The Gary Null Show - 04.16.21

1.  EMPATHY - BEST SPEECH OF ALL TIME By Simon Sinek | Inspiritory 10 mins 

2. Sweet Uncle Billy

 

Mushrooms boost immunity, suggests research

University of Florida Institute of Food and Agricultural Sciences, April 13. 2021

 

 

Could a mushroom a day help keep the doctor away?

 

A new University of Florida study shows increased immunity in people who ate a cooked shiitake mushroom every day for four weeks.

 

Of the thousands of mushroom species globally, about 20 are used for culinary purposes. Shiitake mushrooms are native to Asia and are cultivated for their culinary and medicinal value.

 

A study led by UF Food Science and Human Nutrition Professor Sue Percival, 52 healthy adults, age 21 to 41, came to the Gainesville campus, where researchers gave them a four-week supply of dry shiitake mushrooms. Participants took the mushrooms home, cleaned and cooked them. Then they ate one, 4-ounce serving of mushrooms each day during the experiment.

 

Through blood tests before and after the experiment, researchers saw better-functioning gamma delta T-cells and reductions in inflammatory proteins.

 

"If you eat a shiitake mushroom every day, you could see changes in their immune system that are beneficial," said Percival, an Institute of Food and Agricultural Sciences faculty member. "We're enhancing the immune system, but we're also reducing the inflammation that the immune system produces."

 

To be eligible for the study, participants could not be vegans or vegetarians. They also could not drink tea, take antioxidant supplements or probiotics before the study. They also could not consume more than 14 glasses of alcoholic beverages per week or eat more than seven servings of fruits and vegetables per day during the experiment.

 

Percival explained the dietary restrictions as follows: Fiber, tea and probiotics help the body's immune system, so researchers didn't want to start with people who already had a strong immune system. Additionally, that much alcohol could suppress immunity, she said.

 

The study was published  in the Journal of the American College of Nutrition.

 

 

Metabolic changes in fat tissue in obesity associated with adverse health effects

University of Helsinki (Finland), April 9, 2021

Researchers at the Obesity Research Unit of the University of Helsinki have found that obesity clearly reduces mitochondrial gene expression in fat tissue, or adipose tissue. Mitochondria are important cellular powerplants which process all of our energy intake. If the pathways associated with breaking down nutrients are lazy, the changes can often have health-related consequences.

A total of 49 pairs of identical twins discordant for body weight participated in the study conducted at the University of Helsinki: their body composition and metabolism were studied in detail, and biopsies from adipose and muscle tissue were collected. Multiple techniques for analysing the genome-wide gene expression, the proteome and the metabolome were used in the study. 

The study was recently published in the journal Cell Reports Medicine.

According to the findings, the pathways responsible for mitochondrial metabolism in adipose tissue were greatly reduced by obesity. Since mitochondria are key to cellular energy production, their reduced function can maintain obesity. For the first time, the study also compared the effects of obesity specifically on the mitochondria in muscle tissue in these identical twin pairs: muscle mitochondria too were found to be out of tune, but the change was less distinct than in adipose tissue. 

The study provided strong evidence of a connection between the low performance of adipose tissue mitochondria and a proinflammatory state. Furthermore, the findings indicate that metabolic changes in adipose tissue are associated with increased accumulation of fat in the liver, prediabetic disorders of glucose and insulin metabolism as well as cholesterol.

"If mitochondria, the cellular powerplants, are compared to the engine of a car, you could say that the power output decreases as weight increases. A low-powered mitochondrial engine may also generate toxic exhaust fumes, which can cause a proinflammatory state in adipose tissue and, consequently, the onset of diseases associated with obesity," says Professor Kirsi Pietiläinen from the Obesity Research Unit, University of Helsinki.

"What was surprising was that the mitochondrial pathways in muscle had no association with these adverse health effects," Pietiläinen adds.

Obesity also affected amino acid metabolism

In the study, changes in mitochondrial function were also seen in amino acid metabolism. The metabolism of branched-chain amino acids, which are essential to humans, was weakened in the mitochondria of both adipose tissue and muscle tissue.

"This finding was of particular significance because the reduced breakdown of these amino acids and the resulting heightened concentration in blood have also been directly linked with prediabetic changes and the accumulation of liver fat in prior twin studies," says Pietiläinen.

