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We’ve lined up another great collection of news stories for this issue of the Science Digest, curated just for you. Read on to learn how…
People with obesity and COVID-19 produce mostly autoimmune SARS-CoV-2 antibodies, not neutralizing.
The SARS-CoV-2 virus infects adipose tissue, increasing inflammation during COVID-19 illness.
Older adults with a higher BMI spread more infectious SARS-CoV-2 aerosol particles.
And much more!
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Rhonda and team
Science Digest – November 19, 2021
People with obesity and COVID-19 produce mostly autoimmune SARS-CoV-2 antibodies, not neutralizing.
Obesity is a strong independent risk factor for COVID-19, the disease caused by the SARS-CoV-2 virus. Scientists have found that people with obesity generate fewer antibodies in response to viral infection or vaccination; but they don’t know whether obesity also affects antibody quality. Findings published in a new report show that the majority of the antibodies found in people with obesity are autoimmune and not able to neutralize the SAR-CoV-2 virus, putting individuals with obesity at greater risk of severe COVID-19.
Obesity increases the rate of inflammaging, the process of chronic low-grade inflammation that wears down the body’s tissues over time, putting people with obesity at greater risk of many diseases. Inflammaging increases the risk of autoimmunity by increasing the concentration of damaged cellular components in the blood, potentially triggering the immune system to generate antibodies against its own cells. Previous research has shown that many people with severe COVID-19 generate autoimmune antibodies that increase the risk of long-term complications. Because people with obesity often have higher baseline inflammaging, they may be at greater risk of developing long-term autoimmune complications for COVID-19.
The investigators collected blood from 15 participants with a lean body mass index (BMI; less than 25) and 15 participants with an obese BMI (greater than 30) who tested positive for SARS-CoV-2. The investigators also collected blood from 30 participants who had not had a SARS-CoV-2 infection and were matched for age, sex, and BMI. The researchers measured the concentration of neutralizing antibodies (antibodies that bind to the SARS-CoV-2 spike protein and prevent viral entry into cells), non-neutralizing antibodies, and autoimmune antibodies.
Participants with obesity had fewer SARS-CoV-2 antibodies than those with a lean BMI, confirming previous reports. While all 15 SARS-CoV-2-positive participants with a lean BMI had circulating neutralizing antibodies, only a few participants with obesity did. The researchers found that SARS-CoV-2 infection increased the concentration of autoimmune antibodies in all participants, but the concentration of autoimmune antibodies was always higher in participants with obesity. Finally, they found that participants with the highest concentration of autoimmune antibodies also had the highest levels of serum C-reactive protein, a marker of chronic inflammation, suggesting that inflammation is integral to developing autoimmunity.
These findings confirm previous reports that obesity reduces the effectiveness of the immune response in COVID-19 patients and increases the risk of autoimmunity. Learn more about the risks of COVID-19 in people with and without obesity in this episode featuring Dr. Roger Seheult.
Link to full publication.
SARS-CoV-2 infects adipose tissue, increasing inflammation during COVID-19 illness.
SARS-CoV-2 is the novel coronavirus that causes COVID-19. Since its emergence nearly two years ago, the virus has infected more than 255 million people worldwide. Obesity and related diseases such as type 2 diabetes and hypertension are strong, independent risk factors for infection, severe disease, and death. Findings of a new report indicate that SARS-CoV-2 infiltrates adipose tissue, causing inflammation and worsening disease severity.
Severe COVID-19 is characterized by immune hyperreactivity that creates systemic inflammation mediated by excessive production of pro-inflammatory proteins. Obesity is also characterized by excessive immune reactivity and inflammation, potentially putting people with obesity at greater risk of COVID-19 complications. However, further investigation is needed to understand the mechanisms by which obesity increases COVID-19 severity and whether these mechanisms are independent of type 2 diabetes, hypertension, and other obesity-related conditions.
The investigators recruited adults with obesity who were patients of a bariatric surgery center and had not had a SARS-CoV-2 infection. They collected adipose tissue samples from multiple fat depots around the body, such as subcutaneous fat (under the skin), visceral fat (wrapped around internal organs), and pericardial and epicardial fat (around the heart), on the day participants underwent bariatric surgery. The researchers also collected adipose tissue samples from adults who had died from COVID-19 illness. They isolated cells from the connective tissue, sorted them based on type (such as mature adipocyte, pre-adipocyte, and adipose tissue macrophage) and characterized their gene expression and surface receptor population. Then, they exposed the cells to the SARS-CoV-2 virus and observed changes.
