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Mind & Matter

Nick Jikomes
Mind & Matter
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  • Mitochondrial Transfer, Obesity & Immune-Metabolism Interactions | Jon Brestoff | 261
    Send us a textHow mitochondria travel between cells and how this hidden communication shapes metabolism, immunity, and even potential therapies.Episode Summary: Dr. Jon Brestoff talks about mitochondrial dynamics inside cells, their transfer between unrelated cells (distinct from inheritance during division), and its roles in adipose tissue communication, macrophage cleanup, and systemic metabolic signaling; they explore how high-fat diets disrupt this process, potential hormetic benefits, therapeutic mitochondria transplantation for diseases like Leigh syndrome and obesity, and broader immunometabolism crosstalk.About the guest: Jon Brestoff, MD, PhD is an associate professor of pathology and immunology at Washington University School of Medicine in St. Louis, where he directs the Initiative for Immunometabolism.Discussion Points:Mitochondria per cell range from ~100-5000; they move via fusion/fission, vertical inheritance (cell division), or horizontal transfer without division.Transfer mechanisms: free release, extracellular vesicles, or tunneling nanotubes using cytoskeleton transport.In healthy fat tissue, adipocytes routinely donate mitochondria to macrophages for degradation (quality control); high-fat (lard-based, long-chain FA) diets block macrophage uptake, diverting mitochondria to other organs.Diverted mitochondria may induce “mito-hormesis” (mild oxidative stress boosting antioxidants) or signal adipocyte metabolic status inter-organ.Mitochondria transplantation shows promise in animal models for ischemia-reperfusion, obesity, and mitochondrial diseases.Immune cells prefer glycolysis but have low mitochondrial biomass; transplanted mitochondria tilt T-cells toward anti-inflammatory regulatory phenotype.Circulating cell-free mitochondria rival immune cell numbers.Obesity inflammation stems from dying oversized adipocytes releasing lipids/mitochondria, forming crown-like structures with pro-inflammatory macrophages.Leigh syndrome from genetic mutations disrupting the electron transport chain.Transfer may be an evolutionary relic of endosymbiosis; cells may selectively use exogenous mitochondria like a “generator” during metabolic crisis.Reference Paper:Study: The power and potential of mitochondria transferRelated Episode:M&M 260: Energy Resistance Principle in Life, Healing & Disease | Martin Picard & Nirosha MuruganSupport 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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  • Energy Resistance Principle in Life, Healing & Disease | Martin Picard & Nirosha Murugan | 260
    Send us a textA biophysical rethink of life, health, and disease through the lens of the Energy Resistance Principle (ERP).Episode Summary: A reframe of biology as energy flow through resistance rather than mere molecular machinery, introducing the Energy Resistance Principle (ERP): life requires a Goldilocks balance of electron flow from food to oxygen via mitochondria; too much or too little resistance drives aging, disease, and death. Explain mitochondria as energy transformers, link ERP to insulin resistance, psychiatric disorders, and healing, and explore health as a dynamic field-like state optimized by flux modulation.About the guest: Nirosha Murugan, PhD is a biophysicist studying how physical signals pattern biology to decode and reprogram health; Martin Picard, PhD is a mitochondrial psychobiologist at Columbia University, exploring how mitochondrial energy dynamics connect to human experiences, health, and healing. They collaborate on biophotons, light emission, and multi-scale energy signaling.Discussion Points:Mitochondria transform electrons from food into versatile electricity via proton gradients.Energy Resistance Principle: transformation needs resistance; chronic high resistance causes dissipative heat, damage, aging.GDF15 cytokine signals mitochondrial stress to brain, triggering energy conservation/mobilization.Insulin resistance: adaptive defense against electron overload, reversible by fasting/exercise.Psychiatric illness: excess brain energy resistance; exercise, keto, psychedelics redistribute flux.Health: dynamic optimization of energy resistance, not absence of disease.Healing: daily recovery from micro-damage via balanced resistance.Future: energy-based diagnostics/therapies (light, TMS) over molecule-only drugs.*Not medical advice.Reference Paper: The energy resistance principleRelated Episode:M&M 70: Mitochondria, Aging, Cellular Energy, Metabolism, Gray Hair Reversal & Brain-Body Communication | Martin PicardSupport 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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  • Menstrual & Lunar Cycle Synchrony, Circadian Rhythms | Charlotte Förster | 259
