The Peter Attia Drive

View the Show Notes Page for This Episode
Become a Member to Receive Exclusive Content
Sign Up to Receive Peter's Weekly Newsletter
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.
Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode
Become a Member to Receive Exclusive Content
Sign Up to Receive Peter's Weekly Newsletter
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.
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 AMA #82 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
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.
Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode
Become a Member to Receive Exclusive Content
Sign Up to Receive Peter's Weekly Newsletter
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.
Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode
Become a Member to Receive Exclusive Content
Sign Up to Receive Peter's Weekly Newsletter
Lisa Mosconi is a world-renowned neuroscientist and the director of the Women's Brain Initiative at Weill Cornell Medicine, where she studies how sex differences and hormonal transitions influence brain aging and Alzheimer's disease risk. In this episode, Lisa explores why Alzheimer's disease disproportionately affects women and why longer lifespan alone does not explain their nearly twofold risk compared to men. She explains why Alzheimer's disease may be best understood as a midlife disease for women, beginning decades before symptoms appear, and how menopause represents a fundamental brain event that reshapes brain energy use, structure, and immune signaling. The conversation also examines what advanced brain imaging reveals about preclinical Alzheimer's disease, estrogen receptors in the brain, and why genetic risks such as APOE4 appear to affect women differently from men. Finally, Lisa discusses the nuanced evidence around menopause hormone therapy, the legacy of the WHI, her new CARE Initiative to cut women's Alzheimer's risk in half by 2050, and practical, evidence-based strategies to support brain health through midlife—including lifestyle, sleep, metabolism, mood, and emerging therapies such as GLP-1 agonists and SERMs (selective estrogen receptor modulators).
We discuss:
How Lisa's personal family history and scientific background led her to focus on the intersection of women's health, brain aging, and Alzheimer's disease (AD) [2:45];
The long preclinical phase of AD and the emotional burden carried by patients before dementia becomes severe [7:15];
How AD compares to other common forms of dementia: prevalence, pathology, symptoms, diagnostic challenges, and more [10:45];
Why AD disproportionately affects women: how AD is not simply a disease of old age or longevity but a midlife disease in which women develop pathology earlier [16:15];
Menopause as a leading explanation for women's increased Alzheimer's risk, and how advanced braining imaging can detect early changes in the brain [26:15];
How a new method for imaging estrogen receptors in the brain is changing how we think about the menopause transition [35:45];
What estrogen receptor imaging can and cannot tell us about hormone therapy's potential impact on brain health [48:45];
Lisa's studies on the relationship between levels of systemic estrogen and density of estrogen receptors in the brain [58:00];
Why blood estrogen levels poorly reflect brain estrogen signaling, and how tightly regulated brain hormone dynamics complicate our understanding of menstrual-cycle and lifestyle effects [1:02:15];
The CARE Initiative: Lisa's research program looking to slash AD rates in women [1:07:45];
The dramatic difference in AD risk between men and women associated with APOE4 [1:10:45];
What the evidence suggests about menopausal hormone therapy (MHT) and AD risk, and why timing, formulation, and uterine status appear to matter [1:12:00];
How the CARE initiative plans to study MHT and AD risk, within the practical constraints of a three-year research window [1:17:30];
How to think about starting hormone therapy during perimenopause: balancing symptom relief, hormonal variability, and individualized care [1:21:00];
Investigating selective estrogen receptor modulators (SERMs) as a targeted approach to brain health during and after menopause [1:25:00];
Why estrogen became wrongly associated with cancer risk and what the evidence actually shows [1:29:30];
Why better biomarkers are central to advancing women's Alzheimer's research [1:38:30];
Modifiable risk factors for dementia, the limitations of risk models, and questionable conclusions drawn from observational data [1:44:15];
GLP-1 agonists and brain health: exploring potential neuroprotective effects of GLP-1 agonists beyond metabolic benefits [1:49:00];
The importance of lifestyle factors in reducing risk of dementia: practical strategies for women to support brain health [1:53:45];
Why long-term, consistent lifestyle habits are essential for building cognitive resilience and protecting brain health over decades [2:01:15]; and
More.
Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode
Become a Member to Receive Exclusive Content
Sign Up to Receive Peter's Weekly Newsletter
Layne Norton is a nutrition scientist and accomplished power athlete,who returns to The Drive for a conversation that departs from the show's usual format. In this episode, Layne presents the evidence-based case that seed oils are not uniquely harmful under isocaloric conditions, while Peter steelmans the strongest versions of the opposing argument that seed oils are inherently harmful. They examine how scientific bias and evidence are evaluated, revisit the historical randomized controlled trials that shaped the seed oil controversy, and explore the mechanistic biology underlying LDL oxidation and atherosclerosis. Along the way, Layne unpacks the chemistry and processing of modern seed oils, assesses evolutionary and ancestral nutrition arguments, clarifies the relationship between seed oils, ultra-processed foods, and contemporary dietary patterns, and situates these questions within the larger context of lifestyle factors that drive cardiometabolic health. Layne concludes by offering practical considerations around dietary fats, cooking oils, and real-world food choices.
We discuss:
The idea behind this episode, biases, and evidence-based thinking [5:15];
The four core arguments behind claims that seed oils are harmful [12:30];
The Minnesota Coronary Experiment (MCE) [14:30];
The differences among saturated, monounsaturated, polyunsaturated, and trans fats, and why those differences matter for cardiovascular disease [18:30];
Missing trans fat data as a confounder in the Minnesota Coronary Experiment, other limitations of that study, and the challenge detecting meaningful differences in hard outcomes through nutrition research [24:00];
The Sydney Diet Heart Study (SDHS): an attempt to address the "duration problem" by enrolling a much higher-risk population [28:30];
Debating whether evidence from randomized trials supports the idea that seed oils are uniquely harmful once major confounders are removed [34:00];
The Rose Corn Oil trial: an often-cited study used to argue against polyunsaturated fats [36:30];
Three studies where replacing saturated fat with polyunsaturated fat produced different results than earlier trials [41:30];
Layne's explanation for why the evidence is pointing towards cardiovascular risk reduction when substituting polyunsaturated fat for saturated fat [47:30];
What Mendelian randomization says about the causal role of LDL cholesterol in ASCVD [56:45];
The compounding effects of life-long exposure to high LDL cholesterol [1:06:45];
Does the linoleic acid (omega-6) content of seed oils cause inflammation? [1:13:45];
Does the linoleic acid (omega-6) content of seed oils increase oxidized LDL? [1:19:30];
Layne's analogy to explain why lower LDL particle number outweighs higher per-particle oxidation risk when comparing polyunsaturated fats to saturated fats [1:26:15];
The role of oxidized LDL in CVD: exploring differences in a diet high in polyunsaturated fat (seed oils) versus high in saturated fat [1:28:00];
Examining whether industrial processing and solvent extraction of seed oils—especially residual hexane—could plausibly cause long-term harm [1:34:00];
The evolutionary and "ancestral diet" argument against seed oils [1:40:45];
Weighing concerns about industrial processing of seed oils against the totality of metabolic and cardiovascular evidence [1:47:30];
Practical considerations around dietary fats, cooking oils, and real-world food choices [1:50:00];
Comparing the health impact of seed oils with that of caloric intake and activity levels, and how to prioritize interventions [2:00:15];
More.
Connect With Peter on Twitter, Instagram, Facebook and YouTube