Restore Youthfulness & Vitality to the Aging Brain & Body | Dr. Tony Wyss-Coray
In this episode of the Huberman Lab, Dr. Tony Wyss-Coray discusses research on how blood proteins might influence aging and cellular function. Through experiments connecting young and old mice's circulatory systems, researchers found that young blood can reactivate stem cells, reduce inflammation, and improve memory function in older mice. The findings have led to human trials testing young blood factors for conditions like Alzheimer's and Parkinson's disease.
The conversation explores how different organs age at varying rates and how blood protein analysis can determine specific cellular ages. Wyss-Coray and Huberman also examine lifestyle factors that may affect longevity, including exercise's role in producing beneficial compounds and the potential impact of breathing practices. The discussion covers both current research findings and practical applications for maintaining vitality as we age.
This is a preview of the Shortform summary of the Feb 23, 2026 episode of the Huberman Lab
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1-Page Summary
Factors in Young Blood That May Reverse Aging
Tony Wyss-Coray and his colleagues explore how proteins in blood might influence cellular function and aging processes, focusing on the potential rejuvenating effects of young blood.
Young Blood's Impact on Aging
Through parabiosis experiments, Wyss-Coray and Saul Villada demonstrated that exchanging blood between young and old mice led to significant rejuvenation effects. The researchers found that young blood reactivated stem cells, reduced inflammation, and improved memory function in older mice. Tom Randle's model showed that old muscle tissue could appear nearly young again after exposure to young blood.
Building on these findings, Wyss-Coray's company, Alkahest, began testing young blood factors in human trials for conditions like Alzheimer's and Parkinson's disease. While proteins like GDF11 and IGF-1 showed promise, researchers emphasize the need for careful clinical trials to ensure safety and efficacy.
Organ-Specific Aging Rates and Biomarkers
Wyss-Coray explains that different organs age at varying rates, with some remaining stable before sudden decline while others deteriorate gradually. His company, Vero Biosciences, uses advanced biotechnology to profile organ ages through blood protein analysis, measuring thousands of proteins to determine specific cellular ages.
According to Huberman and Wyss-Coray, the gap between an organ's biological and chronological age can predict disease risk. For instance, rapidly aging hearts might indicate increased risk of heart disease, while faster-aging brains could suggest higher Alzheimer's risk.
Lifestyle Interventions for Vitality and Longevity
The researchers discuss various lifestyle factors affecting health and longevity. Wyss-Coray highlights John Long's research on LAC-V, a modified amino acid produced during intense exercise that may offer unique benefits. Huberman emphasizes the importance of voluntary exercise, noting that forced physical activity can lead to negative psychological impacts.
The discussion extends to other lifestyle factors, including breathing practices, diet, and social connections. Huberman points out the potential benefits of deliberate breathing techniques from practices like Qigong and Tai Chi, while both researchers stress the importance of personalized interventions based on individual needs and data.
1-Page Summary
Additional Materials
Clarifications
- Parabiosis is a scientific technique where two living animals are surgically joined to share a common circulatory system. This allows blood and its components to flow between the animals, enabling researchers to study the effects of blood factors on aging and disease. The process involves careful surgery and post-operative care to ensure both animals survive and function normally. It helps identify how substances in young blood might rejuvenate older tissues.
- Stem cells are special cells that can develop into many different cell types and have the ability to self-renew. They play a key role in repairing and regenerating tissues throughout life. As we age, stem cell function declines, reducing the body's ability to heal and maintain organs. Rejuvenation aims to restore stem cell activity to improve tissue repair and slow aging effects.
- GDF11 is a protein involved in regulating cell growth and development, shown to potentially reverse age-related decline in tissues. IGF-1 (Insulin-like Growth Factor 1) promotes cell growth and survival, playing a key role in muscle repair and brain function. Both proteins are studied for their ability to rejuvenate aging cells and improve tissue regeneration. Their exact mechanisms and safety in humans remain under investigation.
- Blood protein analysis measures specific proteins whose levels change predictably with aging in different organs. These proteins serve as biomarkers reflecting cellular health, damage, or regenerative capacity. By comparing protein patterns to known age-related profiles, scientists estimate an organ's biological age. This method provides a non-invasive way to assess organ function and disease risk.
