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Charles Duhigg is a Pulitzer Prize-winning journalist and best-selling author known for distilling complex neuroscience and psychology into practical strategies for behavior change, performance, and decision-making. In this episode, Charles explores the neuroscience behind habit formation, including how cue-routine-reward loops drive nearly half of our daily actions and why positive reinforcement is far more effective than punishment. He explains how institutions like the military and Alcoholics Anonymous engineer environments to change behavior at scale, as well as discussing the limits of willpower and how to preserve it by shaping context. The conversation also covers the real timeline of habit formation, how to teach better habits to kids, the role of failure and self-compassion in lasting change, and the power of social accountability. Charles further discusses how cognitive routines enhance productivity and creativity, how to gamify long-term goals through immediate rewards, why identity and purpose are often the strongest forces behind sustainable behavior change, and the potential of AI to power habit change.

We discuss:

• How Charles’s background in journalism and personal experiences led to his interest in habit formation [3:15];
• The science behind reinforcement: why positive rewards outperform punishment in habit formation [10:15];
• How the military uses habit science to train soldiers using cues, routines, and rewards [17:15];
• Methods for creating good habits and eliminating bad ones: environmental control, small wins, rewards-based motivation, and more [24:00];
• How parents can teach kids to build habits and strengthen willpower [32:15];
• How adults experience changes in motivation and cue effectiveness over time, and why willpower must be managed like a finite resource [34:30];
• Keys to successful habit change: planning for relapse, learning from failure, and leveraging social support [38:00];
• Advice for parents: praise effort, model habits, and normalize failure [47:45];
• The time required for making or breaking a habit [50:45];
• The different strategies for creating new habits vs. changing existing ones, and the crucial role of cues and reward timing [55:15];
• How to create habits around long-term goals when the rewards are delayed (like saving money) [1:01:45];
• How to stick with good habits that offer no immediate reward: designing reinforcements and identity-based motivation [1:11:15];
• The potential for AI to provide social reinforcement [1:16:45];
• Mental habits: how thought patterns and contemplative routines shape deep thinking, innovation, and high-stakes performance [1:23:30];
• How cognitive routines boost productivity and habit formation but may stifle creativity [1:35:15];
• Contemplative routines: using stillness to unlock deeper productivity and creativity [1:40:45];
• How habits reduce decision fatigue and enable deep, high-quality productivity [1:44:15];
• New research that reveals the power of environment and social feedback in habit formation [1:49:45];
• How AI may transform work, identity, and our sense of purpose [1:53:45];
• The potential of AI-powered habit change, and the essential—but often lacking—element of motivation [2:02:30]; and
• More.

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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.

If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the episode #358 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

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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In this episode from July 2022, Peter dives deep into the topic of bone health and explains why this is an important topic for everyone, from children to the elderly. He begins with an overview of bone mineral density, how it’s measured, how it changes over the course of life, and the variability between sexes largely due to changes in estrogen levels. From there he provides insights into ways that one can improve bone health, from exercise to nutrition supplements to drugs. Additionally, Peter discusses what happens when one may be forced to be sedentary (e.g., bedrest) and how you can work to minimize the damage during these periods.

While this original episode is an AMA, it is available in full to all listeners as a special rebroadcast.

We discuss:

