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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 effectiveness with age: shrinking of the thymus gland and diminished T-cell diversity [44:15];
• Exploring growth hormone, thymic regeneration, and the role of exercise in slowing immune aging [48:45];
• The challenges of identifying reliable biomarkers for immune function, and the potential of rapamycin analogs to enhance vaccine response in older adults [57:45];
• How rapamycin’s effects on the immune system vary dramatically by dosage and frequency [1:03:30];
• The limitations of mouse models in aging research and the need for cautious interpretation of rapamycin’s benefits in humans [1:08:15];
• NAD, sirtuins, and aging: scientific promise amid commercial hype [1:15:45];
• How CD38 drives age-related NAD decline, influences immune function, and may impact longevity [1:23:45];
• 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];
• Intravenous NAD: limited evidence and serious risks [1:37:00];
• 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];
• Biological aging clocks: types of clocks, promise, major limitations, and future outlook [1:48:30];
• The potential of proteomics-based aging clocks for detecting organ-specific decline and frailty [2:00:45]; and
• More.

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In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from his discussions with Paul Turek and Paula Amato on male and female fertility; Rachel Rubin on menopause and hormone replacement therapy; Brian Kennedy on the biology of aging; Tanuj Nakra and Suzan Obagi on facial aging and skin rejuvenation; and BJ Miller and Bridget Sumser on lessons we can learn from the dying about how to live. Peter highlights the most important insights from each episode and any behavioral changes he’s made for himself or his patients as a result of these fascinating discussions.

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We discuss:

• Summary of episode topics [1:15];
• Episodes on fertility with Paul Turek and Paula Amato: insights on all things male and female fertility [4:45];
• How men can optimize fertility [20:15];
• How women can optimize fertility [26:00];
• Rachel Rubin episode: insights on women’s sexual health, menopause, and HRT [31:45];
• How women can prepare for menopause: proactive care, evidence-based HRT, and more [41:45];
• Brian Kennedy episode: understanding aging, role of inflammation and mTOR, and current limitations of aging clocks and biomarkers [46:30];
• Advice from Brian Kennedy on testing longevity interventions [56:45];
• Tanuj Nakra/Suzan Obagi episode: causes of facial aging and practical strategies for prevention and treatment [57:30];
• Skincare: making sense of the wide range of skin resurfacing treatments [1:06:45];
• How to create a realistic, sustainable skincare routine [1:12:30];
• The dangers of following unqualified aesthetic advice online and the importance of getting professional medical guidance for cosmetic treatments [1:18:00];
• BJ Miller/Bridget Sumser episode: lessons about living from the dying [1:21:45]; and
• More.

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Brian Kennedy is a renowned biologist, leader in aging research, and director of the Center for Healthy Longevity at the National University of Singapore. In this episode, Brian shares insights from ongoing human aging studies, including clinical trials of rapamycin and how dosing strategies, timing, and exercise may influence outcomes. He presents two key models of aging—one as a linear accumulation of biological decline and the other as an exponential rise in mortality risk—and explains why traditional models of aging fall short. He also explains why most current aging biomarkers lack clinical utility and describes how his team is working to develop a more actionable biological clock. Additional topics include the potential of compounds like alpha-ketoglutarate, urolithin A, and NAD boosters, along with how lifestyle interventions—such as VO2 max training, strength building, and the use of GLP-1 and SGLT2 drugs—may contribute to longer, healthier lives.

We discuss:

• Brian’s journey from the Buck Institute to Singapore, and the global evolution of aging research [2:45];
• Rethinking the biology of aging: why models like the hallmarks of aging fall short [9:45];
• How inflammation and mTOR signaling may play a central, causal role in aging [14:15];
• The biological role of mTOR in aging, and the potential of rapamycin to slow aging and enhance immune resilience [17:30];
• Aging as a linear decline in resilience overlaid with non-linear health fluctuations [22:30];
• Speculating on the future of longevity: slowing biological aging through noise reduction and reprogramming [33:30];
• Evaluating the role of the epigenome in aging, and the limits of methylation clocks [39:00];
• Balancing the quest for immortality with the urgent need to improve late-life healthspan [43:00];
• Comparing the big 4 chronic diseases: which are the most inevitable and modifiable? [47:15];
• Exploring potential benefits of rapamycin: how Brian is testing this and other interventions in humans [51:45];
• Testing alpha-ketoglutarate (AKG) for healthspan benefits in aging [1:01:45];
• Exploring urolithin A’s potential to enhance mitochondrial health, reduce frailty, and slow aging [1:05:30];
• The potential of sublingual NAD for longevity, and the combination of NAD and AKG for metabolic and exercise enhancement [1:09:00];
• Other interventions that may promote longevity: spermidine, 17𝛼-estradiol, HRT, and more [1:17:00];
• Biological aging clocks, clinical biomarkers, and a new path to proactive longevity care [1:23:15];
• Evaluating rapamycin, metformin, and GLP-1s for longevity in healthy individuals [1:32:15];
• Why muscle, strength, and fitness are the strongest predictors of healthspan [1:37:30];
• Why combining too many longevity interventions may backfire [1:39:30];
• How increased funding and AI integration could accelerate breakthroughs in aging research [1:41:45];
• The research Brian is most excited about, and the need to balance innovation with safety in longevity clinics [1:47:00];
• Peter’s reflections on emerging interventions and the promise of combining proven aging compounds [1:54:00]; and
• More.

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