Mind & Matter

Terence Capellini, a Harvard evolutionary biology professor, dives deep into the astonishing evolution of bipedalism in humans. He discusses how environmental shifts, like shrinking forests, pushed early hominins to walk upright around 3.5 million years ago. Capellini reveals the vital anatomical changes to the pelvis and limbs that supported this, along with the complex genetic mechanisms, emphasizing the role of numerous small-effect changes rather than single genes. He also connects these evolutionary processes to the development of larger brains and endurance running capabilities.

In this engaging discussion, Gero Miesenböck, a renowned Professor of Physiology at Oxford and pioneer in optogenetics, explores the biological roots of sleep. He reveals how mitochondrial metabolism in neurons creates a need for sleep to manage harmful byproducts. From jellyfish to humans, Gero explains sleep's universal presence and links it to ancient metabolic adaptations. He discusses how sleep-inducing neurons in fruit flies sense lipid peroxidation and the impact of body size on sleep requirements. Dive into the intricate relationship between sleep and cellular health!

Dr. Pekka Karhunen, a medical doctor and forensic pathologist, shares fascinating insights from his extensive research on the connection between oral bacteria and heart disease. He discusses how oxidized LDL cholesterol triggers inflammation in arteries, while oral bacteria can infiltrate arterial plaques, creating biofilms that evade immune detection. Pekka highlights the importance of oral hygiene and cholesterol control in preventing cardiovascular diseases, emphasizing lifestyle changes that can reduce risks associated with plaque buildup.

Send us a textHow nutrition and medications impact mitochondrial health.Wide release date: October 1, 2025.Episode Summary: Dr. Chris Masterjohn talks about the intricate relationships between nutrition, prescription drugs, and mitochondrial health, discussing how molecules like acetaminophen and SSRIs affect the body beyond their intended purposes, particularly impacting inflammation and energy metabolism. The discussion gets into the broader implications of serotonin outside the brain, the side effects of commonly used medications, and the importance of personalized nutritional strategies to optimize mitochondrial function.About the guest: Chris Masterjohn, PhD holds a doctorate in nutritional sciences and is a co-founder of Mitome, a company focused on mitochondrial testing to optimize cellular energy production.Discussion Points:Acetaminophen & Inflammation: Acetaminophen (Tylenol) may contribute to chronic low-grade inflammation by blocking both the initiation and resolution of inflammation, potentially linked to health issues like autism when used during pregnancy.Serotonin’s Role Beyond the Brain: Approximately 95% of serotonin is found in the gut, regulating motility, with SSRIs causing side effects like nausea due to increased extracellular serotonin.SSRIs & Mitochondrial Function: SSRIs disrupt serotonin uptake into cells, reducing mitochondrial melatonin production, which impairs the body’s ability to handle hypoxic stress and produce ATP efficiently.Statins & Mitochondrial Impact: Statins, used to lower cholesterol, inhibit the mevalonate pathway, affecting not just cholesterol but also CoQ10 and vitamin K2, crucial for mitochondrial function, potentially leading to side effects like myopathy.Mitochondrial Testing with Mitome: Masterjohn’s company, Mitome, uses cheek swab tests to measure mitochondrial respiratory chain activity, providing personalized dietary and lifestyle recommendations to optimize cellular energy production.Nutrition & Mental Health: Masterjohn shares his personal experience of severe mental health issues on a vegan diet, which improved dramatically with a nutrient-dense diet rich in organ meats, highlighting individual nutritional needs.Energy Metabolism’s Universal Role: Mitochondrial ATP production governs everything from daily energy levels to long-term health, with personalized testing helping identify and address specific bottlenecks.*Not medical advice.Support the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts

Jacob Raber, a neuroscientist from Oregon Health & Science University, explores the intricate relationship between genetics and environmental influences on brain health. He delves into ApoE's role in Alzheimer's risk and how different isoforms can affect cognitive decline. The conversation also covers fascinating findings on how space radiation impacts aging and brain function, alongside discussions about diet's effect on vascular health. Raber emphasizes practical tips for maintaining brain health through lifestyle choices.