- Chronological age is the actual time a person has been alive, measured in years. Biological age reflects how well or poorly their body and organs are functioning compared to typical age-related norms. It is influenced by genetics, lifestyle, and environmental factors. Biological age can be younger or older than chronological age, indicating better or worse health status.
- Modified amino acids like LAC-V are amino acids that have been chemically altered after being produced in the body, often changing their function or activity. These modifications can enhance their stability, signaling ability, or interaction with other molecules, influencing biological processes. LAC-V, produced during intense exercise, may act as a signaling molecule that promotes cellular repair and vitality. Understanding these modified amino acids helps reveal how exercise benefits aging and health at a molecular level.
- Voluntary exercise is chosen freely, which enhances motivation and enjoyment, leading to positive mental health effects. Forced exercise, imposed without personal choice, can cause stress, anxiety, and reduced motivation. This difference affects how the brain's reward and stress systems respond, influencing overall psychological well-being. Therefore, voluntary exercise is more likely to promote lasting mental and physical health benefits.
- Deliberate breathing techniques in Qigong and Tai Chi regulate the autonomic nervous system, reducing stress and promoting relaxation. They improve oxygen exchange and circulation, enhancing cellular function and energy levels. These practices also stimulate the vagus nerve, which supports heart rate variability and immune response. Regular use can lower blood pressure and improve mental focus, contributing to overall vitality.
- Alkahest develops therapies based on proteins found in young blood to treat age-related diseases by targeting cellular aging mechanisms. Vero Biosciences specializes in measuring biological age through blood protein analysis to provide personalized health insights. Both companies use biotechnology to translate aging research into practical medical applications. Their work bridges basic science and clinical treatments for aging and related conditions.
- Different organs age at different speeds due to genetic, environmental, and lifestyle factors. When an organ ages faster biologically than the person's actual age, it may function less effectively and become more vulnerable to diseases. For example, an older biological heart may have reduced pumping ability, increasing heart disease risk. Measuring organ-specific aging helps identify early signs of disease before symptoms appear.
Counterarguments
- The rejuvenating effects observed in parabiosis experiments with mice may not translate directly to humans due to biological differences between species.
- The long-term effects and potential risks of young blood transfusion as a treatment for aging or age-related diseases in humans are not yet fully understood.
- The ethical implications of using young blood for rejuvenation in humans need to be considered, including the sourcing of such blood and the potential for exploitation.
- The role of proteins like GDF11 and IGF-1 in aging is complex, and their effects may vary depending on the context and individual differences.
- The use of blood protein analysis to determine organ-specific biological age is still an emerging field, and the accuracy and predictive power of such tests may be limited.
- The relationship between biological and chronological age is not fully understood, and other factors besides protein biomarkers may be significant in predicting disease risk.
- While lifestyle factors like exercise and diet are important for health, the specific interventions and their effects can vary widely among individuals, and not all recommendations may be beneficial for everyone.
- The benefits of specific amino acids or breathing techniques may be overstated or require more scientific evidence to support their efficacy and safety.
- Personalized lifestyle interventions require access to advanced biotechnology and data analysis, which may not be available or affordable to all individuals, potentially increasing health disparities.
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Factors in Young Blood That May Reverse Aging
Tony Wyss-Coray and his colleagues delve into how various proteins in blood, changing from young to old individuals, may actively influence cellular and organ function, exploring the rejuvenation process associated with young blood.
Parabiosis Experiments Show Young Blood Factors Rejuvenate Stem Cells, Reduce Inflammation, and Enhance Memory In Aged Mice
Young Blood Rejuvenates Brain and Tissues in Old Mice
Wyss-Coray and Saul Villada conducted parabiosis experiments, where the exchange of blood between young and old mice led to rejuvenation effects. They demonstrated that exercise benefits could be transmitted via blood by injecting non-exercised mice with blood from exercised young mice. The young blood impacted the old mice's brains, reactivating stem cells, reducing inflammation, and boosting activity. This also led to improved memory functions.
Tom Randle's model, which paired an old mouse with a young mouse for blood exchange, resulted in old muscle appearing nearly young again. Effects were observed in the brain's stem cells, inflammation levels, and neuronal electrical activity, ultimately improving memory functions in aged mice. Wyss-Coray refers to increased inflammatory proteins in older mice, which, when neutralized, enhance cognition. The young blood contains factors that not only inhibit detrimental aging factors but also contain active pro-growth factors stimulating cell activity, demonstrating rejuvenation of brain and tissues.
