here: https://bit.ly/4o9PlSB Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ 0:00:00 0:01:20-Eric’s journey from virology to geroscience 0:04:16-How dysfunction in the immune system & central nervous system can drive aging 0:08:28-Role of metabolism & oxidative stress in aging 0:17:32-Other aspects of metabolism linked to aging: mitochondrial efficiency, fuel utilization, & glucose-modulating drugs 0:23:42-How inefficient glucose metabolism drives insulin, IGF-1 signaling, & accelerates aging 0:29:45-Metabolic effects of GLP-1 agonists 0:40:48-Immune health as a “fifth horseman” 0:45:11-How the innate & adaptive immune systems work together to build immune memory 0:50:26-Why vaccines lose effectiveness with age 0:55:48-Exploring growth hormone, thymic regeneration, & the role of exercise in slowing immune aging 1:06:09-Challenges of identifying reliable biomarkers for immune function, & the potential of rapamycin analogs to enhance vaccine response 1:13:08-How rapamycin’s effects on the immune system vary dramatically by dosage & frequency 1:18:50-Limitations of mouse models & the need for cautious interpretation of rapamycin’s benefits in humans 1:27:50-NAD, sirtuins, & aging: scientific promise amid commercial hype 1:37:10-How CD38 drives age-related NAD decline, influences immune function, & may impact longevity 1:45:41-How NMN & NR supplementation interact with CD38 & NAD metabolism 1:52:24-Intravenous NAD: limited evidence & serious risks 1:59:50-Interleukin-11 (IL-11) as a new target in immune aging, the dual role of chronic inflammation in aging, & the need for better biomarkers to guide interventions 2:06:26-Biological aging clocks 2:20:48-Potential of proteomics-based aging clocks for detecting organ-specific decline -------- About: The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, & 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, & 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 & 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/

Peter AttiahostEric Verdinguest
Aug 4, 20252h 31mWatch on YouTube ↗

Episode Details

EPISODE INFO

Released
August 4, 2025
Duration
2h 31m
Channel
Peter Attia MD
Watch on YouTube
▶ Open ↗

EPISODE DESCRIPTION

Eric Verdin is a physician-scientist & the CEO of the Buck Institute for Research on Aging. In this episode, Eric traces his scientific journey from studying viruses to leading aging research at the Buck Institute, offering insights into how aging impairs immune & nervous system function—including thymic shrinkage, chronic inflammation, & reduced vaccine response—& how these changes impact lifespan. He explores the metabolic underpinnings of aging, such as oxidative stress & insulin & IGF-1 signaling, & he discusses practical tools like zone 2 cardio, ketogenic diets, & GLP-1 drugs. The conversation also covers declining NAD levels with age, the roles of NAD-consuming enzymes such as sirtuins & CD38, & what current NAD-boosting strategies can & can’t accomplish. Eric weighs in on promising longevity interventions including rapamycin, growth hormone for thymic regeneration, & anti-inflammatory therapies, the promise & limitations of current biological age tests, & the potential of combining epigenetic, proteomic, & organ-specific metrics with wearables to guide personalized longevity care. View show notes here: https://bit.ly/4o9PlSB Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ 0:00:00 0:01:20-Eric’s journey from virology to geroscience 0:04:16-How dysfunction in the immune system & central nervous system can drive aging 0:08:28-Role of metabolism & oxidative stress in aging 0:17:32-Other aspects of metabolism linked to aging: mitochondrial efficiency, fuel utilization, & glucose-modulating drugs 0:23:42-How inefficient glucose metabolism drives insulin, IGF-1 signaling, & accelerates aging 0:29:45-Metabolic effects of GLP-1 agonists 0:40:48-Immune health as a “fifth horseman” 0:45:11-How the innate & adaptive immune systems work together to build immune memory 0:50:26-Why vaccines lose effectiveness with age 0:55:48-Exploring growth hormone, thymic regeneration, & the role of exercise in slowing immune aging 1:06:09-Challenges of identifying reliable biomarkers for immune function, & the potential of rapamycin analogs to enhance vaccine response 1:13:08-How rapamycin’s effects on the immune system vary dramatically by dosage & frequency 1:18:50-Limitations of mouse models & the need for cautious interpretation of rapamycin’s benefits in humans 1:27:50-NAD, sirtuins, & aging: scientific promise amid commercial hype 1:37:10-How CD38 drives age-related NAD decline, influences immune function, & may impact longevity 1:45:41-How NMN & NR supplementation interact with CD38 & NAD metabolism 1:52:24-Intravenous NAD: limited evidence & serious risks 1:59:50-Interleukin-11 (IL-11) as a new target in immune aging, the dual role of chronic inflammation in aging, & the need for better biomarkers to guide interventions 2:06:26-Biological aging clocks 2:20:48-Potential of proteomics-based aging clocks for detecting organ-specific decline -------- About: The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, & 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, & 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 & 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/

SPEAKERS

  • Peter Attia

    host

    Physician and host of The Drive podcast focused on longevity and performance medicine.

  • Eric Verdin

    guest

    MD and aging researcher; leads the Buck Institute for Research on Aging.

EPISODE SUMMARY

In this episode of Peter Attia MD, featuring Peter Attia and Eric Verdin, 359 ‒ How metabolic and immune system dysfunction drive the aging process, NAD, aging clocks, & more explores eric Verdin on Metabolism, Immunity, NAD, Rapamycin and Aging Clocks Verdin argues that the immune system and central nervous system are rate-limiting organs for aging, and Attia says he should have added immune health as a fifth horseman to his four horsemen of chronic disease.

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