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Mind & Matter

Nick Jikomes
Mind & Matter
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  • Scarring, Fibrosis, Oxidative Stress, and Psilocybin & Aging | Louise Hecker | 252
    Send us a textAging, tissue repair, and the longevity benefits of psilocin.Episode Summary: Dr. Louise Hecker discusses her research on tissue repair and regeneration, explaining how fibroblasts drive wound healing by forming scar tissue but fail to resolve properly with age, leading to fibrotic diseases like pulmonary fibrosis and liver cirrhosis; they discuss aging hallmarks such as oxidative stress and telomere shortening, and highlight Hecker's study showing psilocybin's active metabolite, psilocin, extends cellular lifespan in lab cultures by reducing oxidants and preserving telomeres, while monthly doses in aged mice improved appearance and survival rates.About the guest: Louise Hecker, PhD is an Associate Professor of Medicine at Baylor College of Medicine, specializing in repair and regeneration processes, particularly in aging and fibrotic diseases.Discussion Points:Fibroblasts are dormant cells that activate during injury to pull wounds closed and form scars, then de-differentiate or die; aging impairs this, causing persistent scarring and disease.Aging reduces the body's regenerative capacity; different organs vary in repair efficiency, with skin healing better than heart tissue.Oxidative stress, like "rust" in the body, accumulates with age due to imbalanced reactive oxygen species production and antioxidant defenses, contributing to cellular damage.Telomeres act as protective DNA caps that shorten with cell divisions, serving as a hallmark of biological aging; sirtuins are master regulators influencing aging processes.Hecker's in vitro study showed psilocin dose-dependently extended fibroblast lifespan by 29-50%, lowering oxidative stress below young cell levels and preserving telomeres.In aged mice (equivalent to 60-65 human years), monthly high-dose psilocybin (15 mg/kg) led to healthier appearance, regrown fur, and 80% survival when controls reached 50% mortality after 10 months.Psilocybin's effects may stem from serotonin receptors expressed in many cell types beyond the brain, suggesting broader anti-aging potential; future work explores mechanisms, optimal dosing, and applications for age-related diseases.Fungi like magic mushrooms represent an under-explored "kingdom" for medicine, with psilocybin's durable effects hinting at systemic impacts on aging.Reference Paper:Study: Psilocybin treatment extends cellular lifespan and improves survival of aged miceRelated content: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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  • Protein Restriction & Liver Hormones: Appetite, Brain, Behavior | Chris Morrison | 251
    Send us a textThe effects of protein restriction on metabolism, liver hormones, brain, and behavior.Episode Summary: Dr. Christopher Morrison talks about how animals sense and prioritize nutrients like protein, discussing defense mechanisms for essentials such as oxygen, water, sodium, and energy; the brain's role in detecting protein deprivation via signals like FGF21; trade-offs between growth, reproduction, and longevity under protein restriction; and reconciling high-protein diets for satiety and muscle maintenance with low-protein benefits for metabolic health and lifespan extension.About the guest: Christopher Morrison, PhD is a professor and researcher at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, where he has worked for over 22 years focusing on nutrition, metabolism, and chronic diseases like obesity and diabetes.Discussion Points:The body prioritizes nutrients hierarchically: oxygen and water first, then sodium, energy, and protein, with weaker defenses for carbs or fats.Animals develop specific appetites for deprived nutrients, like salt or protein, often through post-ingestive learning rather than just taste.Protein restriction (e.g., 5% vs. 20% in diets) increases food intake and energy expenditure in mice to maintain protein levels, even at the cost of extra calories.FGF21, a liver hormone, signals protein deprivation to the brain (via NTS region), driving protein-seeking behavior and metabolic changes; it's essential for low-protein responses.Protein restriction extends lifespan in lab animals by suppressing growth signals like IGF-1 and mTOR, but may impair immunity or wound healing in real-world conditions.High protein aids satiety, weight loss, and muscle building, but overconsumption may shorten lifespan; optimal intake depends on age, activity, and goals (e.g., not for pregnant or elderly).No one-size-fits-all for protein: mild restriction may benefit middle-aged sedentary people for health, while athletes need more; balance avoids excesses.Related content:M&M 106: Diet, Macronutrients, Micronutrients, Taste, Whole vs. Processed Food, Obesity & Weight Loss, Comparative Biology of Feeding Behavior | Stephen Simpson & David Raubenheimer*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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  • Cognition, Form, Regeneration & Metaphysics: Does Biology Arise From Math? | Michael Levin | 250
    Send us a textSupport 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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  • Fructose, Microglia, Anxiety & Brain Development | Justin Perry | 249
    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
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  • Autism, Acetaminophen (Tylenol) & Oxidative Stress | William Parker | 248
    Send us a textThe potential link between acetaminophen (Tylenol) and autism, with a surprise phone call from RFK partway through.Episode Summary: Dr. William Parker talks about autism spectrum disorder (ASD), its rising prevalence since the 1980s, and the controversial hypothesis that acetaminophen exposure in susceptible infants and children triggers most cases via oxidative stress. They discuss ASD's clinical definition; historical misconceptions like the "refrigerator mother" theory; genetic susceptibilities; acetaminophen's metabolism, which produces toxic byproducts in underdeveloped livers, leading to brain effects.About the guest: William Parker, PhD spent nearly 30 years as a professor at Duke University researching underlying causes of chronic conditions, including discovering the immune function of the human appendix and pioneering studies on immune systems in wild animals.Discussion Points:Autism is a spectrum disorder with core symptoms like social deficits, repetitive behaviors, and aversion to new stimuli.Parker argues overwhelming evidence points to acetaminophen as the primary trigger in susceptible individuals, causing oxidative stress via toxic metabolite NAPQI.Acetaminophen, marketed as Tylenol or paracetamol, was not tested for neurodevelopmental effects in neonatal animals until 2014, despite widespread use since 1886; it's metabolized differently in babies, whose livers lack mature detox pathways.Susceptibility factors include low glutathione (an antioxidant), poor sulfation/glucuronidation metabolism, folate receptor autoantibodies, and events like immune reactions that prompt acetaminophen use during oxidative stress.Regressive autism, where children lose milestones after seeming normal, often follows acetaminophen given for fevers or illnesses, explaining parental vaccine suspicions (as shots coincide with drug use).Adult acetaminophen is generally safe but causes liver toxicity in overdoses or with alcohol; antidote is NAC to boost glutathione.Parker has suggested to policymakers that we should avoid acetaminophen during pregnancy, birth, and early childhood (under age 3-5); parents should plan ahead for fevers/pain without it, but seek medical help for unusual symptoms.*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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