The authors found that the SARS-CoV-2 virus infects adipose tissue from multiple depots around the body, but that macrophages (white blood cells) were the main cell type infected. They found low expression of the angiotensin converting enzyme (ACE)-2 receptor in these macrophages, indicating that the virus enters through a different route than the primary entry points in cells of the lungs and gut. Upon exposure to the SARS-CoV-2 virus, these cells increased production of pro-inflammatory proteins. In adipose tissue samples from participants who had died of COVID-19, the investigators found SARS-CoV-2 infection in mature adipocytes in addition to macrophages.
These results are the first to show that the SARS-CoV-2 virus can infect adipose tissue in vivo and that this tissue type may contribute to excess inflammation during COVID-19 illness, especially in people with obesity.
Link to full publication.
Learn more about the inflammatory response to COVID-19 in this clip featuring Dr. Roger Sehuelt.
Older adults with a higher BMI spread more infectious SARS-CoV-2 aerosol particles.
The SARS-CoV-2 virus is transmitted through aerosols that are generated when an infected person breathes, talks, sneezes, or coughs. The amount and size of aerosol droplets a person exhales can vary drastically between individuals and may be affected by diet and age. Findings of a recent study suggest that humans and non-human primates with greater age and body mass index (BMI) produce more aerosol droplets during COVID-19 infection.
Aerosol droplets are produced when air passes over mucus-coated airways during breathing. This mucus determines the size of aerosol droplets produced. A healthy mucus layer forms large droplets, while a dysfunctional mucus layer produces droplets that aerosolize into many smaller infectious droplets. Mucus structure and composition are influenced by age, environment, disease, and the microbiota. A Western, obesity-promoting diet is often deficient in fiber, starving the beneficial bacteria in the gut that produce metabolites such as short chain fatty acids that regulate the lung mucus barrier. Older adults also experience degradation of the lung mucus layer, potentially influencing aerosol droplet size.
The researchers recruited 194 participants from the United States. They asked participants to breathe into a particle detector to measure the quantity of exhaled particles in the size range of three to five micrometers. They characterized participants who exhaled 156 particles per liter of air or less during the breath test as “low spreaders” and participants above this level as “superspreaders.”
The particle detector was connected to an air filter that collected the particles so the concentration of SARS-CoV-2 virus could be measured. The investigators also studied eight non-human primates to better understand the effects of SARS-CoV-2 infection. They exposed rhesus macaques and green monkeys to either the SARS-CoV-2 or tuberculosis virus and monitored them for up to 60 days. The non-human primates performed a similar breath test as the one used by the human participants.
The authors found no relationship between sex and aerosol particle number, but there were significant statistical relationships among age, BMI, and particle size. The strongest correlation was found between particle size and BMI-years, which is calculated as BMI multiplied by age. Participants in the bottom 50 percent for BMI-years exhaled significantly less aerosol than participants in the top 50 percent. In non-human primates, SARS-CoV-2 or tuberculosis infection increased the number of aerosol particles exhaled in proportion to the amount of viral RNA measured from mucus swabs.
The authors concluded that age, BMI, and active infection decrease aerosol particle size and may contribute to viral spread. Future models of pandemic progression should take these factors into account.
Link to full publication.
Sugar consumption increases appetite for fatty foods.
The Western diet, rich in fats and sugar, is a key driver of obesity. But questions remain about whether fats and sugar share equal causal roles in the disease. A recent animal study suggests that consuming sugar co-opts the brain’s internal opioid signaling system, triggering a robust appetite for fat.
The brain’s internal opioid system is composed of an array of receptors and ligands present throughout the central and peripheral nervous systems and other parts of the body. It plays a critical role in modulating the brain’s reward center, which directs mood, behavior, and appetite. Because the opioid system is highly sensitive to stimulation, overactivation of opioid receptors causes brain cells to internalize opioid receptors to avoid overstimulation, leading to tolerance and a craving for greater intake.
In this study, researchers gave adult rats constant access to a high-fat diet for two weeks. During the second week, they placed the animals in two groups: an experimental group that had five minutes of access to a 30 percent sugar-water solution every day and a group that had equivalent access to plain water. At the end of the two-week period, they administered the rats either a synthetic opioid or an inactive substance and observed the animals’ eating behavior.
