The Peter Attia Drive Peter Attia, MD

In this episode, Joan and Nir discuss their extensive research into rapamycin (including the category of analogs to rapamycin known as rapalogs) and metformin, respectively. Based on his work with metformin, Nir shares how he believes it could be a pro-longevity drug and the clinical trial he’s leading to test this belief. Joan discusses her work with rapalogs, their ability to suppress the immune system as well as provide immune-enhancement, and the clinical trials she has led that inform her insights. We also talk about the potential beneficial roles of both metformin and rapamycin in reducing mortality from COVID-19, reducing the risk of neurodegenerative diseases, and delaying aging as well as its related diseases.
  
We discuss:
Joan’s career, interest in aging, and work with rapamycin analogs [3:45]; When Nir became convinced metformin could be a pro-longevity agent [15:00]; How metformin and rapamycin impact the hallmarks of aging and extend lifespan [24:15]; Enhancing the immune system with rapalogs and metformin [34:15]; Potential of metformin and rapamycin in reducing mortality from COVID-19 [41:30]; Insights from Joan’s studies investigating the immune-enhancing effects of rapalogs [59:30]; Vaccines and treatments strategies for COVID-19, and the likelihood of long-term immunity [1:08:15]; The potential role of rapalogs and metformin in neurodegenerative disease [1:14:30]; Nir’s TAME trial—primary objectives and latest updates [1:18:00]; Potential synergistic effect when combining metformin with rapamycin [1:25:45]; Why Peter stopped taking metformin and started taking rapamycin [1:27:30]; Story from Nir’s book that demonstrates the challenge of doing good scientific studies [1:37:30]; The biology of aging—epigenetic clocks, proteomics, and Nir’s centenarian data [1:42:00]; Joan’s dream experiment to test immune-enhancing effect of RTB101 [1:57:15]; Concluding thoughts on COVID-19 [1:59:45]; and More. Learn more: https://peterattiamd.com/

Show notes page for this episode: http://peterattiamd.com/joanmannick-nirbarzilai/

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Lori Gottlieb is a psychotherapist and the bestselling author of Maybe You Should Talk to Someone. In this episode, Lori extracts important lessons from her experiences as both a therapist and a patient. The stories Lori shares has provided her the material for insights into living a more fulfilling life. In our conversation, Lori also dispels some misconceptions about therapy, explains the process of big therapeutic breakthroughs, and reveals the most important steps for enduring emotional health.
We discuss:
Lori’s unique path to becoming a therapist [3:00]; Dissecting cadavers—a profound experience during med school [12:30]; The sunk cost fallacy—How Lori was able to walk away from med school [17:15]; Being aware of the gift of life, and other lessons from Lori’s terminally ill patient [24:00]; How underlying pain can manifest in obnoxious behavior [32:45]; Counseling versus therapy [36:15]; The story of John—why men hide their feelings, breaking down his shield, and uncovering his pain [38:30]; “Breaking open”—A shocking revelation about John that tests Lori’s resolve as a therapist [46:30]; Rewriting your story, the recovery process, and the most important step for lasting change [49:00]; The process of  many big therapeutic breakthroughs [56:00]; The 2 types of suicidal thoughts, and the importance of talking about it [1:01:00]; The most common issues that bring patients to therapy with Lori [1:02:45]; Clinging to the familiar—why change is so hard [1:05:15]; A story of shame, lack of self-compassion, and self-sabotage [1:07:00]; The importance of managing mental health to reduce unnecessary suffering [1:15:45]; Dispelling the misconceptions about therapy [1:23:15]; and More. Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/LoriGottlieb

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Azra Raza is a physician, scientist, author, and outspoken advocate for reconfiguring the current model of research in cancer. In this episode, Azra discusses the content of her book, The First Cell, which takes a critical look at the outdated models being used to study cancer resulting in a lack of progress in survival rates for cancer patients. Azra offers a solution which focuses on early detection and prevention, and she concludes with an optimistic outlook for the future of cancer research.
 
We discuss:
Azra’s upbringing, interest in oncology, and the basis for writing her book [3:30]; The lack of progress in cancer treatment over the decades [18:45]; What is holding the oncology field back? [33:15]; Do the purported advances in oncology reflect the billions of dollars spent on cancer research? [40:00]; Economics of new cancer drugs—how small increases in survival come with staggering financial burdens [47:00]; How good intentions can still lead to misaligned incentives and a broken system [1:03:00]; Why 95% of new cancer drugs fail—a critical review of the cancer research model [1:11:15]; Early detection and prevention—a potential solution to the cancer problem [1:22:30]; Coping with the loss of her husband to cancer [1:46:00]; Azra’s optimistic view of the future [1:49:30]; and More. Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/azraraza

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In part 2 of this special AMA episode, ketosis expert Dom D’Agostino once again joins Bob Kaplan, Peter’s Head of Research, to discuss the impact of ketosis on various chronic diseases as well as the latest research on the metabolic management of cancer. Dom also discusses the numerous applications of hyperbaric oxygen therapy, provides insights into the application of ketosis on female health and performance, and much more. If you’re not a subscriber and 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 on the website show notes page.
 
