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Protein Intake featured article

Protein is one of nutrition's most essential and debated topics. It goes far beyond its reputation as the building block of muscle, playing a crucial role in metabolism, insulin sensitivity, and the prevention of diseases like type 2 diabetes and sarcopenia. But questions abound: How much protein is enough, and can too much, particularly from animal sources, be harmful?

Protein intake, paired with resistance training, drives muscle repair and growth, enhancing athletic performance, improving metabolic health, and promoting longevity by protecting against age-related frailty. Research suggests that higher protein intakes—ranging from 1.2 to 1.6 grams per kilogram of body weight—are more beneficial than the standard RDA of 0.8 grams, with even higher amounts being optimal for body recomposition.

Despite concerns about the links between high-protein diets and health risks like cancer, heart disease, or kidney dysfunction, lifestyle factors such as physical activity...

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Dr. Andy Galpin: The Optimal Diet, Supplement, & Recovery Protocol for Peak Performance

Posted on April 22nd 2025 (about 2 months)

Dr. Andy Galpin & Dr. Rhonda Patrick discuss nutrition, supplement, and recovery strategies for improving exercise performance.

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Q&A #67 with Dr. Rhonda Patrick (2/8/25)

Posted on February 18th 2025 (4 months)

Dr. Rhonda Patrick discusses microdosing nicotine, GlyNac benefits, intermittent fasting and hair loss, and cold & flu relief.

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8 Takeaways on Protein Intake From Rhonda Patrick

Posted on January 22nd 2025 (5 months)

In this clip, Dr. Rhonda Patrick shares practical insights on protein intake, including timing, distribution, plant vs. animal sources, and health impacts.

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  • Protein Intake

    Protein intake supplies amino acids that drive endogenous protein synthesis, modulating nitrogen balance, muscle repair, and overall proteostasis.

News & Publications

  • Regular infrared sauna use increases blood vessel density in aged muscles by 33%, though muscle size, strength, and protein synthesis remain unchanged. pubmed.ncbi.nlm.nih.gov
    Aging Heat Stress Muscle Sauna Protein

    Scientists have speculated that regular heat exposure, such as that experienced in a sauna, might help aging muscles adapt in ways that preserve strength and mass. A recent study found that older adults who engaged in infrared sauna sessions regularly experienced a 33% increase in the number of small blood vessels surrounding their muscle fibers.

    Researchers asked 14 healthy older adults (65 to 85 years old) to sit in an infrared sauna (60°C, 140°F) for 45 minutes, three times weekly, for eight weeks. They collected muscle biopsies before and after the heat exposure to measure capillarization—the number of capillaries around each muscle fiber—as well as muscle size. They also tracked muscle protein synthesis using amino acid infusions and ultrasound imaging to assess how well blood flowed through muscle tissue after eating. Finally, they measured leg strength using a one-repetition maximum test.

    After eight weeks of heat therapy, participants had 31% to 33% more capillaries surrounding both type I and type II muscle fibers. However, muscle blood flow, protein synthesis rates, leg strength, and muscle size did not improve. Body weight, body composition, and walking speed also stayed the same. The only physical performance measure that improved was handgrip strength, which increased slightly. Interestingly, systolic blood pressure dropped by 2%, while diastolic pressure and resting heart rate were unchanged.

    These findings suggest that passive heat treatment can increase blood vessel density in older muscle tissue, but this change alone doesn’t improve nutrient delivery, muscle building, or strength. Heat exposure might support muscle health in other ways, but it doesn’t appear to be a replacement for resistance or aerobic exercise. Learn more about the benefits of heat exposure in Aliquot #96: Thermal Stress, Part I: The Science Behind Heat Stress and its Positive Effects on Health.

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  • Beta-hydroxybutyrate, a ketone used by the brain during fasting or exercise, may help counteract toxic protein buildup in aging and Alzheimer's disease. pmc.ncbi.nlm.nih.gov
    Brain Alzheimer's Diet Ketosis Dementia Protein Ketogenic Diet

    Protein misfolding in the brain is a central player in both aging and Alzheimer’s disease, driving toxic protein buildup and brain cell dysfunction. However, evidence indicates that ketones—a critical brain fuel produced during fasting or exercise—may help reduce or prevent this damage. A recent cell study found that beta-hydroxybutyrate, a type of ketone, helps protect the brain by targeting toxic proteins for disposal.

    Researchers delivered beta-hydroxybutyrate to brain cells collected from mice and monkeys via an exogenous ketone ester. They examined the cells for changes in protein solubility and pathways involved in protein breakdown. They also studied beta-hydroxybutyrate’s effects on pathological proteins, such as amyloid-beta, in a nematode model of Alzheimer’s disease.

    They found that beta-hydroxybutyrate made pathological proteins insoluble, preventing their toxic spread while promoting their clearance through autophagy, the cell’s natural recycling process. This effect was specific to pathological proteins and wasn’t the result of changes in acidity or random chemical interactions. Beta-hydroxybutyrate also reduced amyloid-beta toxicity in nematodes.

    These findings suggest that a ketone ester of beta-hydroxybutyrate counteracts the toxic buildup of proteins in aging and Alzheimer’s disease. Further research is needed to translate these results to humans. Learn more about how ketone ester supplementation may improve brain health in this episode featuring Dr. Mark Mattson.

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  • Food antigens, proteins in meat and milk that trigger allergic reactions, activate immune responses that reduce the risk of small intestinal tumors. www.frontiersin.org
    Cancer Diet Immune System Allergies Protein

    Proteins in milk, meat, and other foods can trigger allergic reactions in some people. However, these proteins—called antigens—can also interact with the immune system to suppress small intestinal tumors. A recent study in mice found that food antigens help activate immune responses in the small intestine, potentially reducing the risk of tumors.

    Researchers fed mice genetically prone to developing intestinal tumors—similar to the genetic predisposition to familial adenomatous polyposis in humans—an antigen-free diet to pinpoint the role of food components in immune activation. They also depleted immune tissues in the animals' small intestines called Peyer’s patches to investigate how food antigens trigger immune cells.

    They found that food antigens activate immune cells in Peyer’s patches, suppressing small intestinal tumor formation. This immune response is crucial for maintaining a tumor-suppressive environment in the gut.

    These findings suggest that food antigens help protect against small intestinal tumors in mice by activating immune cells that promote tumor suppression, highlighting their potential as a protective factor in gut health. The microbiome plays a key role in gut health, too. Learn more in this episode featuring Dr. Eran Elinav.

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  • High-protein, low-calorie diets—whether animal or plant-based—lead to an average weight loss of ~18 pounds and improved glucose metabolism in people at risk for type 2 diabetes. dom-pubs.pericles-prod.literatumonline.com
    Diet Obesity Diabetes Muscle Protein Weight Loss

    The global obesity epidemic is driving a marked increase in the incidence of type 2 diabetes, and some experts estimate that by 2024, more than 780 million adults worldwide will develop the disease. A recent study found that high-protein, low-calorie diets promote weight loss and improve cardiometabolic markers in people at risk for type 2 diabetes.

    The study involved 117 adults with either prediabetes or type 2 diabetes and a body mass index (BMI) over 27.5—considered overweight or obese. Participants consumed an animal- or plant-based high-protein diet that provided 35% of their total calories for six months. The remainder of their calories came from fat (30%) and carbohydrates (35%).

    Participants in both groups saw similar improvements in body composition, including an average weight loss of approximately 8 kilograms (~18 pounds) and reduced visceral (abdominal) fat. Glucose metabolism indicators, such as fasting glucose and glycated hemoglobin levels, improved equally in both groups, as did lipid levels, liver enzymes, and inflammatory markers.

    These findings suggest that high-protein, low-calorie diets—whether animal- or plant-based—can improve body composition, glucose metabolism, and other cardiometabolic markers in people with prediabetes or type 2 diabetes.

    Dietary protein supports muscle hypertrophy and maintenance—critical aspects of glucose metabolism. Learn how to optimize protein intake to support muscle health when following a plant-based diet in this clip featuring Dr. Luc van Loon.

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  • Vegans show prolonged side effects and slower healing following photodynamic therapy, demonstrating diet's influence on therapeutic outcomes. www.tandfonline.com
    Nutrition Cancer Diet Vegetarian Protein Red Light Therapy

    Photodynamic therapy is a widely used treatment for actinic keratoses—rough, scaly patches on the skin that may develop into cancer if not treated. Typically, complete skin healing after photodynamic therapy takes between five and ten days, but a recent study found that healing rates differ markedly between vegans and omnivores.

    The study involved 60 patients (30 omnivores and 30 vegans) who were treated with photodynamic therapy for actinic keratosis. Researchers compared side effects using a local skin response score at three intervals: three days, seven days, and 30 days post-treatment. They also noted the time required for complete skin healing in both groups.

    They found that vegans experienced higher total local skin response scores at each interval, indicating they had more severe side effects. On day three, vegans had considerably more swelling and blistering than omnivores. By day seven, they had more redness, peeling, swelling, and blistering. At thirty days, redness and peeling were still more noticeable in vegans. The time required for complete skin healing was notably longer for the vegan group.

    These findings suggest that diet influences healing time following photodynamic therapy, with vegans being more prone to prolonged side effects and slower healing.

    Photodynamic therapy involves the use of a photosensitizing agent (a drug that becomes activated by light) and a specific wavelength of light. When the photosensitizer is exposed to this light, it produces reactive oxygen species that can destroy targeted cells. It differs from photobiomodulation—often called red-light therapy—which uses low-intensity light to stimulate cellular processes and promote healing and pain relief. Learn more about photobiomodulation in our overview article.

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  • Individualized responses to macronutrients influence metabolic health, with consequences for people with type 2 diabetes. www.sciencedaily.com
    Diet Diabetes Fat Insulin Protein Carbohydrates

    Carbohydrates are the principal driver of insulin secretion, facilitating the uptake and metabolism of this macronutrient. However, a recent study found that fats and proteins also stimulate insulin secretion, potentially affecting people with type 2 diabetes.

    Researchers collected pancreatic islet cells responsible for insulin secretion from 140 donors after their deaths. About half of the donors had type 2 diabetes. They exposed the cells to carbohydrates, fats, and proteins and assessed insulin secretion.

    They found that most donors' islet cells exhibited a robust insulin response to carbohydrates, a moderate response to protein, and a low response to fat. However, some donors' cells elicited responses to protein (9%) and fat (8%) greater than their response to carbohydrates. Cells from donors with type 2 diabetes exhibited diminished responses to carbohydrates and fats, but their protein response was preserved.

    These findings suggest that insulin responses to macronutrients differ among individuals, with some preferentially responding to proteins and fats over carbohydrates. They also suggest that higher protein diets could benefit people with type 2 diabetes. Some evidence suggests that current guidelines for protein intake are too low, with implications for people more responsive to protein. Learn more about protein requirements in this clip featuring Dr. Stuart Philips.

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  • Older adults improve muscle strength, waist circumference, and cholesterol levels by boosting protein intake and engaging in regular exercise. onlinelibrary.wiley.com
    Nutrition Exercise Diet Aging Muscle Protein

    Maintaining muscle mass as we age requires a comprehensive approach encompassing nutrition and regular physical activity. However, many older adults don’t consume adequate dietary protein and may lead sedentary lives, due to injuries, chronic illnesses, or joint problems. A recent study found that older adults who increased their dietary protein intake and engaged in regular exercise showed marked improvements in multiple health and fitness parameters.

    The study involved 97 older adults (average age, 64) with low dietary protein intake (less than 1 gram per kilogram of body weight daily) who had experienced at least one fall in the past year. Half of the participants received a daily serving of a protein-enriched soup (providing 24 to 30 grams of protein) and engaged in one hour of group exercise (aerobic and resistance) each week for 12 weeks. The other half received nutrition education training at the beginning of the study and maintained their normal activity levels.

    At the end of the study, sedentary participants showed improvements in handgrip strength only. However, the participants who consumed the protein-rich soup and exercised regularly showed improvements in waist circumference, walking distance, lower body strength, functional mobility, handgrip strength, nutritional status, serum triglycerides, HDL cholesterol, and DHEA-S.

    DHEA-S (dehydroepiandrosterone sulfate) is a naturally occurring precursor to estrogen and testosterone. These steroid hormones exert anabolic effects by enhancing the bioavailability of insulin-like growth factor-1 in muscles, facilitating muscle growth and repair.

    These findings suggest that increasing dietary protein and activity levels in older adults improves multiple health and fitness parameters. Interestingly, most of the participants in this study were female. Evidence suggests women typically consume less protein than men. In this clip, Dr. Stuart Phillips provides some insights to help older women get sufficient protein to support muscle health.

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  • Increasing protein intake during breakfast increases muscle mass, particularly in older adults. pubmed.ncbi.nlm.nih.gov
    Nutrition Diet Muscle Protein

    Although exercise is the primary stimulus for maintaining muscle mass and strength, nutritional support is essential, too, especially in the form of dietary protein. However, most people’s protein intake is skewed toward later in the day, with little to no protein at breakfast. A recent review found that older adults with higher protein intake at breakfast had greater muscle mass.

    Researchers reviewed the findings of 15 studies examining associations between protein intake and muscle mass. The various studies included cross-sectional, case-control, cohort, and randomized controlled trials involving primarily older males and females. However, one study included middle-aged females, and one included young males.

    The researchers found that consuming a high-protein breakfast (ranging between 0.27 and 0.53 grams per kilogram bodyweight) increased muscle mass, particularly in older adults. While some of the studies' findings suggested that a high-protein breakfast enhanced muscle strength, the evidence was inconsistent across all studies.

    These findings suggest that increasing protein intake at breakfast supports muscle mass maintenance. The investigators posited that increasing protein intake during breakfast could be a beneficial strategy for supporting muscle health for active adults or those in resistance training. However, individual results may vary, indicating the need for more personalized dietary recommendations. Learn more about the role of dietary protein in building and maintaining muscle in this episode featuring Dr. Stuart Phillips.

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  • A daily protein intake of greater than 1.8 grams per kilogram of body weight likely pays the greatest dividends for promoting muscle protein synthesis in trained women. onlinelibrary.wiley.com
    Exercise Diet Muscle Protein

    Robust evidence supports dietary protein intake to support muscle protein synthesis after resistance training. However, most studies investigating the effects of dietary protein have been conducted in men. A recent study found that a daily protein intake greater than 1.8 grams per kilogram of body weight optimized muscle protein synthesis in trained women.

    Researchers asked 24 young women who regularly engaged in resistance training to engage in two resistance training sessions separated by a four-hour break. After each session, the women consumed 15, 30, or 60 grams of whey protein. These amounts provided the women 1.8, 2.3, and 3.2 grams of protein per kilogram of body weight, respectively. Over 24 hours post-workout, the researchers measured the women’s muscle protein synthesis and blood amino acid levels.