The researchers found that rats that drank the sugar water ate approximately 25 percent more fat in the five hours that followed their drink compared to mice that drank plain water. They also found that administering a synthetic opioid to the rats that drank plain water triggered an immense appetite for fat that mimicked the effects of drinking sugar water. The synthetic opioid had no effects on fat consumption in rats that drank sugar water, indicating that the sugar had already pre-activated the same neurochemical pathways.
These findings suggest that the opioid system participates in regulation of fat intake, potentially offering a new way to think about the factors that drive obesity. The authors posited that the high sugar content of modern Western diets may drive the development of lower-sensitivity opioid receptor systems. This leads people to crave and consume more sugar and high-calorie fatty foods, causing weight gain.
Link to full publication.
Learn more about how sugar affects the body in this podcast featuring Dr. Rhonda Patrick.
Compounds in green tea strengthen cellular defenses by stressing the mitochondria.
Green tea is one of the most popular beverages in the world. Its consumption is linked to a wide range of health benefits, including lower blood pressure, improved blood sugar regulation, and greater weight loss in people with obesity. Findings from a recent study suggest that catechins present in green tea promote longevity via hormesis.
Catechins are bioactive compounds found in many edible fruits, vegetables, and plant leaves. Evidence indicates that catechins exert potent antioxidant, anti-cancer, and neuroprotective effects. However, catechins are poorly absorbed in the human gut and have low bioavailability, effectively limiting plasma concentrations in humans to levels that are 20 to 120 times lower than those linked to longevity in many research animals.
Hormesis is a compensatory defense response following exposure to a mild stressor that is disproportionate to the magnitude of the stressor. Hormesis triggers a vast array of protective mechanisms that not only repair cell damage but also provide protection from subsequent exposures to more devastating stressors.
The researchers placed colonies of worms in edible jelly-like environments infused with low doses of epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) – the most abundant catechins in green tea – or an inactive substance. They then measured the worms’ lifespans, as well as a variety of indicators of general stress tolerance and overall health. The researchers also measured levels of oxidative stress inside the mitochondria.
They found that low levels of EGCG and ECG generated a significant spike in reactive oxygen species (chemically reactive molecules that contain oxygen) and reduced mitochondrial respiration and glucose oxidation by 20 percent, inducing a state of oxidative stress and cellular “starvation.” Despite these hardships, the worms’ lifespans increased from 28.8 to 30.7 days – a longevity boost of over 6 percent. Exposure to EGCG and ECG also improved the worms’ stress tolerance and general health.
These findings suggest that rather than acting as a traditional antioxidant, green tea may work by triggering bouts of mitochondrial stress, ultimately boosting cellular resilience and lifespan, a phenomenon referred to as mitohormesis– hormesis specific to the mitochondria. Learn more about how some dietary compounds promote longevity in this episode featuring Dr. David Sinclair.
Link to study abstract.
Exposure to air pollution increases depression risk.
Depression is a complex neuropsychiatric disorder that affects millions of people worldwide. Although many factors contribute to a person’s risk for developing depression, such as childhood trauma or stressful life events, genetic predisposition for the condition plays a prominent role. Findings from a recent study suggest that air pollution exerts harmful neuropsychiatric effects, especially among people genetically predisposed to depression.
Air pollution contains myriad toxic substances, including chemicals, gases, and particulate matter – a mixture of solid particles and liquid droplets that may have neurotoxic properties. Exposure to air pollution promotes oxidative stress and increases the risk of developing many chronic diseases, including cardiovascular disease, cancer, hypertension, and diabetes, markedly shortening people’s lives.
The new study involved 352 healthy adults living in Beijing, China, a city known for its high levels of air pollution and relatively homogeneous population. The investigators determined each participant’s genetic propensity for developing depression – referred to as a polygenic risk score – and tracked air quality near the participants’ homes. Participants completed various mental tasks while undergoing brain scans.
The scans revealed that people who were exposed to air pollution performed poorly on mental tasks. This effect was more pronounced among those who had a higher polygenic risk score for depression as well as those exposed to the highest levels of air pollution. The findings held true even after considering other factors, such as age, sex, and education, which can influence depression risk.
