<p><a href="https://peterattiamd.com/ericverdin/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250804-pod-ericverdin&utm_content=250804-pod-ericverdin-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250804-pod-ericverdin&utm_content=250804-pod-ericverdin-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250804-pod-ericverdin&utm_content=250804-pod-ericverdin-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>Eric Verdin is a physician-scientist and the CEO of the Buck Institute for Research on Aging whose career has centered on understanding how epigenetics, metabolism, and the immune system influence the aging process. In this episode, Eric traces his scientific journey from studying viruses and histone deacetylases (HDACs) to leading aging research at the Buck Institute, offering insights into how aging impairs immune and nervous system function—including thymic shrinkage, chronic inflammation, and reduced vaccine response—and how these changes impact lifespan. He explores the metabolic underpinnings of aging, such as oxidative stress and insulin and IGF-1 signaling, and he discusses practical tools like zone 2 cardio, ketogenic diets, and GLP-1 drugs. The conversation also covers declining NAD levels with age, the roles of NAD-consuming enzymes such as sirtuins and CD38, and what current NAD-boosting strategies (like NMN, NR, and IV NAD) can and can't accomplish. Eric weighs in on promising longevity interventions including rapamycin, growth hormone for thymic regeneration, and anti-inflammatory therapies, while also examining the promise and limitations of current biological age tests and the potential of combining epigenetic, proteomic, and organ-specific metrics with wearables to guide personalized longevity care.</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>Eric's scientific journey from virology to the field of geroscience [2:45];</li> <li>How dysfunction in the immune system and central nervous system can drive aging throughout the body [5:00];</li> <li>The role of metabolism and oxidative stress in aging, and why antioxidant strategies have failed to deliver clear benefits [8:45];</li> <li>Other aspects of metabolism linked to aging: mitochondrial efficiency, fuel utilization, and glucose-modulating drugs [16:30];</li> <li>How inefficient glucose metabolism drives insulin, IGF-1 signaling, and accelerates aging [21:45];</li> <li>The metabolic effects of GLP-1 agonists, and the need to move beyond crude metrics like BMI in favor of more precise assessments of metabolic health [27:00];</li> <li>The case for immune health as a "fifth horseman" [36:00];</li> <li>How the innate and adaptive immune systems work together to build immune memory [39:45];</li> <li>Why vaccines lose effectiveness with age: shrinking of the thymus gland and diminished T-cell diversity [44:15];</li> <li>Exploring growth hormone, thymic regeneration, and the role of exercise in slowing immune aging [48:45];</li> <li>The challenges of identifying reliable biomarkers for immune function, and the potential of rapamycin analogs to enhance vaccine response in older adults [57:45];</li> <li>How rapamycin's effects on the immune system vary dramatically by dosage and frequency [1:03:30];</li> <li>The limitations of mouse models in aging research and the need for cautious interpretation of rapamycin's benefits in humans [1:08:15];</li> <li>NAD, sirtuins, and aging: scientific promise amid commercial hype [1:15:45];</li> <li>How CD38 drives age-related NAD decline, influences immune function, and may impact longevity [1:23:45];</li> <li>How NMN and NR supplementation interact with CD38 and NAD metabolism, and potential risks like homocysteine elevation and one-carbon cycle depletion [1:31:00];</li> <li>Intravenous NAD: limited evidence and serious risks [1:37:00];</li> <li>Interleukin-11 (IL-11) as a new target in immune aging, the dual role of chronic inflammation in aging, and the need for better biomarkers to guide interventions [1:43:00];</li> <li>Biological aging clocks: types of clocks, promise, major limitations, and future outlook [1:48:30];</li> <li>The potential of proteomics-based aging clocks for detecting organ-specific decline and frailty [2:00:45]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights
1. Optimize Exercise First
Prioritize and optimize physical activity and exercise in all its forms as the most profoundly anti-aging intervention before considering other longevity interventions.
2. Prioritize Zone 2 Cardio
Engage in zone 2 cardio training for specific periods throughout the week to maximize fat oxidation and improve mitochondrial health and function, which may reduce degradation of function over time.
3. Aim for Lower Glucose
Strive for lower average blood glucose levels, as indicated by A1C, because in non-diabetics, a lower A1C is monotonically associated with lower all-cause mortality.
4. Aim for Lower Blood Pressure
Aim for lower blood pressure (e.g., 105/65 mmHg) as it is generally better for health outcomes, provided you remain asymptomatic.
5. Exercise for Immune Health
Engage in regular physical activity and exercise in all its forms, as it is the best anti-aging intervention and clearly benefits immune function, leading to better responses to infection and vaccination.
6. Optimize Fuel Utilization
Prioritize burning “cleaner” fuels like ketones, followed by fatty acids, as they produce fewer byproducts and less oxidative stress compared to glucose, which is considered a “dirty” fuel.
7. Use a Continuous Glucose Monitor
Wear a continuous glucose monitor (CGM) to identify foods and activities that cause glucose spikes, with the goal of mitigating intense peaks of insulin secretion.
8. Order Tests for Actionability
Only order medical tests if you are prepared to act on the potential outcomes or if the results will genuinely change your behavior or treatment decisions, rather than just for information.
9. Avoid Predatory Health Companies
Be wary of companies that sell unvalidated health tests and simultaneously offer supplements to “fix” the results, as this often indicates a lack of scientific rigor and potential exploitation.
10. Consider Risks of Over-Testing
Be mindful of the potential for over-testing, as procedures like whole-body MRIs can lead to incidental findings (e.g., thyroid nodules) that cause anxiety and unnecessary invasive follow-up without clinical benefit.
11. Maintain Scientific Open-Mindedness
When evaluating complex scientific fields like sirtuins and NAD, avoid premature dismissal due to controversy, as science is inherently messy and clarity emerges over time.
12. Consider GLP-1 Agonists
GLP-1 agonists can help mitigate peaks of insulin secretion and improve glycemic control, potentially leading to benefits like satiety and weight loss, but this is based on self-experimentation and not an endorsement.
13. Exercise with GLP-1 Agonists
If using GLP-1 agonists, ensure you are exercising to prevent loss of muscle mass, as observed in self-experimentation.
14. Avoid Impractical Diets
Do not adhere to extremely low or no-carbohydrate diets, such as a strict ketogenic diet, as they are often impractical for long-term adherence and may not be beneficial for everyone.
15. Consider NR/NMN Supplementation
For individuals aged 60 or above, consider taking 250 mg each of NR and NMN daily (total 500 mg) as a relatively safe dose, but monitor homocysteine levels as a precaution.
16. Monitor Homocysteine with NMN/NR
If supplementing with NMN (and potentially NR), monitor homocysteine levels, as high doses can increase homocysteine by depleting the one-carbon cycle, and some people take trimethylglycine (TMG) to offset this.
17. Be Aware of NAD Supplementation Risks
Be cautious with NAD supplementation, as increasing NAD levels might inadvertently increase pro-inflammatory markers (SASP) and could potentially accelerate tumor growth in individuals with early-stage cancer.
18. Be Aware of Supplement Dosing
Be aware that the doses of supplements like NR and NMN used in animal studies to show benefits are often 10 times higher than what is typically available in commercial supplements.
19. Use Multiple Epigenetic Clocks
If determined to use epigenetic clocks, use multiple different ones as they offer varied perspectives on your biological reality, but understand they are still research tools.
20. Exercise Caution with Novel Tests
Approach novel diagnostic tests with caution, especially those that report multiple abnormalities without clear clinical correlation, as they can lead to false positives, unnecessary anxiety, and further invasive procedures.
21. Insight 21
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