    They found that 15 grams of whey protein had little effect on muscle protein synthesis. However, after consuming 30 or 60 grams of whey protein, the women’s muscle protein synthesis increased, especially in the first eight hours post-workout. Interestingly, there was little difference in muscle protein synthesis between the 30- and 60-gram doses.

    Current dietary guidelines recommend that healthy adults consume 0.8 grams of protein per kilogram of body weight per day. However, this intake level is likely too low for building and maintaining muscle mass. The findings from this study suggest that increasing the recommended amount, ensuring a daily intake of greater than 1.8 grams per kilogram of body weight, will pay the greatest dividends for promoting muscle protein synthesis in trained women. Learn more about the importance of dietary protein in this episode featuring Dr. Stuart Philips.

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  • Resistance training counters the potential harms of a high-protein diet in mice. www.sciencedaily.com
    Exercise Diet Metabolism Protein

    A high-protein diet may increase the risk of heart disease, diabetes, and increased body fat, especially in sedentary people. However, a new study in mice demonstrates that resistance training may counter these effects. Mice that ate a high-protein diet and performed resistance exercises gained muscle – not fat – and were more metabolically healthy than sedentary mice on the same diet.

    Researchers fed one group of mice a low-protein diet (7 percent of total calories) and another a high-protein diet (36 percent of total calories). Half of each group performed resistance exercises three times weekly for three months, while the other half remained sedentary. The researchers then compared various parameters, such as body composition, weight, and metabolic indicators, across the different groups.

    They found that the sedentary mice that ate a high-protein diet gained more fat than those on a low-protein diet. However, mice that ate a high-protein diet but engaged in resistance-based training gained muscle mass but not excess body fat. Interestingly, the high-protein-fed mice gained strength faster but, by the study’s end, did not outperform the low-protein group.

    These findings suggest that resistance training can offset the harmful effects associated with a high-protein diet.

    Current recommendations for protein intake for healthy adults – 0.8 grams per kilogram (0.36 grams per pound) of body weight per day – are likely too low for building and maintaining muscle mass. Doubling the recommended amount, ensuring a daily intake of 1.6 to 1.8 grams per kilogram (0.7 to 0.8 grams per pound) of body weight, will pay the greatest dividends for promoting muscle protein synthesis for non-novices. Learn more about the importance of dietary protein in this episode featuring Dr. Stuart Philips.

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  • High-intensity interval training counteracts muscle protein loss induced by sleep deprivation. www.ncbi.nlm.nih.gov
    Exercise Sleep Muscle Protein Aerobic

    Sleep deprivation profoundly affects the human body, negatively influencing cognitive performance, cardiovascular health, and more. Findings from a 2020 study suggest that sleep deprivation impairs muscle protein synthesis, but exercise counters this effect. People who slept only four hours per night but engaged in high-intensity interval training (HIIT) exhibited muscle protein synthesis comparable to those who slept a full night.

    Researchers assigned 24 healthy young men to one of three five-night sleep protocols: normal sleep (eight hours nightly), sleep restriction (four hours nightly), and sleep restriction with HIIT. Researchers collected muscle biopsies to assess muscle protein synthesis before and after the intervention.

    They found that the group with sleep restriction had lower rates of muscle protein synthesis than those with normal sleep and those who combined sleep restriction with HIIT.

    HIIT is a time-efficient strategy to promote cardiovascular fitness and metabolic health. Its flexibility accommodates a wide range of exercises, including walking, running, cycling, and even resistance training, making it accessible to people of different fitness levels and abilities.

    This was a small study, but the findings suggest that sleep restriction reduces muscle protein synthesis, potentially contributing to muscle loss. However, engaging in HIIT during periods of sleep restriction helps maintain muscle protein synthesis, potentially counteracting the adverse effects of sleep loss on muscle mass. Learn more about the benefits of HIIT in this episode featuring Dr. Martin Gibala

    Former FMF guest Dr. Stuart Phillips was a collaborator and participant in this study. Learn more about Dr. Phillips' research in this episode.

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  • Higher protein intake may bolster mood in teens. www.psypost.org
    Diet Depression Development Protein

    According to a new study in teens, higher dietary protein intake improves mood. Adolescent athletes who ate more protein in their diets experienced fewer symptoms of depression.

    The study involved 97 adolescent athletes who reported their depressive symptoms before and after a span of 10 months. About three months into the study period, they completed a three-day diary of their typical dietary intake.

    The food diaries revealed that, in general, the teens ate fewer healthy fats and carbohydrates than recommended, but more sugar than recommended. Their dietary protein intake met recommendations but was typically lower among females than males. Teens that ate higher amounts of protein were less likely to report depressive symptoms than those with lower intake.

    Dietary protein is essential for human health. It provides the building blocks for many biological components, including neurotransmitters in the brain, which play crucial roles in mood, sleep, appetite, and other physiological processes. Although this study did not assess the teens' athletic performance, it’s important to note that protein supports muscle growth and maintenance, ultimately influencing aspects of performance. Learn more about the importance of dietary protein in this episode featuring Dr. Philip Stuart.

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  • Study shows that high protein does not affect kidney function across a wide variety of metrics. journals.humankinetics.com
    Muscle Protein

    “We’ve got 40 years’ worth of data with people on [protein supplementation] now. And we’re not seeing some sort of rife wave of people who used it getting various forms of cancer, etc., which you would expect. Forty years is enough to see the effect.” - Stuart Phillips, Ph.D. on high protein supplementation

    High protein intake is often believed to be harmful to kidney function, but robust evidence indicates that this concern is unfounded. A 2000 study demonstrated that athletes with high protein consumption do not have an increased risk for kidney dysfunction.

    Researchers asked bodybuilders and other athletes to keep detailed dietary records for one week after following their normal dietary patterns for one month. Then the researchers assessed the participants' kidney function via blood tests and urinalysis. They also measured their nitrogen balance – an assessment of the net balance of protein metabolism in the body drawn from estimates of nitrogen losses that occur via urine, feces, sweat, and other means.

    They found that, on average, daily protein intake was approximately 1.97 grams per kilogram of body weight among the bodybuilders and 1.35 grams per kilogram of body weight among the other athletes. Despite their high protein intake, the participants' urinary output of creatinine, urea, and albumin was normal, as were other kidney health parameters. Both the bodybuilders and the other athletes achieved nitrogen balance when their daily protein intake exceeded 1.26 grams per kilogram of body weight.

    The current recommended dietary allowance for protein intake is 0.8 grams per kilogram of body weight (~0.36 grams per pound) per day – about 68 grams for a 150-pound adult. Nutrition experts established this guideline several decades ago, based on evidence from nitrogen balance studies, which are often inaccurate due to problems with collection and overestimation of losses. Based on findings from more recent stable isotope studies, which more accurately assess muscle protein anabolism and catabolism, evidence suggests that eating 1.2 to 1.6 grams of protein per kilogram of body weight is likely optimal for muscle protein synthesis, especially as one ages. Learn more in this episode featuring Dr. Stuart Phillips.

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  • Higher protein intake reduces the risk of hip fracture in women. www.clinicalnutritionjournal.com
    Aging Protein

    For every 25 grams of protein consumed per day – about the amount in a four-ounce serving of fish – the risk of hip fracture in underweight women drops by nearly half, a recent study has found. Drinking tea or coffee reduces the risk of hip fracture, too.

    Researchers tracked the health of more than 26,000 middle-aged women for about 22 years. The women provided information about the types and quantities of foods they ate on a regular basis.

    The researchers found that for every 25 grams of protein consumed per day, the women’s risk of experiencing a hip fracture decreased by 14 percent. However, when the researchers separated the women according to whether they were underweight, healthy weight, or overweight, they found that for every 25 grams of protein consumed per day, the risk of hip fracture for a woman who was underweight decreased by 45 percent.

    Other dietary components influenced hip fracture risk, too. For example, for every additional cup of tea or coffee the women consumed, their risk decreased by 4 percent. And although calcium and vitamin D play important roles in bone health, their consumption reduced hip fracture risk only in women who were underweight.

    These findings suggest that dietary protein protects against hip fractures, especially in women who are underweight. Learn more about the importance of dietary protein in this episode featuring Dr. Stuart Phillips.

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  • Higher protein intake reduces the risk of hip fracture in women.
    Aging Protein

    For every 25 grams of protein consumed per day – about the amount in a four-ounce serving of fish – the risk of hip fracture in underweight women drops by nearly half, a recent study has found. Drinking tea or coffee reduces the risk of hip fracture, too.

    Researchers tracked the health of more than 26,000 middle-aged women for about 22 years. The women provided information about the types and quantities of foods they ate on a regular basis.

    The researchers found that for every 25 grams of protein consumed per day, the women’s risk of experiencing a hip fracture decreased by 14 percent. However, when the researchers separated the women according to whether they were underweight, healthy weight, or overweight, they found that for every 25 grams of protein consumed per day, the risk of hip fracture for a woman who was underweight decreased by 45 percent.

    Other dietary components influenced hip fracture risk, too. For example, for every additional cup of tea or coffee the women consumed, their risk decreased by 4 percent. And although calcium and vitamin D play important roles in bone health, their consumption reduced hip fracture risk only in women who were underweight.

    These findings suggest that dietary protein protects against hip fractures, especially in women who are underweight. Learn more about the importance of dietary protein in this episode featuring Dr. Stuart Phillips.

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  • NIH clinical trial of investigational vaccine for COVID-19 begins. www.nih.gov
    Virus Protein COVID-19

    At the time of this writing, the worldwide death toll from COVID-19 has exceeded 10,000 people. As spread of the disease escalates, a phase 1 clinical trial of an investigational vaccine using an RNA vaccine has begun in Seattle, Washington.

    Conventional vaccines typically employ antigens – inactivated disease-promoting organisms or proteins produced by a virus or bacterium. Antigens mimic the infectious agent to provoke an immune response and provide immunity from future exposures.

    RNA vaccines, on the other hand, utilize a messenger RNA (mRNA) strand that codes for a disease-specific antigen. The vaccine delivers the mRNA strand to the body’s cells, where the genetic information is used to produce the antigen. Similar to the conventional vaccine-derived antigen, these cell-derived antigens drive an immune response.

    The phase 1 clinical trial involves approximately 45 healthy men and women between the ages of 18 and 55 years. The study participants will be enrolled into one of three cohorts to receive either a 25 microgram (mcg), 100 mcg, or 250 mcg dose, via intramuscular injection in their upper arm. A repeat dose will be given four weeks later. The patients will be monitored via follow-up visits after the vaccinations to gauge the vaccine’s safety and effectiveness.

    The mRNA vaccine used in this trial, known as mRNA-1273, has shown promise in animal studies, but this is the first trial to test it in humans. Enrollment has already begun for the trial. If you live in the Seattle area and would like to participate, read this information.

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  • US military scientists working to develop a therapeutic strategy against SARS-CoV-2. www.defenseone.com
    Immune System Protein COVID-19

    There are currently no vaccines to prevent infection with SARS-CoV-2, the virus that causes COVID-19. Although at least one clinical trial of an investigational vaccine is currently underway, the release of such a vaccine could take months or even years. Scientists at DARPA, the Defense Advanced Research Projects Agency, are working to develop a therapeutic strategy against SARS-CoV-2 using monoclonal antibodies.

    Antibodies are proteins that identify pathogens for destruction by the immune system. They arise from different cell lineages and bind to multiple epitopes – regions on viral proteins to which immune cells bind to drive a targeted immune response. Monoclonal antibodies, on the other hand, are made by identical immune cells cloned from a single, unique parent cell. They bind to a single, specific epitope.

    DARPA’s research is part of the Pandemic Prevention Program, or P3. Their goal is to determine which monoclonal antibodies the body produces when it encounters a particular virus, such as SARS-CoV-2, and then stimulate the body’s production of those antibodies. The process involves sequencing the RNA of B-cells taken from a person who has recovered from a particular pathogen and then producing antibodies against the pathogen. The antibodies can then be injected into a healthy person to promote immunity or injected into a sick person to facilitate recovery.

    This strategy can serve as a sort of stopgap measure until a vaccine is developed. Although identifying and producing these antibodies is a lengthy process, DARPA is working to facilitate discovery and accelerate capacity to produce the antibodies at scale.

    • Read this review of COVID-19 monoclonal antibody research for more information.
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  • Potential targets for immune responses to novel coronavirus have been identified, a crucial step in vaccine development. www.eurekalert.org
    Immune System Virus Protein COVID-19

    Coronaviruses, a genus of the Coronaviridae family, are enveloped viruses with a large positive-strand RNA genome. The recently identified SARS-CoV-2, the cause of the disease known as COVID19, is one of seven coronaviruses known to infect humans. Others include SARS-CoV (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). A team of scientists recently identified several epitopes in the SARS-CoV-2 virus, a crucial step in vaccine development strategies.

    Epitopes are regions on viral proteins that immune cells bind to drive a targeted immune response. Most epitopes are approximately five or six amino acids in length. A typical full-length viral protein sequence may contain many different epitopes to which antibodies can bind.

    The authors of the study drew on data from the Immune Epitope Database as well as Virus Pathogen Resource, a compilation of information about known pathogenic viruses. The team compiled known epitopes from other coronaviruses, mapped the corresponding regions to SARS-CoV-2, and used the information to predict likely epitopes.

    They identified several specific regions in SARS-CoV-2 that have high homology to the SARS virus, indicating that SARS-CoV is the closest related virus to SARS-CoV-2. Specifically targeting these epitopes may generate immunity to related coronaviruses and promote resistance to viral evolution.

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  • Diet-induced thermogenesis is higher after breakfast than after dinner. academic.oup.com
    Obesity Fasting Protein Dairy

    Eating increases the body’s metabolic rate, a phenomenon referred to as diet-induced thermogenesis (also known as the “thermic effect” of food). Diet-induced thermogenesis begins about an hour after eating, peaks about two hours later, and then maintains a steady level for several more hours. Approximately 5 to 15 percent of a person’s daily energy expenditure– an estimate of how many calories a person burns per day – is due to diet-induced thermogenesis.

    A few factors influence the degree of diet-induced thermogenesis, including meal size, macronutrient content (protein versus fat, for example) and environmental temperature. Age and physical activity may also play roles in diet-induced thermogenesis. Findings from a new study suggest that circadian variations in energy expenditure influence diet-induced thermogenesis.

    The randomized, cross-over, laboratory study involved 16 healthy, normal-weight men. Each of the men ate three meals per day in the laboratory for three days and maintained a regular sleep pattern. The authors of the study conducted indirect calorimetry tests to determine the participants' energy expenditure and collected participants' blood samples before and after meals to gauge glucose tolerance. The participants rated their feelings of hunger on a Likert scale.

