Treatment for Parkinson’s could now get even better

February 18, 2022

Science Daily/University of Copenhagen - The Faculty of Health and Medical Sciences

Specialized groups of neurons within the brainstem control movement. Now researchers  have found that activation of such neurons is sufficient to restore full movement function in mice with symptoms of Parkinson's Disease. The study helps clinicians to focus Deep Brain Stimulation to the right therapeutic spot and hopefully could improve treatment of motor symptoms in Parkinson's Disease.

Parkinson's is a neurodegenerative disease where dopaminergic neurons progressively die in the brainstem. Tremor and difficulties to walk are recognizable movement symptoms for many people suffering from Parkinson's. Over time, nearly a quarter of patients will have so much trouble walking that they often end up freezing on the spot and falling, and many become housebound.

People are primarily treated with medicine, but in some cases doctors use Deep Brain Stimulation (DBS). In DBS, the surgeon places a thin metal wire in the brain, which can be used to send electrical pulses. DBS is effective in treating tremor, but alleviating difficulties in walking and freezing remains a challenge.

Now, a study from the University of Copenhagen conducted in mice demonstrate that DBS treatment of walking problems in Parkinson's could be optimised by targeting specific eurons in the brainstem -- possibly benefitting some of the more than 7 to 10 million people suffering from the disease worldwide.

"Brainstem DBS are the right strategy to facilitate patients to walk properly again"

Based on previous animal studies of motor circuits, which are responsible for the planning, control, and execution of voluntary movements, scientists has hypothesized that freezing of walking in Parkinson's could be alleviated. That would require DBS to stimulate neurons in the pedunculopontine nucleus (PPN), which is located in the brainstem. The PPN was thought to send signals from the brain to the spinal cord leading to body movements.

"However, initial results from clinical trials with DBS of the PPN had very variable effect on movement recovery, particularly in patients who experience freezing of walking. It has therefore been debated where within the brainstem an optimal stimulation should be. Our study brings new knowledge to the table regarding the best area for DBS in order to alleviate this particular symptom," says corresponding author Professor Ole Kiehn at the Department of Neuroscience.

Previous results from the group showed that stimulation of so-called excitatory neurons in the PPN could initiate locomotion in normal mice. It raised the possibility that these nerve cells could indeed be used to treat movement symptoms in mice with features of Parkinson's Disease.

"We use a technology to target specific group of cells in the PPN in order to close in on what areas are the best to stimulate, if we want to alleviate these particular symptoms. The result shows that the motor improvement is optimal, if we stimulate what we call excitatory neurons in the caudal area of the PPN," explains Ole Kiehn.

"We believe that clinical trials with brainstem DBS are the right strategy to facilitate patients to walk properly again. But the variable clinical results occur, because DBS would require higher precision to target the particular group of neurons in the caudal PPN. It is a very delicate area, because if we were to stimulate excitatory neurons in other areas than the caudal PPN, it would cause complete immobilization instead."

The key is the activation of PPN neurons

In Parkinson's Disease, nerve cells that produce dopamine progressively die. Since the 1960s, doctors have relied on medication to replace the missing dopamine, but it is notoriously difficult to fully control symptoms as the disease progresses.

"In many people the movement symptoms do not respond well to medical treatment in the later stages of this disease, so there has been done a lot of research into alternative treatments, including a search for optimal targets for deep brain stimulation," explains Postdoc Debora Masini, first author of the new study, which included several different strategies to substantiate their findings.

"When we stimulated these specific neurons in the caudal area of the PPN, the animals were able to walk normally, across longer distances and with normal walking speed, as opposed to before the stimulation, where they would display symptoms of Parkinson's Disease," says Debora Masini.

"We systematically compared stimulation of different locations and cell types in a series of complementary experiments. And they all pointed towards the same conclusion. It strongly indicates these excitatory neurons in the caudal PPN are an ideal target for recovery of movement loss," she says.

The researchers hope that the new study could aid clinicians when they pick the exact location for DBS in the brainstem.

"The mice in our study only partially represents the complexity of this disease, but the results have been very telling. Nearly everything we have learned in the beginning on how to treat Parkinson's Disease comes from animal models, including the medication we use nowadays for patients. In this sense, it is a valid approach, and we hope our study can help provide better treatment for human patients," says Debora Masini.

https://www.sciencedaily.com/releases/2022/02/220218100701.htm

Musical preferences unite personalities worldwide

February 9, 2022

Science Daily/University of Cambridge

Research involving more than 350,000 participants from over 50 countries and 6 continents has found that links between musical preferences and personality are universal. The findings suggest that music could play a greater role in overcoming social division, as well as offering currently untapped therapeutic benefits.

Ed Sheeran's song Shiversis as likely to appeal to extraverts living in the UK as those living in Argentina or India. Those with neurotic traits in the US are as likely to be into Nirvana's Smells like Teen Spirit as people with a similar personality living in Denmark or South Africa. Agreeable people the world over will tend to like Marvin Gaye's What's Going On, or Lady Gaga and Bradley Cooper's Shallow; while national borders cannot stop open people from replaying David Bowie's Space Oddity or Nina Simone. But it does not matter where a conscientious person lives, they are unlikely to enjoy Rage Against the Machine.

These are the kind of assumptions supported by new research led by Dr David Greenberg, an Honorary Research Associate at the University of Cambridge and a Postdoctoral Scholar at Bar-Ilan University.

Across the world, without significant variation, the researchers found the same positive correlations between extraversion and contemporary music; between conscientiousness and unpretentious music; between agreeableness and mellow and unpretentious music; and between openness and mellow, contemporary, intense and sophisticated music. They also identified a clear negative correlation between conscientiousness and intense music.

Greenberg, who wears many hats as a musician, neuroscientist, and psychologist, said: "We were surprised at just how much these patterns between music and personality replicated across the globe. People may be divided by geography, language and culture, but if an introvert in one part of the world likes the same music as introverts elsewhere, that suggests that music could be a very powerful bridge. Music helps people to understand one another and find common ground."

The study, published in the Journal of Personality and Social Psychology, explains why personality traits are linked to musical styles. The researchers accurately predicted that extraversion, which is defined by excitement-seeking, sociability, and positive emotions, would be positively associated with contemporary music that has upbeat, positive, and danceable features. Similarly, they were not surprised to find that conscientiousness, which is associated with order and obedience, clashed with intense musical styles, which is characterized by aggressiveness and rebellious themes.

But one finding is proving more puzzling. Greenberg said: "We thought that neuroticism would have likely gone one of two ways, either preferring sad music to express their loneliness or preferring upbeat music to shift their mood. Actually, on average, they seem to prefer more intense musical styles, which perhaps reflects inner angst and frustration.

"That was surprising but people use music in different ways -- some might use it for catharsis, others to change their mood. So there may be subgroups who score high on neuroticism who listen to mellow music for one reason and another subgroup which is more frustrated and perhaps prefer intense music to let off steam. We'll be looking into that in more detail."

The researchers also found that the correlation between extraversion and contemporary music was particularly strong around the equator, above all in Central and South America. This could suggest that climatic factors influence musical preferences and that people in warmer climates tend to have personality traits which make them more likely to prefer rhythmic, danceable music.

Greenberg, who continues to perform as a professional saxophonist, has a very diverse playlist which is typical of people who score high on openness. He said: "I've always loved jazz and now I'm also really into the music of different world religions, which makes perfect sense based on my personality traits."