Obesity, with its numerous associated diseases, is a common phenomenon that is continuously increasing in prevalence. While lifestyle influence the onset of obesity, genes also have a significant role. 

"Identical twins have the same genes, and their weight is usually fairly similar. In fact, studying twins is the best way to investigate the interplay between genes and lifestyle. In spite of their identical genome, the genes and even mitochondria of twins can function on different activity levels. We utilised this characteristic in our study when looking into the effects of weight on tissue function," Pietiläinen says.

 

 

Research suggests selenium supplementation may extend lifespan

Orentreich Foundation for the Advancement of Science (Cold Spring), April 12, 2021

 

Adding the nutrient selenium to diets protects against obesity and provides metabolic benefits to mice, according to a study published in eLife.

The results could lead to interventions that reproduce many of the anti-aging effects associated with dietary restriction while also allowing people to eat as normal.

Several types of diet have been shown to increase healthspan - that is, the period of healthy lifespan. One of the proven methods of increasing healthspan in many organisms, including non-human mammals, is to restrict dietary intake of an amino acid called methionine.

Recent studies have suggested that the effects of methionine restriction on healthspan are likely to be conserved in humans. Although it might be feasible for some people to practice methionine restriction, for example, by adhering to a vegan diet, such a diet might not be practical or desirable for everyone. In the current study, a research team from the Orentreich Foundation for the Advancement of Science(OFAS), Cold Spring, New York, US, aimed to develop an intervention that produces the same effects as methionine restriction, while also allowing an individual to eat a normal, unrestricted diet.

An important clue for developing such a treatment is that methionine restriction causes a decrease in the amounts of an energy-regulating hormone called IGF-1. If a treatment could be found that causes a similar decrease in IGF-1, this might also have beneficial effects on healthspan. Previous research has shown that selenium supplementation reduces the levels of circulating IGF-1 in rats, suggesting that this could be an ideal candidate.

The team first studied whether selenium supplementation offered the same protection against obesity as methionine restriction. They fed young male and older female mice one of three high-fat diets: a control diet containing typical amounts of methionine, a methionine-restricted diet, and a diet containing typical amounts of methionine as well as a source of selenium. For both male and female mice of any age, the authors found that selenium supplementation completely protected against the dramatic weight gain and fat accumulation seen in mice fed the control diet, and to the same extent as restricting methionine.

Next, they explored the effects of the three diets on physiological changes normally associated with methionine restriction. To do this, they measured the amounts of four metabolic markers in blood samples from the previously treated mice. As hoped, they found dramatically reduced levels of IGF-1 in both male and female mice. They also saw reductions in the levels of the hormone leptin, which controls food intake and energy expenditure. Their results indicate that selenium supplementation produces most, if not all, of the hallmarks of methionine restriction, which suggests that this intervention may have a similar positive effect on healthspan.

To gain insight into the beneficial effects of selenium supplementation, the researchers used a different organism - yeast. The two most widely used measurements of healthspan in yeast are chronological lifespan, which tells us how long dormant yeast remain viable, and replicative lifespan, which measures the number of times a yeast cell can produce new offspring. The team previously showed that methionine restriction increases the chronological lifespan of yeast, so they tested whether selenium supplementation might do the same. As it turned out, yeast grown under selenium-supplemented conditions had a 62% longer chronological lifespan (from 13 days to 21 days) and a replicative lifespan extended by nine generations as compared with controls. This demonstrates that supplementing yeast with selenium produces benefits to healthspan detectable by multiple tests of cell aging.

“One of the major goals of aging research is to identify simple interventions that promote human healthspan,” notes senior author Jay Johnson, Senior Scientist at OFAS. “Here we present evidence that short-term administration of either organic or inorganic sources of selenium provides multiple health benefits to mice, the most notable of which being the prevention of diet-induced obesity. In the long term, we expect that supplementation with these compounds will also prevent age-related disease and extend the overall survival of mice. It is our hope that many of the benefits observed for mice will also hold true for humans.”

 

 

Adherence to Mediterranean Diet Is Associated With Lung Function in Older Adults

Kapodistrian University (Greece), April 3, 2021

Objective: The aim of this work was to examine the association between adherence to a Mediterranean diet (MD) and lung function in older adults.

Design: This was an observational and cross-sectional study.