    Meals consisted of a high-calorie breakfast and low-calorie dinner or the converse – a low-calorie breakfast and a high-calorie dinner. The high-calorie meals provided 69 percent of the participants' calorie needs and the low-calorie meals provided 11 percent. All lunches were identical and provided 20 percent of the participants' calorie needs.

    The indirect calorimetry tests revealed that the participants' diet-induced thermogenesis after breakfast was generally 2.5 times higher than after dinner. The participants' glucose levels were, on average, lower after breakfast than after dinner. Glucose levels were 17 percent higher after eating the low-calorie dinner compared with levels after eating the low-calorie breakfast. The participants reported having greater feelings of hunger, especially for sweet foods, on days when they ate the low-calorie breakfast.

    These findings highlight the role of circadian variation in metabolism and underscore the need for modifying food intake to exploit this variation.

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  • Obesity promotes diversity and virulence of influenza virus. www.eurekalert.org
    Obesity Immune System Protein

    Global estimates indicate that more than half of all adults are either overweight or obese. Obesity carries many health risks because it impairs the body’s immune response and creates a pro-inflammatory environment. In particular, being obese increases the disease severity of influenza infection. A recent study suggests that the impaired immune response commonly exhibited in people who are obese promotes the emergence of more virulent influenza strains.

    Influenza is a highly contagious respiratory infection caused by the influenza virus. More than 20,000 people die every year in the United States from influenza-related complications. Many different influenza viruses exist, and they undergo constant change, necessitating regular changes to influenza vaccines. Some of the changes to the influenza virus are due to the health and nutritional status of infected hosts. For example, diet-induced oxidative stress, micronutrient status, and aging can influence influenza virus virulence.

    The authors of the study serially infected lean and obese mice with the influenza virus to replicate the spread of influenza within the real-world setting. They found that serial infection of obese mice promoted changes in the virus that produced more virulent strains of the virus. The key driver associated with these changes was an impaired interferon response. Interferons are proteins produced by the body’s cells as a defensive response to viruses. This delayed interferon response also occurred in obesity-derived human bronchial epithelial cells.

    These findings suggest that obesity promotes influenza virus diversity and virulence and underscores concerns about the growing obesity problem.

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  • Excess visceral fat promotes inflammation and drives cognitive decline. www.eurekalert.org
    Brain Obesity Depression Neurons Protein Metabolic Syndrome NLRP3 Visceral Fat

    Visceral fat – body fat that is stored in the abdominal cavity in close proximity to important internal organs such as the liver, pancreas, and intestines – plays a central role in the interrelationship between obesity and systemic inflammation. Excess visceral fat, often referred to as central or abdominal obesity, is a strong predictor of age-related cognitive decline. A new study in mice demonstrates that having excess visceral fat may impair cognition by activating the NLRP3 inflammasome and promoting the release of interleukin-1 beta (IL-1β).

    Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. Cryopyrin, also known as NLRP3, is a protein that drives the formation and activation of the NLRP3 inflammasome.

    Interleukin-1 beta is a proinflammatory protein present in many cells. NLRP3 inflammasome-driven release of IL-1β activates microglia, the brain’s resident immune cells. Microglia serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and harm.

    The authors of the study first determined that mice lacking the gene for NLRP3 did not experience visceral fat-induced brain inflammation and cognitive decline. They also determined that when visceral fat from normal, obese mice was transplanted into these mice, they exhibited higher levels of IL-1β in their hippocampus, an area of the brain associated with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation.

    To understand the effects of IL-1β on brain function, the authors of the study fed the mice a high- or low-fat diet for 12 weeks and then assessed the animals' capacity to navigate a water maze. The mice that ate the higher-fat diet experienced greater difficulties negotiating the water maze, compared to those that ate the lower-fat diet. Examination of the animals' brains revealed that the mice that ate the high-fat diet (as well as those that received the fat transplants) had weaker synapses between the neurons involved in learning and memory.

    These findings suggest that chronic inflammation driven by excess visceral fat may contribute to cognitive decline by promoting the release of IL-1β and increasing inflammation. Inflammation drives other aspects of brain dysfunction, including those associated with depression. Watch this clip in which Dr. Charles Raison discusses how a pro-inflammatory environment can contribute to the risk of depression.

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  • Adherence to the Mediterranean diet for one year promotes gut bacteria linked to healthy aging in older adults. www.sciencedaily.com
    Diet Aging Saturated Fat Vitamin A Protein Metabolic Syndrome

    Frailty is a syndrome that commonly manifests in older adults. It carries an increased risk for poor health outcomes including falls, disability, hospitalization, and death. A key driver in the development of frailty is inflammation, which often accompanies diet-induced changes in the gut microbiota. Findings from a recent study suggest that eating a Mediterranean diet, which is rich in fruits, vegetables, legumes, fish, and fiber, and low in saturated fat and red meat, alters the gut microbiome in older adults to reduce the risk of frailty.

    The intervention study involved more than 600 older, non-, pre-frail, or frail older adults living throughout Europe. Roughly half of the participants followed a Mediterranean diet for one year, while the other half, which served as the control group, ate their regular diets. Before and after the one-year intervention, the authors of the study profiled the microbial makeup of the participants' gut microbiome. Whereas the microbiome of the participants from the northern European countries shared many similarities, the participants from Italy had a distinct microbiome.

    At the end of the study, the participants who adhered to the Mediterranean diet showed reductions in biomarkers associated with inflammation (such as C-reactive protein and interleukin 17) and improvements in frailty-associated measures (such as handgrip strength, gait speed time, and cognitive function). The authors of the study observed notable changes in the participants' gut microbiomes, which were associated with higher numbers of bacteria that produce short-chain fatty acids – byproducts of dietary fiber metabolism that reduce gut inflammation.

    These findings suggest that dietary interventions that promote adherence to a Mediterranean diet may be beneficial in reducing the risk of developing frailty among older adults due to changes in gut microbiota and reduced inflammation.

    Interestingly, some of the benefits observed among the participants in this study may be related to their increased intake of essential vitamins and minerals. Without these nutrients, the body has to compensate for the shortages – a concept known as “triaging.” Long-term compensation contributes to aging. Watch this clip in which Dr. Bruce Ames explains this phenomenon in what he calls his triage theory.

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  • Dietary olive oil may improve healthspan and delay aging by switching on the activity of sirtuins. www.sciencedaily.com
    Aging Insulin Monounsaturated Fat Protein

    Olive oil, the principal fat consumed in the Mediterranean diet, is widely consumed for its flavor, versatility, and health-promoting attributes. A recent study demonstrates that the monounsaturated fats (MUFAs) in olive oil may extend lifespan by switching on the activity of key cellular proteins called sirtuins.

    Monounsaturated fats are dietary fats found in plant foods, such as nuts, avocados, and vegetable oils, especially olive oil, which contains approximately 75 percent of the MUFA known as oleic acid. The body stores MUFAs in lipid droplets – intracellular fat storage depots that facilitate the movement and signaling activities of fatty acids. During times of increased energy demand (such as during exercise) or decreased energy supply (such as during fasting), the fatty acids stored in lipid droplets can be released for the body’s use.

    Sirtuins are highly conserved enzymes that play key roles in healthspan and longevity in multiple organisms. Sirtuin 1 (SIRT1) is linked to the regulation of a variety of metabolic processes, including the release of insulin, mobilization of lipids, response to stress, and modulation of lifespan.

    The authors of the study first investigated the role of perilipin 5 (PLIN5), a protein found in lipid droplets that regulates fatty acid oxidation in oxidative tissues. They found that PLIN5 binds to lipid droplet MUFAs and delivers them to the cell nucleus, where they modulate the activity of SIRT1.

    Then they studied the effects of MUFA consumption in mice. They fed the mice a control diet rich in lard and soybean oil or a diet rich in olive oil for 12 weeks. The mice that ate the olive oil-rich diet lost weight and had higher energy expenditure than mice fed the control diet. These effects were attributed to activation of SIRT1.

    These findings suggest that the health-promoting benefits associated with the Mediterranean diet may be attributable to the diet’s high olive oil content. In addition, olive oil as part of a healthy eating pattern such as the Mediterranean diet may increase healthspan and longevity.

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  • Weight loss and health improvements with Mediterranean, intermittent fasting, and Paleo diets www.sciencedaily.com
    Diet Blood Pressure Protein Dairy Blood Sugar Weight Loss

    Roughly two-thirds of all adults living in the United States are overweight or obese. Losing weight presents many challenges, however, and popular weight-loss diets and dietary patterns are not always successful or sustainable. A recent study found that people who followed an intermittent fasting, Mediterranean, or Paleo diet lost weight and showed improvements in health, but adherence to the diets varied.

    Intermittent fasting is a broad term that describes periods of fasting between meals that can last several hours to days. Intermittent fasting increases the production of ketones due to the use of stored fat as an energy source. It also activates some of the same genetic pathways as caloric restriction. The authors of this study defined intermittent fasting as 25 percent of the participants' usual dietary intake two days per week.

    The Mediterranean diet is a dietary pattern thought to confer health benefits found traditionally in Mediterranean countries. It is characterized by high consumption of vegetables, olive oil, and dairy products and moderate consumption of protein. The Paleo diet is based mainly on foods presumed to be available to Paleolithic humans. It includes vegetables, fruits, nuts, roots, meat, and organ meats and excludes dairy products, grains, refined sugar, legumes, and other processed foods. The authors of this study modified the typical Paleo plan to include limited consumption of dairy, legumes, and grains.

    The study mimicked “real world” dieting strategies in that each participant could choose which of the three dietary patterns they would follow for 12 months. In addition, they received no nutritional counseling other than a single, 30-minute session in which they learned about their self-selected diet. The authors of the study collected information about the participants' dietary intake, body weight and composition, blood pressure, physical activity, and various blood biomarkers, including glycated hemoglobin, a measure of long-term blood glucose control (also known as HbA1c).

    Approximately 54 percent of the participants chose to follow the intermittent fasting diet, 27 percent chose the Mediterranean diet, and 18 percent chose the Paleo diet. At the end of the 12-month study period, adherence to the three diet plans was 54 percent for intermittent fasting, 57 percent for the Mediterranean, and 35 percent for Paleo.

    Study participants lost weight with all three plans, but those who practiced intermittent fasting lost more (4 kg) than those who followed the Mediterranean (2.8 kg) or Paleo diets (1.8 kg). Those who followed the intermittent fasting and Mediterranean diet plans showed reductions in blood pressure (4.9 mm Hg and 5.9 mm Hg, respectively). Those who followed the Mediterranean diet experienced a 0.8 mmol/mol reduction in HbA1c.

    These findings suggest that people can lose weight and improve health while following different dietary patterns as long as those patterns include healthful foods and are personally sustainable.

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  • Sauna use reduces pneumonia risk in healthy, middle-aged men. www.telegraph.co.uk
    Immune System Sauna Protein

    Sauna use promotes mild hyperthermia, which, in turn, induces a wide array of physiological responses. These responses reduce oxidative stress and inflammation and activate cellular defense systems that provide protection against many diseases. Data from a 2017 study suggest that sauna use reduces the risk of developing certain chronic or acute respiratory illnesses, including pneumonia.

    Pneumonia is an acute respiratory illness characterized by cough, fever, chills, and difficulty breathing. It is a common complication of influenza and other viral infections (including the newly emerging coronaviruses) as well as bacterial infections. Pneumonia affects people of all ages, but children, older adults, and people who are immunocompromised are most vulnerable.

    The study, which drew on data from a population-based prospective cohort study of more than 2,000 healthy middle-aged men (42 to 65 years old), was conducted in Finland, where most people have a home sauna. The average sauna exposure reported in the study was approximately 20 minutes per session at 79°C (174°F).

    The data were adjusted for body mass index, smoking status, education level, alcohol consumption, total energy intake, socioeconomic status, physical activity, inflammatory status (measured by C-reactive protein), and history of diabetes, heart disease, asthma, bronchitis or tuberculosis. They revealed that the frequency of sauna use was inversely associated with the incidence of respiratory illness, especially pneumonia. Men who used the sauna two to three times weekly were 27 percent less likely to develop pneumonia than those who used the sauna once weekly or not at all. Men who used the sauna four to seven times weekly were 41 percent less likely to develop pneumonia compared to infrequent or non-users.

    The authors of the study suggested that sauna’s protective effects may be due to reduced oxidative stress associated with hyperthermia or direct beneficial effects on lung tissue.

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  • Increasing stem cell populations improves learning and memory in old mice. tu-dresden.de
    Neurons Protein

    As we age, our ability to learn things and form new memories decreases. Navigation, which incorporates multiple cognitive processes including memory, attention, and our perception of direction and distance, becomes particularly difficult with aging. Findings from a recent study suggest that increasing adult neurogenesis may improve navigation capacity in older mice.

    Neurogenesis is the process of forming new neurons. It is essential during embryonic development, but also continues in certain brain regions throughout human lifespan to facilitate learning and memory formation.

    The study authors increased the expression of Cdk4/cyclinD1, a multi-protein complex that governs the cell cycle and its progression, in neural stem and progenitor cells (NSC) to enhance both their cell cycle activity and proliferation in mice. This increased neurogenesis in the animals' brains and improved their ability to perform navigation skills.

    These findings suggest that age-related cognitive impairments may be reversed in old age by tapping into the brain’s neurogenic processes.

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  • Fish oil supplementation provides protection against fine particulate air pollution www.onlinejacc.org
    Omega-3 Glutathione Protein Dairy

    An estimated 4.2 million deaths each year, many of which are cardiovascular disease-related, are associated with exposure to air pollution. The mechanisms that drive this association include systemic inflammation, endothelial dysfunction, oxidative stress, hypertension, and metabolic dysfunction. Findings from a recent study suggest that supplemental omega-3 fatty acids may reduce the risk of cardiovascular disease-related death associated with exposure to particulate air pollutants.

    Particulate matter in air pollution is a mixture of solid particles and liquid droplets. It is present in fine inhalable particles, with diameters that are generally 2.5 micrograms (PM2.5) or less. The daily standard for PM2.5 in the United States is 35 micrograms per cubic millimeter per day, as long as the average annual exposure is less than 12 micrograms per cubic millimeter daily.

    Omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are derived from marine sources, elicit a wide array of health benefits. The American Heart Association recommends that people who have coronary heart disease consume approximately 1 gram of DHA and EPA daily in foods or supplemental form.