These findings suggest that air pollution impairs neurocognitive function, especially among people genetically predisposed to depression. They also underscore public health efforts to ameliorate the harmful effects of pollution. Some evidence indicates that dietary components, such as omega-3 fatty acids and sulforaphane (a bioactive compound derived from broccoli), may negate some of the harmful effects of exposure to air pollution. Watch this clip in which Dr. Jed Fahey describes how sulforaphane provides protection from benzene, a carcinogenic compound present in air pollution.
Link to study abstract.
Learn more about depression in our overview article.
Perceptions of sleep depth don’t correlate with sleep phase.
Sleep scientists generally categorize the various phases of human sleep as REM (rapid-eye movement – the period when dreams occur) and NREM (non-rapid-eye movement – the period typically described as “deep sleep”). Subjective perceptions of sleep and sleep quality, or “depth,” vary, however. Findings from a recent study suggest that some people’s perceptions of how deeply they sleep don’t align with objective measures of their sleep.
Objective measures of sleep quality are based on multiple physiological and neurological parameters that gauge the depth, quality, and duration of a person’s sleep. Typical measures include assessments of brain waves (via electroencephalogram, or EEG), heart rate, and respiration rate, among others.
The authors of the study recruited 20 healthy adults (average age, 38 years) who considered themselves good sleepers and 10 healthy adults of similar ages who had insomnia. While the participants slept, the authors measured the participants’ brain waves via EEG, periodically waking them to obtain subjective assessments of their sleep depth and quality.
The good sleepers reported that their sleep was lightest in the first two hours of NREM sleep (generally considered “deep sleep”) and deepest during REM sleep. Conversely, participants with insomnia reported feeling awake more often during the first two hours of NREM sleep and often reported having lighter REM sleep. Interestingly, the EEGs revealed that the participants with insomnia were asleep during periods when they reported being awake. During periods of subjective deep sleep, participants reported having dream-like mental activity.
These findings suggest that subjective perceptions about how deeply a person is sleeping don’t necessarily align with the phase of sleep they are in. Such findings could have relevance for future sleep studies, especially those aimed at improving sleep quality for people with insomnia.
Link to full publication.
Learn more about sleep in this episode featuring sleep expert Dr. Matthew Walker.
Blood-brain barrier dysfunction may drive Parkinson’s disease progression.
Parkinson’s disease is a progressive neurodegenerative disorder that affects more than 10 million people worldwide. The neuropathological hallmarks of Parkinson’s disease are the loss of dopamine-producing neurons in the substantia nigra region of the brain and the aggregation of alpha synuclein, a type of protein. People who have Parkinson’s disease experience both motor symptoms (such as tremors and a shuffling gait) and non-motor symptoms (such as pain, fatigue, and difficulty concentrating or remembering). Findings from a new study suggest that people with Parkinson’s disease have defects that promote poor blood-brain barrier function, impairing angiogenesis and autophagy.
The blood-brain barrier is a lining of epithelial (skin-like) cells that exchanges nutrients, waste, and signaling molecules. The integrity of the blood-brain barrier relies on angiogenesis, the process by which new blood vessels form. Autophagy also supports epithelial health by sequestering protein aggregates, pathogens, and damaged or dysfunctional organelles so they can be broken down and re-used. It performs both a general housekeeping role and a targeted cleansing strategy to maintain cellular health. Autophagy is impaired in Parkinson’s disease, reducing clearance of alpha synuclein aggregates and driving neuronal death.
The investigators previously found that nilotinib, a drug commonly used to treat chronic myelogenous leukemia, halted some of the motor and non-motor symptoms of Parkinson’s disease. The current study clarified the mechanisms that drove these improvements by analyzing cerebrospinal microRNAs, small, non-coding RNA molecules that play important roles in regulating gene expression. Previous research has identified abnormal levels of microRNAs that control genes associated with autophagy in the cerebrospinal fluid of people with Parkinson’s disease. These microRNAs drive the upregulation of proteins that promote degradation of the blood-brain barrier.
The investigators randomly assigned 75 people with Parkinson’s disease to receive 150 or 300 milligrams of nilotinib or a placebo every day for a year. They collected cerebrospinal fluid samples from the participants at the end of the year and conducted genetic sequencing of RNA that they had isolated in the fluid.
They found that after participants were on nilotinib for one year, their cerebrospinal fluid levels of microRNAs that control genes and pathways involved in angiogenesis, autophagy, and collagen (a component of the blood-brain-barrier) increased, and their symptoms improved. Participants who received the placebo did not experience these changes and improvements.