Setting: This research was conducted among community-dwelling older adults from the 2014 Health and Retirement Study (HRS).

Subjects: Subjects were 2108 adults aged 50 years or older, 1234 (58.5%) of whom were female.

Measures: Dietary intakes from respondents of the Health and Retirement Study (HRS) were used for the current analysis. Adherence to MD was evaluated using the MedDietScore, while lung function was evaluated through peak expiratory flow rate (PEF; l/min). Multiple linear regression and logistic regression were performed, adjusted for potential confounders, to examine the relation between adherence to MD and lung function.

Results: Mean MedDietScore was 28.0 (± 5.0), indicating a moderate adherence to MD. Multiple linear regression showed a significant association between the MedDietScore and lung function (β = 0.072, 95% confidence interval [CI]: 0.039–0.104) after adjusting for age, gender, body mass index, race, comorbidities, education, height, grip strength, smoking history, physical activity, and daily caloric intake. Specific food groups such as grains, dairy products, and fish consumption were also associated with PEF rate (p < 0.05). Logistic regression confirmed these findings, and high adherence to MD was associated with reduced risk of having PEF rate < 80% of its peak predictive value (odds ratio: 0.65, 95% CI: 0.48–0.89).

Conclusions: The results of this study indicate that adherence to MD is an independent predictor of lung function in older adults, and dietary interventions could be a possible preventive measure in adults with a high risk of developing lung function decline.

 

Leaking calcium in neurons an early sign of Alzheimer's pathology

Yale University, April 9, 2021

Alzheimer's disease is known for its slow attack on neurons crucial to memory and cognition. But why are these particular neurons in aging brains so susceptible to the disease's ravages, while others remain resilient?

A new study led by researchers at the Yale School of Medicine has found that susceptible neurons in the prefrontal cortex develop a "leak" in calcium storage with advancing age, they report April 8 in the journal Alzheimer's & Dementia, The Journal of the Alzheimer's Association. This disruption of calcium storage in turns leads to accumulation of phosphorylated, or modified, tau proteins which cause the neurofibrillary tangles in the brain that are a hallmark of Alzheimer's.

These changes occur slowly, building over many years, and can be seen within neurons in the brains of very old monkeys, the researchers report.

"Altered calcium signaling with advancing age is linked to early-stage tau pathology in the neurons that subserve higher cognition," said corresponding author Amy Arnsten, the Albert E. Kent Professor of Neuroscience and professor of psychology and member of the Kavli Institute of Neuroscience at Yale University.

These vulnerable neurons face another problem. As they age, they tend to lose a key regulator of calcium signaling, a protein called calbindin, which protects neurons from calcium overload, and is abundant in the neurons of younger individuals.

"With age, these neurons face a double whammy, with an excessive calcium leak that initiates toxic actions, as well as diminished levels of the protectant, calbindin," said Arnsten.

Neurons in the prefrontal cortex require relatively high levels of calcium to perform their cognitive operations, but the calcium must be tightly regulated. However, as regulation is lost with increasing age, neurons become susceptible to tau pathology and degeneration. Essentially, neurons "eat" themselves from within.

"Understanding these early pathological changes may provide strategies to slow or prevent disease progression," Arnsten said.

 

 

Magic mushroom compound performs at least as well as leading antidepressant medication in small study

 

Imperial College London, April 14, 2021

 

Psilocybin, the active compound in magic mushrooms, may be at least as effective as a leading antidepressant medication in a therapeutic setting.

This is the finding of a study carried out by researchers at the Centre for Psychedelic Research at Imperial College London.

In the most rigorous trial to date assessing the therapeutic potential of a ‘psychedelic’ compound, researchers compared two sessions of psilocybin therapy with a six-week course of a leading antidepressant (a selective serotonin uptake inhibitor called escitalopram) in 59 people with moderate-to-severe depression.

The results, published today in the New England Journal of Medicine, show that while depression scores were reduced in both groups, the reductions occurred more quickly in the psilocybin group and were greater in magnitude.

However, the researchers caution that the main comparison between psilocybin and the antidepressant was not statistically significant. They add that larger trials with more patients over a longer period are needed to show if psilocybin can perform as well as, or more effectively than an established antidepressant.

For the psilocybin dosing sessions, volunteers received an oral dose of the drug in a specialist clinical setting, while they listened to a curated music playlist and were guided through their experiences by a psychological support team, which included registered psychiatrists. All volunteers on the study received the same level of psychological support.

