Podcast Summary: The Peter Attia Drive – Episode #359 with Dr. Eric Verdin
Release Date: August 4, 2025
Introduction
In Episode #359 of "The Peter Attia Drive," host Dr. Peter Attia engages in an in-depth conversation with Dr. Eric Verdin, a renowned physician-scientist and President/CEO of the Buck Institute for Research on Aging. Their discussion delves into the intricate mechanisms driving the aging process, focusing on metabolic and immune system dysfunction, the role of NAD, promising interventions, aging clocks, and more.
Dr. Eric Verdin’s Journey into Aging Research
Dr. Verdin shares his unconventional path to aging research, highlighting his background in virology and epigenetics. His transition from studying viruses like HIV and herpes to focusing on aging stemmed from cloning HDACs (histone deacetylases) and recognizing their importance in aging.
Dr. Eric Verdin [03:17]: “I ended up becoming interested in the reason for the etiology of type 1 diabetes and worked on viruses and autoimmunity. This eventually led me to mostly a career in virology… Starting in around 1995, 1996, my lab slowly shifted towards the study of aging.”
Metabolism and Its Role in Aging
Dr. Verdin emphasizes the critical role metabolism plays in aging, particularly through oxidative stress. He explains how mitochondrial dysfunction leads to increased leakage of electrons, generating reactive oxygen species (ROS) that cause cellular damage.
Dr. Eric Verdin [09:22]: “I still think oxygen is one of the major problems associated with the aging process. We have not been able to target the oxidative stress using antioxidant. That has failed.”
He discusses the nuances of the oxidative stress theory, noting that while ROS contribute to aging, they also play essential roles in signaling and protective inflammatory responses.
Dr. Eric Verdin [12:03]: “These radical oxygen species can have a protective role and actually a signaling role.”
Dr. Attia adds that exercise, particularly zone 2 cardio, may enhance mitochondrial efficiency, potentially mitigating oxidative stress.
Dr. Eric Verdin [18:29]: “Fuel utilization is essential. Ketones are probably the cleanest fuel to burn in terms of byproducts, especially oxidative stress.”
Immune System Dysfunction in Aging
The conversation shifts to the immune system's central role in aging. Dr. Verdin explains that both the central nervous system and the immune system are rate-limiting organs in aging due to their widespread influence throughout the body.
Dr. Eric Verdin [05:26]: “Immunology is Central to aging in many respects… if you induce mitochondrial dysfunction only in the immune system, you induce secondary senescence in the whole organ.”
He highlights how aging leads to thymus shrinkage, loss of T cell diversity, chronic inflammation, and weaker vaccine responses, all contributing to a shortened lifespan.
Dr. Eric Verdin [07:35]: “Chronic inflammation is tied cause and effect in the whole aging process.”
Dr. Attia shares insights from his book, mentioning that immune health should be considered a "fifth horseman" of aging, alongside atherosclerosis, cancer, dementia, and metabolic diseases.
NAD, Sirtuins, and Aging
A significant portion of the discussion centers on NAD (Nicotinamide Adenine Dinucleotide) and sirtuins. Dr. Verdin explains NAD's pivotal role in redox reactions and as a substrate for sirtuins, which are involved in DNA repair and metabolic regulation.
Dr. Eric Verdin [77:11]: “NAD is a critical intermediary metabolite… Sirtuins have a relatively narrow range of KD for NAD, so changes in NAD levels affect their activity.”
Despite the decline in NAD levels with age, supplementing NAD precursors like NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) has shown mixed results. Dr. Verdin cautions that simply increasing NAD may not be beneficial due to complex metabolic pathways and potential side effects, such as elevated homocysteine levels.
Dr. Eric Verdin [15:22]: “Live in an oxidative environment is one of the mechanisms that leads to aging. Aging is pleomorphic.”
Dr. Attia expresses skepticism about the efficacy of NAD supplementation, pointing out that clinical trials have not consistently demonstrated significant health benefits.
Rapamycin and Its Dual Roles
The conversation then explores rapamycin, a drug known for its immunosuppressive properties and potential anti-aging effects. Dr. Verdin and Dr. Attia discuss the contrasting outcomes of rapamycin in clinical settings versus animal studies.
Dr. Eric Verdin [84:15]: “Rapamycin is immunosuppressive by itself… What differentiates immunosuppressive and geroprotective effects is the amount and frequency of dosing.”