We discuss:
Update on Dom’s Press-pulse therapeutic strategy for the metabolic management of cancer [2:05]; Potential role for vitamin C in cancer treatment [12:45]; Glutamine targeting in cancer therapy—evidence that the mitochondria in cancer are damaged? [17:45]; Can a ketogenic diet lessen the toxicity of cancer therapies? [24:45]; 3BP—a promising agent in cancer therapy [26:45]; The relationship between cancer and ketogenic diets [29:30]; Hyperbaric oxygen therapy (HBOT)—primer, protocols, and therapeutic uses [33:30]; Is there a potential role for HBOT in treating COVID-19 patients? [44:15]; Non-cancer applications of HBOT [47:30]; The inverse relationship between glucose and ketones [50:30]; Is a ketogenic diet appropriate for type 1 diabetics? [54:00]; How ketosis may reduce the risk for Alzheimer’s disease and Parkinson’s disease [1:00:30]; Ketosis for females—considerations, fertility, performance, and the latest research [1:11:00]; Low-carb diets during pregnancy and postpartum [1:17:00]; A high-protein diet to counteract common hormonal issues associated with the ketogenic diet [1:21:15]; Nutritional tips for remaining metabolically flexible [1:22:45]; What is one belief Dom has changed his mind about? [1:26:45]; In utero experiments, and other interesting questions Dom wants to explore [1:29:45]; The anti-catabolic effect of ketones, cancer cachexia, and nutritional interventions for cancer patients [1:38:30]; What is the one interesting experiment Dom would do if money and time were not a barrier? [1:46:25]; and More. Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/domdagostinoama02/

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Terry Real, a renowned family therapist and best-selling author, helps people create the connections they desire in their relationships. In this episode, Terry describes how his upbringing with an abusive father forged his path to become a therapist, develop his Relational Life Therapy (RLT) framework, and write I Don't Want to Talk About It—a book that reveals the hidden legacy of male depression. Terry discusses the link between childhood trauma and the deep-rooted shame, anger, and depression, which can result in feeling disconnected. Using real-life examples, Terry explains how he implements RLT to confront trauma, discover its origin, and teach the skills to break the cycle of pain, in order to live a satisfying life.
 
We discuss:
Terry’s upbringing with a depressed and abusive father [3:15]; The importance of the repair process, after relational disharmony, to break the trauma cycle [15:15]; The impact of a patriarchal society, and relational growth as the next step for feminism [19:00]; Origins of deep-rooted shame, and the difference between feeling ashamed and feeling guilty [27:15]; Preventing the propagation of trauma without over-coddling kids [35:30]; The one-up/one-down cycle from grandiosity to shame [37:30]; Covert depression—Steps to fixing the secret legacy of male depression [40:00]; Three forms of false self-esteem [50:00]; Narcissism—A misunderstood concept [51:45]; The interplay of shame, anger, and grandiosity, and how to break the cycle [54:15]; The Relational Life Therapy framework [1:06:30]; How the adaptive child becomes the maladaptive adult [1:15:30]; Speaking the language of social relationships [1:21:45]; When does it make sense for a couple to separate? [1:26:30]; Witness abuse—Consequences of screaming at your partner in the presence of children [1:28:15]; Cases of instantaneous change, and other behavioral changes that may take more time [1:30:45]; Reconciling with his father—Terry’s final conversation with his dad [1:33:45]; and More. Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/terryreal

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Lloyd Klickstein is the Chief Science Officer at resTORbio, a biopharmaceutical company that develops medications to target the biology of aging. In this episode, Lloyd discusses his company’s clinical application of rapamycin and its derivatives. He also elucidates details of his 2014 paper—a paper that greatly influenced Peter’s perspective of rapamycin in the context of longevity. Peter and Lloyd go on to discuss the dose-dependent effect of rapamycin on immune function and compare rapamycin, fasting, and caloric restriction.
 
We discuss:
His background and decision to leave academia for translational medicine [6:15]; Translational medicine—bridging the gap between basic science and clinical medicine [10:30]; What prompted Lloyd to focus on mTOR inhibition? [18:00]; Defining mTOR, TORC1, and TORC2, and the consequences of inhibiting them with rapamycin [21:30]; Dose-dependent impact of rapamycin on immune function, mTOR inhibition, and toxicity [42:15]; Lloyd’s 2014 experiment—mTOR inhibition improves immune function in the elderly [53:00]; Insights into autophagy, antigen presentation, and the pleiotropic benefits of a rapalog, and how it compares to fasting [1:13:00]; Lloyd’s 2018 experiment—TORC1 inhibition enhances immune function and reduces infections in the elderly [1:18:45]; Creation of resTORbio, subsequent studies, and takeaways about dosing, TORC2 inhibition, and tissue selectivity [1:29:00]; Comparing the longevity effect of rapamycin, fasting, and caloric restriction [1:40:00]; Excitement around RTB101—resTORbio’s mTOR inhibiting molecule [1:47:00]; Identifying rapalogs selective for TORC1 [1:56:15]; Treating depression with ketamine, an activator of mTOR [2:00:00]; Epigenetic clocks, rapalogs, and metformin [2:03:30]; and More. Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/LloydKlickstein

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