    The randomized, double-blind study involved 65 healthy students attending Fudan University in Shanghai, China. Participants received either a 2.5-gram EPA- and DHA-rich fish oil supplement or a placebo daily for a period of four months. The authors of the study measured PM2.5 levels throughout the study. They also collected blood samples from the participants to assess levels of 18 cardiovascular disease-related biomarkers.

    The average PM2.5 level during the study period was 38 micrograms per cubic millimeter. Whereas the participants who took the fish oil supplement had biomarker profiles that were cardioprotective, the participants who took the placebo had biomarker profiles associated with inflammation and cardiovascular disease. In particular, taking the fish oil supplement was associated with having higher levels of glutathione peroxidase (an enzyme that protects against oxidative stress) but the supplement was associated with having higher levels of C-reactive protein (a driver of inflammation).

    These findings suggest that the intake of fish oil supplements rich in EPA and DHA may provide cardiovascular protection to people living in areas of high air pollution.

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  • One night of sleep deprivation in healthy young men caused increased blood levels of tau, a protein that forms tangles in the brain. www.eurekalert.org
    Alzheimer's Sleep Neurons Protein

    Sleep disruption is intrinsically linked with Alzheimer’s disease and its pathophysiology, with characteristic changes in sleep emerging early in life, well before the clinical onset of the disease. A key player in the development of Alzheimer’s disease is amyloid-beta. Insufficient sleep increases the production of amyloid-beta, and amyloid-beta deposition, in turn, impairs sleep in a vicious, self-perpetuating loop. Findings from a new study demonstrate that sleep deprivation also increases blood levels of tau, a protein found in the brain.

    Tau is a microtubule-bound protein that forms the neurofibrillary “tau tangles” associated with Alzheimer’s disease. Tau tangles disrupt the transport of metabolites, lipids, and mitochondria across a neuron to the synapse where neurotransmission occurs. Diminished slow-wave sleep is associated with higher levels of tau in the brain. Elevated tau is a sign of Alzheimer’s disease and has been linked to cognitive decline.

    The two-condition crossover study involved 15 healthy young men who were randomized to regimens of either two nights of consecutive sleep or one night of sleep followed by one night of sleep deprivation. Following the one night of sleep deprivation, participants' blood levels of tau increased approximately 17 percent, compared to an approximately 2 percent increase following the night of sleep. Other biomarkers of Alzheimer’s disease-associated proteins were unchanged. While tau tangle formation in neurons can disrupt normal function, it is unclear what elevated blood levels of tau protein mean. Future studies are needed to elucidate this finding.

    Watch this clip featuring Dr. Matthew Walker in which he describes current research focused on identifying age-related sleep deprivation vulnerability windows for prevention of Alzheimer’s disease.

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  • Decreasing the insulin signaling pathway and the TOR pathway increased lifespan of worms by 500 percent. www.eurekalert.org
    Aging Depression Insulin Protein

    The insulin and insulin-like signaling (IIS) pathways and the target of rapamycin (TOR) pathway are critical elements of the aging process. Findings from a new study suggest that decreasing the activity of these highly conserved pathways markedly increases the lifespan of worms.

    The IIS pathways are involved in maintaining glucose homeostasis. They facilitate the uptake of glucose into fat and muscle cells while inhibiting gluconeogenesis – the production of glucose in the liver. These pathways are dysregulated in obesity and type 2 diabetes.

    The TOR pathway senses amino acid concentrations and regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. It integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids and plays a key role in mammalian metabolism and physiology. The pathway is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers.

    The study focused on altering the activity of orthologs of these pathways (called DAF-2 and RSKS-1) in C. elegans, a type of nematode worm, which is often used in aging studies. The authors of the study introduced double mutations in the worms to block the activities of DAF-2 and RSKS-1 and conducted genome-wide translational state analysis to identify genes associated with the worms' lifespan.

    Knocking DAF-2 and RSK-1 elicited a synergistic effect that increased the lifespan of the worms by 500 percent, suggesting that regulation of these two pathways is integral to the aging process in worms. Watch this clip for learn more about the evidence that altered growth hormone and insulin signaling may improve healthspan in humans, too.

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  • Stressed mitochondria leak DNA fragments that induce inflammation. www.sciencemagazinedigital.org
    Immune System Mitochondria Protein Autoimmunity

    Oxidative stress drives many disease processes. In mitochondria, in particular, it promotes the release of mitochondrial DNA into surrounding cytosol where it can trigger cellular responses involved in autoimmunity.

    A critical aspect of mitochondrial DNA release is the formation of pores created by the oligomerization of specific proteins called voltage-dependent anion channels (VDACs), which are found in the outer mitochondrial membrane. A new study in a mouse model of lupus suggests that inhibition of VDAC oligomerization blocks mitochondrial DNA release, preventing subsequent immune responses.

    These findings suggest that inhibition of VDAC oligomerization may be an alternative therapeutic approach for a wide range of diseases likely associated with mitochondrial DNA release, such as lupus and Parkinson’s disease.

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  • Exercise mitigates muscle mass losses during severe energy deficit by inhibiting the induction of autophagy. www.mdpi.com
    Exercise Fasting Protein

    Severe energy deficit, such as would occur during dieting or prolonged hospitalization, promotes skeletal muscle losses. A recent study demonstrated that exercise mitigates some of these losses by inhibiting the induction of autophagy.

    Autophagy is a highly conserved cellular defense mechanism that sequesters protein aggregates, pathogens, and damaged or dysfunctional organelles into vesicles called autophagosomes and then delivers them for destruction. The primary goal of autophagy is to allow the cell to adapt to changing conditions and external stressors, including energy deficit.

    The study involved 15 overweight or obese men between the ages of 30 and 50 years. In the first phase of the study, the participants ate a very low-calorie diet consisting solely of sucrose or whey protein and engaged in endurance exercise consisting of 45 minutes of arm exercises and eight hours of walking for four days. This diet/exercise protocol created an energy deficit of approximately 5,500 calories per day. In the second phase, they ate a control diet and engaged in limited exercise for three days.

    At the end of each phase, participants provided muscle biopsies for analysis, which revealed that severe energy deficit induced autophagy in skeletal muscle, but endurance exercised inhibited this induction, especially in the lower extremities. Interestingly, dietary intake of protein had little effect in preserving muscle mass.

    The authors of the study proposed that exercise may sensitize the skeletal muscle to the anabolic signals that inhibit autophagy induction during energy deficit. These findings underscore the importance of exercise during dietary restriction, especially during prolonged hospital stays, to prevent or reduce skeletal muscle losses.

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  • More abdominal fat drives loss of fluid intelligence whereas more muscle mass protects against loss. www.sciencedaily.com
    Brain Fat Muscle Protein Intelligence Weight Loss

    Fluid intelligence – the ability to creatively solve problems without prior knowledge or learning – declines with age, often as early as the third decade of life. Evidence from a new study suggests that body composition influences declines in fluid intelligence, and these declines may be related to immune system activation.

    Body composition describes an individual’s body fat and lean mass. Excess body fat promotes systemic inflammation (which can promote neuroinflammation) and drives immune-related inflammatory processes. Lean muscle mass, however, may be protective against inflammation.

    The study involved more than 4,400 middle-aged and older men and women living in the United Kingdom. The participants' body composition, cognitive function, blood leukocytes (white blood cells), and variables such as age, education level, and socioeconomic status were measured every other year for a period of six years.

    The authors of the study found that higher levels of body fat, especially abdominal fat, were associated with greater losses of fluid intelligence. The losses appeared to be related to sex-specific increases in blood leukocyte counts and inflammation, as evidenced by higher levels of C-reactive protein.

    These findings point to the importance of maintaining a healthy body weight throughout life as a strategy to reduce or prevent cognitive decline.

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  • Post-workout ice baths may hinder muscle protein synthesis www.sciencedaily.com
    Muscle Cold Stress Protein

    Post-workout ice baths and increased dietary protein intake have long been used by athletes as strategies to build muscle. Findings from a new study suggest that ice baths may hinder muscle protein synthesis by interfering with dietary protein uptake into muscles.

    The study participants included 12 healthy young men who engaged in a single resistance‐type exercise session and then immersed both their legs in water for 20 minutes. One leg was immersed in cold water (8°C, 46°F) while the other leg was immersed in water that was slightly warmer than room temperature (30°C, 86°F). Afterward, the participants consumed an amino acid-rich beverage.

    The authors of the study monitored the uptake of the amino acids and subsequent muscle protein synthesis for two weeks. Analyses of blood, saliva, and muscle tissue revealed that cold water immersion after resistance‐type exercise reduces muscle protein synthesis, which could impair muscle conditioning.

    Interestingly, an older study found that cold water immersion reduced the risk of cancer and enhanced longevity in mice. The contradictory findings of these two studies suggest that cold exposure may be harmful in certain contexts, but beneficial in others, and that timing of the exposure is critical.

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  • Effects of hyperthermic baths on depression, sleep, and heart rate variability in patients with depressive disorder www.ncbi.nlm.nih.gov
    Depression Heat Stress Antioxidant Protein

    Depression is a mood disorder characterized by profound sadness, cardiovascular dysfunction, altered sleep patterns, and feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. Roughly a third of people who have depression fail to respond to antidepressant drugs. Findings from a clinical trial suggest that hyperthermic baths may reduce some of the symptoms associated with depression.

    Hyperthermia, a state of elevated core body temperature, stresses the body, activating molecular mechanisms that mitigate protein damage and aggregation and activate endogenous antioxidant, repair, and degradation processes. Whole-body hyperthermia is a therapeutic strategy used to treat various medical conditions, including cancer, fibromyalgia, and others. Hyperthermic baths – immersion in very hot water (40°C, 104°F) – offer a means to achieve hyperthermia.

    The randomized two-arm placebo-controlled, eight-week pilot trial involved 36 adults who had moderate depression. Half of the group was randomized to take hyperthermic baths, while the control group received a sham, low-lux green light exposure. Participants received the treatments twice weekly for four weeks.

    The hyperthermic baths involved immersion in 40°C water with the participant’s head out. Participants stayed in the water to the point of discomfort, with a target duration of 30 minutes. These 20 to 30-minute hot water baths typically increased the participants' core body temperature by approximately 1.7°C (3°F). Upon exiting the bath, the participants were wrapped in warm blankets and hot water bottles and kept warm for another 30 minutes.

    At the end of the trial, the participants who received the hyperthermic bath treatment demonstrated clinically significant improvements in measures of depressive symptoms that lasted up to four weeks after the baths were discontinued. They also exhibited improvements in sleep quality. No changes in heart rate variability were noted, however. These findings suggest that hyperthermic baths may be beneficial in treating the symptoms of depression.

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  • Immunization against flagellin provides protection against chronic inflammatory disease in mice presse.inserm.fr
    Inflammation Protein

    A common feature in many chronic inflammatory diseases is dysbiosis – alterations in the type and number of microbes that typically reside in the human gut. Some of these microbes are highly motile due to the presence of flagella, which contributes to the microbes' pathogenic qualities. A new study suggests that immunization against the protein flagellin may confer protection against some chronic inflammatory diseases.

    Flagellins are structural components of the flagella of gram-negative bacteria. Flagella provide bacteria motility, which facilitates penetration of the gut mucosa and drives the activation of pro-inflammatory responses.

    The study involved wild type mice that received weekly peritoneal injections of purified bacterial flagellin for 10 weeks. The injections elicited a robust immune response to the flagellin, manifested in elevated antibody counts that lasted approximately three months after the injections ceased. Furthermore, the gut microbial composition of the mice was changed to a more favorable makeup, and the mice were protected against mucosal penetration, experimentally-induced colitis, and the negative effects of diet-induced obesity.

    These findings suggest that repeated exposure to flagellin proteins immunizes mice against chronic diseases by reducing immune response-related inflammation.

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  • Early epigenetic changes in mice regulate voluntary exercise behavior www.the-scientist.com
    Exercise Epigenetics Protein

    Maintaining a healthy weight requires balancing energy intake with expenditure. A variety of elements influence how physically active we are, including genetic, cultural, and environmental factors. Evidence from a new study suggests that epigenetic changes in agouti-related proteins may regulate voluntary exercise behavior in mice.

    Agouti-related proteins are neuropeptides produced primarily in the hypothalamus. They regulate appetite, metabolism, and energy expenditure.

    Epigenetic changes are biological mechanisms that regulate gene expression (how and when certain genes are turned on or off). DNA methylation – the addition of methyl groups to the nucleotide bases of DNA – is a common epigenetic change. Previous research has shown that DNA methylation influences hypothalamic development in mice at specific time points early in life.

    In this study, transgenic mice that lacked the enzymes that facilitate DNA methylation in agouti-related proteins developed a sedentary phenotype later in life. This was manifested by low energy output in the form of voluntary exercise, with the transgenic mice running roughly half the distance on exercise wheels as their wild type counterparts.

    These findings point to the complexity of identifying ways to motivate people to exercise as a means to regulate body weight.

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  • A compound that blocks a key inflammatory pathway in the brain reverses cognitive decline in mice. news.berkeley.edu
    Aging Protein

    Cognitive decline is a common feature of aging, affecting more than 16 million people living in the United States. Findings from a new study in mice suggest that reducing inflammation in the brain may slow or reverse cognitive decline.

    Chronic inflammation is a key element of the aging process and drives many age-related diseases and conditions. The blood-brain barrier (BBB) is critical to healthy brain function, but chronic, systemic inflammation may cause changes in the BBB, allowing toxic blood-borne molecules to enter the brain. For example, rodent models of traumatic brain injury (TBI) demonstrate that loss of BBB function following TBI allows albumin, a type of protein, to enter the brain. This, in turn, activates the transforming growth factor-beta (TGF-ß) signaling pathway, which drives a pro-inflammatory environment and compromises cognitive function. Roughly two-thirds of all adults over the age of 70 years have some degree of BBB dysfunction.

    The authors of this study measured serum albumin in mice and found that it was detectable in the brains of mice as early as 12 months of age (which corresponds roughly to “middle age”), suggesting that BBB dysfunction occurred much earlier than commonly believed. Then they gave the mice a drug that inhibited the action of the TGF-ß receptor, impairing TGF-ß signaling and reversing the accompanying cognitive dysfunction.

    These findings suggest that reducing inflammation in the brain could serve as a means to restore cognitive function in older adults.

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  • A group of proteins identified in human plasma predicts both chronological and biological age. www.sciencedaily.com
    Aging Protein

    Aging is the primary risk factor for many chronic diseases in humans, including cancer, Alzheimer’s disease, and cardiovascular disease. Individuals age at different rates, however, a phenomenon observed across sexes, ethnic groups, and races. A recent study has identified a group of proteins in human plasma that predicts both chronological and biological age.

    Proteins regulate key cellular pathways. The overall composition of proteins in the body changes with time, reflecting the effects of aging. Blood is the primary vehicle for most of the body’s proteins, and some studies have shown that transfusing the blood of young mice into old mice restores cognitive function to a more youthful phenotype.

    The authors of this study analyzed blood samples from more than 4,300 healthy adults between the ages of 18 and 95 years to quantify proteins involved in signaling, metabolism, and other physiological functions. They found that hundreds of proteins – many of which are associated with age-related diseases – changed at specific times in a person’s life, typically at the ages of 34, 60, and 78 years.

    The proteins that changed varied by sex, emphasizing the importance of including more women in clinical trials. In addition, the findings highlight the dynamic nature of aging and suggest that blood may be a useful tissue for identifying proteins that alter the aging process as a means to develop disease prevention strategies and more targeted treatments.

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  • Mice fed a high-fat, low-carbohydrate diet were better able to combat the flu virus and had better survival rates than mice fed a normal diet. www.sciencedaily.com
    Ketosis Immune System Protein Carbohydrates Weight Loss Ketogenic Diet

    More than 20,000 people die every year in the United States from influenza-related complications. Findings from a new study demonstrate that a ketogenic diet confers protection against the influenza virus and improves survival rates in mice.

    A ketogenic diet is a high fat, moderate protein, low carbohydrate eating pattern that causes the body to oxidize fat to produce ketones for energy. The ketogenic diet has been used in the clinical setting to reduce seizures in children and is being investigated for the treatment of traumatic brain injury, Alzheimer’s disease, weight loss, and cancer.

    The authors of the study fed a ketogenic diet or regular chow to mice for seven days and then infected them with influenza virus. The mice that ate the ketogenic diet lost less weight, maintained better blood oxygen levels, and had improved survival rates compared to the mice that ate the regular chow. In addition, the mice on the ketogenic diet had higher levels of specialized T-cells in their lungs that enhanced airway cell mucus production to improve lung barrier function.

    Interestingly, the beneficial effects of a high fat diet were only observed with the ketogenic diet. Feeding the mice a high-fat, high-carbohydrate diet or providing exogenous ketones in the diet had no beneficial effects against influenza virus.

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  • Inflammation may play a causal role in diminishing certain cognitive functions. www.birmingham.ac.uk
    Brain Inflammation Depression Protein

    Inflammation is a critical element of the body’s immune response that involves the activity of immune cells, cell-signaling proteins, and pro-inflammatory factors. Chronic inflammation, which occurs on the cellular level in response to toxins or other stressors, is implicated in the development of many chronic illnesses, including cancer, cardiovascular disease, and diabetes. Findings from a new study indicate that inflammation may be a factor in the “brain fog” that commonly accompanies chronic illness.

    The double-blinded placebo-controlled study involved 20 young men (average age, 24 years) who were injected with either a typhoid vaccine or saline. The purpose of the vaccine was to induce mild, transient inflammation, which was confirmed by the participants' blood levels of interleukin-6, a pro-inflammatory molecule.

    Six hours after the participants received their injection, three measures of their brain activity – alerting, orienting, and executive control – were assessed via electroencephalogram (EEG). The EEG results indicated that the participants' capacity for staying alert in preparation for a task was diminished post-vaccine but their other brain activities were unaffected. These findings point to a causal link between inflammation and diminished brain function and may explain why people who suffer from chronic disease often complain of difficulty concentrating or carrying out tasks.

    Interestingly, other studies have used methods similar to those used in this study to show that inflammation plays a causal role in depression. To learn more about the role of inflammation in depression, check out the FMF topic page on depression. Read the whole article or skip to the section on inflammation.

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  • Waves of Fluid Bathe the Sleeping Brain, Perhaps to Clear Waste www.the-scientist.com
    Brain Alzheimer's Sleep Neurons Protein

    The glymphatic system – a vast arrangement of cerebrospinal fluid-filled cavities surrounding the small blood vessels in the brain – facilitates the removal of proteins and metabolites from the central nervous system. During sleep, these interstitial spaces increase by more than 60 percent. A new study demonstrates that large quantities of cerebrospinal fluid flow through these spaces in a rhythmic fashion during deep sleep to remove waste.

    The study involved 13 young, healthy men and women whose neuronal activity, blood levels, and cerebrospinal fluid (CSF) flow were measured during sleep. As the study subjects slept, a large wave of CSF flowed through their brains roughly every 20 seconds, preceded by changes in brain neuronal activity and blood flow.

    Poor sleep – which would impair glymphatic function – has been linked to a variety of neurodegenerative diseases. For example, disruption in deep sleep is highly pronounced in people with Alzheimer’s disease and typically precedes diagnosis.

    Glymphatic activation has also been shown to play a key role in the transport of biomarkers of traumatic brain injury (TBI). In particular, cerebrospinal fluid-mediated removal of tau protein in the brain via glymphatic routes is crucial for limiting secondary neuronal damage following traumatic brain injury. Unfortunately, some types of TBI impair glymphatic function and may be one reason why people with TBI are at a higher risk for neurodegenerative diseases.

    Taken together, these data suggest that sleep – especially deep sleep – is not only important for the prevention of Alzheimer’s disease but also may be key in the treatment of TBI.

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  • Infants given formula containing milk fat globule membranes (found in human breast milk) scored better on tests of cognitive, language & motor skills. news.ku.edu
    Pregnancy Protein Breast Milk

    The fatty acids in breast milk are encapsulated in fat globules surrounded by a triple-layered structure called a milk fat globule membrane, or MFGM. The MFGM is interspersed with a variety of proteins, enzymes, and cholesterol that confer many of the antibacterial and anti-inflammatory properties of breast milk – the gold standard of infant nutrition.

    MFGM influences many aspects of infant growth, especially cognitive development. Unfortunately, most infant formulas do not contain MFGM. However, a recent clinical trial found that MFGM from cows' milk exerts similar beneficial effects on human infants when included in infant formula. The double-blind, randomized, controlled trial involved 451 healthy, full-term infants who received either regular formula or formula containing MFGM and lactoferrin (a protein found in human and cows' milk) at concentrations similar to human milk.

    At the end of the 18-month-long study, the infants who received formula with the MFGM and lactoferrin scored higher on cognitive, language, and motor development tests than infants who received ordinary formula. In fact, their scores were similar to those observed in children who were breastfed, suggesting that the addition of MFGM and lactoferrin to infant formulas could narrow the gap in cognitive development commonly observed between formula-fed infants and breastfed infants.

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  • Human longevity was associated with decreased levels of genes involved in neural overactivity. www.nature.com
    Brain Aging Stress Protein

    Healthy brain activity is achieved by maintaining a balance between neural excitation and inhibition. Impairment in this balance is related to many neurological and neurodegenerative disorders, including epilepsy, autism, Parkinson’s, Alzheimer’s, and schizophrenia. In Caenorhabditis elegans, a model organism for studying both the nervous system and aging, neural excitation increases with age and age-related cognitive decline, but lifespan increases with inhibition. A recent study demonstrates that extended longevity in humans is associated with lower levels of genes related to neural excitation.

    The multi-arm study focused on three organisms: C. elegans, humans, and mice. The authors of the study found that global inhibition of neural excitation increased the lifespan of C. elegans. RNA sequencing and microarray analysis of human genes revealed that long-lived people (older than 85 years) have higher levels of REST, a gene-silencing transcription factor that downregulates neural excitation-related genes. In addition, they found that mice that are deficient in REST exhibit higher levels of neural excitation. REST and lower levels of neural excitation activate FOXO1, a longevity-associated transcription factor in mammals, suggesting that REST regulates a conserved mechanism of aging.

    The authors of the study suggested that REST activation and subsequent reduction of excitatory neural activity may be a means to slow aging in humans.

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  • Daily heat treatments, applied during 10 days of immobilization, prevented the loss of mitochondrial function and prevented muscle atrophy. www.physiology.org
    Heat Stress Muscle Sauna Protein Dairy

    A new study found that daily heat treatments applied locally to muscle during 10 days of immobilization prevented the loss of mitochondrial function, increased heat shock protein levels, and attenuated skeletal muscle atrophy by 37% compared to sham control in a small trial in humans.

    I am really glad to see this replicated now in humans. There’s were two similar studies that I covered in past videos, which showed that whole body heat treatment (similar to a sauna) prevented muscle atrophy and increased muscle regrowth after immobilization, however, these were done in mice. The difference is that this shows a pretty similar phenomenon in humans! This isn’t too surprising. The main reason for that is because the mechanism in animal research was already all worked out. The prevention of muscle atrophy and muscle regrowth in mice was shown to be dependent on the robust activation of heat shock proteins. These proteins are highly conserved in humans in function, playing an extremely apparent similar molecular role. More importantly, we already knew from prior research that heat shock proteins increase by ~50% after 30 minutes in a 163 ºF (73 ºC).

    The results of this new study have important implications. While exercise interventions remain the most effective strategy to maintain or increase muscle mass and respiratory capacity, during periods of immobilization due to injury or for other reasons exercise can become more challenging. Heat therapy through modalities such as a sauna or even local heating (as is the case in this study) may ultimately serve as a very useful alternative or adjunct therapy to maintain skeletal muscle metabolic function and preserve muscle mass!

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  • A pro-inflammatory diet including fast food, processed food, and refined sugar is associated with a 40% increased risk of depression. www.clinicalnutritionjournal.com
    Inflammation Depression Protein

    A pro-inflammatory diet including fast food, processed food, and refined sugar is associated with a 40% increased risk of depression according to a meta-analysis of 11 studies.

    It is always difficult to establish causality with associative studies. With respect to inflammation and depression, there have been some studies establishing causality. For example, healthy individuals injected with proinflammatory cytokines exhibit depressive symptoms compared to those injected with a placebo.

    Moreover, inflammation can be clinically monitored by well-known biomarkers for systemic inflammation, making it amenable to potentially tracking therapeutic success: the risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein.

    To learn more about the role inflammation plays in depression, check out the animated video we put together on the role inflammation plays in depression.

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  • 10 potential "longevity vitamins" including ergothioneine, PQQ, queuine, taurine, lutein, zeaxanthin, astaxanthin & more. www.ucsf.edu
    Aging Vitamin A Antioxidant Protein Taurine Polyphenol Carotenoids

    A new study by my mentor Dr. Bruce Ames proposes that 10 known compounds be classified as potential longevity vitamins due to their interaction with proteins that protect against diseases of aging. The concept is based on the Triage Theory, which classifies proteins and enzymes as either survival proteins, needed for survival and reproduction, or longevity proteins, which protect against future damage and are sacrificed in case of vitamin shortage, leading to an acceleration of insidious diseases of aging.

    These putative “longevity vitamins” include: ergothioneine (a fungal antioxidant found in mushrooms), queuine (a bacterial metabolite found in the gut), PQQ (a bacterial metabolite in soil that is taken up by plants ), lutein and zeaxanthin (concentrated in leafy greens), lycopene (found in tomatoes), alpha- and beta-carotene, and cryptoxanthin (all plant antioxidant carotenoids), astaxanthin (a marine carotenoid found in salmon and krill), and taurine (found in meat).

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  • Cellular stress with changes in microbial profile promotes colorectal cancer development www.sciencedaily.com
    Cancer Microbiome Inflammation Protein Toll-Like Receptors

    Activation of ATF6, a regulator of ER (Endoplasmatic Reticulum) stress, combined with changes in cecal microbial profile, promoted colon adenoma formation.

    [Abstract]

    Methods: We analyzed data from 541 patients with CRC in the TCGA database for genetic variants and aberrant expression levels of unfolded protein response genes. Findings were validated in a cohort of 83 patients with CRC in Germany. We generated mice with intestinal epithelial cell-specific expression of the active form of ATF6 (nATF6IEC) from 2 alleles (homozygous), mice with expression of nATF6IEC from 1 allele (heterozygous), and nATF6IECfl/fl mice (controls). All nATF6IEC mice were housed under either specific-pathogen free or germ-free conditions. Cecal microbiota from homozygous nATF6IEC mice or control mice was transferred into homozygous nATF6IEC mice or control mice. nATF6IEC mice were crossed with mice with disruptions in the myeloid differentiation primary response gene 88 and toll-like receptor adaptor molecule 1 gene (Myd88/TRIF knock-out mice). Intestinal tissues were collected from mice and analyzed by histology, immunohistochemistry, immunoblots, gene expression profiling of unfolded protein response and inflammatory genes, array-based comparative genome hybridization, and 16S rRNA gene sequencing.

    Results: Increased expression of ATF6 was associated with reduced disease-free survival times of patients with CRC. Homozygous nATF6IEC mice developed spontaneous colon adenomas at 12 weeks of age. Compared to controls, homozygous nATF6IEC mice had changes in the profile of their cecal microbiota, increased proliferation of intestinal epithelial cells, and loss of the mucus barrier—all preceding tumor formation. These mice had increased penetration of bacteria into the inner mucus layer and activation of STAT3, yet inflammation was not observed at the pre-tumor or tumor stages. Administration of antibiotics to homozygous nATF6IEC mice greatly reduced tumor incidence, and germ-free housing completely prevented tumorigenesis. Analysis of nATF6IEC MyD88/TRIF knock-out mice showed that tumor initiation and growth required MyD88/TRIF-dependent activation of STAT3. Transplantation of cecal microbiota from nATF6IEC mice and control mice, collected before tumor formation, caused tumor formation in ex–germ-free nATF6IEC mice.

    Conclusions: In patients with CRC, ATF6 was associated with reduced time of disease-free survival. In studies of nATF6IEC mice, we found sustained intestinal activation of ATF6 in the colon to promote dysbiosis and microbiota-dependent tumorigenesis.

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  • Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection www.sciencedirect.com
    Alzheimer's Immune System Virus Protein

    Summary

    Amyloid-β peptide (Aβ) fibrilization and deposition as β-amyloid are hallmarks of Alzheimer’s disease (AD) pathology. We recently reported Aβ is an innate immune protein that protects against fungal and bacterial infections. Fibrilization pathways mediate Aβ antimicrobial activities. Thus, infection can seed and dramatically accelerate β-amyloid deposition. Here, we show Aβ oligomers bind herpesvirus surface glycoproteins, accelerating β-amyloid deposition and leading to protective viral entrapment activity in 5XFAD mouse and 3D human neural cell culture infection models against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6A and B. Herpesviridae are linked to AD, but it has been unclear how viruses may induce β-amyloidosis in brain. These data support the notion that Aβ might play a protective role in CNS innate immunity, and suggest an AD etiological mechanism in which herpesviridae infection may directly promote Aβ amyloidosis.

