Huberman Lab

Restore Youthfulness & Vitality to the Aging Brain & Body | Dr. Tony Wyss-Coray

February 23, 2026

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  • Experiments using parabiosis (connecting the circulatory systems of young and old mice) demonstrated that factors in young blood can reactivate brain stem cells, reduce inflammation, and improve memory function in older brains. 
  • Blood composition changes dramatically with age, containing both a loss of beneficial pro-youthful factors and an accumulation of detrimental factors, which can be measured to estimate organ-specific biological age (age gap). 
  • Factors released into the blood following physiological states like exercise or caloric restriction can transmit beneficial effects to other organs, such as the brain, suggesting organs communicate systemically via blood-borne molecules. 
  • The composition of cerebrospinal fluid (CSF) changes dramatically with age, and specific ratios of synaptic proteins within the CSF are strong predictors of cognitive resilience or decline, independent of established Alzheimer's pathology. 
  • Certain forms of exercise, particularly explosive/fast-twitch activities like sprinting or pole vaulting, may confer a greater longevity effect than endurance exercise, suggesting specific exercise-induced molecules (like lacti) drive potent benefits. 
  • The subjective experience of exercise matters significantly, as forced exercise can lead to negative physiological outcomes (increased stress markers, memory deficits), whereas electing to push through challenging but enjoyable activities yields greater benefit. 

Segments

Young Blood Rejuvenation in Mice
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(00:00:00)
  • Key Takeaway: Infusing factors from young organisms reactivated brain stem cells, reduced inflammation, and improved memory function in old mice.
  • Summary: Experiments demonstrated that factors present in young blood can reverse key features of aging in the brain. This rejuvenation involved reactivating dormant stem cells and decreasing inflammatory markers. The most significant outcome observed was an improvement in memory function in the aged subjects.
Parabiosis and Blood Factor Research
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(00:03:38)
  • Key Takeaway: Parabiosis experiments showed young circulation regenerated aged muscle tissue, prompting research into young blood factors for brain health.
  • Summary: The parabiosis model, where young and old mice share circulation, was used to determine if blood factors drive aging or merely reflect it. Initial work showed muscle regeneration in old mice connected to young circulation. This success led to exploring similar rejuvenating effects in the aging brain.
Blood Biomarkers and Alzheimer’s
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(00:04:54)
  • Key Takeaway: Proteins in blood show striking concentration differences between young and old people, correlating with and potentially predicting Alzheimer’s disease.
  • Summary: Researchers observed protein signatures in blood that were predictive of Alzheimer’s disease, highlighting a major difference between young and old individuals. This observation prompted the need to determine if these protein changes cause or result from brain aging. The parabiosis model allowed testing the causal role of these blood factors.
Translating Young Blood Factors to Humans
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(00:06:26)
  • Key Takeaway: Clinical trials are underway using fractions of human plasma, derived from young donors, to test for reversal of aging features in Alzheimer’s and Parkinson’s patients.
  • Summary: The beneficial effects seen in mice are being translated to humans through testing fractions of pooled plasma from young donors. One company conducted a large, blinded trial using therapeutic plasma exchange and albumin infusion in Alzheimer’s patients, showing clear benefits. Smaller trials using plasma fractions have also suggested improvements in epigenetic clocks, indicating potential rejuvenation.
Sponsor Break: David Protein Bars
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(00:12:50)
  • Key Takeaway: David protein bars offer 20g of protein with only 150 calories and zero sugar, tasting like candy bars.
  • Summary: David protein bars, particularly the Bronze Bar, provide high protein content with minimal calories and no sugar. Flavors like cookie dough and caramel chocolate are noted for tasting like candy bars. Listeners can receive a deal for a free fifth carton via the sponsor link.
Sponsor Break: LMNT Electrolytes
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(00:14:09)
  • Key Takeaway: Element electrolyte drinks provide essential sodium, magnesium, and potassium without sugar, crucial for optimal cognitive and physical performance.
  • Summary: Proper hydration and electrolyte balance are vital for nerve cell function and overall performance, as dehydration diminishes cognitive and physical output. Element delivers electrolytes in correct ratios without added sugar, making it easy to maintain hydration, especially upon waking or during exercise. The speaker uses it first thing in the morning and during physical activity.
Pro-Youthful vs. Damage-Inhibiting Factors
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(00:15:29)
  • Key Takeaway: Young blood contains both pro-growth factors that stimulate cell activity and factors that inhibit age-related inflammatory damage, both contributing to rejuvenation.