How the study worked

Greenberg and his colleagues used two different musical preference assessment methods to assess an unprecedented number of participants living in more than 50 countries. The first required people to self-report the extent to which they liked listening to 23 genres of music as well as completing the Ten-Item Personality Inventory (TIPI) and providing demographic information. The second used a more advanced approach and asked participants to listen to short audio clips from 16 genres and subgenres of Western music on the musicaluniverse.io website and then give their preferential reactions to each (people can still visit the site to receive their scores).

The researchers focused on Western music primarily because it is the most listened to globally and results based on Western music offer the strongest potential to be applied in real-world and therapeutic settings globally.

The researchers used the MUSIC model, a widely accepted framework for conceptualizing musical preferences, which identifies five key musical styles:

'Mellow' (featuring romantic, slow, and quiet attributes as heard in soft rock, R&B, and adult contemporary genres),

'Unpretentious' (uncomplicated, relaxing, and unaggressive attributes as heard in country genres),

'Sophisticated' (inspiring, complex, and dynamic features as heard in classical, operatic, avant-garde, and traditional jazz genres),

'Intense' (distorted, loud, and aggressive attributes as heard in classic rock, punk, heavy metal, and power pop genres), and

'Contemporary' (rhythmic, upbeat, and electronic attributes as heard in the rap, electronica, Latin, and Euro-pop genres).

Why the findings matter

For thousands of years humans have broadcast sounds to other groups to establish whether they have similar values, whether they could share resources or whether they are about to fight. Today, people are using music as a way to signal their personality and so, the study argues, there is potential to use music to address social division.

Greenberg, who lives in Jerusalem, already employs music as a bridge to work with Israelis and Palestinians. In fact, he recently gave a TEDx talk expanding on the ways that music can bond people and cultures. Greenberg also believes that the findings could improve music streaming services and support wellbeing apps but this is not as easy as it might sound.

Greenberg said: "If people who score high for neuroticism, for example, are being fed more intense music and they're already feeling stressed and frustrated, is that helping with their anxiety or is it just reinforcing and perpetuating? These are the questions we now need to answer."

The study does not seek to pigeonhole music-lovers. Greenberg says: "Musical preferences do shift and change, they are not set in stone. And we are not suggesting that someone is just extroverted or just open, we all have combinations of personality traits and combinations of musical preferences of varying strengths. Our findings are based on averages and we have to start somewhere to begin to see and understand connections."

Greenberg thinks that future research could combine streaming data with EEG hyperscanning technologies to establish a more nuanced understanding of the biological and cultural factors that contribute to our musical preferences and responses. He also says that future research should rigorously test the links between music and personality in real-world settings to see how music can be a bridge between people from different cultures around the globe.

https://www.sciencedaily.com/releases/2022/02/220209093441.htm

Lifetime of knowledge can clutter memories of older adults

February 11, 2022

Science Daily/Cell Press

When a person tries to access a memory, their brain quickly sifts through everything stored in it to find the relevant information. But as we age, many of us have difficulty retrieving memories. In a review publishing in the journal Trends in Cognitive Sciences on February 11, researchers propose an explanation for why this might be happening: the brains of older adults allocate more space to accumulated knowledge and have more material to navigate when attempting to access memories. While this wealth of prior knowledge can make memory retrieval challenging, the researchers say it has its upsides -- this life experience can aid with creativity and decision-making.

Researchers Tarek Amer (@tarekamerphd) of Columbia University and Harvard University, Jordana Wynn (@jordwynn) of Harvard University, and Lynn Hasher of the University of Toronto looked at several behavioral and neuroimaging studies, which show that older adults have difficulty suppressing information that is no longer relevant and that when searching for a specific memory, they often retrieve other, irrelevant memories along with it. The studies also showed that when given a cognitive task, older adults rely more heavily on previous knowledge than younger adults do.

While the researchers focus primarily on the difficulties that these cluttered memories may pose, they also highlight a few situations in which these crowded memoryscapes may be useful. "Evidence suggests that older adults show preserved, and at times enhanced, creativity as a function of enriched memories," the researchers write. They further hypothesize that older adults may be well served by their prior knowledge when it comes to decision-making, where they can pull on their accumulated wisdom.

With continued study and increased understanding of how memory works in older adults, researchers are hopeful that they may be able to find new ways to help them. They write, "It is possible that the increased binding and richer encodings of older adults can even be leveraged to improve older adults' learning and memory."

https://www.sciencedaily.com/releases/2022/02/220211111852.htm

Lifetime of knowledge can clutter memories of older adults

February 11, 2022

Science Daily/Cell Press

When a person tries to access a memory, their brain quickly sifts through everything stored in it to find the relevant information. But as we age, many of us have difficulty retrieving memories. In a review publishing in the journal Trends in Cognitive Sciences on February 11, researchers propose an explanation for why this might be happening: the brains of older adults allocate more space to accumulated knowledge and have more material to navigate when attempting to access memories. While this wealth of prior knowledge can make memory retrieval challenging, the researchers say it has its upsides -- this life experience can aid with creativity and decision-making.

Researchers Tarek Amer (@tarekamerphd) of Columbia University and Harvard University, Jordana Wynn (@jordwynn) of Harvard University, and Lynn Hasher of the University of Toronto looked at several behavioral and neuroimaging studies, which show that older adults have difficulty suppressing information that is no longer relevant and that when searching for a specific memory, they often retrieve other, irrelevant memories along with it. The studies also showed that when given a cognitive task, older adults rely more heavily on previous knowledge than younger adults do.

While the researchers focus primarily on the difficulties that these cluttered memories may pose, they also highlight a few situations in which these crowded memoryscapes may be useful. "Evidence suggests that older adults show preserved, and at times enhanced, creativity as a function of enriched memories," the researchers write. They further hypothesize that older adults may be well served by their prior knowledge when it comes to decision-making, where they can pull on their accumulated wisdom.

With continued study and increased understanding of how memory works in older adults, researchers are hopeful that they may be able to find new ways to help them. They write, "It is possible that the increased binding and richer encodings of older adults can even be leveraged to improve older adults' learning and memory."

https://www.sciencedaily.com/releases/2022/02/220211111852.htm

Psilocybin treatment for major depression effective for up to a year for most patients

February 15, 2022

Science Daily/Johns Hopkins Medicine

Previous studies by Johns Hopkins Medicine researchers showed that psychedelic treatment with psilocybin relieved major depressive disorder symptoms in adults for up to a month. Now, in a follow-up study of those participants, the researchers report that the substantial antidepressant effects of psilocybin-assisted therapy, given with supportive psychotherapy, may last at least a year for some patients.

A report on the new study was published on Feb. 15, 2022 in the Journal of Psychopharmacology.

"Our findings add to evidence that, under carefully controlled conditions, this is a promising therapeutic approach that can lead to significant and durable improvements in depression," says Natalie Gukasyan, M.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. She cautions, however, that "the results we see are in a research setting and require quite a lot of preparation and structured support from trained clinicians and therapists, and people should not attempt to try it on their own."

Over the last 20 years, there has been a growing renaissance of research with classic psychedelics -- the pharmacological class of compounds that include psilocybin, an ingredient found in so-called magic mushrooms. According to the National Institute on Drug Abuse, psilocybin can produce perceptual changes, altering a person's awareness of their surroundings and of their thoughts and feelings. Treatment with psilocybin has shown promise in research settings for treating a range of mental health disorders and addictions.

