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In this episode, Peter takes a deep dive into the science and application of aging clocks, unpacking what they are, the differences between chronological age, biological age, and the pace of aging, and what epigenetic clocks may actually be measuring. He explores key research in the field, including a randomized controlled trial that tested simple lifestyle interventions against several commonly used aging clocks, as well as a study using brain MRI to assess the pace of aging and its relationship to dementia risk and mortality. Throughout the episode, Peter highlights the promises and pitfalls of these tools, ultimately focusing on the field's central question: whether improving an aging clock score truly translates into meaningful clinical outcomes.

We discuss:

• Why aging clocks are being used as proxies for long-term health outcomes and the uncertainty surrounding their clinical value [2:00];
• How aging clocks use DNA methylation to predict age and how they compare to traditional mortality prediction models [5:00];
• The shift from aging clocks that predict chronological age to newer models that aim to measure biological age, lifespan differences, and the pace of aging [11:45];
• The limitations of second-generation aging clocks: biological and measurement noise affecting reliability and interpretation [14:45];
• Why aging clocks are exciting tools—compression, speed, and individual feedback [17:15];
• The DO-HEALTH randomized trial: the study design and how different aging clocks were used to measure biological age and the pace of aging [22:00];
• The DO-HEALTH study results: findings, takeaways, and open questions [27:45];
• The promise and limitations of aging clocks in measuring meaningful biological aging and predicting health outcomes [33:00];
• Why aging clocks are not yet reliable as consumer tools and why traditional health metrics still matter most [37:00]; and
• More.

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In this "Ask Me Anything" (AMA) episode, Peter answers listener questions across a wide range of topics, focusing on practical decision-making and real-world application. He explores how health priorities and strategies should evolve across different decades of life, which chronic diseases are most challenging to manage and how to think about risk hierarchies, and which emerging interventions—beyond exercise—show the most promise for dementia prevention. Peter also breaks down the utility of wearables and explains how to use and interpret DEXA scans effectively. He discusses the challenges of behavior change and how to make healthy habits stick, along with training strategies for balance, stability, and injury resilience, drawing lessons from his own setbacks. Additional topics include high-protein diets and mTOR, how to weigh mechanisms versus outcomes, how to evaluate diet sodas and non-nutritive sweeteners in context, and a range of listener questions covering health fads, emotional health, and sleep routines.

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We discuss:

• Overview of episode topics, emphasizing the goal of providing actionable, real-world health guidance [1:30];
• How health priorities and training strategies should evolve from early adulthood through older age [2:45];
• Comparing the four major chronic diseases: which are most preventable, most uncertain, and most concerning [8:00];
• Emerging strategies for dementia prevention: biomarkers, early detection, and new pharmacologic approaches [15:00];
• How to use wearable data effectively: when it's helpful, when it's not, and how to avoid over-reliance [19:00];
• DEXA scans: timing, interpretation, and limitations in body composition and bone density tracking [23:00];
• Best practices for building sustainable health habits [30:15];
• How to train your balance and stability [33:30];
• How to recover from injuries and use setbacks to build strength and resilience [36:15];
• High protein intake and the impact on mTOR: evaluating mechanisms versus real-world evidence on longevity [38:30];
• Diet soda and artificial sweeteners: evaluating risks, benefits, and the importance of context [47:00];
• How to balance enjoying life today with making choices that support long-term health and longevity [51:45]; and
• More.

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In this special episode, Peter takes a deep dive into obicetrapib, an investigational drug that has captured his attention and renewed interest in an entire class of therapies known as CETP inhibitors. He explains what obicetrapib is and how it works, revisits the history of CETP inhibitors and why earlier versions of these drugs failed—sometimes dramatically—and breaks down the key clinical trials designed to evaluate their impact on cardiovascular risk. Peter examines how obicetrapib influences major lipid biomarkers, including LDL cholesterol and lipoprotein(a) [Lp(a)], and discusses emerging evidence from a study that explored the drug's effects on Alzheimer's-related blood biomarkers. He also highlights intriguing findings in individuals carrying the APOE4 allele and reflects on what these early results may mean for both cardiovascular disease prevention and potential implications for Alzheimer's risk, as well as how he is thinking about this therapy in the context of caring for his own patients.

We discuss:

• Introducing obicetrapib: CETP inhibitor history, lipid biology, and early Alzheimer's biomarker signals in APOE4 carriers [2:15];
• CETP biology explained: lipoproteins, reverse cholesterol transport, and how CETP inhibition alters HDL and LDL particles [5:15];
• The early CETP inhibitor story: why raising HDL cholesterol alone failed to deliver cardiovascular protection [13:45];
• The rise and fall of early CETP inhibitors: torcetrapib, dalcetrapib, evacetrapib, and anacetrapib [18:30];
• Why obicetrapib may succeed where earlier CETP inhibitors failed [23:30];
• The BROADWAY trial: obicetrapib's effects on LDL, ApoB, Lp(a), and residual cardiovascular risk [26:00];
• Brain lipid metabolism and APOE4: how CETP inhibition may influence cholesterol transport in Alzheimer's disease [30:45];
• Findings from the substudy of the BROADWAY trial which looked at changes in biomarkers of Alzheimer's disease [40:00];
• Interpreting the BROADWAY Alzheimer's biomarker results: limitations, cautious optimism, and the need for a dedicated prevention trial [46:45];
• Why Peter is optimistic about obicetrapib: cardiovascular benefits, Lp(a) reduction, and the path toward approval [50:00]; and
• More.

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