Mind & Matter

• Evolution of Bipedality, Human Pelvis, Muscle & Brain | Terence Capellini | 258

  Send us a textThe genetic & developmental changes behind bipedalism & human anatomy.Wide release date: October 15, 2025.Episode Summary: Dr. Terence Capellini talks about the evolution of bipedalism in humans, exploring when and why it emerged, the anatomical changes required, and the genetic mechanisms behind these adaptations. They discuss how environmental shifts, like shrinking forests, drove the need for upright walking, the gradual skeletal changes in the pelvis and limbs, and how these changes may have facilitated larger brain sizes. Capellini highlights the complexity of evolutionary processes, emphasizing the role of multiple genetic changes in regulatory regions rather than single genes.About the guest: Terence Capellini, PhD is a professor and chair of the Department of Human Evolutionary Biology at Harvard University. His research focuses on developmental genetics and human evolution.Discussion Points:Bipedalism likely became common ~3.5 million years ago with Australopithecus afarensis, with earlier hominins like Ardipithecus showing mosaic traits.Environmental changes, such as shrinking forests and expanding grasslands, created selective pressures favoring bipedal locomotion.The human pelvis evolved to be shorter, wider, and curved, with muscles like the gluteus medius shifting to stabilize upright walking.Genetic changes in non-coding regulatory regions, not protein-coding genes, drive the developmental shifts in pelvic growth, with hundreds of small-effect changes involved.Bipedalism may have widened the birth canal, potentially enabling the evolution of larger brains in later hominins like Homo erectus.Humans have more slow-twitch muscle fibers than chimpanzees, supporting endurance activities like long-distance running, possibly linked to energetic trade-offs with brain growth.Shoulder and arm adaptations for throwing and tool use evolved more gradually, becoming prominent ~2 million years ago with Homo erectus.Reference paper:Study: The evolution of hominin bipedalism in two stepsRelated content:M&M 171: Comparative Brain Evolution: Mammals, Primates & Humans | Robert Barton*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

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• Sleep, Mitochondrial Metabolism & Oxidative Stress | Gero Miesenbock | 257

  Send us a textThe biological roots of sleep are tied to mitochondrial metabolism.Episode Summary: Dr. Gero Miesenböck discusses the evolutionary and metabolic basis of sleep, exploring how mitochondrial energy production in neurons, particularly in fruit flies, drives the need for sleep to manage harmful byproducts like reactive oxygen species and lipid peroxides. They discuss how sleep-inducing neurons sense these byproducts, the role of mitochondrial dynamics, and the broader implications for why all animals, from jellyfish to humans, require sleep. The conversation also touches on how body size and metabolism influence sleep needs across species.About the guest: Gero Miesenböck, MD is a professor of physiology at the University of Oxford, renowned for his pioneering work in optogenetics and his research on the neurobiology of sleep using fruit flies and mice.Discussion Points:Sleep is universal across animals, even in jellyfish without centralized brains, suggesting a fundamental metabolic purpose tied to mitochondrial energy production.Mitochondria produce energy efficiently using oxygen but generate reactive oxygen species that can damage cells through lipid peroxidation, necessitating sleep to repair this damage.Sleep-inducing neurons in fruit flies contain sensors that track lipid peroxidation products, acting like a digital memory to signal when sleep is needed.Smaller animals with faster metabolisms, like mice, require more sleep and have shorter lifespans due to higher oxygen consumption and oxidative stress.Mitochondrial diseases in humans often cause intense tiredness, likely due to increased electron leaks in the mitochondrial energy production process.The evolutionary origin of sleep likely stems from the oxygen revolution 2.5 billion years ago, enabling complex life but requiring mechanisms like sleep to manage metabolic side effects.Caloric restriction reduces sleep need by lowering the production of harmful metabolic byproducts, supporting the link between metabolism and sleep.Reference paper:Study: Mitochondrial origins of the pressure to sleepRelated content:M&M 12: Organisms, Cities, Companies & the Science of Scale | Geoffrey West*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

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• Bacterial Infection, Oral Hygiene, Atherosclerosis & Heart Disease | Pekka Karhunen | 256