For this study, the researchers recruited 27 participants with a long-term history of depression, most of whom had been experiencing depressive symptoms for approximately two years before recruitment. The average age of participants was 40, 19 were women, and 25 identified as white, one as African American and one as Asian. Eighty-eight percent of the participants had previously been treated with standard antidepressant medications, and 58% reported using antidepressants in their current depressive episodes.

After screening, participants were randomized into one of two groups in which they received the intervention either immediately, or after an eight-week waiting period. At the time of treatment, all participants were provided with six to eight hours of preparatory meetings with two treatment facilitators. Following preparation, participants received two doses of psilocybin, given approximately two weeks apart between August 2017 and April 2019 at the Behavioral Biology Research Center at Johns Hopkins Bayview Medical Center. Participants returned for follow-up one day and one week after each session, and then at one, three, six and 12 months following the second session; 24 participants completed both psilocybin sessions and all follow-up assessment visits.

The researchers reported that psilocybin treatment in both groups produced large decreases in depression, and that depression severity remained low one, three, six and 12 months after treatment. Depressive symptoms were measured before and after treatment using the GRID-Hamilton Depression Rating Scale, a standard depression assessment tool, in which a score of 24 or more indicates severe depression, 17-23 moderate depression, 8-16 mild depression and 7 or less no depression. For most participants, scores for the overall treatment decreased from 22.8 at pretreatment to 8.7 at one week, 8.9 at four weeks, 9.3 at three months, 7 at six months and 7.7 at 12 months after treatment. Participants had stable rates of response to the treatment and remission of symptoms throughout the follow-up period, with 75% response and 58% remission at 12 months.

"Psilocybin not only produces significant and immediate effects, it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression," says Roland Griffiths, Ph.D., the Oliver Lee McCabe III, Ph.D., Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine, and founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research. "Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments."

The researchers emphasize that further research is needed to explore the possibility that the efficacy of psilocybin treatment may be substantially longer than 12 months. Johns Hopkins is one of the sites of a national multisite randomized, placebo-controlled trial of psilocybin for major depressive disorder.

https://www.sciencedaily.com/releases/2022/02/220215090157.htm

COVID-19 vaccination boosts mental health along with immunity

February 15, 2022

Science Daily/Elsevier

Getting vaccinated for COVID-19 measurably improved the psychological well-being of participants in the Understanding Coronavirus in America study, a large longitudinal look at the impact of the pandemic on individuals in the United States. Vaccination was associated with declines in distress and perceived risks of infection, hospitalization, and death. The study, appearing in the American Journal of Preventive Medicine, published by Elsevier, validates the intuitive but previously unanswered questions of whether becoming vaccinated reduces perceived risks associated with COVID-19, and whether the reduction of these fears leads to improvements in mental health and quality of life.

"Our study documents important psychological benefits of vaccination beyond reducing the risk of severe illness and death associated with COVID-19," said lead investigator Jonathan Koltai, PhD, Department of Sociology, University of New Hampshire, Durham, NH, USA.

Psychologic distress and anxiety increased sharply across the population following the onset of the COVID-19 pandemic. Several factors contributed, such as widespread job and income loss, food insecurity, social isolation, caregiving burdens, substance abuse, and racialized discrimination. Depressive symptoms persisted and increased into 2021 for those experiencing an accumulation of stress exposures. Not surprisingly, many individuals are also experiencing anticipatory fears that contribute to rising mental health problems.

Data from a nationally representative study of 8,090 adults who were interviewed regularly between March 2020 and June 2021 revealed declines in COVID-related risk perceptions and psychological distress following vaccination. Specifically, adults who received at least one dose of the COVID-19 vaccine between December 2020 and June 2021 reported a 7% relative reduction in mental distress, as measured using the Patient Health Questionnaire 4 (PHQ-4) distress scores, from average levels in the survey period immediately prior to vaccination.

Reductions in distress were partially explained by declining risk perceptions following vaccination. Becoming vaccinated was associated with a 7.77 percentage point decline in perceived risk of infection, a 6.91 percentage point decline in perceived risk of hospitalization, and a 4.68 percentage point decline in perceived risk of death. Adjusting for risk perceptions decreased the vaccination?distress association by 25%.

These effects persisted and became stronger up to at least eight weeks following vaccination. It is noteworthy that while responses from vaccinated and never-vaccinated participants followed similar trends pre-vaccination, they significantly diverged post-vaccination. Becoming vaccinated made people feel safer in addition to being safer.

The impact of vaccination on mental health varied by race/ethnicity. The largest reductions in distress were observed among American Indians (AI) and Alaska Native (AN) individuals, who have suffered disproportionately from COVID-19. The breakout among racial/ethnic groups was proportional to the overall US population during the study period, with the highest rates of vaccination observed among Asian and Pacific Islanders, and the lowest rates of vaccination observed among Black participants.

With the rapid rise of the Omicron variant in late 2021 and early 2022, urgent measures are needed to increase vaccination rates and achieve vaccine equity, both locally and globally. These efforts need to be coupled with effective communication about the benefits, both physical and mental, associated with vaccination.

Dr. Koltai stressed, "To ensure these benefits are widely shared, efforts to increase vaccination and booster rates in early 2022 need to prioritize equitable distribution and access to vaccines."

https://www.sciencedaily.com/releases/2022/02/220215125454.htm

Calorie restriction trial reveals key factors in extending human health

February 10, 2022

Science Daily/Yale University

Decades of research has shown that limits on calorie intake by flies, worms, and mice can enhance life span in laboratory conditions. But whether such calorie restriction can do the same for humans remains unclear. Now a new study led by Yale researchers confirms the health benefits of moderate calorie restrictions in humans -- and identifies a key protein that could be harnessed to extend health in humans.

The findings were published Feb. 10 in Science.

The research was based on results from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) clinical trial, the first controlled study of calorie restriction in healthy humans. For the trial, researchers first established baseline calorie intake among more than 200 study participants. The researchers then asked a share of those participants to reduce their calorie intake by 14% while the rest continued to eat as usual, and analyzed the long-term health effects of calorie restriction over the next two years.

The overall aim of the clinical trial was to see if calorie restriction is as beneficial for humans as it is for lab animals, said Vishwa Deep Dixit, the Waldemar Von Zedtwitz Professor of Pathology, Immunobiology, and Comparative Medicine, and senior author of the study. And if it is, he said, researchers wanted to better understand what calorie restriction does to the body specifically that leads to improved health.

Since previous research has shown that calorie restriction in mice can increase infections, Dixit also wanted to determine how calorie restriction might be linked to inflammation and the immune response.

"Because we know that chronic low-grade inflammation in humans is a major trigger of many chronic diseases and, therefore, has a negative effect on life span," said Dixit, who is also director of the Yale Center for Research on Aging. "Here we're asking: What is calorie restriction doing to the immune and metabolic systems and if it is indeed beneficial, how can we harness the endogenous pathways that mimic its effects in humans?"

Dixit and his team started by analyzing the thymus, a gland that sits above the heart and produces T cells, a type of white blood cell and an essential part of the immune system. The thymus ages at a faster rate than other organs. By the time healthy adults reach the age of 40, said Dixit, 70% of the thymus is already fatty and nonfunctional. And as it ages, the thymus produces fewer T cells. "As we get older, we begin to feel the absence of new T cells because the ones we have left aren't great at fighting new pathogens," said Dixit. "That's one of the reasons why elderly people are at greater risk for illness."