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  • Transcriptional Effects of ApoE4: Relevance to Alzheimer’s Disease | SpringerLink link.springer.com
    Alzheimer's Protein

    The major genetic risk factor for sporadic Alzheimer’s disease (AD) is the lipid binding and transporting carrier protein apolipoprotein E, epsilon 4 allele (ApoE4). One of the unsolved mysteries of AD is how the presence of ApoE4 elicits this age-associated, currently incurable neurodegenerative disease. Recently, we showed that ApoE4 acts as a transcription factor and binds to the promoters of genes involved in a range of processes linked to aging and AD disease pathogenesis. These findings point to novel therapeutic strategies for AD and aging, resulting in an extension of human healthspan, the disease-free and functional period of life. Here, we review the effects and implications of the putative transcriptional role of ApoE4 and propose a model of Alzheimer’s disease that focuses on the transcriptional nature of ApoE4 and its downstream effects, with the aim that this knowledge will help to define the role ApoE4 plays as a risk factor for AD, aging, and other processes such as inflammation and cardiovascular disease.

    https://www.ncbi.nlm.nih.gov/pubmed/?cmd=historysearch&querykey=5

    Theendakara, V., Peters-Libeu, C.A., Bredesen, D.E. et al. Mol Neurobiol (2018) 55: 5243. https://doi.org/10.1007/s12035-017-0757-2

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  • Four weeks of using the sauna increased resting anti-inflammatory biomarkers (IL-10). www.ncbi.nlm.nih.gov
    Inflammation Heat Stress Protein

    Four weeks of using the sauna increased resting anti-inflammatory biomarkers (IL-10) and this adaptation happened faster in the already physically active. There was also a small increase in some of the heat shock proteins.

    The sauna protocol used in this study was a little different than other studies I have talked about. This study used two 15 minutes in 208 degrees F separated by a 5-minute cool shower. Previous studies that have shown cardiovascular and brain benefits used a 174 degree F sauna for at least 20 minutes, 4 times a week.

    If you have not already, check out my podcast with Dr. Jari Laukkannen, one of the world’s leading sauna researchers. He gets into the specifics on his research on sauna use for the prevention of cardiovascular disease and Alzheimer’s disease. We also talk about what heat shock proteins are and how they may play a role in Alzheimer’s disease prevention.

    Episode link: https://www.foundmyfitness.com/episodes/jari-laukkanen

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  • A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling papers.ssrn.com
    Brain Obesity Depression Saturated Fat Protein

    Obesity is associated with an increased risk of depression. The aim of the present study was to investigate whether obesity is a causative factor for the development of depression and what is the molecular pathway(s) that link these two disorders. Using lipidomic and transcriptomic methods we identified a mechanism that links exposure to a high-fat diet (HFD) in mice with alterations in hypothalamic function that lead to depression. Consumption of an HFD selectively induced accumulation of palmitic acid in the hypothalamus, suppressed the 3´, 5´-cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and increased the concentration of free-fatty acid receptor 1 (FFAR1). Deficiency of phosphodiesterase 4A (PDE4A), an enzyme that degrades cAMP and modulates stimulatory regulative G-protein (Gs)-coupled G protein-coupled receptor signaling, protected animals either from genetic- or dietary induced depression phenotype.

    These findings suggest that dietary intake of saturated fats disrupts hypothalamic functions by suppressing cAMP/PKA signaling through activation of PDE4A. FFAR1 inhibition and/or an increase of cAMP signaling in the hypothalamus could offer potential therapeutic targets to counteract the effects of dietary or genetically induced obesity on depression.

    https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3188483

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  • Role of dietary transition metals on host microbiota and risk of disease www.gutmicrobiotaforhealth.com
    Nutrition Gut Diet Microbiome Metabolism Immune System Micronutrients Iron Protein

    Transition metals are required cofactors for many proteins that are critical for life, and their concentration within cells is carefully maintained to avoid both deficiency and toxicity. To defend against bacterial pathogens, vertebrate immune proteins sequester metals, in particular zinc, iron, and manganese, as a strategy to limit bacterial acquisition of these necessary nutrients in a process termed “nutritional immunity.” In response, bacteria have evolved elegant strategies to access metals and counteract this host defense. In mammals, metal abundance can drastically shift due to changes in dietary intake or absorption from the intestinal tract, disrupting the balance between host and pathogen in the fight for metals and altering susceptibility to disease. This review describes the current understanding of how dietary metals modulate host-microbe interactions and the subsequent impact on the outcome of disease.

    https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30262-2

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  • Nutrient-induced Mitochondrial Activation (NiMA): A Novel Lysosome-to-Mitochondria Signaling Pathway Disrupted by Amyloid-β Oligomers papers.ssrn.com
    Nutrition Alzheimer's Metabolism Mitochondria Neuron Insulin Neurons Protein

    The mechanisms of mitochondrial dysfunction in Alzheimer’s Disease (AD) are incompletely understood. We show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Amyloid-β oligomers, which are precursors of amyloid plaques in AD brain and stimulate mTORC1 protein kinase activity at the plasma membrane, but not at lysosomes, block this nutrient-induced mitochondrial activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in AD brain. NiMA was also disrupted in fibroblasts derived from a patient with tuberous sclerosis complex, a genetic disorder that causes dysregulation of lysosomal mTORC1. Thus, lysosomal mTORC1 couples nutrient availability to mitochondrial activity, and links mitochondrial dysfunction to AD by a mechanism dependent on soluble building blocks of plaques and tangles. https://ssrn.com/abstract=3188445

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  • Microbial Genetic Composition Tunes Host Longevity (2017) www.cell.com
    Protein

    Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.

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  • Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1 papers.ssrn.com
    Nutrition Metabolism Biomarkers Circadian Rhythm Behavior Autophagy Protein

    The circadian clock coordinates behavioral and circadian cues with the availability and utilization of nutrients. Proteasomal degradation of clock repressors, e.g., cryptochrome (CRY)1 maintains periodicity of the clock. Whether autophagy, a quality control pathway, degrades circadian proteins remains unknown. Here we show that circadian proteins BMAL1, CLOCK, REV-ERB, and CRY1 are lysosomal targets, and that α macroautophagy (hereafter autophagy) specifically degrades CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that degradation of CRY1 is time-imprinted to maintenance of blood glucose levels. CRY1 contains several light chain 3 (LC3)-interacting region (LIR) motifs, which facilitate the interaction of cargo proteins to the autophagosome marker LC3. Using mutational analyses, we identified two distinct LIRs on CRY1 that exert circadian control over blood glucose levels by regulating CRY1 degradation, revealing CRY1 LIRs as potential targets in regulation of glucose metabolism.

    Toledo, Miriam and Tarabra, Elena and Batista-Gonzalez, Ana and Merlo, Paola and Feng, Daorong and Sarparanta, Jaakko and Botrè, Francesco and Pessin, Jeffrey E. and Singh, Rajat, Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1 (2018). Available at SSRN: https://ssrn.com/abstract=3155564 or http://dx.doi.org/10.2139/ssrn.3155564

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  • Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1 papers.ssrn.com
    Brain Aging Circadian Rhythm Neuron Glutathione Neurons Protein

    Abstract

    Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults, and plays a critical role in brain health and disease. We report that the core clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism, and via a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation in vitro and in vivo, mediated in part by suppression of glutathione-s-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a novel mechanism by which the circadian clock could influence many aspects of brain function and neurologic disease.

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  • Genesis of Toxic Tau in Alzheimer's Disease Revealed www.medscape.com
    Protein

    Abstract Tauopathies feature progressive accumulation of tau amyloids. Pathology may begin when these amplify from a protein template, or seed, whose structure is unknown. We have purified and characterized distinct forms of tau monomer—inert (Mi) and seed-competent (Ms). Recombinant Ms triggered intracellular tau aggregation, induced tau fibrillization in vitro, and self-assembled. Ms from Alzheimer’s disease also seeded aggregation and self-assembled in vitro to form seed-competent multimers. We used crosslinking with mass spectrometry to probe structural differences in Mi vs. Ms. Crosslinks informed models of local peptide structure within the repeat domain which suggest relative inaccessibility of residues that drive aggregation (VQIINK/VQIVYK) in Mi, and exposure in Ms. Limited proteolysis supported this idea. Although tau monomer has been considered to be natively unstructured, our findings belie this assumption and suggest that initiation of pathological aggregation could begin with conversion of tau monomer from an inert to a seed-competent form.

    https://doi.org/10.7554/eLife.36584.001

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  • Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice www.nature.com
    Aging Autophagy Protein

    [Abstract]

    Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established. Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1F121A/F121A) that decreases its interaction with the negative regulator BCL2. We demonstrate that the interaction between beclin 1 and BCL2 is disrupted in several tissues in Becn1F121A/F121A knock-in mice in association with higher levels of basal autophagic flux.

    Compared to wild-type littermates, the lifespan of both male and female knock-in mice is significantly increased. The healthspan of the knock-in mice also improves, as phenotypes such as age-related renal and cardiac pathological changes and spontaneous tumorigenesis are diminished. Moreover, mice deficient in the anti-ageing protein klotho3 have increased beclin 1 and BCL2 interaction and decreased autophagy. These phenotypes, along with premature lethality and infertility, are escued by the beclin 1(F121A) mutation. Together, our data demonstrate that disruption of the beclin 1–BCL2 complex is an effective mechanism to increase autophagy, prevent premature ageing, improve healthspan and promote longevity in mammals.

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  • Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice. www.ncbi.nlm.nih.gov
    Alzheimer's Sulforaphane Protein NRF2

    Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice engineered to get Alzheimer’s disease.

    The sulforaphane also increased heat shock proteins in the brain. Heat shock proteins play a role in disaggregating protein aggregates.

    The precursor to sulforaphane is found in cruciferous vegetables but is highest in broccoli sprouts which can contain up to 100 times more than mature broccoli.

    To learn more about the role sulforaphane plays in human health, check out my comprehensive video and the podcast I did with sulforaphane expert Dr. Jed Fahey.

    Sulforaphane video: https://www.foundmyfitness.com/episodes/sulforaphane

    Dr. Jed Fahey podcast: https://www.foundmyfitness.com/episodes/jed-w-fahey

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  • Fat Tissue Has Receptors for Sunlight and They Affect Fat Metabolism blog.humanos.me
    Circadian Rhythm Fat Nitric Oxide Neurons Vitamin A Blue Light Protein

    You probably already know that ambient light regulates circadian rhythms by interacting with light-sensitive neurons in the eye.

    But let’s review anyway: In full white light (which contains all colors of light), the rays of the blue and green light spectrum activate melanopsin, a photosensitive protein in specific cells of the retina in the back of the eye. When light hits these cells, a signal transmits information to the brain’s master clock. By detecting various intensities and tones of light, the brain can keep track of what time of day it is.

    This is relatively well established. We also know that sunlight can stimulate the production of vitamin D and nitric oxide, both of which have important effects on health. But are these all of the effects that light has on our physiology?

    It has been known for several decades that a small percentage of blue light can penetrate human skin, and can even reach white subcutaneous adipose tissue. But the relevance of this finding on our physiology was not obvious.

    Curiously, it has also been reported that high OPN4 (the gene that encodes the photopigment melanopsin) mRNA levels are found in human subcutaneous fat. Kind of weird: what the heck are these light-sensitive eye proteins doing in our fat tissue? Additionally, we now know that fat cells contain transient receptor potential cation (TRPC) channels – membranes that are found in the retina that open in response to varying intensities of light.

    So, we know that blue light can get to subcutaneous fat tissue, and fat cells seem to have the machinery needed to respond to the signal that is transmitted by light. Very interesting. Is it possible that visible light penetrates the skin, and exerts physiological effects by activating a melanopsin / TRPC channel signaling pathway in human fat? And if so, could exposure to visible light have an impact on the regulation of body fat? The answer appears to be yes.

    My guest in this episode (inadvertently) found the answer to this novel questions…

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  • Itaconate, an anti-microbial metabolite, decreases inflammation via Nrf2-activation www.nature.com
    Inflammation Microbes Antioxidant Protein NRF2 Lipopolysaccharide

    The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.

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  • A small randomized controlled trial shows curcumin improves memory in older people. www.sciencedaily.com
    Alzheimer's Curcumin Protein Dairy

    A small randomized controlled trial shows that a bioavailable form of curcumin improves memory in older people with mild memory complaints.

    The curcumin group had a 28% improvement in their memory/attention abilities and fewer amyloid plaques and tau tangles in the brain via PET analysis while the placebo group showed no improvements.

    The curcumin was a bioavailable form of curcumin called Theracurmin. Those in the curcumin group took 90 mg of curcumin twice daily for 18 months.

    The mechanisms by which curcumin affect memory and plaque accumulation in humans are not known. However, animal studies have shown that curcumin prevents proteins from aggregating and amyloid plaque accumulation. Larger trials with the bioavailable form of curcumin need to be done before conclusions can be made particularly since clinical trials with non-bioavailable curcumin supplements have yielded mixed results.

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  • Depression may be treated by lowering inflammation. www.telegraph.co.uk
    Inflammation Depression Protein

    The risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein (inflammatory biomarker). Inflammation is caused by a variety of factors including emotional/social stress, poor diet, sedentary lifestyle, poor sleep, and more. While it’s very possible (likely?) that there may be more going on with depression than just inflammation, I believe it’s an incredibly useful lens through which to look at promising avenues to treat or prevent it. We may find in years to come that measuring inflammation may also be useful as a way to track the therapeutic success of a whole lifestyle intervention intended to treat an important biological root cause. Inflammation isn’t just an important component (seemingly) of mental health, however… it’s also an important source of DNA damage, which is a fundamental mechanism of aging itself. This is one reason why it shouldn’t surprise us that lower inflammation is also associated with longer lifespan, prolonged physical function and also cognitive abilities in old age. In fact, it has been suggested that inflammation may be the most important driver of successful longevity that actually increases in its importance with advancing age. My team put together a short animated video explaining how inflammation plays a causal role in depression. I hope you check it out and perhaps we will also find that it’s also visually interesting enough to reach a wider, interested group of people. Animated video: https://www.youtube.com/watch?v=fqyjVoZ4XYg

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  • Genetically lowering plasma insulin levels by 25% extended median lifespan by 11% in female mice fed a low-calorie, high-carb low-fat diet. www.cell.com
    Diet Aging Insulin Resistance Insulin Protein Carbohydrates

    Genetically lowering plasma insulin levels by 25% extended median lifespan by 11% in female mice fed a low-calorie/high-carb/low-fat diet and by 3% in female mice fed a high-calorie/high-fat/low-carb diet.

    This study looked at the effects of genetically lowering insulin levels in older mice. Unfortunately, the male mice did not have lower plasma levels of insulin despite genetically lowering insulin-genes and so the effect on lifespan could not be determined in male mice.