    Send us a textHow artificial light impacts female menstrual cycles and their relationship to lunar cycles of the moon.Summary: Dr. Förster talks about how biological clocks, including circadian, tidal, lunar, and annual cycles, regulate behaviors in various species, with a focus on lunar cycle effects on human menstrual cycles. They explore historical and modern data suggesting that menstrual cycles may synchronize with lunar phases, a phenomenon potentially disrupted by modern artificial lighting, particularly blue light from LEDs post-2010. The conversation also covers circadian rhythm mechanisms in fruit flies and humans, highlighting the role of light and neuropeptides in maintaining biological synchrony.About guest: Charlotte Förster, PhD is a senior professor at the University of Würzburg specializing in chronobiology, particularly circadian rhythms in fruit flies, and has recently explored lunar cycle influences on human menstrual cycles.Discussion Points:Biological Clocks: Various clocks (circadian, tidal, lunar, annual) regulate behaviors; circadian clocks manage 24-hour cycles, while lunar clocks influence reproduction in marine species like corals and Christmas Island crabs.Lunar Cycle & Menstruation: Historical data (pre-2010) showed many women’s menstrual cycles synchronized with lunar phases (full or new moon), but this decreased post-2010, possibly due to blue light from LEDs disrupting biological rhythms.Blue Light Impact: Blue light from modern devices mimics daylight, potentially desynchronizing circadian and lunar clocks, with melanopsin in the eyes playing a key role in light sensitivity.Winter Synchronization: Menstrual cycle synchrony with lunar phases is stronger in winter, particularly January, possibly due to brighter moonlight or gravitational effects when Earth is closest to the Sun.Circadian Mechanisms: In fruit flies, 240 neurons manage circadian rhythms via clock genes with a 24-hour feedback loop, conserved in humans, where neuropeptides regulate slower, sustained rhythms.Health Implications: Disrupted circadian rhythms can desynchronize body clocks, impacting digestion, immunity, and increasing risks of cardiovascular issues, obesity, and cancer.Lifestyle Tips: To maintain synchrony, maximize daytime light exposure, minimize nighttime blue light, time meals appropriately, and exercise during the day, not late at night.Reference paper:Study: Synchronization of women’s menstruation with the Moon hasSupport 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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  • 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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About Mind & Matter

Whether food, drugs or ideas, what you consume influences who you become. Learn directly from the best scientists & thinkers alive today about how your mind-body reacts to what you feed it.The weekly M&M podcast features conversations with the most interesting scientists, thinkers, and technology entrepreneurs alive today.Not medical advice.At M&M, we are interested in trying to figure out how things work, not affirming our existing beliefs. We prefer consulting primary rather than secondary sources and independent rather than institutional voices. If we encounter uncomfortable truths or the evidence suggests unfashionable ideas may be valid, so be it.As the host, my aim is to help you better understand how the body & mind work by curating & synthesizing information in a way that yields science-based insights that you can choose to use or disregard in your own life. Taking ownership of your health starts with taking ownership of your information diet.I am motivated to connect the dots and distill general principles from what I learn, preferring to ask questions and play devil’s advocate to debating or incessantly pushing my own viewpoint.My beliefs:Taking ownership of your health starts with taking ownership of your information diet.All knowledge is provisional and we must work hard to prevent ourselves from becoming attached to our favorite ideas & preferred conclusions.Wisdom comes from an iterative, trial-and-error process of learning and unlearning. Letting go of pre-conceived notions can be painful, but pain is information.Sometimes modern discoveries teach us we must unlearn received wisdom. Other times, modern information overload & historical chauvinism cause us to forget ancient wisdom which stills applies. The framework for learning that I embody is inspired by three Ancient Greek maxims inscribed in the Temple of Apollo at Delphi:“Γνῶθι σεαυτόν” (Know thyself)“Μηδὲν ἄγαν” (Nothing in excess)“Ἐγγύα πάρα δ Ἄτα” (Certainty brings insanity)
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