For the study, the research team used magnetic resonance imaging (MRI) to determine if there were functional differences between the thymus glands of those who were restricting calories and those who were not. They found that the thymus glands in participants with limited calorie intake had less fat and greater functional volume after two years of calorie restriction, meaning they were producing more T cells than they were at the start of the study. But participants who weren't restricting their calories had no change in functional volume.

"The fact that this organ can be rejuvenated is, in my view, stunning because there is very little evidence of that happening in humans," said Dixit. "That this is even possible is very exciting."

With such a dramatic effect on the thymus, Dixit and his colleagues expected to also find effects on the immune cells that the thymus was producing, changes that might underlie the overall benefits of calorie restriction. But when they sequenced the genes in those cells, they found there were no changes in gene expression after two years of calorie restriction.

This observation required the researchers to take a closer look, which revealed a surprising finding: "It turns out that the action was really in the tissue microenvironment not the blood T cells," Dixit said.

Dixit and his team had studied adipose tissue, or body fat, of participants undergoing calorie restriction at three time points: at the beginning of the study, after one year, and after two. Body fat is very important, Dixit said, because it hosts a robust immune system. There are several types of immune cells in fat, and when they are aberrantly activated, they become a source of inflammation, he explained.

"We found remarkable changes in the gene expression of adipose tissue after one year that were sustained through year two," said Dixit. "This revealed some genes that were implicated in extending life in animals but also unique calorie restriction-mimicking targets that may improve metabolic and anti-inflammatory response in humans."

Recognizing this, the researchers then set out to see if any of the genes they identified in their analysis might be driving some of the beneficial effects of calorie restriction. They honed in on the gene for PLA2G7 -- or group VII A platelet activating factor acetylhydrolase -- which was one of the genes significantly inhibited following calorie restriction. PLA2G7 is a protein produced by immune cells known as macrophages.

This change in PLA2G7 gene expression observed in participants who were limiting their calorie intake suggested the protein might be linked to the effects of calorie restriction. To better understand if PLA2G7 caused some of the effects observed with calorie restriction, the researchers also tracked what happened when the protein was reduced in mice in a laboratory experiment.

"We found that reducing PLA2G7 in mice yielded benefits that were similar to what we saw with calorie restriction in humans," said Olga Spadaro, a former research scientist at the Yale School of Medicine and lead author of the study. Specifically, the thymus glands of these mice were functional for a longer time, the mice were protected from diet-induced weight gain, and they were protected from age-related inflammation.

These effects occurred because PLA2G7 targets a specific mechanism of inflammation called the NLRP3 inflammasome, researchers said. Lowering PLA2G7 protected aged mice from inflammation.

"These findings demonstrate that PLA2G7 is one of the drivers of the effects of calorie restriction," said Dixit. "Identifying these drivers helps us understand how the metabolic system and the immune system talk to each other, which can point us to potential targets that can improve immune function, reduce inflammation, and potentially even enhance healthy lifespan."

For instance, it might be possible to manipulate PLA2G7 and get the benefits of calorie restriction without having to actually restrict calories, which can be harmful for some people, he said.

"There's so much debate about what type of diet is better -- low carbohydrates or fat, increased protein, intermittent fasting, etc. -- and I think time will tell which of these are important," said Dixit. "But CALERIE is a very well-controlled study that shows a simple reduction in calories, and no specific diet, has a remarkable effect in terms of biology and shifting the immuno-metabolic state in a direction that's protective of human health. So from a public health standpoint, I think it gives hope."

https://www.sciencedaily.com/releases/2022/02/220210154204.htm

Your microbiome shapes your life. But where did it come from?

The role of chance in microbiome composition

February 9, 2022

Science Daily/Carnegie Institution for Science

The gut microbiome is an ecosystem of hundreds to thousands of microbial species living within the human body. These populations affect our health, fertility, and even our longevity. But how do they get there in the first place?

New collaborative work led by Carnegie's William Ludington reveals crucial details about how the bacterial communities that comprise each of our individual gut microbiomes are acquired. These findings, published in the Proceedings of the National Academy of Sciences, have major implications for treatments such as fecal transplants and probiotic administration.

"There is a huge amount of variation in microbiome composition between individuals," Ludington explained. "For example, if you look at the sum total of all of the bacterial species that are adapted to live in the gastrointestinal systems of humans, most of these are not present in a majority of people. That's how incredibly diverse these gut microbial populations are."

A combination of elements, including genetics, diet, and environment contribute to the differences between our microbiomes. But there isn't a direct line between these inputs and the species that successfully colonize our guts. There's an element of chance at play each time we are exposed to a new microbe as to whether it will be acquired and become a member of our gut ecosystem. Ludington and his collaborators set out to understand the factors that shape the odds of this colonization process.

Although many researchers have studied microbiome compositions in natural populations, there have been few attempts to use a controlled environment to reveal the process by which new species successfully join the gut microbial ecosystem. Ludington and his collaborators -- Eric Jones and David Sivak of Simon Fraser University and Jean Carlson of UC Santa Barbara -- developed a new ecological model to understand how we acquire the specific mix of microbes that are individual to our own particular gut communities.

Working in the comparatively much less complicated microbiomes of fruit flies, the team showed that exposure to a microbial species does not guarantee its successful incorporation into the microbiome ecosystem. They found that the state of the microbiome, and interactions between existing microbiome member species, sets the odds for whether a newly encountered bacteria is added into the mix.

"Even among genetically identical flies that lived in the same housing and were fed the same diets, we saw variations in microbiome composition," Sivak said.

The researchers then used these results to build mathematical models that could probe increasingly complex scenarios by which new microbiome species could be acquired, leading to their breakthrough understanding of the community factors that shape membership in the microbiome ecosystem.

"Think of microbiome composition as a big party where the social dynamics determine who leaves early and who stays until dawn," said Ludington.

Added Jones, the paper's first author: "Bacterial colonization depends on a number of complicated factors that we're just starting to understand. We showed, for example, that some groups of species facilitate each other's colonization and are therefore more likely to coexist."

These group interactions have exciting implications for how microbiomes are transmitted between individuals, including how medical professionals might drive a person's microbiome towards a desired composition.

"The beauty of the mathematical approach we deployed is that it acknowledges that colonization is a roll of the dice, but we are now able to attribute the weighting of the dice to biological interactions with a molecular basis that has been honed by evolution," said Carlson.

The team's findings provide a framework for quantitatively examining the mechanisms that therapies such as fecal transplants and probiotics depend upon, advancing toward the eventual goal of personalized microbiome medicine.

https://www.sciencedaily.com/releases/2022/02/220209155020.htm

Clearance of protein linked to Alzheimer's controlled by circadian cycle

Ability of immune system to destroy Alzheimer's-related protein oscillates with daily circadian rhythm

February 10, 2022

Science Daily/Rensselaer Polytechnic Institute

The brain's ability to clear a protein closely linked to Alzheimer's disease is tied to our circadian cycle, according to research published today in PLOS Genetics. The research underscores the importance of healthy sleep habits in preventing the protein Amyloid-Beta 42 (AB42) from forming clumps in the brain, and opens a path to potential Alzheimer's therapies.

"Circadian regulation of immune cells plays a role in the intricate relationship between the circadian clock and Alzheimer's disease," said Jennifer Hurley, an expert in circadian rhythms, and associate professor of biological science at Rensselaer Polytechnic Institute. "This tells us a healthy sleep pattern might be important to alleviate some of the symptoms in Alzheimer's disease, and this beneficial effect might be imparted by an immune cell type called macrophages/microglia."