Researchers Test Young Blood Factors On Aging In Mice and Early Alzheimer's and Parkinson's Trials
Factors from young blood are tested in humans with Alzheimer's and Parkinson's. Wyss-Coray’s company, Alkahest, mimicked the rejuvenating effects observed in mice using young human blood. Proteins identified in young blood, such as GDF11 and IGF-1, were tested in clinical trials, showing promise. The experiments with recombinant synthetic clusterin mimicked some rejuvenation effects observed with exercise. The discussion suggests that future research may lead to treatments tailored for different organs, although caution is urged with the unregulated use of substances like GDF11.
Challenges In Translating Young Blood Research To Therapies
Identifying Beneficial Factors in Young Blood and Safely Delivering Them Is Complex
Wyss-Coray discusses the use of CRISPR tools to identify crucial factors in promoting rejuvenation and the complexity of conducting physiological experiments to isolate and test individual factors. The re ...
Here’s what you’ll find in our full summary
Factors in Young Blood That May Reverse Aging
Additional Materials
Clarifications
- Parabiosis is a surgical technique that joins two living animals so they share a common circulatory system. This allows blood and its factors to circulate between both animals continuously. Researchers use it to study how blood-borne molecules from one animal affect the other’s tissues and organs. It helps identify factors in young blood that may influence aging in older animals.
- GDF11 is a protein involved in regulating growth and development, shown to improve muscle and brain function in aging models. IGF-1 (Insulin-like Growth Factor 1) promotes cell growth and survival, playing a key role in tissue repair and regeneration. Clusterin acts as a molecular chaperone, helping to clear damaged proteins and reduce inflammation. These proteins contribute to rejuvenation by supporting cell health and reducing age-related damage.
- Exercise triggers the release of specific proteins and molecules into the bloodstream, known as exercise-induced factors. These factors can influence other cells and organs by promoting repair, reducing inflammation, and enhancing metabolism. When transferred via blood, they carry the beneficial signals of exercise to recipients, even if those recipients did not exercise themselves. This mechanism explains how injecting blood from exercised individuals can mimic exercise benefits in others.
- Stem cells are special cells that can develop into different types of cells and help repair damaged tissues, which declines with age. Inflammation is the body's response to injury or infection, but chronic inflammation can damage tissues and accelerate aging. Neuronal electrical activity refers to the signals neurons use to communicate, essential for brain functions like memory, which often weaken as we age. Improving these factors can help restore tissue function and cognitive abilities in older individuals.
- Therapeutic plasma exchange is a medical procedure that removes a patient’s blood plasma and replaces it with a substitute fluid. This process can eliminate harmful substances like antibodies or inflammatory proteins from the blood. It is used to reset or improve the blood environment, potentially reducing disease symptoms or slowing aging effects. The procedure requires careful monitoring to maintain blood balance and patient safety.
- CRISPR is a gene-editing technology that allows precise changes to DNA sequences. Researchers use CRISPR to turn specific genes on or off in cells to see which ones affect aging or rejuvenation. By editing genes in mice or cells, they can identify proteins or factors that promote youthful functions. This helps isolate key molecules in young blood responsible for anti-aging effects.
- Epigenetic clocks measure biological age by analyzing chemical changes to DNA called methylation patterns. These patterns change predictably as we age, reflecting the functional state of cells and organs. By comparing epigenetic age to chronological age, researchers assess how well organs are aging or responding to treatments. Improvements in epigenetic clock readings suggest slowed or reversed aging processes in organ function.
- Unregulated use of substances like GDF11 can cause unpredictable side effects due to unknown dosing and purity. Stem cell therapies without proper oversight risk immune reactions, tumor formation, or infection. Lack of clinical testing means safety and effectiveness are not guaranteed. Regulatory approval ensures treatments meet strict safety and efficacy standards.
- Synthesizing proteins involves replicating their complex three-dimensional structures accurately, which is technically challenging. Proteins must remain stable and active in the body without triggering immune reaction ...
Counterarguments
- The rejuvenating effects observed in mice may not translate directly to humans due to significant biological differences between species.