  Send us a textThe surprising link between oral bacteria and heart disease.Episode Summary: Dr. Pekka Karhunen explains the connection between oral bacteria, cholesterol, and cardiovascular disease, discussing how oxidized LDL cholesterol triggers inflammation in arteries, how bacteria from the mouth can infiltrate arterial plaques to form biofilms, and the implications for heart disease prevention through lifestyle changes like better oral hygiene.About the guest: Pekka Karhunen, MD, PhD is a medical doctor and forensic pathologist with decades of experience, specializing in cardiovascular diseases. He has created a unique biobank of coronary arteries from over 10,000 autopsies conducted in Finland. His research focuses on the role of bacteria in atherosclerosis, particularly through studying coronary artery plaques.Discussion Points:Cholesterol is essential for life, but oxidized low-density lipoprotein (LDL) cholesterol is seen as a foreign substance by the immune system, leading to chronic inflammation in coronary arteries.Macrophages ingest oxidized LDL, turning into dysfunctional foam cells that contribute to plaque buildup, known as atheromas, in arteries.Plaque rupture, potentially caused by increased pressure from cholesterol accumulation or hemorrhage within the plaque, can trigger heart attacks.Bacteria, especially from the mouth, can enter arterial plaques via bacteremia (e.g., from dental procedures) and form biofilms, evading immune detection.Biofilms in plaques, made of extracellular matrix like polysaccharides, protect bacteria and may contribute to plaque instability or calcification over time.Poor oral hygiene is linked to higher cardiovascular disease risk, as bacteria from dental infections can enter plaques, suggesting dental care as a preventive measure.Karhunen’s research found oral bacteria, like Viridans streptococci, in coronary plaques, with unpublished data also detecting gut and skin bacteria, indicating diverse bacterial involvement.Related content:M&M 247: Cholesterol: Immune Benefits, Heart Health, Statins & Research Malpractice | Uffe Ravnskov*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

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• Unlocking Energy: How Nutrition & Drugs Impact Your Mitochondria | Chris Masterjohn | 255

  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

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• How Genes & Environment Shape Your Brain: ApoE, Alzheimer's & Space Radiation | Jacob Raber | 254

  Send us a textGenetic & environmental factors that affect brain health, including why people age faster in outer space. (Note: technical difficulties affected the audio quality of this recording somewhat)Episode Summary: Dr. Jacob Raber explains how apolipoproteins, particularly ApoE, influence brain health and disease risk; their role in cholesterol metabolism, Alzheimer’s disease, and responses to environmental stressors like radiation and viral infections; interplay between genetics, diet, and lifestyle factors, highlighting how these affect cognitive function and resilience to stress; research into space radiation, the gut-brain axis, and potential interventions for neurodegenerative diseases.About the guest: Jacob Raber, PhD, is a neuroscientist at Oregon Health & Science University (OHSU) in Portland, where he leads a lab studying genetic and environmental influences on brain health, particularly using mouse models with human genes.Discussion Points:Apolipoproteins (ApoE2, E3, E4) are proteins involved in cholesterol and lipid metabolism in the brain, with ApoE4 increasing risks for Alzheimer’s and cardiovascular disease.ApoE4 carriers may face higher risks for cognitive decline but could have advantages in specific contexts, like fertility or certain infections.Environmental stressors, such as space radiation and viral infections like West Nile, can exacerbate oxidative stress, impacting brain health.The gut microbiome influences brain function indirectly via the gut-liver-brain axis, with ongoing studies exploring its role in Alzheimer’s and traumatic brain injury.Lifestyle factors like diet, exercise, and sleep are critical for brain health, potentially mitigating genetic risks like ApoE4.Statins, commonly used for cholesterol management, may impair learning in healthy animals, suggesting context-dependent effects.Research into space radiation reveals potential therapeutic applications, such as using heavy ion radiation for cancer treatment.Genetic variations, including ethnicity and sex, influence ApoE-related disease risks, with women and certain populations showing higher Alzheimer’s susceptibility.Chronic low-level stressors, like air pollution, may pose greater risks to brain health than acute exposures due to insufficient activation of protective mechanisms.Related content:M&M 165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet*Not medical adviceSupport 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

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