Hey, friends!
We’ve lined up another great collection of news stories for this issue of the Science Digest, curated just for you, our Premium Members. Read on to learn how…
One night of sleep deprivation reduces muscle protein synthesis.
Intermittent fasting improves long term memory retention in mice.
Bone marrow cells produce long-lasting immunity following recovery from COVID-19.
In other news: We’ve got another Crowdcast Live Q&A coming up Saturday, June 5, at 9:30 a.m. PDT. The code for this event is quercetin. Remember, you can always access the most recent event code and Q&A calendar on your member’s dashboard.
And coming soon: An early release of a brand-new podcast featuring Dr. Michael Snyder, a pioneer and powerful advocate in the field of “wearables” – including continuous glucose monitors. You won’t want to miss this one, so be sure you’re subscribed to The Aliquot, available on your member dashboard, to get notified when it’s released!
Enjoy!
Rhonda and team
Science Digest – June 4, 2021
Sleep deprivation impairs skeletal muscle protein synthesis.
Poor sleeping habits impair normal cognitive and metabolic function, leading to poor mental and physical health outcomes in the short- and long-term. Sleep loss may also interfere with protein synthesis, driving skeletal muscle losses, a risk factor for obesity, type 2 diabetes, and frailty. Authors of a recent report measured the effects of sleep deprivation on muscle protein synthesis.
Skeletal muscle is metabolically active. Having more muscle mass promotes insulin sensitivity and reduces the risk of developing type 2 diabetes. Previous research in rats has shown that sleep deprivation reduces the activity of enzymes that build muscle, such as testosterone and insulin-like growth factor (IGF)-1, and increases the activity of enzymes that break down muscle, such as cortisol. The same shift in hormones may occur in humans deprived of sleep.
Thirteen young adults (average age, 21 years) completed two testing days in random order in which they experienced one night of sleep deprivation and one night of normal sleep. On one day, participants consumed a standardized meal at home at 7 p.m., reported to the laboratory at 9 p.m., and were not permitted to sleep until 7 a.m. During the night, participants were allowed to engage in quiet activities and eat low-protein fruits and vegetables as snacks. On the other day, participants consumed a standardized meal at home at 7 p.m., then slept at home between 10 p.m. and 7 a.m.. On both days, researchers collected blood samples and muscle tissue samples, following a standardized breakfast meal.
One night of sleep deprivation reduced muscle protein synthesis by 18 percent. This was accompanied by a 24 percent reduction in serum testosterone levels in male participants and a 21 percent increase in cortisol levels in all participants. There was no difference in plasma insulin or IGF-1 levels and no difference in markers of muscle protein degradation.
The authors concluded that just one night of sleep deprivation interferes with muscle protein synthesis. Chronic sleep deprivation may cause loss of muscle mass due to long-term suppression of muscle-building enzymes. Fortunately, evidence indicates that exercise counters at least some of the negative effects of sleep loss on metabolism. For example, high-intensity interval training before a night of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids caused by lost sleep in healthy males.
Link to full report.
Learn more about cortisol and sleep in this episode featuring sleep expert Dr. Matthew Walker.
And watch this short video on the hidden connection between sleep and dementia.
Intermittent fasting improves long term memory retention in mice.
Intermittent fasting is a broad term that describes periods of fasting between meals, lasting several hours to days. Intermittent fasting increases ketone production because it uses stored fat as an energy source. It also activates genetic pathways associated with enhanced healthspan and longevity. Caloric restriction, which typically involves a 10 to 40 percent reduction in total caloric intake, activates similar pathways. Findings from a new study suggest that intermittent fasting is more effective than caloric restriction in activating klotho, a longevity gene, to improve long-term memory retention in mice.
The klotho gene provides the instructions for making the klotho protein in mammals, including mice and humans. Klotho is produced primarily in the kidneys, but some is produced in the brain, where it appears to play a role in cognition and in neurogenesis, the process of forming new neurons. Neurogenesis is the basis for memory formation, but it declines with age, leading to cognitive decline.
The authors of the study assigned mice to one of three feeding regimens: intermittent feeding every other day (approximately 10 percent fewer calories over a one-week period); 10 percent calorie restriction every day; or eating freely. After the mice had followed their respective feeding regimens for three months, the authors of the study subjected them to behavioral studies (to assess spatial learning and memory, conducted at 24 hours and ten days post regimen) or gene expression studies.