Send us a textHow maternal obesity epigenetically reprograms liver metabolism in offspring, predisposing them to metabolic disease.Episode Summary: Dr. Elvira Mass talks about macrophages, specialized immune cells that vary by tissue and play crucial roles beyond fighting infections, such as supporting organ function; Kupffer cells (liver macrophages) and how maternal obesity during pregnancy reprograms these cells in offspring, leading to fatty liver disease, fibrosis, and even cancer later in life, based on mouse studies showing epigenetic and metabolic shifts like increased glycolysis, with insights into developmental windows, nutritional mismatches, and broader implications for human health.About the guest: Elvira Mass, PhD, is a Professor of Developmental Immunology at the University of Bonn in Germany, where her lab focuses on the development and function of macrophages in various tissues.Discussion Points:Macrophages are diverse, tissue-specific cells that develop from embryonic precursors, performing unique tasks like providing growth factors in organs.Kupffer cells in the liver monitor blood from the gut and are exposed to maternal nutrients during fetal development.Maternal obesity (induced in mice via high-fat diets) programs offspring Kupffer cells epigenetically, leading to fatty liver in newborns and progression to diseases like cancer, even on normal diets.A "nutritional mismatch" between in utero high-fat exposure and postnatal normal diets worsens liver issues, as cells are "prepared" for excess high-fat intake but face scarcity.Key mechanism: Reprogrammed Kupffer cells overproduce apolipoproteins, driving excess lipid uptake in liver cells (hepatocytes), linked to transcription factor HIF-1α and a shift to inefficient glycolysis.Offspring from obese mothers show sex differences (males affected earlier) and persistent changes.Human parallels: Rising childhood fatty liver (once rare and tied to alcoholism) correlates with maternal obesity; studies like Dutch Hunger Winter show early gestational disruptions cause lifelong issues.Broader factors: Microbiome changes, specific fatty acids, and environmental toxins like microplastics may also reprogram macrophages; diets in studies vary beyond fat content, affecting results.Advice: Maintain consistent healthy habits pre- and during pregnancy; avoid sudden diet shifts, as developmental windows are critical for long-lived cells like Kupffer cells.Reference Paper:Study: Kupffer cell programming bySupport the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts

Dr. Louise Hecker, an Associate Professor at Baylor College of Medicine, discusses her groundbreaking research on aging and tissue repair. She explains how fibroblasts, crucial for healing, decline in function with age, leading to fibrotic diseases. The conversation dives into oxidative stress and the role of telomeres in cellular aging. Intriguingly, Hecker shares her findings on psilocybin's metabolite, psilocin, showing it can enhance cellular longevity and vitality in aged mice, suggesting a promising avenue for combating age-related decline.

In this engaging discussion, Chris Morrison, a professor and researcher at the Pennington Biomedical Research Center, unpacks the intricate connections between protein restriction and metabolism. He reveals how animals prioritize nutrients, the fascinating role of the liver hormone FGF21 in signaling protein deprivation, and the balancing act between protein intake and longevity. Listeners will learn about the body's defenses against nutrient deprivation and the surprising impacts on behavior and appetite—offering insights that could reshape our understanding of dietary choices.

Michael Levin, a biologist and director at Tufts University, dives into the fascinating intersection of biology and mathematics. He discusses how bioelectric patterns guide tissue development, encoding anatomical information like memory. Levin explores the regeneration differences among species, attributing them to both genetic and bioelectric factors. He intriguingly posits that biology operates within a structured mathematical space, sparking a conversation on the implications for neuroscience and our understanding of intelligence.

Send us a textCellular clean up by immune cells and how early-life fructose exposure leads to neurodevelopmental problems.Episode Summary: Dr. Justin Perry talks about the body's constant cellular turnover—about 3 million cells die per second in adults (double in children and women)—handled by phagocytes like macrophages that engulf and digest debris to prevent diseases like lupus. They explore phagocytosis steps, macrophage adaptations in tissues like the brain (microglia), and how high fructose intake impairs microglial function in developing mice, leading to uncleared brain cells and anxiety-like behaviors, with implications for human neurodevelopmental disorders amid rising fructose consumption.About the guest: Justin Perry, PhD is an immunologist and clinical psychologist who leads a lab at Memorial Sloan Kettering Cancer Center focusing on how the body clears dead cells and debris to maintain homeostasis.Discussion Points:The body turns over 1-2% of its 30 trillion cells daily, mostly blood cells, but neurons in kids and endometrium in women turnover at ~2x this ratePhagocytosis involves "find me," "eat me," and digestion signals; failures can cause autoimmunity.Microglia are brain macrophages that uptake fructose via GLUT5 transporter.Early high fructose exposure (comparable to one soda daily) impairs the pruning of synapses and dead neurons.In mice, prenatal or postnatal fructose causes phagocytosis deficits in the prefrontal cortex, leading to heightened fear responses and poor fear extinction, mimicking anxiety disorders.Fructose correlates with rising neurodevelopmental issues like autism and anxiety; it's passed via breast milk, and liquid forms (e.g., sodas) overwhelm metabolic shields more than solid fruits.Macrophages may hold keys to diseases from atherosclerosis to cancer; deleting GLUT5 in microglia reverses fructose's effects, hinting at evolutionary roles in aging or low-oxygen states.Related content:M&M 215: Cancer Metabolism: Sugar, Fructose, Lipids & Fasting | Gary PattiArticle | Dietary Fructose & Metabolic Health: An Evolutionary PerspectiveReference Paper:Study | Early life high fructose impairs microglial phagocytosis and neurodevelopment*Not medical advice.Support the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts