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#272 ‒ Rapamycin: potential longevity benefits, surge in popularity, unanswered questions, and more | David Sabatini, M.D., Ph.D. and Matt Kaeberlein, Ph.D.

The Peter Attia Drive

Release Date: 09/25/2023

#280 ‒ Cultivating happiness, emotional self-management, and more | Arthur Brooks Ph.D. show art #280 ‒ Cultivating happiness, emotional self-management, and more | Arthur Brooks Ph.D.

The Peter Attia Drive

Arthur Brooks is a social scientist, professor at Harvard University, columnist for The Atlantic, and bestselling author. In this episode, Arthur returns to the podcast to discuss his new book, Build the Life You Want. He delves into the nuanced concept of happiness, differentiating between momentary feelings and overall wellbeing. He explains the importance of understanding one’s personality pattern with respect to positive and negative emotions in order to better self-manage emotions. He delves into the three key elements of happiness, offering practical strategies for enhancing those...

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The world’s most important doctor to millions in the war-torn and remote villages of Sudan | Tom Catena, M.D. (#40 rebroadcast) show art The world’s most important doctor to millions in the war-torn and remote villages of Sudan | Tom Catena, M.D. (#40 rebroadcast)

The Peter Attia Drive

To support Tom’s mission and work, please visit: https://africanmissionhealthcare.org/donation/catena/.   In this episode, Tom Catena, a missionary physician who runs Mother of Mercy Hospital in the Nuba Mountains in Sudan, describes some of his extraordinary work as the only doctor in a remote, war-torn region of Africa. In terms of individual lives saved, you could argue that there is no other person on the front lines doing more than Tom. Additionally, we explore the manner in which the Nuba people die, which is in striking contrast to the ubiquity of chronic disease and self-harm...

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#279 - AMA #53: Metabolic health & pharmacologic interventions: SGLT-2 inhibitors, metformin, GLP-1 agonists, and the impact of statins show art #279 - AMA #53: Metabolic health & pharmacologic interventions: SGLT-2 inhibitors, metformin, GLP-1 agonists, and the impact of statins

The Peter Attia Drive

In this “Ask Me Anything” (AMA) episode, Peter explores various pharmacologic tools commonly utilized to improve metabolic health and treat diabetes, including SGLT-2 inhibitors, metformin, and GLP-1 agonists. He examines the available data on these drugs, assessing their comparative effectiveness and their potential in the context of lifestyle interventions. Additionally, he offers insights into whether SGLT2 inhibitors hold promise as geroprotective agents beyond their effects on glycemic control. Next, Peter analyzes the relationship between statin usage and the risk of developing...

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#278 ‒ Breast cancer: how to catch, treat, and survive breast cancer | Harold Burstein, M.D., Ph.D. show art #278 ‒ Breast cancer: how to catch, treat, and survive breast cancer | Harold Burstein, M.D., Ph.D.

The Peter Attia Drive

Harold (Hal) Burstein is an internationally renowned breast cancer expert. In this episode, Hal discusses a broad range of topics related to breast cancer, starting with the intricacies of breast anatomy and the endocrinological factors at play. He covers the spectrum of breast cancer, from precancerous lesions to invasive breast cancer, classifying these conditions into a helpful framework. He delves into various screening methods, including self-exams, mammograms, ultrasounds, and MRIs, and addresses the ongoing debate surrounding early screening and detection. Hal provides insights into...

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#277 ‒ Food allergies: causes, prevention, and treatment with immunotherapy | Kari Nadeau, M.D., Ph.D. show art #277 ‒ Food allergies: causes, prevention, and treatment with immunotherapy | Kari Nadeau, M.D., Ph.D.

The Peter Attia Drive

Kari Nadeau is a physician scientist with expertise in treating food allergies. In this episode, Kari first explains the fascinating workings of the immune system, exploring how it adeptly defends against bacteria and viruses but how the same system can lead to food allergies. She proceeds to explore the complexities of food allergies, detailing their typical developmental patterns, underscoring the significance of preventative approaches like early exposure, and highlighting the potentially life-threatening nature of severe food allergies. Kari illuminates the latest advancements in...

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#276 ‒ Special episode: Peter answers questions on longevity, supplements, protein, fasting, apoB, statins, and more show art #276 ‒ Special episode: Peter answers questions on longevity, supplements, protein, fasting, apoB, statins, and more

The Peter Attia Drive

In this special episode of The Drive, Peter discusses a variety of topics, breaking away from the typical deep-dive format to explore a wide range of common questions submitted by listeners. Peter tackles subjects like the viability of living to 120 and beyond, addressing some of the optimistic theories regarding achievement of this remarkable feat. Peter then shares his drug and supplement regimen while emphasizing how individualized these protocols need to be. The conversation also touches on lowering apoB, the long-term use of statins, the myth of good vs. bad cholesterol, the...

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#275 - AMA #52: Hormone replacement therapy: practical applications and the role of compounding pharmacies show art #275 - AMA #52: Hormone replacement therapy: practical applications and the role of compounding pharmacies

The Peter Attia Drive

In this "Ask Me Anything" (AMA) episode, the discussion zeroed in on the practical application of hormone replacement therapy in women. Peter walks through the signs, symptoms, and hormonal changes in women approaching – and going through – menopause. He provides an overview of the FDA-approved HRT formulations and explains how women might go about choosing the right option for themselves. Peter also describes the significant changes in testosterone levels in women over time and the options, as well as the considerations and challenges of testosterone replacement therapy (TRT) for...