- The long-term effects and potential risks of using young blood factors for rejuvenation in humans are not yet fully understood.
- There may be ethical concerns regarding the sourcing of young blood or blood factors for such treatments.
- The cost and accessibility of therapies developed from young blood factors could limit their availability to a wider population.
- There is a risk of oversimplification in attributing aging reversal to a few proteins without considering the complexity of aging as a biological process.
- The placebo effect could contribute to perceived improvements in clinical trials, necessitating more rigorous testing to isolate the true impact of the treatments.
- The focus on young blood factors might divert attention and resources from other promising avenues of aging research and treatment. ...
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Organ-Specific Aging Rates and Biomarkers
Andrew Huberman engages in a discussion on the nuances of organ-specific aging, exploring the idea that various organs and cells within the same organism can age at different rates.
Organs and Cells Age At Different Rates
Research has uncovered a fascinating aspect of our biology: different organs in our body age at varying speeds. Some organs demonstrate remarkable stability over time, then abruptly decline, while others may start deteriorating from early adulthood. Puberty highlights a rapid aging phase that people experience at a bewildering array of different rates.
Protein Biomarkers Estimate Organ "Age"
Tony Wyss-Coray elaborates on the concept of epigenetic clocks, which serve as tools to gauge the biological age of the body or particular organs. Advances in biotechnology now permit the measurement of protein concentrations in just a drop of blood. This capacity means scientists can profile blood to deduce the different ages of organs based on changes in protein levels that correspond with particular tissues such as the brain, lungs, liver, or heart.
Organ Age vs. Chronological Age Predicts Disease Risk
Wyss-Coray details the mission of his company, Vero Biosciences, which focuses on profiling organ ages with the aim to predict which organs will age using a biological signature. By building models that predict cellular aging in the body, and by measuring thousands of proteins, scientists can ascertain specific cellular ages.
Huberman raises the possibility that differing rates of organ aging, distinct from chronological aging, might influence the risk of developing certain diseases. There is an "age gap," the disparity between one's actual age and the biologically estimated age of an organ. This gap is a powerful indicator of prospective disease development in the respective organ. For instance, if an organ like the heart is biologically aging faster than one’s chronological years, there's an increased chance of heart disease. Similarly, kidneys that age rapidly might indicate a higher risk of kidney disease, and a brain that ages faster could suggest a raised risk of Alzheimer's disease. The detection of this accelerated aging process may offer an opportunity for intervention aimed at delaying aging and thus prolonging healthspan.
Mapping Human Proteome Changes in Genetic Diseases
Wyss-Coray talks about his work to study the plasma of individuals with single-gene mutations (monogenic diseases). By comparing their protein profiles with those of healthy individuals and doing this across a broad spectrum of diseases, it's possi ...
Here’s what you’ll find in our full summary
Organ-Specific Aging Rates and Biomarkers
Additional Materials
Clarifications
- Epigenetic clocks measure biological age by analyzing chemical modifications called DNA methylation on specific sites of the genome. These methylation patterns change predictably as cells age, allowing scientists to estimate how "old" a tissue or organ is biologically. Unlike chronological age, epigenetic age reflects cellular health and aging processes influenced by genetics and environment. This method helps identify accelerated aging linked to disease risk.
- Protein biomarkers are specific proteins whose levels change in the body as organs age or experience stress. These proteins can be detected in blood samples, providing clues about the health and biological age of particular organs. Changes in these protein levels reflect cellular processes like inflammation, damage, or repair occurring within the organ. By measuring these biomarkers, scientists can estimate how quickly an organ is aging compared to normal expectations.
- Chronological age is the actual time a person has lived since birth. Biological age reflects the condition and function of their body and organs, which can be younger or older than their chronological age. Biological age is influenced by genetics, lifestyle, environment, and disease. It provides a more accurate measure of health and aging than simply counting years.
- Plasma is the clear, yellowish fluid component of blood that carries cells and proteins throughout the body. It contains thousands of proteins that reflect the health and function of various organs. Protein profiling of plasma involves measuring these proteins to detect changes linked to diseases or aging. This method provides a non-invasive way to monitor organ-specific biological processes.