The research was conducted at the Rensselaer Center for Biotechnology and Interdisciplinary Studies, which has a focus on neurodegenerative disease. Dr. Hurley worked with Rensselaer professors Robert Linhardt, a glycans expert and inventor of synthetic heparin, and Chunyu Wang, whose ongoing research has detailed several mechanisms in the production and spread of proteins implicated in Alzheimer's.

"This insight reveals a new mechanism and path to treatment of neurodegenerative diseases like Alzheimer's through an interdisciplinary approach, and is emblematic of the CBIS strength in research and discovery and provides a new angle to human health and well-being," said Deepak Vashishth, director of the CBIS.

The circadian system is composed of a core set of clock proteins that anticipate the day/night cycle by causing daily oscillations in the levels of enzymes and hormones, ultimately affecting physiological parameters such as body temperature and the immune response. Disruption of the circadian system is increasingly associated with diseases like diabetes, cancer, and Alzheimer's.

A telltale sign of Alzheimer's disease is plaques, extracellular clumps of AB42 in the brain. Macrophages (referred to as microglia when they reside in the brain), which are immune cells that seek and destroy unwanted material, clear AB42 from the brain by ingesting it in a process called phagocytosis. In earlier research, Dr. Hurley and collaborators at the Royal College of Surgeons in Ireland investigated circadian control of macrophages, amassing an exhaustive dataset that made it possible to see which macrophage RNA and proteins oscillate with a circadian rhythm. The researchers noticed oscillations in enzymes that help to make two proteins on the macrophage cell surface -- heparan sulfate proteoglycan and chondroitin sulfate proteoglycan- both of which are known to play a role in regulating clearance of AB42.

Could these cell surface proteoglycans be a link between the circadian system and Alzheimer's? In a series of elegant experiments testing this hypothesis, the team established that the amount of AB42 ingested by healthy macrophages oscillates with a daily circadian rhythm. That pattern did not occur in macrophages without a circadian clock. They also measured daily oscillations in the levels of heparan sulfate proteoglycans and chondroitin sulfate proteoglycans produced on the surface of macrophage cells with healthy circadian cycles. Peak AB42 clearance occurred as production of surface cell proteoglycans was at its lowest level, and removal of these proteoglycans increased ingestion, which suggests that the proteoglycans inhibit AB42 clearance.

"What's clear is that this is all timed by the circadian clock," said Dr. Hurley. "When there's a lot of these cell surface proteoglycans, the macrophages don't ingest the AB42. We're not certain why that would be, but there is definitely a relationship."

That relationship could be used to develop therapies that would encourage greater AB42 clearance, perhaps by boosting the amplitude of daily oscillations, which tend to diminish as we age.

"In theory, if we could boost that rhythm, perhaps we could increase the clearance of AB42 and prevent damage to the brain," said Dr. Hurley.

https://www.sciencedaily.com/releases/2022/02/220210154215.htm

Stargazing in the brain: 'Star-like' cells display unique activity patterns

February 9, 2022

Science Daily/Okinawa Institute of Science and Technology (OIST) Graduate University

The way we experience the world occurs due to complex and intricate interactions between neurons in the brain. Now, a study, published 9th February 2022 in Science Advances, suggests that astrocytes -- star-shaped, non-neuronal cells in the brain -- might also play an important role in processing information, and perhaps even memory.

Using advanced imaging and analysis techniques, researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) recorded signaling within single astrocytes at a previously unseen level of detail and speed in the brains of awake mice.

Their findings, including ultra-fast signals on par with those seen in neurons and patterns of signaling activity that correspond to different behaviors, suggest that astrocytes may play a crucial role in many functions of our brain, including how we think, move, and learn.

"If these implications are true, it will fundamentally transform how we think about neuroscience, and the way the brain works," said first author Dr. Leonidas Georgiou, a former PhD student in the Optical Neuroimaging Unit at OIST.

When we picture our brain, we typically imagine a messy tangle of long, wire-like neurons that send electrical signals to each other across different regions of the brain. But neurons only make up half the cells in our brain. Crammed into all the remaining space between the jumble of neurons are many other types of brain cells, including astrocytes.

"Compared to neurons, astrocytes have received very little attention. It was thought that astrocytes are just helper cells, supplying the neurons with nutrients and removing their waste," said Professor Bernd Kuhn, senior author and head of the Optical Neuroimaging Unit.

But in recent years, there's been increasing amounts of evidence that astrocytes can listen to chemical messages sent between neurons at synapses, and can respond with their own signals, providing an extra layer of complexity to how our brain receives and responds to information.

Still, the previously detected signals in astrocytes were about ten times slower than signals seen in neurons, with scientists therefore believing the cells were too slow for information processing.

However, by developing a new toolkit that allows the study of astrocyte activity in awake mice with unprecedented detail, the researchers at OIST showed for the first time that astrocytes generate signals in vivo which are as fast as that of neurons, lasting fewer than 300 milliseconds.

Their toolkit relied on a new discovery: that a virus regularly used for gene therapy could "jump" from neurons to connected astrocytes. The scientists used an adeno-associated virus that contained a gene that makes infected cells fluoresce. The fluorescence increases in intensity in the presence of calcium -- an important indicator of signal activity within living cells.

Once labelled, the research team were able to use a powerful, homebuilt microscope to pinpoint and image a single astrocyte, over multiple days for up to an hour at a time, while the mouse was awake and moving.

The scientists then used an advanced computer program to analyze the recorded images, allowing them to detect the never-before-seen ultra-fast flashes of calcium signals, and evaluate signal patterns in an unbiased way.

They found that sensory stimulation, by tickling the whiskers, resulted in very little calcium signaling, while certain behaviors, like running or walking, resulted in high levels of activity.

The scientists also realized that there were certain areas in the astrocyte, or hotspots, where levels of activity were higher.

"These hotspot maps are like fingerprints -- for a specific behavior, they are stable over time, remaining the same over a period of days, and unique to each astrocyte," said Dr. Georgiou.

Even more surprisingly, the team noticed that different behaviors corresponded to unique hotspot patterns.

"So, when the mouse is resting, you see one pattern. And then when the mouse is running, you see a different pattern," said Prof. Kuhn.

One hypothesis suggested by Prof. Kuhn is that these hotspot maps could represent memory engrams -- a pattern that represents a specific behavior or a memory. Different neuron networks are active during specific behaviors or when learning and recalling information, which could also change the activity of nearby astrocytes. Memory engrams are still theoretical, and highly controversial, he acknowledged.

"We still don't know how memories are stored in a brain, but it's incredible to think that it could involve astrocytes," he said. "It's likely too good to be true, but it's an exciting hypothesis to follow up on."

https://www.sciencedaily.com/releases/2022/02/220209154813.htm

Fecal implants drive behavioral and cognitive changes in Alzheimer’s model

Gut microbiome could be path toward treating or forestalling cognitive decline

February 8, 2022

Science Daily/Oregon Health & Science University

New research in mice for the first time draws a definitive causal connection between changes in the gut microbiome to behavioral and cognitive changes in an animal model of Alzheimer's disease.

The study, published today in the journal Frontiers in Behavioral Neuroscience, suggests new avenues involving the use of probiotics to treat and potentially forestall symptoms of dementia associated with neurodegenerative diseases including Alzheimer's.