The memory assessment conducted at 10 days post regimen revealed that the mice in the intermittent feeding group performed 25 percent better than those in the caloric restriction group and 30 percent better than those that ate freely. The mice in the intermittent feeding group also exhibited more signs of hippocampal neurogenesis and upregulation of the klotho gene. Further analysis revealed that adult hippocampal neurogenesis is dependent upon klotho activity.
These findings demonstrate that the longevity gene klotho is necessary for neurogenesis and that intermittent feeding may be beneficial in promoting memory retention in humans. A ketogenic diet also improves memory in mice. Learn more about the effects of the ketogenic diet on memory in this episode featuring aging expert Dr. Eric Verdin.
Link to full study.
Bone marrow cells produce long-lasting immunity following recovery from COVID-19.
COVID-19 is caused by infection with SARS-CoV-2, a type of coronavirus. Following SARS-CoV-2 infection, the immune system produces antibodies specific for the SARS-CoV-2 spike protein that prevent reinfection. However, research from early in the COVID-19 pandemic reported a rapid loss of these antibodies a few months after infection. Findings of more recent research suggest SARS-CoV-2 immunity may last longer than previously thought.
During an infection, mature B cells, a type of white blood cell that originates in the bone marrow. enter the bloodstream as plasma cells. There they are activated to produce antibodies specific for the active pathogen. When the infection has resolved, B cells called long-lived bone marrow plasma cells return to the bone marrow, where they lie dormant until exposure to the same pathogen reoccurs, providing long-lasting immunity.
The researchers collected blood from 77 patients who had recovered from mild SARS-CoV-2 infection, at approximately one month following the onset of symptoms and then every three months thereafter. They also collected bone marrow samples from 18 participants seven to eight months after infection and from 11 healthy volunteers with no history of SARS-CoV-2 infection or vaccination. Finally, they collected a second bone marrow sample from six participants 11 months after infection.
In the first four months following infection, the concentration of plasma spike antibodies decreased by almost 10 percent; however, this rate slowed over time so that only seven percent of antibodies were lost between four and 11 months. At seven months post-infection, bone marrow samples from most recovered patients contained plasma cells specific for SARS-CoV-2, and the concentration of these cells remained stable at 11 months post-infection. Participants had no spike antigen-producing cells in their blood at the time of bone marrow sampling, meaning all antibody-producing cells were located in bone marrow only at 7 and 11 months post-infection.
These findings demonstrate that infection with the SARS-CoV-2 virus results in long-term immunity from long-lived bone marrow plasma cells, even though concentrations of antigen in the bloodstream decrease over time.
Link to full report.
Learn more about COVID-19 immunity in this Q&A with Dr. Rhonda Patrick.
Vitamin D treatment reduces the risk of severe outcomes and death in patients with COVID-19.
Vitamin D deficiency in the setting of COVID-19 can lead to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system can drive poor outcomes, such as acute respiratory distress syndrome (ARDS) and death in COVID-19. Findings from a recent study suggest that supplementation with calcifediol, an intermediate molecule in the production of the active form of vitamin D, reduces the risk of death due to COVID-19.
Calcifediol is a prescription vitamin D analog. It differs from vitamin D3 (the typical form of vitamin D in supplements) because it is in an intermediate form of vitamin D, called 25-hydroxyvitamin D, which is formed in the liver. Giving patients calcifediol bypasses the need for conversion in the liver and is therefore faster acting than ordinary vitamin D3.
The retrospective cohort study involved 537 patients living in Spain who were hospitalized with COVID-19 during a three-month period in early 2020. Of these patients, 79 received vitamin D treatment that provided 532 micrograms (~21,000 IU) of calcifediol on the first day of their hospital stay and 266 micrograms of calcifediol (~9,300 IU) on days 3, 7, 14, 21, and 28. The primary outcome measure was death during the first 30 days of hospitalization.
During the study period, 20 percent of patients who did not receive vitamin D treatment died. More of the patients in the untreated group had chronic kidney disease, but fewer had diabetes, cancer, high blood pressure, or other cardiovascular diseases, compared to the treated group. They also had low oxygen saturation levels and were more likely to have elevated inflammatory markers. Twenty-five percent of this group developed ARDS. Only 5 percent of those who received vitamin D treatment died, and only 10 percent of these developed ARDS, even though the patients in this group were more likely to have comorbidities (coexisting health conditions), compared to the untreated group.
These findings suggest that vitamin D reduces the risk of severe outcomes, including death, in patients with COVID-19. The authors of the study noted that this small study was observational in design, possibly limiting the interpretation of these findings. They also noted that although none of the patients in this cohort were assessed for vitamin D deficiency, most of the people who live in southern Spain tend to be deficient during the time of year when the study was conducted.