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#274 - Performance-enhancing drugs and hormones: risks, rewards, and broader implications for the public | Derek: More Plates, More Dates show art #274 - Performance-enhancing drugs and hormones: risks, rewards, and broader implications for the public | Derek: More Plates, More Dates

The Peter Attia Drive

We discuss: Derek’s interest in weightlifting and experimentation with anabolic steroids at a young age [3:15]; Derek’s experience acquiring steroids from underground labs and the potential long-term fertility concerns early in his bodybuilding career [12:00]; The backstory on More Plates, More Dates and Derek’s unique ability to blend scientific knowledge with personal observation [17:00]; Growth hormone – from extreme use-cases to the more typical – and the misconception that it’s the “elixir of life” [21:30]; Growth hormone 101: definition, where it comes from, and the...

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#273 ‒ Prostate health: common problems, cancer prevention, screening, treatment, and more | Ted Schaeffer, M.D., Ph.D. show art #273 ‒ Prostate health: common problems, cancer prevention, screening, treatment, and more | Ted Schaeffer, M.D., Ph.D.

The Peter Attia Drive

Ted Schaeffer is an internationally recognized urologist who specializes in prostate cancer. In this episode, Ted delves deep into the realm of prostate health, starting with strategies for vigilance and effective management of the issues that can arise with aging, including urinary symptoms, prostatitis, pelvic pain, and prostate inflammation. Ted sheds light on the popular drug finasteride, renowned for its dual purpose in prostate shrinkage and hair loss prevention, as well as the contentious topic of post-finasteride syndrome. Ted then shifts to the topic of cancer, explaining how...

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#272 ‒ Rapamycin: potential longevity benefits, surge in popularity, unanswered questions, and more | David Sabatini, M.D., Ph.D. and Matt Kaeberlein, Ph.D. show art #272 ‒ Rapamycin: potential longevity benefits, surge in popularity, unanswered questions, and more | David Sabatini, M.D., Ph.D. and Matt Kaeberlein, Ph.D.

The Peter Attia Drive

In this episode of The Drive, Peter welcomes guests David Sabatini and Matt Kaeberlein, two world-leading experts on rapamycin and mTOR. David and Matt begin by telling the fascinating story of the discovery of rapamycin and its brief history as a pharmacological agent in humans. They then unravel the function of mTOR, a central regulator of numerous biological processes, and they discuss the pathways through which rapamycin exerts its potential benefits on lifespan. They touch upon initial studies that suggested rapamycin may have geroprotective effects and the ongoing research that...

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In this episode of The Drive, Peter welcomes guests David Sabatini and Matt Kaeberlein, two world-leading experts on rapamycin and mTOR. David and Matt begin by telling the fascinating story of the discovery of rapamycin and its brief history as a pharmacological agent in humans. They then unravel the function of mTOR, a central regulator of numerous biological processes, and they discuss the pathways through which rapamycin exerts its potential benefits on lifespan. They touch upon initial studies that suggested rapamycin may have geroprotective effects and the ongoing research that continues to shed light on this unique molecule. Furthermore, they discuss the elusive details surrounding the frequency and dosing of rapamycin use in humans, and Peter emphasizes his reservations about indiscriminately prescribing rapamycin as a longevity drug for patients.

We discuss:

  • David and Matt’s expertise in mTOR and rapamycin [3:00];
  • The discovery of rapamycin and its first use in humans as an immunosuppressant [13:15];
  • The emergence of rapamycin as a molecule with the potential to prolong lifespan [19:30];
  • The groundbreaking rapamycin study on mouse lifespan extension and the open questions about the timing and frequency of dosing [26:00];
  • Explaining mTOR and the biology behind rapamycin’s effects [35:30];
  • Differences in how rapamycin inhibits mTOR complex 1 (MTORC1) versus mTOR complex 2 (MTORC2) [45:15];
  • Reconciling the biochemical mechanism of rapamycin with its longevity benefit [49:15];
  • Important discoveries about the interplay of amino acids (leucine in particular) and mTOR [54:15];
  • Reconciling rapamycin-mediated mTOR inhibition with mTOR's significance in building and maintaining muscle [1:01:30];
  • Unanswered questions around the tissue specificity of rapamycin [1:08:30];
  • What we know about rapamycin’s ability to cross the blood-brain barrier and its potential impacts on brain health and neurodegeneration [1:13:45];
  • Rapamycin may act as an immune modulator in addition to immunosuppressive effects [1:21:30];
  • Might rapamycin induce changes in T cell methylation patterns, potentially reversing biological aging? [1:34:15];
  • Rapamycin side effects and impacts on mental health: fascinating results of Matt’s survey on off-label rapamycin use [1:42:00];
  • The impact of taking rapamycin in people who contracted COVID-19: more insights from Matt’s survey [1:51:15];
  • What David would like to study with mTOR inhibitors [1:54:45];
  • Joan Mannick’s studies of RTB101 and other ATP-competitive inhibitors of mTOR [2:00:30];
  • The impact of mTOR inhibition on autophagy and inflammation and a discussion of biomarkers [2:10:00];
  • The Dog Aging Project: what we’ve learned and what’s to come from testing rapamycin in companion dogs [2:17:30];
  • Preliminary results of primate studies with rapamycin [2:24:45];
  • Dosing of rapamycin [2:27:45];
  • The effect of rapamycin on fertility [2:36:45];
  • The outlook for future research of rapamycin and the development of rapalogs [2:39:00]; and
  • More.

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