The research was led by scientists at Oregon Health & Science University.

"We found that modulating the gut microbiome by fecal implants in germ-free mice induces behavioral and cognitive changes in an Alzheimer's disease model," said senior author Jacob Raber, Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. "To the best of my knowledge, no one has shown that before in an Alzheimer's disease model."

The work follows on a previous OHSU study in mice, published last year, that revealed a correlation between the composition of the gut microbiome and the behavioral and cognitive performance of mice carrying genes associated with Alzheimer's.

In the new study, researchers carefully manipulated the digestive tract of mice using fecal implants.

They found changes in measures of behavior and cognition among three different genotypes and between males and females. Two of the genotypes involved mirror those associated with a predisposition to Alzheimer's in people.

Researchers found that changes in the gut microbiome clearly affected behavioral and cognitive changes measured in mice.

The study suggests possible avenues for forestalling dementia through targeted use of probiotics or fecal transplants, which already have been used to manipulate the gut microbiome in people. However, Raber said much more research needs to be conducted to ascertain the mechanism of these behavioral and cognitive effects, because the relationship between these effects and gut microbiome is influenced by genotype and sex.

"People can buy probiotics over the counter, but we want to make sure the right treatment is being used for each patient, and that it actually benefits them," Raber said. "The gut microbiome is a complex environment. If you change one element, you'll also change other elements, so you want to make sure to select a probiotic that promotes brain health and brain function for each patient, while limiting any negative side effects."

https://www.sciencedaily.com/releases/2022/02/220208124437.htm

Eating prunes may help protect against bone loss in older women

February 9, 2022

Science Daily/Penn State

It's already well known that prunes are good for your gut, but new Penn State research suggests they may be good for bone health, too.

In a research review, the researchers found that prunes can help prevent or delay bone loss in postmenopausal women, possibly due to their ability to reduce inflammation and oxidative stress, both of which contribute to bone loss.

"In postmenopausal women, lower levels of estrogen can trigger a rise of oxidative stress and inflammation, increasing the risk of weakening bones that may lead to fractures," said Connie Rogers, associate professor of nutritional sciences and physiology. "Incorporating prunes into the diet may help protect bones by slowing or reversing this process."

The review was recently published in the journal Advances in Nutrition.

Osteoporosis is a condition in which bones become weak or brittle that can happen to anyone at any age, but according to the researchers is most common among women over the age of 50. The condition affects more than 200 million women worldwide, causing almost nine million fractures each year.

While medications exist to treat osteoporosis, the researchers said there is a growing interest for ways to treat the condition with nutrition.

"Fruits and vegetables that are rich in bioactive compounds such as phenolic acid, flavonoids and carotenoids can potentially help protect against osteoporosis," said Mary Jane De Souza, professor of kinesiology and physiology, "with prunes in particular gaining attention in previous research."

According to the researchers, bones are maintained throughout adult life by processes that continually build new bone cells while removing old ones. But after the age of 40, this breaking down of old cells begins to outpace the formation of new ones. This can be caused by multiple factors including inflammation and oxidative stress, which is when free radicals and antioxidants are unbalanced in the body.

Prunes, however, have many nutritional benefits such as minerals, vitamin K, phenolic compounds and dietary fiber -- all which may be able to help counter some of these effects.

For their review, the researchers analyzed data from 16 preclinical studies in rodent models, ten preclinical studies and two clinical trials. Across the studies, the researchers found evidence that eating prunes helped reduce inflammation and oxidative stress and promoted bone health.

For example, the clinical trials found that eating 100 grams of prunes -- about 10 prunes -- each day for one year improved bone mineral density of bones in the forearm and lower spine and decreased signs of bone turnover.

Additionally, eating 50 or 100 grams of prunes a day for six months prevented loss of total bone mineral density and decreased TRAP-5b -- a marker of bone resorption -- compared to women who didn't eat prunes.

"Taken together, evidence from in vitro, preclinical studies, and limited clinical studies suggest prunes may help to reduce bone loss," Rogers said. "This may be due to altered bone turnover and by inhibiting inflammation and suppressing markers of oxidative stress."

The researchers said one potential mechanism for the effects is prunes triggering a change in the gut microbiome that then lowers inflammation in the colon. This may then lower levels of pro-inflammatory cytokines and markers of oxidative damage.

In the future, the researchers plan to further report on the effects of prune consumption for 12 months on bone outcomes, inflammatory pathways and the gut microbiota in a randomized controlled trial that was led by De Souza.

Janhavi Damani, graduate student in the Huck Institutes of the Life Sciences; Hannah VanEvery, graduate student in nutritional sciences; and Nicole Strock, postdoctoral scholar in kinesiology, also participated in this work.

The California Dried Plum Board helped support this research.

https://www.sciencedaily.com/releases/2022/02/220209112110.htm

How does cannabis use affect brain health? Caution advised, more research needed, experts say

American Heart Association Scientific Statement

February 10, 2022
Science Daily/American Heart Association

Despite the perception that marijuana is harmless, there is some scientific evidence challenging that belief, and there are many unanswered questions about its impact on brain health, according to a new American Heart Association scientific statement published today in the Association's journal Stroke. This scientific statement will be presented and discussed during a symposium at the Association's International Stroke Conference in New Orleans, today at 7 a.m. CT/ 8 a.m. ET. An American Heart Association scientific statement is an expert analysis of current research and may inform future clinical practice guidelines.

"There's a lot of uncertainty in the medical community about the health effects of marijuana. This scientific statement is intended to guide health care professionals in having a balanced and intentional discussion with patients about the potential known and unknown effects of marijuana on brain health," said writing group Chair Fernando D. Testai, M.D., Ph.D., FAHA, a professor of neurology and rehabilitation at the University of Illinois at Chicago.

This is the Association's first scientific statement on cannabis and brain health, following a statement on marijuana and cardiovascular health, published in August 2020. Both statements are important since marijuana use in the U.S. is increasing, particularly among adolescents and young adults, with about one-third of 12thgraders and nearly half of college students reporting marijuana use in 2018. In addition, the use of marijuana medicinally and/or recreationally has been legalized or decriminalized in many states across the U.S. in the past 2 decades, and the concentration of tetrahydrocannabinol (THC, the psychoactive component in marijuana) in cannabis products has increased significantly, from about 4% in 1995 to 15% in 2018.

The most studied chemicals in cannabis are THC and CBD. THC is the compound in marijuana that gives the sensation of being high. CBD (cannabidiol) has antioxidant and anti-inflammatory properties but does not have psychoactive effects. The potential therapeutic benefits of CBD continue to be investigated in clinical trials.

The U.S. Drug Enforcement Agency (DEA) and the Food and Drug Administration (FDA) classify cannabis as a Schedule I controlled substance, on par with heroin and LSD, for having a "high potential for abuse and little to no medical benefit." In contrast, CBD is legal when derived from hemp, which is the same species of plant as cannabis and contains less than 0.3% THC.

To fully understand the potential impact of marijuana, it's important to know that the human body naturally produces compounds called endocannabinoids that are similar to those in marijuana. Endocannabinoids are involved in the regulation of many body processes throughout life (including learning, memory, pain control and sleep), and the action of endocannabinoids is essential to prenatal brain development and to brain maturation during adolescence.

Endocannabinoids, as well as THC, can attach to neurons in the brain through molecules called cannabinoid receptors. When THC activates cannabinoid receptors in the brain, it can disrupt the normal actions of endocannabinoids. "These receptors are highly concentrated in brain areas related to cognition," said Testai.