    The female mice were fed two diets: (diet A: moderate-energy diet of 4.68 kcal/g, with 20% of calories from protein, 25% from fat, and 55% from carbohydrate; diet B: high-energy diet of 5.56 kcal/g, with 16% of calories from protein, 58% from fat, and 26% from carbohydrate).

    Interestingly, the lowering of circulating insulin through gene manipulation had a more profound effect on median lifespan in female mice fed the low-calorie/high-carb/low-fat diet (11% extension) versus the high-calorie/low-carb/high-fat diet (3% extension). It is important to note that diets A and B were not matched for the type of fat content, protein levels, or micronutrient composition, so there are numerous potential factors that could have impacted diet-dependent outcomes.

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  • Consumption of broccoli sprouts during late gestation & lactation confers protection against developmental delay induced by maternal inflammation. www.sciencedirect.com
    Nutrition Brain Diet Development Sulforaphane Protein Lipopolysaccharide

    This is an interesting rodent study. The problem is, however, broccoli sprouts are not usually advisable for women that are pregnant because they can be a source of foodborne illness. If proven safe, however, it seems (at the surface) plausible that there could be ways to reduce the risk of in the future. Perhaps through supplementation?

    FTA:

    Methods: Pregnant Long-Evans rats were administered i.p. Injections of saline (100 μl) or lipopolysaccharide (LPS, 200 μg/kg), every 12 h on embryonic day (E) 19 and 20. In the treatment groups, dams were supplemented with 200 mg/day of dried BrSp from E14 until postnatal day 21. Pups underwent a series of neurodevelopmental reflex tests from postnatal day 3–21 followed by neuropathological analyses.

    Note: LPS elicits a strong immune response.

    Results: Pups born from the LPS group were significantly growth restricted (p < 0.001) and delayed in hindlimb placing (p < 0.05), cliff avoidance (p < 0.05), and gait (p < 0.001) compared to controls. […] Dietary supplementation with [broccoli sprouts] to offspring exposed to LPS had increased birth weights (p < 0.001), were no longer delayed in acquiring hindlimb placing, cliff avoidance, gait, and posture, and groomed less compared to LPS alone pups (p < 0.01). Histological analyses revealed that LPS pups had reduced myelin basic protein compared to controls.

    The discussion had some interesting things to say about why mitigating the fetal inflammatory response is a big deal:

    An important recognized antepartum risk factor is the systemic fetal inflammatory response (FIR) [3], which is associated with a four-fold increase in the risk of developing [cerebral palsy]. Both clinical and experimental studies have provided strong evidence supporting the association between FIR and brain injury leading to [cerebral palsy].

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  • Lifestyle And Diet May Stop Or Reverse Prostate Cancer Progression (Dean Ornish Study) www.sciencedaily.com
    Exercise Cancer Diet Prostate Vitamin A Protein Aerobic

    FTA:

    The research team studied 93 men with biopsy-proven prostate cancer who had elected not to undergo conventional treatment for reasons unrelated to this study. The participants were randomly divided into either a group who were asked to make comprehensive changes in diet and lifestyle or a comparison group who were not asked to do so.

    […] After one year, the researchers found that PSA levels (a protein marker for prostate cancer) decreased in men in the group who made comprehensive lifestyle changes but increased in the comparison group. There was a direct correlation between the degree of lifestyle change and the changes in PSA. Also, they found that serum from the participants inhibited prostate tumor growth in vitro by 70 percent in the lifestyle-change group but only 9 percent in the comparison group. Again, there was a direct correlation between the degree of lifestyle change and the inhibition of prostate tumor growth.

    Participants in the lifestyle-change group were placed on a vegan diet consisting primarily of fruits, vegetables, whole grains, and legumes supplemented with soy, vitamins and minerals. They participated in moderate aerobic exercise, yoga/meditation, and a weekly support group session.

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  • A conserved NAD+ binding pocket that regulates protein-protein interactions during aging | Science science.sciencemag.org
    Aging DNA Damage Protein

    This is from a press release on www.eurekalert.org “UNSW researchers have made a discovery that could lead to a revolutionary drug that actually reverses ageing, improves DNA repair and could even help NASA get its astronauts to Mars.”

    From the link above “NAD+ binding modulates protein interactions An unexpected function of the oxidized form of nicotinamide adenine dinucleotide (NAD+) could underlie some effects of aging and propensity to age-related diseases. Li et al. found that the protein DBC1 (deleted in breast cancer 1) contains a domain that specifically binds NAD+. Binding of NAD+ inhibited the interaction of DBC1 with PARP1 [poly(adenosine diphosphate–ribose) polymerase 1], an enzyme important in DNA repair. Activity of PARP1 is inhibited by interaction with DBC1. Thus, the reduced abundance of NAD+ associated with aging may decrease PARP1 activity by promoting the interaction of PARP1 with DBC1. This mechanism could help explain the reported rejuvenating actions of NAD+ supplementation in older animals.”

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  • Epithiospecifier protein activity in broccoli: The link between terminal alkenyl glucosinolates and sulphoraphane nitrile www.sciencedirect.com
    Sulforaphane Isothiocyanates Protein Myrosinase

    Please take note of the graphs and timeline, these can provide valuable information on how to optimize your processing of broccoli sprouts for sulforaphane content.

    Abstract The chemical nature of the hydrolysis products from the glucosinolate-myrosinase system depends on the presence or absence of supplementary proteins, such as epithiospecifier proteins (ESPs). ESPs (non-catalytic cofactors of myrosinase) promote the formation of epithionitriles from terminal alkenyl glucosinolates and as recent evidence suggests, simple nitriles at the expense of isothiocyanates. The ratio of ESP activity to myrosinase activity is crucial in determining the proportion of these nitriles produced on hydrolysis. Sulphoraphane, a major isothiocyanate produced in broccoli seedlings, has been found to be a potent inducer of phase 2 detoxification enzymes. However, ESP may also support the formation of the non-inductive sulphoraphane nitrile. Our objective was to monitor changes in ESP activity during the development of broccoli seedlings and link these activity changes with myrosinase activity, the level of terminal alkenyl glucosinolates and sulphoraphane nitrile formed. Here, for the first time, we show ESP activity increases up to day 2 after germination before decreasing again to seed activity levels at day 5. These activity changes paralleled changes in myrosinase activity and terminal alkenyl glucosinolate content. There is a significant relationship between ESP activity and the formation of sulforaphane nitrile in broccoli seedlings. The significance of these findings for the health benefits conferred by eating broccoli seedlings is briefly discussed.

    Graphical abstract We measured ESP activity over 15 days of broccoli seedling development and correlated these with myrosinase activity and the levels of terminal alkenyl glucosinolates and sulphoraphane nitrile. We show ESP activity increases to day 2 before decreasing to imbibed seed activity at day 5. Terminal alkenyl glucosinolate and sulforaphane nitrile content and ESP activity correlated closely.

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  • Using sauna 4-7x per week lowered dementia risk by 66% & Alzheimer's risk by 65% after adjusting for diet/lifestyle. ageing.oxfordjournals.org
    Fulltext Alzheimer's Aging Heat Stress Dementia Blood Pressure Protein

    This study included over 2,000 middle-aged men that were followed for 20 years. The results were adjusted for many possible confounding factors including baseline age, alcohol consumption, BMI, physical exercise, socioeconomic status, systolic blood pressure, smoking status, type 2 diabetes, previous heart attack, resting heart rate and serum low-density lipoprotein cholesterol.

    One of the reasons I find this study so compelling even though it is associative data and does not establish causality is because the sauna activates heat shock proteins, which have been shown in countless animal studies to play a causal role in preventing Alzheimer’s disease and other neurodegenerative diseases.

    Anyone that follows me knows that I talk about saunas ALOT. I have a couple of videos where I discuss the effects of the sauna on longevity and in muscle mass and endurance. I discuss the role of heat shock proteins in both videos. I also have free reports with references covering all these topics that you can download on my website (foundmyfitness.com). Sauna longevity video: https://www.youtube.com/watch?v=eWKBsh7YTXQ Sauna muscle/endurance video: https://www.youtube.com/watch?v=aHOlM-wlNjM&t=1s

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  • heat-shock protein response in the brains of both young and aged rats supplemented with blueberry extract www.neurobiologyofaging.org
    Brain Neuron Neurons Antioxidant Protein

    (From Life Extension.com/magazine) In a 2005 article published in the journal Neurobiology of Aging, Rachel Galli and her colleagues, also based at Tufts, reported discovering a specific mechanism by which blueberries help reverse the neurological aging process.16 The Galli study—which included Drs. Joseph and Shukitt-Hale as co-investigators—sought to measure the heat-shock protein response in the brains of both young and aged rats supplemented with blueberry extract compared to a control group of aged rats. A protective mechanism produced in the brains of most animals (and humans), heat-shock proteins fight free radicals and inflammation-inducing agents, acting similarly to antioxidants to support healthy brain tissues. As people age, however, their ability to generate heat-shock proteins in sufficient quantity declines,17 sometimes dramatically. The Tufts researchers sought to determine whether blueberries could help restore the heat-shock protein response in rats.16

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  • New 20-page report on cryotherapy just released! Cold shock boosts norepinephrine up to 5-fold & increase type of immune cell that kills tumor cells. www.foundmyfitness.com
    Exercise Brain Alzheimer's Aging Metabolism Inflammation Memory Immune System Norepinephrine Protein

    This 20-page report explains how cold shock is a type of hormesis, which is a description of a type of stress that, in the right doses, is enough to shock the body and kick off adaptive processes and response mechanisms that are hardwired into our genes, and, once on, are able to create a resilience that actually exceeds what was needed to counter the initial stimuli. Rhonda discusses how cold exposure increases norepinephrine up to 5-fold in the brain and what the temperature and duration needed to do this are, how norepinephrine has an effect on mood, vigilance, focus, and attention, how cold exposure increases cold shock proteins including one in the brain that repairs damaged synapses and in muscle prevents atrophy, how cold-induced norepinephrine lowers inflammation and pain by decreasing the levels of 3 inflammatory mediators, how chronic cold shock may increase immune cell numbers and particularly a type of immune cell that kills cancer cells, how cold exposure increases metabolic rate, the number of mitochondria, and the burning of fat, what the effects of different cold exposure temperatures and timing are on athletic performance, recovery time, and muscle mass, and the differences between various types of cold shock modalities, including cold water immersion and whole body cryotherapy.

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  • Packing on the muscle via inhibition of cancer-related protein and myostatin increases cancer survival in mice. www.sciencedaily.com
    Cancer Muscle Protein

    FTA:

    There was evidence to suggest that tumors secrete activin, such that circulating levels of the protein rise in those with cancer. Activin is closely related to another protein, called myostatin, which is known to be important in muscle […]

    Animals lacking myostatin or taking treatments that block it grow bigger muscles. There was some evidence to suggest that activin blockers might have a similar effect.

    Based on that hunch, the researchers treated mice with cancer and associated cachexia with a recombinant and soluble version of the ActRIIB receptor (sActRIIB), a kind of molecular “decoy” that potently inhibited both activin and myostatin activity. That treatment reversed the animals' muscle loss and prolonged their survival by several weeks on average.

    “In tumor-bearing mice with profound cachexia, blocking this pathway not only prevents muscle wasting but completely reverses the loss of muscle, strength and anorexia,” Han said. (Anorexia is another symptom of cachexia, but appetite stimulants and nutritional supplements don’t help much.)

    note: cachexia = muscle wasting

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  • Traumatic brain injury disrupts the brain's waste removal system, allowing toxic proteins to accumulate in the brain. www.sciencedaily.com
    Brain Alzheimer's Parkinson's Performance Concussion Protein Neurodegeneration Blood-Brain Barrier

    From the article:

    The new research focuses on the impact that traumatic brain injury has on the glymphatic system. It has been long observed that the protein tau plays an important role in the long-term damage sustained by the brain after a trauma. Tau helps stabilize the fibers, or axons, that nerve cells send out to communicate with their neighbors.

    However, during trauma, large numbers of these proteins are shaken free from the axons to drift in the space between the brain’s cells. Once unmoored from nerve cells, these sticky proteins are attracted to each other and, over time, form increasingly larger “tangles” that can become toxic to brain function.

    Under normal circumstances, the glymphatic system is able to clear stray tau from the brain. However, when the researchers studied the brains of mice with traumatic brain injury, they found that the trauma damaged the glymphatic system, specifically the ability of astrocytes – a support cell found in the brain – to regulate the cleaning process.

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  • [TIMELINE] Joe Rogan Experience #502 with Dr. Rhonda Patrick www.foundmyfitness.com
    Omega-3 Depression Insulin Fatty Liver Vitamin A Isothiocyanates Antioxidant Protein Dairy Blood Sugar Metabolic Syndrome Myrosinase

    This is the full minute-by-minute timeline for JRE #502. Click here to watch the video on YouTube.