These findings demonstrate that people with Parkinson’s disease have altered expression of genes involved in blood-brain-barrier integrity and autophagy. They further indicate that addressing vascular defects associated with Parkinson’s disease may be beneficial in treating some of the symptoms that accompany the disorder.
Link to full publication.
Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
Novel amyloid-beta vaccine reduces Alzheimer’s-like dementia in mice.
Alzheimer’s disease is a neurodegenerative disease characterized by aggregates of misfolded proteins such as amyloid-beta and tau in the brain. Previous research has attempted to use amyloid-beta vaccines to stall or reverse the progression of Alzherimer’s disease; however, these trials failed to produce a vaccine that was safe and effective. A study released this week has identified a new target for Alzheimer’s disease vaccines that may succeed in clearing amyloid-beta plaques.
Amyloid-beta is a small, 36-43 amino acid protein that is cleaved from a larger amyloid precursor protein in the brain. After being cleaved, the small amyloid-beta protein can become misfolded, lose its function, and form oligomers – aggregate protein structures with many repeating identical units. Some of the amino acids on one end of the amyloid-beta structure fold over, creating a hairpin-like structure and contributing to plaque formation. Previous research has suggested the hairpin site is an effective target for preventing aggregation; however, no vaccine has yet been developed that exploits this molecular pattern.
The study investigators designed a peptide that is a portion of the amyloid-beta protein containing 14 amino acids that are cyclized to form a stable pseudo-hairpin structure. They inoculated healthy mice with the cyclized peptide and measured the antibody response. Next, they immunized mice that exhibit Alzheimer’s-like dementia and measured the effect on amyloid-beta plaques in the brain. They also measured cognitive function and hippocampal volume, both of which decline with Alzherimer’s disease.
The authors found that healthy mice had a robust immune response to immunization and produced antibodies specific to the pseudo-hairpin protein they designed. In mice who develop Alheimer’s-like dementia, immunization significantly reduced the amount of amyloid-beta plaques in regions of the brain such as the cerebral cortex, hippocampus, and thalamus. These regions also exhibited increased glucose metabolism following immunization, indicating better metabolic health in the brain. Finally, immunization increased the number of neurons in the hippocampus, the brain region most associated with learning memory. Immunized mice with greater hippocampal volume performed better on learning and memory tasks.
Immunization with the novel pseudo-hairpin structure reversed amyloid-beta aggregation in the brain and improved brain health and cognitive performance in mice. This exciting research may contribute to the development of Alzheimer’s disease vaccines in humans.
Link to full publication.
Learn more about what causes Alzheimer’s disease from expert Dr. Dale Bredesen in this clip from the FoundMyFitness podcast.
Estrogen may provide protection against Alzheimer’s disease.
Scientists have long known that estrogen, the primary female sex hormone, exerts protective effects on multiple organ systems. For example, estrogen helps maintain healthy blood lipid levels, reduces the risk of cardiovascular disease, and promotes bone health. Findings from a recent study suggest that estrogen protects against age-related cognitive decline and Alzheimer’s disease.
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. The disease disproportionally affects women, and scientists have identified distinct sex-related differences in Alzheimer’s disease symptoms, progression, biomarkers, and risk factors. Interestingly, the pathological hallmarks of Alzheimer’s disease begin to appear 10 to 20 years before the onset of symptoms – roughly coinciding with the period of menopause in women.
The study involved 99 women and 29 men (average ages, 52 years) who were cognitively normal. The women provided information about their reproductive histories, such as when they began menstruating, how many pregnancies they had, when they experienced menopause, and whether they had used hormonal contraceptives or hormone replacement therapy. Both women and men underwent memory testing and brain scans.
Analysis of the brain scans revealed that the women who were peri- or postmenopausal had less gray matter volume in the temporal cortex, an area of the brain vulnerable to the effects of Alzheimer’s disease. Women who were premenopausal or had longer estrogen exposure due to their reproductive histories were more likely to have greater gray matter volumes. Exposure to estrogen did not influence performance on the memory tests directly, but participants with greater gray matter volume tended to perform better than those with lower volume.
These findings suggest that estrogen exposure exerts protective effects on brain health and illuminate the need for sex-specific research on Alzheimer’s disease pathology and therapies. This was a small study, however, and only identified associations between estrogen exposure and brain health, not causes.
Link to study abstract.
Learn more about Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.