- Monogenic diseases are disorders caused by mutations in a single gene. These diseases follow clear inheritance patterns, such as dominant or recessive traits. Examples include cystic fibrosis, sickle cell anemia, and Huntington's disease. Studying them helps scientists understand how specific gene changes affect the body.
- The UK Biobank is a large-scale biomedical database containing genetic, health, and lifestyle information from half a million UK participants. A cross-sectional study analyzes data from many individuals at a single point in time to identify patterns and correlations. This approach helps researchers link biological markers, like muscle cell age, to disease risks such as amyotrophic lateral sclerosis. The UK Biobank's extensive data enables powerful statistical analyses to uncover these associations.
- Astrocytes are star-shaped glial cells in the brain that support neurons by maintaining the chemical environment and providing nutrients. They regulate blood flow, repair brain tissue after injury, and help form the blood-brain barrier. Astrocytes also play a key role in modulating synaptic activity and neural communication. Their dysfunction is linked to neurodegenerative diseases like Alzheimer's.
- The proteome is the entire set of proteins produced by an organism or system at a given time. Mapping the proteome involves identifying and measuring all these proteins to understand their functions and interactions. This helps reveal how genetic changes affect protein production and contribute to diseases. It provides a detailed molecular snapshot beyond what genes alone can show.
- Proteins released by organs enter the bloodstream, reflecting the organ's condition. Changes in specific protein levels correlate with cellular processes linked to aging. Scientists identify patterns of these proteins that match aging signatures unique to each organ. Measuring these proteins in blood provides a non-invasive way to estimate organ-specific biological age.
- Healthspan ref ...
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Lifestyle Interventions: Impact on Vitality and Longevity
Lifestyle interventions hold the potential to significantly impact both vitality and longevity. Experts Tony Wyss-Coray, Andrew Huberman, and others dive into the research and experiences that showcase the effects of various lifestyle factors.
Exercise Impacts Health and Lifespan Through Distinct Mechanisms
Wyss-Coray and Huberman discuss the delicate balance between enhancing vitality and extending lifespan, with a special focus on the influence of exercise. They highlight the antagonistic pleiotropy, where certain factors may be beneficial in youth but have adverse impacts as one ages.
Researching Exercise-Induced Factors Like Lac-v For Benefits
Wyss-Coray talks about John Long's research on a modified amino acid called LAC-V, which spikes with extreme bursts of muscle activity. This discovery offers insight into the diverse effects and benefits of different forms of exercise. It also sheds light on exercise-induced factors, such as proteins released from the liver post-exercise that may improve brain function, adding a new layer of understanding to the physiological effects of exercise.
Psychological Impacts of Forced Exercise
Huberman delves into the negative psychological impacts of forced exercise, drawing from a study where rodents experienced long-term stress and memory issues due to mandatory wheel running. Huberman emphasizes the importance of choosing to engage in challenging activities voluntarily. He describes a brain area, the anterior mid-cingulate cortex, which expands as individuals push through challenges in diet and exercise, indicating the benefits of resilience and the importance of intentional exercise for vitality and longevity.
Breathing Practices: Modulating Blood Flow and Brain Health
Huberman discusses the significance of breathing practices, such as those in Qigong and Tai Chi, in enhancing vitality. He cites studies that suggest deliberate deep breathing may improve circulation and oxygen delivery. Moreover, he points out the correlation between mouth breathing in the elderly and cognitive decline, suggesting a potential role of breathing practices in cognitive health as we age.
Lifestyle Factors: Diet, Social Connection, Light Exposure
Wyss-Coray and Huberman note that various lifestyle factors should be optimized according to individual needs for better healthspan. From the importance of ensuring supplements come from reputable sources to the use of platforms like Vero Compass that tailor lifestyle chan ...
Here’s what you’ll find in our full summary
Lifestyle Interventions: Impact on Vitality and Longevity
Additional Materials
Clarifications
- Antagonistic pleiotropy is a biological concept where a single gene or factor has both beneficial and harmful effects at different life stages. It explains why some traits that improve early-life survival or reproduction may cause aging or diseases later. This trade-off is thought to influence the evolution of aging. Understanding it helps clarify why some interventions might boost youth vitality but harm longevity.