  • Summary: Rejuvenation from young blood involves a dual mechanism: supplying active pro-growth factors and neutralizing detrimental, inflammatory proteins that accumulate with age. Neutralizing specific inflammatory proteins in old mice was shown to improve cognition independently. Identifying the key factors in this complex ’nature’s cocktail’ remains a major scientific challenge.
Blood Factors and Cellular Targets
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(00:18:16)
  • Key Takeaway: Young blood factors induce widespread changes in gene expression across nearly every cell type, with stem cells and mitochondria being key targets for rejuvenation.
  • Summary: Analysis of old mouse cells exposed to young blood showed that almost every cell type altered its gene expression in response to the circulating factors. Stem cells were confirmed as major targets, supporting initial findings on rejuvenation. Furthermore, mitochondria, the cell’s energy producers, were identified as critical organelles benefiting from these youthful signals.
Banking Blood and Dracula Lore
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(00:20:15)
  • Key Takeaway: Banking one’s own blood is unnecessary for these studies as pooled young blood provides the beneficial effect, and the Dracula myth likely stems from recognizing blood’s essential nature.
  • Summary: The beneficial effects observed in studies come from the general composition of young blood, meaning pooling samples from multiple young individuals is sufficient. The concept of drinking young blood, like the Dracula lore, is speculative regarding its origins but likely relates to the fundamental recognition of blood’s role in vitality. The speaker notes that feeding young blood to mice has not been tested.
Organ-Specific Aging Rates
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(00:23:10)
  • Key Takeaway: Different organs age at non-uniform rates, and measuring blood-borne proteins originating from specific organs allows estimation of an individual’s organ-specific biological age.
  • Summary: Organisms do not age uniformly; molecular tools now reveal that some organs age faster or slower than others within the same individual. By profiling thousands of proteins in blood, researchers can identify those originating from the brain, liver, or heart to estimate the biological age of those specific organs. A significant ‘age gap’ between chronological age and organ age strongly predicts future disease risk in that organ.
Vero Biosciences and Organ Age Prediction
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(00:28:27)
  • Key Takeaway: Vero Biosciences uses organ-specific blood signatures combined with clinical and wearable data to predict disease risk and tailor interventions to slow down specific organ aging.
  • Summary: The mission of Vero Biosciences is to profile organ age to maintain health span by detecting which organ is aging fastest. This platform aims to match specific lifestyle or medical interventions to the individual’s needs and then monitor if that intervention successfully alters the organ’s biological age. This personalized approach could prevent diseases by intervening before clinical diagnosis.
NAD/NMN Supplements and Longevity
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(00:33:02)
  • Key Takeaway: While NMN/NR supplements increase NAD levels in the blood, there is currently no human evidence that they extend lifespan or improve tangible health outcomes in healthy older adults.
  • Summary: Increasing NAD levels via supplements like NMN has been shown to raise blood concentrations, but this has not translated into proven lifespan extension or frailty reduction in humans. Exercise and diet remain the only lifestyle factors with proven effects on health span. Furthermore, testing of NMN supplements revealed that many products do not contain the labeled amount due to instability.
Vitality vs. Longevity Trade-offs
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(00:36:44)
  • Key Takeaway: Hormones that boost immediate vitality, like growth hormone, are often associated with antagonistic pleiotropy, potentially decreasing overall longevity.
  • Summary: Puberty represents the fastest rate of aging, driven by hormonal shifts, illustrating a potential trade-off between youthful vigor and long-term survival. While supplementing hormones like testosterone or growth hormone increases vitality, evidence in animal models (like large dogs) suggests this can decrease lifespan due to elevated IGF-1. The goal is to find factors that simultaneously promote both vitality and health span.
Exercise Factors: Clusterin and GPLDH
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(00:45:22)
  • Key Takeaway: Blood from exercised mice transmits beneficial effects to non-exercised mice, mediated by factors like Clusterin and GPLDH released from the liver.
  • Summary: The benefits of exercise on the brain are transmitted via blood-borne factors, specifically those released from the liver following physical activity. One identified protein is Clusterin (Apolipoprotein J), involved in coagulation and complement pathways, which showed effects when synthetically administered. This highlights that organ systems orchestrate systemic benefits through the bloodstream.
Injury Healing and Scarring Differences
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(00:53:58)
  • Key Takeaway: Younger individuals heal faster and often without scarring compared to older adults, possibly due to an age-related shift in the immune response toward inflammation over healing.
  • Summary: Healing capacity significantly degrades after age 60, where injuries often result in scarring, unlike in childhood. This difference may be linked to an aging immune system exhibiting a stronger, non-specific inflammatory response rather than a targeted healing response. The mouth’s ability to heal without scarring, despite high bacterial load, suggests specific pro-healing factors are present there.