People treated with psilocybin – named ‘COMP360’ by its developers, COMPASS Pathways PLC – showed marked improvements across a range of subjective measures, including in their ability to feel pleasure, and express emotions, greater reductions in anxiety and suicidal ideation, and increased feelings of wellbeing.

Dr Robin Carhart-Harris, head of the Centre for Psychedelic Research at Imperial, who designed and led the study, said: “These results comparing two doses of psilocybin therapy with 43 daily doses of one of the best performing SSRI antidepressants help contextualise psilocybin’s promise as a potential mental health treatment. Remission rates were twice as high in the psilocybin group than the escitalopram group.

“One of the most important aspects of this work is that people can clearly see the promise of properly delivered psilocybin therapy by viewing it compared with a more familiar, established treatment in the same study. Psilocybin performed very favourably in this head-to-head.”

 

GROWING EVIDENCE

During the study, 59 volunteers with moderate-to-severe depression received either a high dose of psilocybin and a placebo, or a very low dose of psilocybin and escitalopram. 

In the psilocybin arm of the trial, 30 people received an initial dose of psilocybin (25mg) at the start of the study, followed by a second dose (25mg) three weeks later. They were given six weeks of daily placebo capsules to take: one per day after the first dosing session, increasing to two per day after the second dosing session.  

In the escitalopram arm of the study, 29 people received 1mg psilocybin at the dosing sessions – a dose so low as to be classed as a non-active and unlikely to have an effect. They were also given six weeks of daily escitalopram: one 10mg capsule per day after the first dosing session, increasing to two per day after the second dosing session (20mg per day) – the maximum dose for this SSRI. 

All participants were assessed using standardised scales of depressive symptom severity. The main measure, the QIDS-SR-16, was used to gauge depressive symptoms on a continuous scale ranging from 0-27, where higher scores indicate greater depression. At the start of the trial, the mean score was 14.5 for the psilocybin group. But after six weeks, scores reduced by an average of 8.0 points.

Response, defined as a reduction in depression scores from baseline of at least 50%, was seen in 70% of people in the psilocybin group, compared with 48% in the escitalopram group. In addition, remission of symptoms – measured as a score of 0-5 at week six – was seen in 57% of the psilocybin group, compared with just 28% in the escitalopram group.

 

ENCOURAGING FINDINGS

The team highlights that while the findings are generally positive, the absence of a straight placebo group and the small number of participants limits conclusions about the effect of either treatment alone. They add that the trial sample was comprised of largely white, majority male, and relatively well-educated individuals, which limits extrapolations to more diverse populations. 

The psilocybin group reported fewer cases of dry mouth, anxiety, drowsiness and sexual dysfunction than the escitalopram group, and a similar rate of adverse events overall. Headaches experienced one day after dosing sessions were the most common side effect of psilocybin.

Dr Rosalind Watts, clinical lead of  the trial and formerly based at the Centre for Psychedelic Research, said: “Context is crucial for these studies and all volunteers received therapy during and after their psilocybin sessions. Our team of therapists were on hand to offer full support through sometimes difficult emotional experiences."

Professor David Nutt, principal investigator on the study and the Edmond J Safra Chair in Neuropsychopharmacology at Imperial, said: “These findings provide further support for the growing evidence base that shows that in people with depression, psilocybin offers an alternative treatment to traditional antidepressants.

“In our study, psilocybin worked faster than escitalopram and was well tolerated, with a very different adverse effects profile. We look forward to further trials, which if positive should lead to psilocybin becoming a licensed medicine.”

 

 

Magnesium has key role in keeping body clocks running on time

University of Edinburgh, April 13, 2021

 

An essential mineral in our diets has an unexpected role in helping living things remain adapted to the rhythms of night and day, scientists have found.

 

Magnesium - a nutrient found in many foods - helps control how cells keep their own form of time to cope with the natural environmental cycle of day and night.

 

The discovery in cells is expected to be linked to whole body clocks which influence daily cycles - or circadian rhythms - of sleeping and waking, hormone release, body temperature and other important bodily functions in people. The surprising discovery may aid the development of chronotherapy - treatment scheduled according to time of day - in people, and the development of new crop varieties with increased yields or adjustable harvesting seasons.