Link to full study.
Short-term diet and lifestyle intervention slows epigenetic aging.
Age-related diseases like heart disease, diabetes, dementia, and cancers are on the rise, placing a significant burden on global healthcare systems and economies. Interventions that can slow the aging process by just two years could save almost $7 trillion over 50 years and increase health and quality of life. Authors of a recent report tested the effects of a diet and lifestyle intervention on the reversal of epigenetic aging.
Epigenetic aging is a way to predict an individual’s risk of age-related disease by biological means instead of just chronology. Epigenetics is a biological mechanism that regulates gene expression (how and when certain genes are turned on or off). Diet, lifestyle, and environmental exposures can drive epigenetic changes throughout an individual’s lifespan to influence aging. The record of these changes can be used to predict biological age. Lifestyle interventions may be able to slow biological aging by reversing some epigenetic modifications.
The authors of the study enrolled 43 healthy males between the ages of 50 and 72 years. They randomly assigned half of the participants to complete an eight-week diet and lifestyle intervention, while the other half did not. The intervention included a diet rich in vegetables (e.g., leafy greens, beets, and cruciferous and other colored vegetables), low-glycemic fruit (e.g., blueberries), seeds, animal proteins, liver, and eggs. The researchers advised participants to choose organic over conventional produce and meat; avoid eating between 7 p.m. and 7 a.m.; stay hydrated; cook with healthy oils (e.g., coconut, olive, or flaxseed oils); avoid sugar, dairy, grains, and beans; and avoid plastic containers. They gave participants a supplement rich in bioactive plant compounds (including quercetin and green tea extract) and a probiotic supplement containing Lactobacillus plantarum, a type of beneficial bacteria. They also asked participants to exercise for 30 minutes five days per week, sleep for at least seven hours per night, and manage stress with prescribed breathing exercises. The researchers measured the participants’ DNA methylation patterns before and after the intervention period to assess epigenetic changes.
The epigenetic age of the participants who completed the diet and lifestyle intervention decreased by more than three years by the end of the eight-week trial compared to participants in the control group. Compared to their own baseline epigenetic age, participants who completed the intervention reversed their epigenetic clocks by almost two years, although this relationship was not statistically significant. The intervention also increased serum folate by 15 percent and reduced blood triglyceride levels by 25 percent. Low folate status and high triglyceride levels are risk factors for cardiovascular disease.
This study is the first randomized controlled trial to find that diet and lifestyle interventions may reverse epigenetic aging in healthy adult males. The authors noted that large-scale trials with longer durations are needed to confirm their results.
Link to full report.
Learn more about lifestyle factors that can slow aging in this clip featuring epigenetic aging expert Dr. Steve Horvath.
How starchy foods are cooked may change post-meal blood sugar response.
Worldwide more than 300 million people live with obesity, and 460 million people live with type 2 diabetes, creating a significant global public health burden. A key contributor to weight gain and the metabolic dysfunction that drives type 2 diabetes is dietary starch, a major energy source for many people around the world. Findings of a recent study describe the relationship between starch structure, cooking techniques, and post-meal blood sugar response.
Starch is a carbohydrate derived from grains, beans, and some vegetables. It is composed of chains of glucose molecules that can be arranged in straight structures (called amylose) or branched structures (called amylopectin). High-amylose starches, which are found in foods like beans, basmati rice, and green bananas, form very tight structures that slow digestion and are less likely to cause blood glucose spikes. High-amylopectin starches, which are found in foods like white bread, sticky rice, and pastries, are more rapidly absorbed and are far more likely to cause blood glucose spikes.
Adding water to starches and heating them, a process known as gelatinization, increases their digestibility and capacity to increase blood glucose, while heating and then cooling starches (e.g., cooking potatoes and eating them in a cold salad) can create beneficial starches (called retrograde starches) that are resistant to digestion and do not increase blood sugar. Evidence suggests that consuming resistant starches improves insulin sensitivity in men with overweight or obesity. Mechanically processing starches (e.g., milling flour or blending fruits) also increases their digestibility and capacity to increase blood glucose.
The authors of the current study conducted a systematic review and meta-analysis in which they searched the literature for studies testing starches and their effects on post-meal metabolism, collected studies based on a set of criteria meant to select for high-quality design, and then combined the data for analysis. The authors found 45 studies that met the selection criteria for this review. These studies investigated starch characteristics, such as gelatinization, retrogradation, protein content, and particle size, and metabolic responses to starch intake, such as blood glucose and insulin levels and appetite suppression.