Moving Toward Causal Treatments
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(00:56:18)
  • Key Takeaway: Achieving causal longevity treatments requires isolating individual factors from young blood, testing them rigorously in animal models, and validating effects in blinded human clinical trials.
  • Summary: The field aims for health span extension by maintaining organ function until death, rather than just extending lifespan into misery. Isolating individual molecules like Klotho or GDF-11 is necessary to move from correlation to causation. The process demands rigorous, blinded clinical trials to confirm safety and efficacy before a factor can be considered a viable drug treatment.
Caution on Unregulated Injections
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(01:00:08)
  • Key Takeaway: Extreme caution is advised regarding unregulated stem cell injections, as they carry high risks of severe complications like infection and paralysis.
  • Summary: A cautionary tale highlighted the danger of receiving unproven cellular injections, such as stem cells into a spinal disc, which resulted in a massive infection and paralysis for a medical doctor. Unlike FDA-approved treatments like Platelet-Rich Plasma (PRP), which contains growth factors, stem cell treatments lack rigorous testing and regulation outside of controlled clinical settings.
PRP and Exosomes Function
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(01:02:37)
  • Key Takeaway: Platelet-Rich Plasma (PRP) is FDA-approved and contains concentrated growth factors beneficial for wound healing, while exosomes are cellular packages delivering molecular information between cells.
  • Summary: PRP, derived from a patient’s own blood, is approved for certain indications due to the high concentration of growth factors released by platelets, aiding tissue repair. Exosomes are small vesicles released by cells, carrying proteins, RNA, and metabolites, functioning to deliver information between cells. Researchers analyze the cargo within exosomes found in blood for diagnostic potential.
Environmental Toxins and Cumulative Damage
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(01:05:43)
  • Key Takeaway: Cumulative, low-level exposure to environmental factors like plastics and potential EMFs poses an unknown long-term risk to DNA and protein health.
  • Summary: The long-term effects of chronic, low-dose exposure to substances like plasticizers (e.g., from containers) and EMFs are currently unknown but warrant consideration due to potential accumulation. Growing up in environments with clean, home-cooked food (like Switzerland) contrasts sharply with modern packaged food consumption, suggesting lifestyle choices impact cumulative toxic load. Data on pesticide residue differences between organic and non-organic food is sometimes inconclusive, but sourcing fresh, local food remains ideal.
Organic Food vs. Pesticides
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(01:09:43)
  • Key Takeaway: Data suggests minimal significant differences in pesticide contamination between organic and non-organic produce batches, though local sourcing is ideal.
  • Summary: The difference in pesticide contamination between organic and non-organic fruits and vegetables may not be significant based on one physician’s son’s experiment. This is reassuring for those who cannot afford organic options. However, sourcing from local farms is still considered potentially cleaner. High rates of endocrine disruptors are often found in rural areas where crops are sprayed, posing serious health risks.
Fasting Mechanisms and Human Data
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(01:13:16)
  • Key Takeaway: Clinical studies showing clear lifespan benefits from intermittent fasting in humans are lacking, and animal data suggests potential detriments in some species like monkeys.
  • Summary: Animal studies clearly show beneficial pathways activated by reduced calorie intake, including reduced inflammation, improved energy metabolism, and better handling of cellular waste. However, translating these broad benefits to tangible human lifespan advantages remains uncertain. Intermittent fasting lacks a consistent definition across research, and some monkey studies indicated worse kidney function with fasting.
Intermittent Fasting Practice
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(01:16:04)
  • Key Takeaway: The speaker rarely practices strict intermittent fasting but finds value in avoiding constant eating, noting that continuous snacking is evolutionarily unnatural.
  • Summary: The speaker occasionally tries diets like Valter Longo’s protocol, which involves a temporary switch to a ketogenic diet. Short-term caloric restriction can increase alertness due to catecholamine release. Avoiding constant eating, such as all-day snacking, aligns better with human evolutionary patterns of periodic starvation.
Sleep and Glymphatic Clearance
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(01:19:07)
  • Key Takeaway: Young cerebrospinal fluid (CSF) infusion can regenerate the brain and improve cognitive function in old mice, highlighting the importance of fluid composition changes with age.
  • Summary: Glymphatic clearance during sleep removes debris from the brain, a process potentially affected by age. Infusing young CSF into old mice regenerated brain tissue and improved cognition, specifically targeting oligodendrocytes which produce myelin. This suggests beneficial factors present in young fluids may be crucial for maintaining neural health.