 

Experiments in three major types of biological organisms - human cells, algae, and fungi - found in each case that levels of magnesium in cells rise and fall in a daily cycle.

 

Scientists found that this oscillation was critical to sustain the 24-hour clock in cells. They were surprised to discover that it also had an enormous impact on metabolism in cells - how fast cells can convert nutrients into energy - throughout the course of a day.

 

Researchers at the University of Edinburgh and the MRC Laboratory for Molecular Biology in Cambridge used molecular analysis to find that concentrations of magnesium rose and fell in a 24-hour cycle in all cell types, and that this impacts on the cells' internal clocks.

 

Further tests showed that magnesium levels were linked to the cells' ability to burn energy. It was already known that magnesium is essential to help living things convert food into fuel, but scientists were surprised to discover that it also controls when this biological function takes place, and how efficiently.

 

Dr Gerben van Ooijen, of the University of Edinburgh's School of Biological Sciences, who led the study, said: "Internal clocks are fundamental to all living things. They influence many aspects of health and disease in our own bodies, but equally in crop plants and micro-organisms. It is now essential to find out how these fundamentally novel observations translate to whole tissue or organisms, to make us better equipped to influence them in complex organisms for future medical and agricultural purposes."

 

The study's other senior author, Dr John O'Neill of the MRC Laboratory of Molecular Biology in Cambridge, said: "Although the clinical relevance of magnesium in various tissues is beginning to garner more attention, how magnesium regulates our body's internal clock and metabolism has simply not been considered before. The new discovery could lead to a whole range of benefits spanning human health to agricultural productivity.

 

 

Exercise promotes healthy living and a healthy liver

Researchers show that in non-alcoholic fatty liver disease, regimented exercise has beneficial effects on the liver that are unrelated to weight loss and reveal the mechanisms underlying these benefits

University of Tsukuba (Japan), April 12, 2021

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide, affecting as much as a quarter of humanity. It is characterized by fat accumulation in liver cells and may progress to inflammation, cirrhosis and liver failure. Now, researchers at the University of Tsukuba reveal the positive effects, beyond the expected weight-loss benefit, of exercise on the liver. 

NAFLD is associated with unhealthy behaviors such as overeating and a sedentary lifestyle. In Japan 41% of middle-aged men have NAFLD and 25% will progress to non-alcoholic steatohepatitis (NASH) and hepatic dysfunction.

Weight reduction is fundamental to NAFLD management. Unfortunately, achieving a targeted bodyweight without supervision is difficult, and maintaining this over time even more so. Hitherto, exercise was considered adjunctive to dietary restrictions for weight loss but the other benefits such as reduced hepatic steatosis (fatty change) and stiffness are being increasingly recognized. However, the underlying mechanisms remain unclear.

"We compared data from obese Japanese men with NAFLD on a 3-month exercise regimen with those on dietary restriction targeting weight loss," senior author Professor Junichi Shoda explains. "We tracked hepatic parameters, reduction in adipose tissue, increase in muscle strength, reductions in inflammation and oxidative stress, changes in organokine concentrations, and expression of target genes of Nrf2, an oxidative stress sensor."

The researchers found that exercise preserved muscle mass better, though with modest decrease of body and fat mass. Remarkably, ultrasound elastography revealed that the exercise regimen reduced liver steatosis by an additional 9.5%, liver stiffness by an additional 6.8%, and the FibroScan-AST Score (a measure of liver fibrosis) by an additional 16.4% over the weight-loss regimen.

Additionally, the exercise regimen altered the circulating concentrations of specific organokines and apparently induced anti-inflammatory and anti-oxidative stress responses through activation of the Nrf2 (nuclear factor E2-related factor 2), an oxidative stress sensor. It also enhanced the phagocytic capacity of Kupffer cells which help maintain liver function.

Professor Shoda explains the relevance of their findings. "Our research shows how exercise prevents liver steatosis and fibrosis in NAFLD and clarifies that this benefit is compounded by preservation of muscle mass and is independent of weight changes. Patients on exercise regimens may become demotivated and drop out if they do not experience significant weight loss. Therefore, moderate to vigorous intensity exercise should be integrated in all NAFLD therapeutic regimens, and patients at risk for NASH should be encouraged to persevere with moderate to high intensity exercise regardless of whether or not they lose weight."