    • 00:02:42 - Starts off by talking about kappa opioids and dynorphin and how you feel stress right before important events
    • 00:04:24 - Joe talks about how great you feel after a competition (fight)
    • 00:05:35 - Talks about how capsaicin in spicy food also induces a release of endorphins via dynorphin agonization
    • 00:06:22 - Briefly mentions sauna/hyperthermic conditioning article featured on 4-Hour Workweek
    • 00:06:45 - Description of hormesis and how this is part of the mechanism of action for things like EGCGs in green tea and polyphenols in fruit.
    • 00:07:50 - Joe brings up that Rhonda suggested mycotoxin might be hormetic previously, Rhonda clarifies this was entirely and highly speculative. Includes jazz hands.
    • 00:08:45 - Joe mentions that his best decisions are made after a good workout. He does not trust his judgment if he has not got a good workout in.
    • 00:09:15 - Discussion of exercise and how it grows new brain cells (neurogenesis) via the BDNF pathway and how the growth of new brain cells allows you to forget other memories.
    • 00:11:20 - Joe mentions how people in highschool that never left your small hometown sometimes remember stuff you don’t. Get out of the small town, highschool friends. Make new memories.
    • 00:12:00 - Talks about how amygdala activation from either extreme excitement or fear increases episodic memory.
    • 00:12:15 - Talks about her new paper and how serotonin plays a role in brain function/dysfunction, behavior, and episodic memory.
    • 00:13:38 - Joe brings up MDMA burnout and suggests serotonin’s role in episodic memory may be why the MDMA/roller burnout stereotype exists
    • 00:15:00 - Explanation of what receptor down-regulation is and why it adds enormous complexity to understanding the effects of drugs, like SSRIs.
    • 00:16:27 - Discussion of “Serotonin Syndrome.”
    • 00:17:22 - Most serotonin is actually made in the gut, not the brain.
    • 00:17:44 - Discussion of how the genes that convert tryptophan to serotonin found in the gut (TPH1) and in the brain (TPH2) are show a characteristic nucleotide sequence known as a “Vitamin D Response Element” that seems to indicate, for the most part, that Vitamin D represses the production of serotonin in the gut (TPH1) and increases serotonin in the brain (TPH2). This is the subject of Rhonda’s most recent academic paper: “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”
    • 00:18:45 - Serotonin made in the gut has been shown to cause gastrointestinal inflammation by activating T cells and causing them to proliferate. Knocking out TPH1 in a mouse model of colitis ameliorates the inflammation associated with the disorder.
    • 00:21:55 - Theoretical vitamin D mechanism may play a role in the development of autism by depriving developing foetus of serotonin that serves as an “early brain morphogen” when mothers are deficient in vitamin D.
    • 00:23:45 - Autism appears to be developing early in utero (during pregnancy) and seems to show indications of being at least partially related to environment.
    • 00:24:00 - Estrogen can activate TPH2 in lieu of Vitamin D and thus may explain why autism is predominantly found in males.
    • 00:24:30 - Gut inflammation is common among autistics.
    • 00:24:45 - Explains 5-HTP bypasses the normal tryptophan hydroxylase (TPH) conversion, and because of that it can be converted into serotonin more rapidly… but (hypothetically) too soon and in the gut instead of the brain.
    • 00:25:35 - Tryptophan gets transported into the brain in order to be converted into serotonin by tryptophan hydroxylase (TPH2) but competes with BCAAs for transport into the brain, which are transported preferentially.
    • 00:25:55 - Tryptophan is less abundant of an amino acid than branch chain amino acids like leucine in protein.
    • 00:26:55 - Joe asks Rhonda if T cell activation/proliferation in the context of TPH1 has relevance for AIDS.
    • 00:28:00 - Joe relates how “New Mood” (Onnit’s product) was originally called “Roll Off.”
    • 00:30:30 - Joe quips that it was recently experimentally validated in mice that DMT is produced in the pineal glands of mice during sleep, goes on to talk about speculation that near death experiences relating to altered perception from endogenous DMT release.
    • 00:35:10 - Plays a video of a jaguar eating hallucinogenic plants.
    • 00:37:20 - Talks about monoamine oxidase
    • 00:38:40 - Merits of “theoretical papers” (like “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”)
    • 00:39:37 - 70% of population is vitamin d deficient. Segways to awesome infographic created by @tjasonwright which covers a ton of the basic facts about vitamin D.
    • 00:43:02 - BaadBobby’s Dad turned Joe onto TA-65. TA-65 has been shown to increase telomere length, but theres a guy who sued the company producing it. Anecdotally, BaadBobby’s dad had improvements in eyesight.
    • 00:45:00 - Explanation of what telomeres are.
    • 00:48:50 - Special enzyme telomerase rebuilds telomeres, but it’s found mostly only in stem cells… and more importantly: cancer cells. Cancer cells hijack this telomerase normally reserved for stem cells to live forever. Strangely… Mice, unlike humans, actually express telomerase in all of their cells and don’t have telomere shortening.
    • 00:50:10 - Werner’s syndrome involves excessive telomere shortening.
    • 00:53:33 - Explains how aging is a function of DNA damage and discusses DNA damage assay (test) that Rhonda performs.
    • 00:55:30 - Obesity link to increased DNA damage.
    • 00:56:50 - Talks about TA-65’s active ingredient in a study was shown to genuinely increase telomerase activity and length of telomeres.
    • 00:58:22 - TA-65 study showed a 40% increase in telomere length in white blood cells in some humans studied.
    • 00:58:44 - Second study on TA-65 using special mouse model from well-known lab also showed re-activation of telomerase, and even began reversing aging of their tissues. Mice notably did not get cancer. Reinforces findings of first study.
    • 01:01:30 - Still concerned TA-65 could encourage the growth of pre-cancerous cells.
    • 01:02:00 - Joe brings up alkalizing diet for cancer prevention (he’s a skeptic).
    • 01:03:05 - Bad bacteria in gut is affected by pH.
    • 01:06:20 - Joe brings up argument that sugar consumption affects growth of cancer.
    • 01:07:50 - Explains because cancer cells become glycolytic which is why people fixate on sugar as a potential cancer cell.
    • 01:08:40 - Rhonda mentions that taking away glucose, but allowing continued presence of glutamine allowed cancer cells to keep growing in vitro.
    • 01:09:50 - Folic acid needed in the absence of cancer because you need it to build new DNA – but this is a problem if you do have a cancer because it can be a bad thing for the same reasons (folic acid needs to produce DNA because cancer cells are highly proliferative).
    • 01:12:00 - Glucosinolates are cleaved into isothiocyanates by myrosinase which is de-activated by heat. Isothiocyanates are potent anti-cancer agents. Recent anti-kale stuff is, in a way, anti-isothiocyanates. Additionally, if you boil kale and de-activate myrosinase you’re actually decreasing the amount of isothiocynates by removing myrosinase.
    • 01:14:00 - Kale thyroid stuff is probably only relevant if you’re very deficient in iodine – probably better to continue getting your isothiocyanates for cancer preventative reasons rather than sweating this stuff.
    • 01:16:35 - Rhonda mentions tumor suppressor genes, which are activated by hormesis (good stress triggered by things like isothiocyanates).
    • 01:19:20 - Joe brings up Dave Asprey’s take on boiling kale to remove oxalic acid.
    • 01:20:10 - Spinach that was either raw, boiled, fried, or frizzled and found that raw and boiling doesn’t affect absorption, but it did very modestly affect minerals in kidneys if raw… didn’t seem to cause kidneys stones (in mice). Probably requires absurd amounts of spinach to cause kidney stones. Just not convinced that it’s bad to eat spinach or kale raw.
    • 01:20:20 - Vegetables do make compounds that are sort of “bad for you” but have a net positive effect because they induce hormesis.
    • 01:24:33 - JRE consensus of #502 –eating raw spinach and kale is good for you.
    • 01:25:10 - Joe throws a curveball by bringing up a documented case of presumed oxalate induced nephropathy (kidney disease) from 1985 to 2010 – only 36 patients documented by paper. Only three patients really suspected that it was caused by raw juicing.
    • 01:27:30 - Discussion of vegetable smoothies begins here – specifically using these powerful blenders which leave the fiber in, not juicing.
    • 01:28:45 - Brock Lesnar allegedly ate nothing but meat, got diverticulitis.
    • 01:29:07 - Putrefying bacteria make nasty smelling hydrogen sulfide farts, use sulfate as source of energy. Needs heme from red meat as a cofactor for creating hydrogen sulfide. Hydrogen sulfide prevents human gut cells from making energy (ATP), and thus causes break-down of gut-mucus barrier.
    • 01:32:25 - Brings up episode with Dr. Offitt on Bryan Callen’s podcast. Offitt claims vitamins and antioxidants cause cancer.
    • 01:35:20 - Beginning of general debunking of Offitt’s claims.
    • 01:36:05 - Randomized double-blind placebo controlled trials are awesome, but using them for nutrition research and expecting the design to perform as effectively is misguided.
    • 01:37:30 - Everyone has different levels of vitamins & minerals in their body, but baseline for drugs is always the same: zero. This is an important fundamental difference.
    • 01:42:20 - Years of research has to be published even if results aren’t great, and this requires salesmanship. This affects some of the misleading presentation of research.
    • 01:43:04 - Joe brings up highly publicized and contentious “Enough is Enough” editorial which was covered at length in podcast #459.
    • 01:46:28 - Begin discussion of Vitamin E prostate cancer study (the SELECT trial).
    • 01:47:35 - Comparison of Alpha Tocopherol & Gamma Tocopherol forms of vitamin E. Alpha tocopherol serves predominantly as an antioxidant, gamma tocopherol serves as an anti-inflammatory agent by reducing reactive nitrogen species (also an anti-oxidant activity). Alpha tocopherol doesn’t serve the same anti-inflammatory behavior, and this is important because inflammation is a cancer initiator (among other things), and excessive alpha tocopherol consumption depletes gamma tocopherol from tissues.
    • 01:50:45 - Study on prostate cancer found that alpha tocopherol and selenium didn’t affect cancer incidence at 5-year followup but at 7.5 year follow-up cancer risk for prostate cancer shot up from taking 400 IU of alpha tocopherol (vitamin E) per day. Importantly, what was found at the 5-year followup was that (relative to baseline) gamma tocopherol was depleted from the tissues. Those who weren’t deficient selenium (& were supplementing) that took the 400 IU of alpha tocopherol didn’t experience the increase in prostate cancer incidence.
    • 01:52:05 - One of the proteins selenium is for is important for preventing damage from reactive nitration products. Nitration damage can cause cancer. This is an interesting novel mechanism by which a depletion of gamma tocopherol through a combination of inflammation and an increase in reactive nitratition products might be responsible for the increase cancer incidence found in this study.
    • 01:54:00 - Discussion of vegetable smoothie as a good source of vitamin E, and also natural magnesium (from chlorophyll molecules – this was mentioned in JRE #459)
    • 01:54:45 - Mixed tocopherol Vitamin E supplements exist which aren’t quite as high dose as 10x the RDA (400 IU) like used in those studies.
    • 02:01:18 - RDA for Vitamin D is 600 IU a day. One study showed that 4,000 IU was more appropriate for actually adequately fixing without toxicity in deficient populations. 2000 to 4000 IU of vitamin D is probably a good range except for in cases of severe deficiency.
    • 02:03:18 - Offit lumped omega-3 in with “antioxidants that cause cancer”, but this is misleading given the fact that randomized controlled trials have shown that omega-3 supplementation actually reduces all-cause mortality.
    • 02:03:39 - 1500 IU of vitamin D a day has been correlated to a 17% reduced cancer risk (overall).
    • 02:04:15 - Study based off of self-reported questionaire found that women who took vitamins (supplements) - on a daily basis had the longest telomeres.
    • 02:05:45 - She tries to get all her micronutrients, as much as she can, from her diet including vegetable smoothies, fish, etc. However, in addition to her diet she takes: omega-3 fatty acids, vitamin D, a multi-vitamin which has selenium and other trace elements, iodine, B-complex.
    • 02:06:30 - B vitamin deficiency is less common due to fortification. However, she supplements B vitamins anyway because changes in mitochondrial membrane rigidity that occurs with age alters the binding affinity (as represented by the constant kM) of important proteins needed to generate energy in the form of ATP which are embedded in the mitochondrial membrane. The Ames lab has partly demonstrated, however, that increasing the concentration of B vitamins compensates for these age related changes caused by changes in the confirmation (shape) of the proteins.
    • 02:08:00 - Rhonda increasingly prefers Swanson brand vitamins, but gets omega-3 from nordic naturals.
    • 02:10:00 - B vitamins are probably less dangerous because they’re water soluble (excess is more readily excreted, similar to Vitamin C)
    • 02:11:00 - Plant form of omega-3, ALA, converts to EPA (normally found in fish) fairly inefficiently at a rate of about 5%.
    • 02:12:13 - Microalgae oil is a good alternative to flaxseed oil if you’re trying to meet EPA/DHA needs and avoiding fish oil for one reason or another.
    • 02:13:30 - Omega-3 EPA is a potent anti-inflammatory, and DHA is a really component of your cell membranes – and makes up about 40% of the brain.
    • 02:13:54 - She takes about 6 pills of her omega-3, which amounts to ~3 “servings” of 800mg of EPA, and 600mg of DHA. (2400 and 1800 mg respectively)
    • 02:15:28 - Omega-3 EPA, which can be bought more concentrated for its particular effects, interacts with the arachnidonic acid pathway to reduce inflammation. The arachnicdonic acid pathway is responsible for creating prostaglandins which activate the COX pathway.
    • 02:16:05 - 2 grams of EPA per day has been shown to reduce C-reactive protein (CRP), which is a generalized systemic marker for inflammation but is most well known for its use to asses risk of cardiovascular disease.
    • 02:17:45 - Omega-3 fatty acids are prone to oxidation. Refrigeration helps with this, however. Also check if they go rancid by smell, if smell bad then probably rancid.
    • 02:20:00 - Talks about krill oil. Joe lists off a bunch of points from a Mercola article, and Rhonda points out it’s talking about ordinary effects of omega-3 and suggesting they may not be unique to krill oil.
    • 02:27:29 - Recommends Linus Pauling Institute for good, objective source of supplemental micronutrient reviews.
    • 02:28:35 - Brief mention of WellnessFX as a useful tool for getting a broad spectrum blood test checking for relevant markers for vitamins, minerals, inflammation, etc.
    • 02:31:00 - Whackiness of homepathy discussed. Homeopathy makes use of official sounding measuring system that measures an absurd amount of dilution that actually guarantees that what you’re taking doesn’t actually include the active ingredient the supplement is being marketed for.
    • 02:33:25 - Discusses how emerging research showing wisdom teeth has dental pulp stem cells in them and they offer promise for eventually being used as a source of cells that can be differentiated into things like brain cells. You can bank children’s teeth or adult wisdom teeth. Usually like $625 to “process” a tooth, and around $125/year to store it.
    • 02:36:16 - They can now take fibroblast cells from skin, the sort that you slough off everyday, and add transcription factors to turn them into “pluripotent” stem cells which can turn into brain cells or liver cells.
    • 02:37:35 - Joe brings up study where they took blood of young mice, injected it into old mice, and found the older mice experienced tissue regeneration. Inverse was also true: injecting young mice with old mouse blood increased rate of aging.
    • 02:38:54 - Human “methylome” now being studied which is revealing a specific pattern of methylation in DNA that can be used to actually identify the chronological age of people. Since epigenetics is obviously playing an important role in age, this is another promising area of new inquiry that may eventually reveal how to reprogram our cells to “be younger”. Cancer cells show a methylation pattern that is ordinarily associated with old age and are clustered around areas related to DNA repair, mitochondrial metabolism, antioxidant genes (all areas associated with aging).
    • 02:43:12 - Scientists are now able to take renal cells excreted in urine and turn them into pluripotent stem cells
    • 02:43:45 - Rant about lack of funding in science reducing room for creativity/moonshots.
    • 02:48:40 - Joe brings up new studies showing its possible to create artificial blood for transplant.
    • 02:50:06 - Inactivating insulin growth factor in c. elegans worms doubles their lifespan from about 15 to 30 days.
    • 02:52:40 - Joe asserts (reasonably so) that by age 200 he will most likely be a wizard.
    • 02:55:42 - Joe relates the fact that he’s actually been evacuated twice due to large fires in his neck of the woods of L.A.
    • 02:57:45 - Rhonda begins plug of iPhone app, website, Twitter, and podcast.
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