View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Mike Joyner is a physician-researcher and one of the world’s leading experts on human performance and exercise physiology. In this episode, Mike discusses how to combat age-related declines in health and fitness levels by using various modes of exercise to improve lifespan and healthspan. Mike explains the impact of exercise on the autonomic nervous system, blood pressure, heart rate, heart rate variability, heart rate recovery, and max heart rate. He dives deep into VO2 max, including how it’s measured, what is driving it, and how to improve it. Mike provides training insights for the average person, including training volume and exercise intensity as well as simple metrics to track. Furthermore, he gives his take on the theoretical “J-curve” relationship between exercise and longevity, as well as whether possible health dangers may be associated with excessive exercise. We discuss: Mike’s training as an anesthesiologist and interest in exercise physiology [2:30]; How exercise increases longevity [7:00]; The impressive data on the benefits of exercise [9:45]; The Centenarian Olympics and other ways to mitigate age-related decline in strength and stability [15:00]; The violent dropoff in strength and activity with age and how exercise preserves fitness in old age [19:00]; Benefits of exercise on mortality and fracture risk, and the interplay of nutrition and exercise [22:00]; How exercise benefits the autonomic nervous system and why this plays an important role in our health [26:30]; VO2 max, heart rate recovery, heart rate variability, and other metrics of fitness positively impacted by exercise [28:30]; Reduction in all-cause mortality with increased fitness levels and VO2 max [32:45]; Does the relationship between exercise and longevity follow a J-curve? [40:00]; Mitigating age-related decline in fitness by elevating your VO2 max at a young age [46:15]; Breaking down the variables that drive VO2 max [54:30]; Learning from elite athletes: Training regimens, aerobic efficiency, and other impressive metrics [1:00:15]; Health benefits of light exercise for the average person [1:09:00]; Simple training metrics to track, and Mike’s current exercise regimen [1:11:15]; How to boost your VO2 max, and the importance of form and tempo with interval training [1:18:15]; Training advice for the average person [1:25:15]; Why professional athletes have longer careers than they’ve had in the past [1:27:30]; Use of performance-enhancing drugs in professional sports [1:29:45]; Can the miracle of exercise be put in a pill? [1:36:00]; Mike’s current research and questions he’s most interested in answering [1:39:00]; Use of convalescent plasma to treat COVID-19 [1:41:15]; Parting thoughts on the current state of fitness and exercise in society [1:47:15]; 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 Josh Rabinowitz is a Professor of Chemistry and Integrative Genomics at Princeton University, where his research focuses on developing a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. In this episode, Josh focuses the discussion on three main topics: metabolomics, NAD (and its precursors), and cancer metabolism. The metabolomics discussion starts with a broad definition of metabolism, metabolites, and fluxomics before diving deep into glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. He then gives a detailed explanation of the electron transport chain and Krebs cycle and their implications with respect to both drugs and nutrition while also explaining how NAD is central to the process of energy generation. He then discusses the age-related decline in NAD and what current literature says about efforts to increase NAD through intravenous or oral supplementation with the precursors NMN and NR, including whether doing so provides any advantage to lifespan or healthspan. Finally, Josh ends the conversation talking about cancer metabolism and how one particular intersection between cancer metabolism and immunotherapy might provide a hopeful outlook on the future of cancer treatment. We discuss: Josh’s background and unique path to becoming a research scientist at Princeton [3:30]; What sparked Josh’s early interest in metabolism [11:15]; Metabolomics 101: defining metabolites and how they are regulated [16:30]; Fluxomics: metabolism as a system in action [26:00]; The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation [33:30]; The important role of lactate as an alternate fuel [36:30]; Fasting lactate levels as a potential early indicator of metabolic dysfunction [48:00]; The beauty of the Krebs cycle and the role of NAD in energy production [53:15]; How the drug metformin acts on complex I of the electron transport chain [1:05:00]; The difference between NADH and NADPH [1:08:45]; NAD levels with age, and the efficacy of supplementing with intravenous NAD [1:10:45]; The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN [1:22:15]; Exploring the hypothesis that boosting NAD levels is beneficial [1:32:30]; Cancer metabolism and the intersection with immunotherapy [1:39:00]; Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more [1:46:15]; The challenge of treating pancreatic cancer [1:50:30]; Epithelial cancers that might respond to metabolic approaches to therapy [1:56:30]; Josh’s hopeful outlook on the future of cancer treatment [1:59:00]; Nutritional approaches to cancer attenuation [2:00:15]; What makes Princeton University special [2:06:15]; 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 Mike Gershon is a Professor of Pathology and Cell Biology at Columbia University and has been at the forefront of studying neural control of the gut for the past 60 years. In this episode, Mike gives a tour de force on the pathways of gut-brain communication but first sets the stage with an overview of gastrointestinal tract development and anatomy. He then explains how the gut communicates with the brain and vice versa, from early observations in physiology and anatomy up to our present understanding of what makes the GI tract so unique and complex relative to other organs. He talks about how the gut responds to meals of different food qualities and how that affects