How metabolic and immune system dysfunction drive the aging process, the role of NAD, promising interventions, aging clocks, and more | Eric Verdin, M.D.

Peter Attia

Aug 4, 2025

Episode description

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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.

We discuss:

Eric’s scientific journey from virology to the field of geroscience [2:45];
How dysfunction in the immune system and central nervous system can drive aging throughout the body [5:00];
The role of metabolism and oxidative stress in aging, and why antioxidant strategies have failed to deliver clear benefits [8:45];
Other aspects of metabolism linked to aging: mitochondrial efficiency, fuel utilization, and glucose-modulating drugs [16:30];
How inefficient glucose metabolism drives insulin, IGF-1 signaling, and accelerates aging [21:45];
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];
The case for immune health as a “fifth horseman” [36:00];
How the innate and adaptive immune systems work together to build immune memory [39:45];
Why vaccines lose effec

Mindsip insights from this episode:

Reevaluate ketogenic diet for social health and well-being

After two years on a ketogenic diet, Dr. Verdon found it socially isolating and did not feel "super healthy.".

#keto

#social

Utilize organ-specific clocks to identify frailty points

New proteomic clocks can generate organ-specific aging scores from a blood draw, potentially identifying an individual's specific "frailty point" or weakest organ.

#aging

#biological-age

Prioritize immune and nervous systems to enhance aging resilience

The immune and central nervous systems are likely the rate-limiting organs in aging because they are distributed throughout the body and can influence every other organ.

#aging

#immune-system

Beware misleading epigenetic clocks in whole blood analysis

Epigenetic clocks measuring whole blood can be misleading, as a simple shift in the ratio of immune cells, which have different epigenetic ages, can create a false impression of rejuvenation.

#biological-age

#epigenetics

Address NAD consumption issues instead of relying on supplements

Taking NAD precursors like NMN is like pouring water into a leaking sink, as the main problem is increased NAD consumption by enzymes like CD38, not a lack of production.

#NAD

#supplement

Reconsider mice as models for human longevity research

Mice may be a poor model for human longevity drugs because they are evolutionarily optimized for high mTOR activity, whereas humans are optimized for longevity.

#evolution

#longevity

Choose ketones for clean metabolic fuel

Ketones are likely the cleanest burning metabolic fuel in terms of producing byproducts like oxidative stress, followed by fatty acids, with glucose being the "dirtiest.".

#metabolism

#oxidative-stress

Address declining vaccine efficacy in elderly populations

For people over 70, the success rate of most vaccinations can drop to as low as 30% due to the aging of the immune system.

#aging

#vaccine

Lower fasting insulin with GLP-1s like Tirzepatide

Contrary to the expectation that they would increase insulin, Dr. Verdon's personal experiment with Tirzepatide lowered his fasting insulin to the lowest measurable level.

#GLP1

#insulin

Monitor homocysteine levels when using NMN supplements

A personal experiment taking one gram of NMN daily caused Dr. Verdon's homocysteine levels to more than double, from 7 to 15.

#supplement

#testing

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