- LAC-V is a modified amino acid that increases in the body during intense muscle activity. It acts as a signaling molecule, helping communicate the benefits of exercise to other organs like the brain. This signaling can promote brain health and overall vitality by triggering protective and regenerative processes. Understanding LAC-V helps explain how different exercise types produce distinct health effects.
- Exercise-induced liver-released proteins, often called hepatokines, are signaling molecules produced by the liver in response to physical activity. They enter the bloodstream and communicate with other organs, including the brain, to regulate metabolism and promote health benefits. These proteins can enhance brain function by supporting neuroplasticity and reducing inflammation. Their release links liver activity to systemic improvements in vitality and longevity.
- The anterior mid-cingulate cortex (aMCC) is a part of the brain located in the middle region of the cingulate cortex, which lies above the corpus callosum. It plays a key role in cognitive functions such as decision-making, emotional regulation, and processing pain and effort. The aMCC is involved in motivation and the ability to persist through challenging tasks. Its expansion is linked to increased resilience and improved mental endurance.
- Forced exercise in rodents, such as mandatory wheel running, induces chronic stress, leading to elevated cortisol levels that impair memory and increase anxiety-like behaviors. This stress response differs from voluntary exercise, which typically promotes brain health and resilience. The findings suggest that the psychological context of exercise—whether it is chosen or imposed—critically affects its benefits. In humans, this implies that exercise done under pressure or obligation may harm mental well-being, unlike self-motivated physical activity.
- Breathing practices like Qigong and Tai Chi use slow, deep breaths that increase lung capacity and efficiency. This enhances oxygen uptake by allowing more air to reach the alveoli, where oxygen enters the blood. Improved oxygen levels in the blood boost circulation by supporting heart and vessel function. Additionally, controlled breathing activates the parasympathetic nervous system, reducing stress and promoting better blood flow.
- Mouth breathing can reduce oxygen intake efficiency and disrupt normal carbon dioxide levels, affecting brain function. It often leads to poorer sleep quality, which is linked to cognitive decline. Chronic mouth breathing may also cause inflammation and reduced nitric oxide production, impairing blood flow to the brain. These factors combined can contribute to worsening memory and cognitive abilities in the elderly.
- mTOR (mechanistic Target of Rapamycin) is a protein that regulates cell growth and metabolism in response to nutrients. Reducing mTOR activity through diet, such as fasting or calorie restriction, can promote cellular repair and longevity. High mTOR activity is linked to aging and age-related diseases, so its reduction may help extend healthspan. This makes mTOR a key target in dietary strategies for improving vitality and lifespan.
- Polyphenols are natural compounds found in plants that have antioxidant properties, helping to protect cells from damage. In chocolate, especially dark chocolate, polyphenols can improve heart health by enhancing blood flow and reducing inflammation. They may also support brain function by promoting better circulation and reducing oxidative stress. The health benefits depend on the chocolate's cocoa content and processing methods.
- Vero Compass is a digital platform that uses personal health data to create customized lifestyle plans. It integrates information like genetics, biomarkers, and habits to recommend targeted interventions. This personalization helps optimize diet, e ...
Counterarguments
- While exercise is generally beneficial, the relationship between exercise intensity and longevity is complex, and extreme exercise may not always lead to increased lifespan.
- The concept of antagonistic pleiotropy is still a theory and may not fully explain the complex relationship between factors that are beneficial in youth and harmful in old age.
- The benefits of LAC-V and other exercise-induced factors need more research to fully understand their roles and potential side effects.
- The psychological impacts of forced exercise may vary among individuals, and some may respond positively to structured exercise programs.
- The expansion of the anterior mid-cingulate cortex as a result of pushing through challenges is an interesting finding, but its direct link to vitality and longevity requires further investigation.
- Breathing practices may have health benefits, but their efficacy can vary widely among individuals, and they are not a substitute for medical treatment.
- The correlation between mouth breathing and cognitive decline does not necessarily imply causation, and other factors may contribute to cognitive health in the elderly.
- Personalized lifestyle interventions are promising, but access to such personalized services may be limited by socioeconomic factors.
- The role of medical interventions like antibiotics in longevity is complex, and overuse can lead to antibiotic resistance, which is a significant public health concern.
- While sunlight exposure has benefits, excessive exposure can increase the risk of skin cancer, and the relationship between sunlight and mental health is n ...
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