satiety signaling to the brain. Additionally, he explains how antidepressants and other drugs impact digestion through effects on serotonin signaling, and he discusses the effects of antibiotics, and what’s really going on with “leaky gut.” Finally, Mike offers his thoughts on the utility—or lack thereof—of gut microbiome diagnostic tests, and wraps up the discussion by considering how diet, probiotics, and prebiotics impact the microbiome and GI tract. We discuss: The basics of the gastrointestinal (GI) system [3:45]; The very early development of the GI system [9:30]; The unique properties of the blood supply and portal system in the GI tract [12:45]; An overview of gut anatomy and innervation [16:30]; Turnover of the epithelial lining and why cancer rarely develops in the small intestine [26:45]; Nutrient and water absorption in the small and large intestine [30:30]; Ways in which the gut and brain communicate [34:30]; The gut's role in the regulation of appetite [43:30]; The impact of gastric bypass surgery on satiety signals [51:15]; How varicella-zoster virus (VZV) can infect neurons in the gut and create issues later in life [54:30]; The relationship between autism and gastrointestinal illness [1:02:45]; The important role of serotonin in the gut, and the impact of SSRIs on serotonin in the gut [1:09:45]; Defining “leaky gut” and its most common causes [1:16:45]; The gut microbiome [1:30:45]; Fecal transplants: use cases, limitations, and how they illustrate the importance of gut microbes [1:40:45]; Gut microbiome diagnostic tests: why they aren’t useful outside of special cases such as cancer detection [1:50:30]; Nutritional approaches to a maintain optimal flora in the gut [1:55:00]; Prebiotics and probiotics, and getting your GI system back on track after a course of antibiotics [2:02:30]; 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 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. 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 our website at the AMA #37 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of bone health topics to be discussed [1:45]; Bones 101: bone function, structure, and more [5:15]; Bone mineral density (BMD), minerals in bone, role of osteoblasts and osteoclasts, and more [8:30]; The consequences of poor bone health [13:30]; The devastating nature of hip fractures: morbidity and mortality data [17:00]; Where fractures tend to occur in the body [23:00]; Defining osteopenia and osteoporosis [24:30]; Measuring BMD with DEXA and how to interpret scores [27:00]; Variability in BMD between sexes [34:15]; When should people have their first bone mineral density scan? [36:45]; How BMD changes throughout the life and how it differs between men and women [39:00]; How changes in estrogen levels (e.g., menopause) impact bone health [44:00]; Why HRT is not considered a standard of care for postmenopausal bone loss [47:30]; Factors determining who may be at higher risk of poor bone health [50:30]; Common drugs that can negatively impact BMD [54:15]; How children can optimize bone health and lay the foundation for the future [57:45]; Types of physical activity that can positively impact bone health [1:02:30]; How weight loss can negatively impact bone health and how exercise can counteract those effects [1:10:45]; Nutrition and supplements for bone health [1:14:15]; Pharmaceutical drugs prescribed for those with low BMD [1:17:15]; Impact of extreme sedentary periods (e.g., bedrest) and how to minimize their damage to bone [1:22:00]; 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 Max Diehn is a Professor of Radiation Oncology at Stanford and a clinical radiation oncologist specializing in lung cancer. Max’s research focuses on developing novel methods for detecting circulating tumor DNA in the blood of cancer patients and on elucidating the molecular pathways and genes associated with cancer. His interests also include uncovering biomarkers that can predict patient survival, responses to therapy, and disease recurrence. In this packed episode, Max discusses the history of blood-based cancer screening and the importance of understanding the predictive value of tests—sensitivity, specificity, negative predictive value, positive predictive value – and how these metrics play into cancer screening. Max then goes in depth on the topic of liquid biopsies, including the history, current landscape, and possible future of liquid biopsies as a cancer detection tool. He discusses how these non-invasive blood tests can detect DNA/RNA from tumor cells released into the blood as well as the different methods one can use to predict if a cancer is present. He gets granular on the topic of cell-free DNA/RNA signature, methylation patterns, and the importance of knowing mutation information, and he ends with a discussion on the exciting future of liquid biopsies and how we can possibly get to the panacea of cancer screening. We discuss: Max’s training that planted the seeds for development of liquid biopsies [4:30]; Max’s decision to specialize in radiation oncology [11:45]; A culture at Stanford that values research and physician scientists [17:00]; The motivation to develop liquid biopsies [19:15]; History of blood-based cancer screening and understanding the predictive value of tests [25:30]; Current state of lung cancer and the need for better screening [32:45]; Low-dose CT scans: an important tool for managing lung cancer but with limitations [42:00]; Using liquid biopsies to identify circulating tumor cells [47:00]; Liquid biopsy research moves from circulating tumor cells to cell-free DNA [1:03:00]; Zeroing-in on circulating tumor DNA in cell-free DNA [1:10:48]; Cell-free RNA and Max’s vision for cancer detection from a blood sample [1:22:00]; Methylation patterns and other informative signatures found in DNA [1:24:30]; Mutation-based methods of liquid biopsies [1:26:30]; Understanding the sensitivity and specificity of a diagnostic test [1:30:30]; Existing clinical liquid biopsy tests and their limitations [1:37:30]; The future of liquid biopsies [1:44:00]; How we get to the panacea of cancer screening [1:52:00]; More. Connect With Peter on Twitter, Instagram, Facebook and YouTube