Analysis of the 45 studies revealed significant reductions in post-meal blood glucose and insulin levels when the starch consumed had a high amylose content, was less-gelatinized, contained retrograded starch, or contained intact and large particles. Investigators used a variety of starchy foods in these studies, including some grains with a naturally high or low amylose to amylopectin ratio. In other trials, investigators used blends of specific flours to achieve their desired amylose to amylopectin ratio. Less gelatinized starches included uncooked rice compared to cooked rice. Retrograded starches included reheated rice, compared to freshly cooked rice. Starches with large and intact particles included whole peas, compared to pea flour. The authors did not have sufficient evidence to report a relationship between starch type and appetite suppression.
The authors concluded that manipulating the structure of starches alters the body’s metabolic response to starchy foods. Consuming starches from raw foods, which have larger, more intact, and less gelatinized particles, or from heated and cooled grains or vegetables with retrograded starches may reduce the risk of type 2 diabetes.
Link to study abstract.
Omega-3 supplementation during pregnancy reduces the risk of early preterm birth.
Early preterm birth (six or more weeks early) is one of the primary contributors to disability and death in children under the age of five years. Infants born early preterm are more likely to experience neurodevelopmental, respiratory, and gastrointestinal difficulties. Nearly 3 percent of infants born in the United States are early preterm, but physicians do not have reliable markers by which to predict whether a woman is at risk for giving birth early preterm. Findings from a new study suggest that maternal high-dose docosahexaenoic acid (DHA) supplementation during pregnancy reduces the risk of early term birth.
DHA is an omega-3 fatty acid found in fatty fish (such as salmon) and other seafood. It plays critical roles in fetal vision and nervous system growth and development. There are no established guidelines for DHA intake for pregnant women, but most prenatal supplements include DHA, typically in amounts of approximately 200 milligrams.
The study involved 1,100 pregnant women in the United States. The authors of the study randomly assigned the women to one of two groups, with one half receiving a high-dose, 1,000-milligram DHA supplement, and the other receiving a low-dose, 200-milligram DHA supplement. Both groups of women took their respective supplements daily for the duration of their pregnancies. The authors noted negative pregnancy outcomes (such as gestational diabetes, preeclampsia, Cesarean delivery, or others), maternal and infant health status (including DHA levels), and serious adverse events post-delivery (such as birth defects, death, or others).
Among women who took the higher dose of DHA, 1.7 percent gave birth early preterm; among those who took the lower dose, 2.4 percent gave birth early preterm. However, if the women had low DHA levels at the beginning of the study, they were half as likely to give birth early preterm if they took the higher dose, compared to those who took the lower dose. Timing was important, too, with lower risk associated with taking the supplements in the first half of pregnancy, rather than the last half. Women who had higher levels of DHA at the beginning of the study had a 1.2 percent risk of giving birth early preterm birth, and this risk did not change when taking a high dose DHA supplement.
These findings suggest that high-dose DHA supplementation during pregnancy reduces the risk of early preterm birth and provide evidence for establishing recommended intakes for pregnant women. The authors recommended that physicians measure DHA levels in pregnant women and offer high-dose DHA supplements to those whose levels are low.
Link to full study.
Maximum human lifespan may be 150 years.
Aging involves a progressive decline in the body’s ability to heal from damage (a property known as resilience) and a gradual increase in the risk of age-related diseases, such as cancer, diabetes, and cardiovascular disease. Aging research aims to increase lifespan and healthspan through pharmacological and lifestyle interventions that enhance cellular repair and reduce exposure to harmful substances. Findings of a recent report propose a possible maximum age for humans.
As the field of aging research grows, several aging “clocks” have been proposed as ways to measure biological age. These clocks use blood markers, DNA patterns, and physical activity measures to estimate the risk of age-related disease more accurately than chronological age. In younger populations, chronological age and biological age are closely aligned, but as populations age, variability between chronological age and biological age increases. By modeling the rate of these aging dynamics, scientists can calculate a theoretical maximum human lifespan.
The authors collected data from over 500,000 participants of the National Health and Nutrition Examination Survey (NHANES), a long-term study of people living in the United States (US), and the United Kingdom (UK) Biobank, a long-term study of people living in the UK. They based their assessments on participants’ complete blood count, which measures the number and type of white blood cells, red blood cells, and platelets and the concentration of hemoglobin. They also retrieved physical activity data measured using a wrist-worn activity tracker from more than 5,000 NHANES participants.