CSF Proteins Predict Cognition
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(01:22:57)
  • Key Takeaway: A ratio derived from two specific synaptic proteins in human CSF strongly predicts cognitive resilience, changing continuously even from early adulthood.
  • Summary: Researchers are measuring thousands of proteins in human CSF to correlate them with cognitive function. A ratio of the top protein that increases versus the one that decreases with cognition is a powerful predictor of cognitive decline. This synaptic protein signal degrades continuously starting in early adulthood and is independent of pathological markers like amyloid beta.
Exercise Type and Longevity
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(01:24:45)
  • Key Takeaway: Athletes specializing in explosive, fast-twitch activities (sprinters, jumpers) show a greater longevity effect than endurance athletes, implying specific molecular signals.
  • Summary: Studies suggest that sprinters and gymnasts gain substantially more longevity (5-8 years) than endurance athletes, indicating that the type of exercise matters. This difference may be driven by specific molecules released during explosive activity, such as the lactate-conjugated amino acid, lacti, which spikes during intense muscle bursts. The field needs to move beyond general exercise advice to identify these potent molecular drivers.
Choice in Exercise and Stress
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(01:28:35)
  • Key Takeaway: The subjective choice and enjoyment of an activity, rather than just the activity itself, dictates the long-term physiological benefit, as demonstrated in rodent studies.
  • Summary: Rodents forced to run on a wheel experienced long-term increases in blood pressure and memory deficits, while freely choosing to run showed benefits. Pushing through challenging activities that one elects to do, even if they are difficult, provides a ‘double benefit’ compared to activities one hates or is forced to perform.
Lifestyle Factors and Dementia Risk
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(01:32:02)
  • Key Takeaway: Optimizing modifiable lifestyle factors like avoiding smoking, excessive alcohol, and obesity significantly lowers the risk for dementia and Alzheimer’s disease.
  • Summary: Numerous studies confirm that lifestyle choices dramatically influence dementia risk, even if some factors like poverty are difficult to overcome. Optimizing factors such as education level, smoking habits, alcohol intake, and obesity can substantially lower susceptibility to cognitive decline. Cognitive gymnastics, like reading or learning new skills, may benefit those who crave stimulation, but data on reversing existing impairment is limited.
Chocolate, Alcohol, and Social Connection
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(01:36:11)
  • Key Takeaway: Social connection, often facilitated by shared meals and drinks like wine, is a common factor among centenarians, potentially overriding the negative effects of moderate alcohol consumption.
  • Summary: The Swiss population has one of the highest caffeine intakes, often paired with high consumption of chocolate, which is rich in polyphenols. While pure alcohol is detrimental, moderate consumption within a social context appears healthy due to stress reduction from social connection. The US culture often emphasizes excessive drinking, contrasting with European traditions where food and drink are tied to nourishment and social bonding.
Breathing, Blood Flow, and Light
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(01:40:50)
  • Key Takeaway: Deliberate, deep breathing exercises improve circulation and may influence blood chemistry, while bright days and dark nights are critical for mental health.
  • Summary: Vigorous inhales increase heart rate, while deliberate exhales decrease it via respiratory sinus arrhythmia, suggesting breathing patterns affect circulation and brain nutrient supply. Older individuals often become mouth breathers, potentially indicating difficulty oxygenating the brain. Furthermore, bright daytime light exposure and complete darkness at night are strongly correlated with reduced susceptibility to all mental health conditions.
Future Research: Cellular Aging Maps
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(01:49:13)
  • Key Takeaway: The Wyss-Coray lab is developing models to estimate the age of 40 specific cell types in the body, finding that aged muscle cells strongly predict ALS risk.
  • Summary: Future work involves building models to estimate the age of specific cell types using thousands of protein measurements, offering finer resolution than whole-organ aging estimates. Extremely old skeletal muscle cells were strongly associated with the development of ALS, and aged astrocytes strongly predict Alzheimer’s risk. The ultimate goal is to map the human proteome across monogenic diseases to understand biological pathways.
Supporting the Podcast and Book
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(01:56:40)
  • Key Takeaway: Listeners can support the Huberman Lab podcast by subscribing, leaving reviews, and checking out the sponsors, while the new book ‘Protocols’ is available for pre-sale.
  • Summary: Zero-cost support includes subscribing on YouTube, Spotify, and Apple, and leaving reviews/comments. The host’s first book, ‘Protocols: an operating manual for the human body,’ covers science-backed protocols for sleep, exercise, and focus and is available for pre-sale at protocolsbook.com. The Neural Network newsletter offers free monthly summaries and PDF protocols.