• Overview of bone health topics to be discussed [2:30];
• Bones 101: bone function, structure, and more [6:15];
• Bone mineral density (BMD), minerals in bone, role of osteoblasts and osteoclasts, and more [9:30];
• The consequences of poor bone health [14:30];
• The devastating nature of hip fractures: morbidity and mortality data [18:00];
• Where fractures tend to occur in the body [23:45];
• Defining osteopenia and osteoporosis [25:30];
• Measuring BMD with DEXA and how to interpret scores [28:00];
• Variability in BMD between sexes [35:15];
• When should people have their first bone mineral density scan? [37:45];
• How BMD changes throughout the life and how it differs between men and women [40:15];
• How changes in estrogen levels (e.g., menopause) impact bone health [45:15];
• Why HRT is not considered a standard of care for postmenopausal bone loss [49:00];
• Factors determining who may be at higher risk of poor bone health [52:00];
• Common drugs that can negatively impact BMD [55:45];
• How children can optimize bone health and lay the foundation for the future [59:30];
• Types of physical activity that can positively impact bone health [1:03:30];
• How weight loss can negatively impact bone health and how exercise can counteract those effects [1:12:15];
• Nutrition and supplements for bone health [1:16:00];
• Pharmaceutical drugs prescribed for those with low BMD [1:18:45];
• Impact of extreme sedentary periods (e.g., bedrest) and how to minimize their damage to bone [1:23:30]; and
• More.

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Tanuj Nakra and Suzan Obagi, two leading experts in aesthetic medicine, join Peter to explore the science of facial aging and skin health as well as the responsibilities physicians face in the world of cosmetic procedures. In this episode, they examine the biological and hormonal drivers of facial aging, the evolutionary and psychological foundations of attractiveness, and the impact of modern media on beauty standards. They discuss the rise in cosmetic procedures among adolescents and the ethical responsibilities of physicians in these cases. The conversation then shifts to a practical, evidence-based guide to skin health—covering the use of mineral sunscreens, retinoids, vitamin C, and tailored skincare routines, as well as the management of acne and the psychology behind aesthetic consultations. The episode culminates in a candid, personal assessment of Peter’s own face, offering a revealing look at what aesthetic medicine can achieve and how to think critically about pursuing it.

We discuss:

• Tanuj’s and Suzan’s training and expertise, and the evolving field of aesthetic medicine [4:00];
• The biology of the aging face [10:45];
• Why facial fat atrophies with age while body fat tends to accumulate [17:00];
• How chronic stress accelerates facial aging [20:30];
• The evolutionary biology of beauty, and how modern lifestyle, culture, and medicine interact with these ancient aesthetic instincts [25:30];
• How social media and influencers have rapidly shifted aesthetic trends toward exaggerated features and unrealistic beauty standards [36:45];
• The ethical challenges, financial incentives, and social pressures shaping modern aesthetic medicine [42:00];
• The concerning trend of teenagers seeking cosmetic enhancements: the ethical and cultural impact of early beauty pressure [51:45];
• Protecting the skin: UV damage and sunscreen recommendations [58:15];
• Strategies for minimizing skin aging: retinoids, vitamin C, and evidence-based application methods [1:09:00];
• Effective daily skincare routine: cleansing, antioxidants, retinoids, moisturization, and more [1:18:45];
• The playbook for managing acne [1:31:00];
• The 4 changes of aging and the complexities of aesthetic consultations including the anatomical, psychological, and ethical factors physicians must navigate [1:39:00];
• The 5 R’s of rejuvenation [1:50:15];
• A facial aging analysis and cosmetic strategy using Peter’s face as a real-time case study [1:53:00];
• The decision-making process between fat grafting and dermal fillers for facial rejuvenation [1:56:30];
• How self-image, eye aesthetics, and fleeting photos drive the desire for cosmetic enhancement [2:01:45];
• Advice for wrinkles, causes of dark circles under the eyes, and the importance of facial symmetry [2:05:45];
• Considerations that shape clinical decision making around fat grafting and other procedures to address the eye area [2:11:00];
• The evolution of facial cosmetic surgery techniques, the serious risks involved, and how physician skill and procedure selection greatly impact outcomes [2:21:30];
• How patients can make informed and safe choices when selecting a cosmetic surgeon [2:27:15];
• A comparison of ablative versus non-ablative skin resurfacing treatments, laser vs. peels, and more [2:38:45];
• How treatments are chosen and customized based on patient-specific factors [2:48:00];
• The lifelong human desire to align physical appearance with self-identity [2:52:45]; and
• More.

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