According to the statement, previous animal studies (in rodents) indicate that prolonged exposure to THC disrupts memory and learning, and impacts brain development and maturation in specific ways if exposed at certain stages of life:

• During prenatal life, an important time for brain development, THC disrupts the normal signaling pathways of the endocannabinoid system and may alter the offspring's thinking, emotional behavior and response to stress.

• During adolescence, an important time for brain maturation, THC changes the structure and function of brain circuits, particularly in areas involved in cognition, emotional regulation and social behavior (such as the prefrontal cortex and hippocampus).

"Data obtained in these animal studies demonstrate that disruption of endocannabinoid pathways leads to behavioral and cognitive abnormalities, such as poorer memory and learning ability and a heightened sensitivity to stress. Also, there may be vital life periods -- gestation and adolescence -- when the brain may be particularly vulnerable to the impact of THC," Testai said.

While the exact timing and amount of marijuana exposure are more easily controlled in animal studies, as well as controlling the animals' social and environmental conditions, human research studies cannot replicate similar strict parameters. Thus, results from existing studies in humans have been mixed, yet raise similar concerns about the impact of marijuana exposure on brain health. Among the studies in humans summarized in the scientific statement, the findings included:

• While actively using marijuana, people demonstrated worse scores on driving road tests when using THC-dominant marijuana, compared to when they were using CBD-dominant marijuana or no marijuana.

• In young adults who were followed for 25 years as part of a heart disease research project, scores on verbal memory tests declined in correlation to more years of self-reported exposure to marijuana.

• There were more psychological problems and poorer cognitive function in children (average age 9) whose mothers reported using marijuana during pregnancy.

• Marijuana use during adolescence has been associated with thinning in an area of the brain involved in cognition (the prefrontal cortex), with greater exposure to marijuana associated with more thinning. However, other studies detected no difference.

• Structural changes in the brain were visible in some studies comparing marijuana users and non-users. Specifically, there was thinning of brain areas important in orchestrating thoughts and actions, or decreased volume in an area of the brain important for memory. Other studies that compared cognitive testing and brain imaging found no differences between marijuana users and non-users.

• Cannabis users were found to have an increased risk of clot-caused stroke, with one study finding 17% more and another finding 24% more strokes among cannabis users.

The statement also highlights numerous open questions on the impact of cannabis on brain health, including:

• Does marijuana's impact on brain health differ depending on the person's age?

• How does marijuana interact with other substances such as prescription medications? This is a particular concern in elderly people who may be using multiple medications such as blood thinners, antiarrhythmia or anticonvulsant medications to treat other chronic health conditions.

• Do the effects of marijuana differ whether it is used recreationally or prescribed for the treatment of a specific medical condition?

• How much marijuana is too much? In older research studies conducted when marijuana was illegal in all U.S. states, there may have been significant under-reporting of how frequently marijuana was used.

• Do different types of marijuana (such as higher THC levels or synthetic cannabinoids) impact the brain differently?

• Are there differences in brain health depending on whether marijuana is smoked or consumed in an edible product?

"Our understanding of the effects of marijuana on the brain is imperfect, and human research in this area is a work in progress. Still, the results of recent animal studies challenge the widely accepted idea that cannabinoids are harmless and call for caution when using marijuana, particularly while pregnant or during adolescence," said Testai.

This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association's Stroke Brain Health Science Subcommittee of the Stroke Council; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; the Council on Lifestyle and Cardiometabolic Health; and the Council on Peripheral Vascular Disease. The American Academy of Neurology has affirmed this scientific statement as an educational tool for neurologists.

American Heart Association scientific statements promote greater awareness about cardiovascular diseases and stroke issues and help facilitate informed health care decisions. Scientific statements outline what is currently known about a topic and what areas need additional research. While scientific statements inform the development of guidelines, they do not make treatment recommendations. American Heart Association guidelines provide the Association's official clinical practice recommendations.

https://www.sciencedaily.com/releases/2022/02/220210084937.htm

Survivors of weather-related disasters may have accelerated aging

February 7, 2022

Science Daily/Arizona State University

When Hurricane Maria slammed into Puerto Rico in September 2017 as a high-end category 4 storm, it left in its wake the largest catastrophe in the history of the island. The storm killed over 3,000 people in its immediate aftermath, knocked out power to nearly all of the island's 3.4 million residents, and caused more than $100 billion in damages.

What was the toll of this stress and adversity on the long-term health of its population? And could exposure to extreme weather events accelerate the aging process?

"While everyone ages, we don't all age at the same rate, and our lived experiences, both negative and positive, can alter this pace of aging. One negative life experience, surviving an extreme event, can lead to chronic inflammation and the early onset of some age-related diseases, like heart disease," said corresponding author Noah Snyder-Mackler, an assistant professor at Arizona State University's School of Life Sciences. "But we still don't know exactly how these events get embedded in our bodies leading to negative health effects that may not show up until decades after the event itself."

As the final impact on the survivors' mental and physical health remains to be tallied, a group of biologists led by Snyder-Mackler have looked toward one of our close evolutionary cousins for the first clues.

Along with the human toll, the devastation impacted all the island's wildlife, including a group of free-ranging rhesus macaques living on the isolated Cayo Santiago island near Puerto Rico. The animals have lived on the island since 1938, when the Caribbean Primate Research Center field station first opened.

Now, the ASU team, led by Snyder-Mackler and lead author Marina Watowich-a graduate student at the University of Washington and research scientist at ASU, and their collaborators at the Caribbean Primate Research Center, University of Pennsylvania, University of Exeter and New York University, have published (will include DOI) one of the first results that shows the effects of natural disasters may have molecularly accelerated aging in the monkeys' immune systems.

Accelerated aging

As a high-end category 4 hurricane, Maria caused massive devastation to the natural habitat and research infrastructure on Cayo Santiago. Remarkably, only 2.75% of the macaque population died in the immediate aftermath of the storm. And in the year after the hurricane, there was no difference in survival. But, was the health of the hurricane survivors affected in other ways?

People of the same chronological age- the number of years since birth-can differ in when and if they develop disease. It is well-established that people who have suffered extremely adverse experiences have higher risk of developing heart disease and other diseases more common in older individuals. How these detrimental experiences 'get under the skin' to promote disease is still unknown. One idea is that this phenomenon is potentially due to extreme adversity 'aging' the body. People can differ in their biological age, which can be measured by molecular signposts embedded in our genes, immune system and physiology.

"From this study, we have measured the molecular changes associated with aging, including disruptions of protein-folding genes, greater inflammatory immune cell marker gene expression and older biological aging," said Watowich.

After a careful analysis of the genes expressed in the macaques' immune cells, the researchers found that the adversity resulting from the hurricane may have accelerated aging of the immune system.

"On average, monkeys who lived through the Hurricane had immune gene expression profiles that had aged 2 extra years, or approximately 7-8 years of human lifespan," said Watowich.

The findings suggest that severe weather events -- -which are becoming more frequent and severe due to climate change -- may lead to biologically detrimental consequences for those who experience them. This is especially pressing given that hurricanes and other extreme weather events are becoming stronger and more common with climate change.

Biological aging

One kilometer off the southeastern coast of Puerto Rico lies Cayo Santiago, a 15.2-hectare island home to a population of 1,800 free-ranging rhesus macaques that have been studied for almost a century.