Dr. Attia highlights the success of rapamycin in the Interventions Testing Program (ITP) with mice, noting that continuous dosing led to lifespan extension, which contrasts with its immunosuppressive effects in humans.
Dr. Eric Verdin [68:18]: “Mice are potentially maximizing TOR activity to do everything quickly, unlike humans who have lower basal TOR activity.”
This discrepancy raises concerns about translating mouse model findings to human applications, given differences in physiology and environmental factors.
Aging Clocks and Biomarkers
Dr. Attia and Dr. Verdin delve into the complexities of aging clocks—tools designed to estimate biological age. They discuss various types of clocks, including epigenetic, proteomic, and transcriptomic, and the challenges in using them for clinical decision-making.
Dr. Eric Verdin [109:38]: “These clocks are not ready for prime time in terms of patient management.”
They express skepticism about commercially available clocks, emphasizing the lack of validation and potential for false positives.
Dr. Eric Verdin [114:32]: “We don't have one single marker. The immune system is so complex.”
Dr. Verdin mentions the development of more refined clocks, such as the Entren Clock, which aims to account for the heterogeneity of blood cell populations and provide more accurate assessments of biological aging.
Interleukin 11 and Inflammation
The discussion briefly touches on a study involving the blockade of Interleukin 11 (IL-11), which showed increased lifespan in mice. Dr. Verdin connects IL-11 to chronic immune activation and inflammaging, suggesting that targeting specific cytokines could be a strategy to mitigate aging-related immune dysfunction.
Dr. Eric Verdin [105:18]: “IL-11 is one of the key markers of this chronically activated immune system.”
Conclusion and Future Directions
As the conversation wraps up, Dr. Attia and Dr. Verdin acknowledge the delicate balance required in managing the immune system to prevent both hyperactivation and immunosuppression. They stress the need for reliable biomarkers to guide interventions and caution against the premature commercialization of unvalidated aging tests and supplements.
Dr. Verdin emphasizes ongoing research efforts to better understand immune aging and develop targeted interventions, such as thymic rejuvenation and cytokine blockade.
Dr. Eric Verdin [120:06]: “We are still in the middle of it… There's something interesting that will emerge.”
Dr. Attia reiterates the importance of evidence-based approaches and the necessity of validating interventions through rigorous clinical trials before widespread adoption.
Key Takeaways
-
Metabolism and Aging: Oxidative stress from mitochondrial dysfunction is a significant driver of aging, but antioxidants have not consistently proven effective due to the dual roles of ROS.
-
Immune System's Central Role: The decline in immune function, particularly T cell diversity and increased chronic inflammation, is a critical factor in aging and associated diseases.
-
NAD and Sirtuins: While NAD levels decline with age and are crucial for sirtuin activity, supplementing NAD precursors has shown mixed results and potential side effects, warranting cautious optimism and further research.
-
Rapamycin's Dual Nature: Rapamycin extends lifespan in mice but poses immunosuppressive risks in humans, highlighting challenges in translating animal research to human therapies.
-
Aging Clocks: Current biological aging clocks, especially those based on epigenetics, lack sufficient validation for clinical use. Advances like the Entren Clock offer more promise but require further development.
-
Future Interventions: Targeting specific cytokines like IL-11 and exploring thymic rejuvenation represent promising avenues for mitigating immune decline in aging.
-
Caution Against Overhype: The podcast underscores the importance of evidence-based interventions and warns against the premature adoption of unvalidated supplements and tests in the aging field.
Notable Quotes
-
Dr. Eric Verdin [09:22]: “I still think oxygen is one of the major problems associated with the aging process… Aging is pleomorphic.”
-
Dr. Eric Verdin [07:35]: “Chronic inflammation is tied cause and effect in the whole aging process.”
-
Dr. Eric Verdin [77:11]: “NAD is a critical intermediary metabolite… Sirtuins have a relatively narrow range of KD for NAD.”
-
Dr. Eric Verdin [114:57]: “The problem of the methylation clocks is that there's a very tenuous link between the change of methylation at any given site.”
Conclusion
This episode provides a comprehensive exploration of the complex interplay between metabolism, immune function, and molecular pathways in the aging process. Dr. Eric Verdin's insights, combined with Dr. Attia's probing questions, offer listeners a nuanced understanding of current aging research and the challenges in translating scientific findings into practical interventions. The discussion emphasizes the importance of rigorous research, validated biomarkers, and cautious optimism in the quest to extend healthy lifespan.