The authors created a statistical model and trained it to predict the risk of disease and death using blood marker data and disease and death rates from the US and UK databases. The model produced a single risk value called the Dynamic Organism State Indicator, which could be used to accurately predict the onset of numerous age-related diseases. The model predicted a loss of resilience and a maximum life span between the ages of 120 and 150 years. The authors used activity tracker data to create a second model of maximum lifespan, which predicted a maximum age between 110 and 170 years.
The authors concluded that human life does have a maximum length due to loss of resilience that cannot be extended by any known interventions. However, they suggested their research may be a step toward the development of life-extending therapies.
Link to full report.
Learn more about factors that influencing aging in this episode featuring aging expert Dr. Judy Campisi.
Age-related brain shrinkage is slower among non-industrialized people.
The brain shrinks with age, a process called brain atrophy, and a faster rate of shrinkage is associated with dementia and cognitive and functional impairments. Heart disease risk factors such as high cholesterol, diabetes, and hypertension are common in industrialized people and increase the risk of brain atrophy. Findings of a recent report compare rates of brain atrophy in industrialized and non-industrialized people.
The indigenous Tsimane people of lowland Bolivia are non-industrialized people who live by foraging, hunting, fishing, and horticulture in the Amazon basin. The Tsimane have the lowest prevalence of coronary heart disease of any known population, likely due to their highly active lifestyle and their diet, which is rich in fiber, unsaturated fats, and omega-3 fats. The Tsimane peoples’ lifestyle also puts them at a high risk for infection, which can cause chronically increased immune activity and inflammation, risk factors for both heart disease and brain atrophy.
The study included over 700 participants aged 60 years or older enrolled in a long-term study measuring lifestyle and health status in Tsimane adults. Clinic staff regularly visited participants in their villages to record infections and inflammation, heart disease risk factors, diet, and physical activity. The participants visited a nearby city to complete a computerized tomography (CT) scan of their heads to measure brain volume. The researchers compared these results to brain volume measurements from participants in the United States and Europe.
When compared to industrialized populations, the Tsimane had a significantly slower rate of brain volume loss with age. For example, compared to one sample of 500 participants aged 40 to 70 years in the Netherlands, Tismane adults in the same age range had half the rate of brain atrophy.
The authors concluded that slower rates of brain atrophy, along with diet and lifestyle factors and low heart disease risk among the Tsimane protect brain health despite high levels of chronic inflammation caused by infection. Future research should explore the relationship between infection, heart disease risk, and dementia.
Link to full report.
Waking just one hour earlier decreases depression risk.
Good sleep habits are important for maintaining good physical and mental health. Epidemiological studies have revealed a decreased risk of major depressive disorder in those who prefer to wake up early and go to sleep early. Authors of a recent report studied the genetic associations between depression and early wake/sleep preference and depression.
Depression is a disease with multiple contributing factors that include environmental, lifestyle, and genetic influences. Untangling the web of factors contributing to late sleep preference and depression risk may help identify interventions to treat depression.
Earlier sleep and wake times align better with typical work and social schedules, increase daily light exposure, and enhance sensitivity to rhythmic changes in brain activity, contributing to a lower risk of depression. While environmental and social factors may dictate a person’s wake and sleep schedule, genetic factors may also play a role in sleep timing preferences.
The authors performed a genome-wide association study, a type of observational study in which researchers look for associations between gene variations called single-nucleotide polymorphisms and disease prevalence. The authors collected genetic data and depression status from more than 500,000 participants in the Psychiatric Genomics Consortium and United Kingdom Biobank studies to determine genetic proxies for depression. They also collected genetic and sleep data from more than 700,000 participants in the United Kingdom Biobank and 23andMe research studies to determine genetic proxies for sleep time preference. Some participants wore an activity monitor to measure their sleep precisely. The researchers calculated the sleep midpoint (halfway between falling asleep and waking) and used this in their model of genetic data as well.
Participants with an earlier sleep preference were 23 percent less likely to have depression. This decreased risk was additive for every hour that the midpoint of sleep occurred earlier in the night. That means shifting sleep one hour earlier at night and waking one hour earlier in the morning may decrease depression risk, but shifting the sleep window even earlier may decrease risk even more. The relationship between early or late waking preference and depression was significant for both physician-diagnosed and self-reported depression.
The authors concluded that the association between genetics, sleep, and depression revealed by their study provides support for sleep interventions in patients with depression.
Link to full report.
Learn more about circadian clocks and their importance in health in this clip featuring Dr. Satchin Panda.