"Cayo Santiago was the first part of Puerto Rico hit by Hurricane Maria and took on the full force of the category 4 storm," said Snyder-Mackler. "The hurricane destroyed homes and infrastructure across Puerto Rico, and on Cayo Santiago it decimated most of the vegetation, as well as the water cisterns and research infrastructure needed to maintain the field station."

The rhesus macaques share many behavioral and biological features of people, including how their bodies age, but compressed into a lifespan one quarter of ours. By studying the macaques, the scientific team knew they could get estimates of aging in years rather than the decades from equivalent human studies.

To test how Hurricane Maria influenced immune cell gene regulation and aging, Marina Watowich and the rest of the team were able to leverage a collection of blood samples and history of detailed demographic data from age-matched subsets of the Cayo Santiago rhesus macaque population.

By performing a global analysis of immune gene expression, they found 4% of genes expressed in immune cells were altered after the hurricane. Of these, genes that had higher expression after the hurricane were involved in inflammation, and genes dampened by the hurricane were those involved in protein translation, protein folding/refolding, the adaptive immune response and T cells.

The down regulation of so-called heat shock genes, which promote the proper function of protein-making in our cells, was most affected, some with two-times lower activity after Hurricane Maria. These genes have also been implicated in cardiovascular and Alzheimer's disease.

Remarkably, they found a strong correlation in the hurricane exposure and aging effects on gene expression, where the effect of the hurricane was similar to the effect of the immune system getting older.

To understand how the hurricane may have affected amounts of immune cell populations, they looked at profiles from single-cell RNA sequencing to identify genes that are preferentially expressed in key immune cell types.

"Overall, cell-specific markers of canonical pro-inflammatory immune cells, such as CD14+ monocytes, had higher expression in older individuals and those that experienced the hurricane. Further, expression of helper T-cell genes, an anti-inflammatory cell type, decreased in older animals and those after the hurricane. Together, this possibly implicates more inflammatory activity in animals after storm, similar to what we see in older individuals," said Snyder-Mackler.

Getting under the skin

From their long-term studies, as part of a collaboration with the Caribbean Primate Research Center, University of Pennsylvania, University of Exeter and New York University, they had four years of data prior to Hurricane Maria (n = 435) and one year after (n = 108) Hurricane Maria. They hypothesized that exposure to the hurricane would recapitulate molecular changes associated with the natural process of aging.

"Our findings suggest that differences in immune cell gene expression in individuals exposed to an extreme natural disaster were in many ways similar to the effects of the natural aging process," said Snyder-Mackler. "We also observed evidence for accelerated biological aging in samples collected after animals experienced Hurricane Maria."

"Importantly, we identify a critical mechanism-immune cell gene regulation-that may explain how adversity, specifically in the context of natural disasters, may ultimately 'get under the skin' to drive age-associated disease onset and progression," said Watowich.

Interestingly, not all monkeys responded similarly to the hurricane. For example, some monkeys' biological ages increased much more than others. The team hypothesizes that there may be other aspects of the monkey's environment that can influence their response to adversity.

For example, just like in people, social support is a critical aspect of the ability to help cope and deal with adversity. It is possible that monkeys with greater social support after the storm were better able to overcome any detrimental effects-an aspect the team hopes to investigate soon. The study did have its limitations, foremost, that they could not measure aging rates within the same individuals before or after the hurricane.

For future studies, they hope the work can expand to include longer-term studies of for every individual within a population to learn more about the intersection between biological aging, adversity and social structures and in the face of a natural disaster.

Lastly, they hope their results will encourage efforts to develop a better understanding of aging and adversity and one day, even a successful mitigation strategy to lessen the toll from natural disasters.

https://www.sciencedaily.com/releases/2022/02/220207155437.htm

Poor sleep can triple risk for heart disease

February 7, 2022

Science Daily/University of South Florida (USF Innovation)

Individual aspects of poor sleep can be detrimental to heart health. But if you combine them, the risk of heart disease can increase by as much as 141 percent. That's the finding of a new study published in the journal Scientific Reports.

The University of South Florida-led study reviewed sleep data of 6,820 U.S. adults with an average age of 53 who self-reported their sleep characteristics and heart disease history. Among the participants, 633 also wore a research device (actigraphy) around their wrist that captured sleep activity.

Researchers focused on multiple aspects of sleep health, such as regularity, satisfaction, alertness during waking hours, timing of sleep, sleep efficiency and sleep duration and linked them to physician-diagnosed heart disease. They found that each additional increase in self-reported sleep health problems was associated with a 54 percent increased risk of heart disease. The estimated risk of heart disease associated with an increase in sleep health problems was much higher for those who provided sleep data by both self-report and the research device. They had a 141 percent increase -- a figure that could be perceived to be more accurate.

"These findings show the importance of assessing 'co-existing sleep health problems' within an individual to capture the risk of heart disease. This is one of the first studies showing that, among well-functioning adults in midlife, having more sleep health problems may increase the risk of heart disease," said lead author Soomi Lee, assistant professor of aging studies and director of the STEALTH lab at USF. "The higher estimated risk in those who provided both self-report and actigraphy sleep data suggests that measuring sleep health accurately and comprehensively is important to increase the prediction of heart disease."

The research team asked participants about their health, including if their physician confirmed a heart condition such as arrythmia, heart murmur or an enlarged heart. High blood pressure was not considered a diagnosis as it's labeled a risk factor for heart disease rather than a heart disease condition. They also controlled for family history of heart disease and sociodemographic factors, such as race, sex, smoking, depression and physical activity.

Researchers found that while women reported having more sleep health problems, men were more likely to suffer heart disease -- yet gender did not impact the overall correlation between the two factors. They also found that Black participants had more sleep health problems and a higher prevalence of heart disease than white participants, but the strong association between sleep health and heart disease did not differ by race in general.

Lee says while sleep health is important for all ages, the team focused on middle adulthood as it spans for a longer period of time and consists of diverse and more stressful life experiences due to work and family roles. This is also when precursors for heart disease and age-related sleep issues begin to arise.

Since sleep health can be modified, researchers say these findings can contribute to future prevention strategies to mitigate the risk of heart disease, which is the leading cause of death in the U.S.

https://www.sciencedaily.com/releases/2022/02/220207155642.htm

Changing your diet could add up to a decade to life expectancy

A new model, available as an online calculator, estimates the impact of dietary changes on life expectancy

February 8, 2022

Science Daily/PLOS

A young adult in the U.S. could add more than a decade to their life expectancy by changing their diet from a typical Western diet to an optimized diet that includes more legumes, whole grains and nuts, and less red and processed meat, according to a new study publishing Feb. 8 in PLOS Medicine by Lars Fadnes of the University of Bergen, Norway, and colleagues. For older people, the anticipated gains to life expectancy from such dietary changes would be smaller but still substantial.

Food is fundamental for health and, globally, dietary risk factors are estimated to lead to 11 million deaths and 255 million disability-adjusted life-years annually. In the new study, researchers used existing meta-analyses and data from the Global Burden of Diseases study to build a model that enables the instant estimation of the effect on life expectancy (LE) of a range of dietary changes. The model is also now available as a publicly available online tool called the Food4HealthyLife calculator (https://food4healthylife.org/).

For young adults in the United States, the model estimates that a sustained change from a typical Western diet to the optimal diet beginning at age 20 would increase LE by more than a decade for women (10.7 [uncertainty interval 5.9-14.1] years) and men (13.0 [6.9-17.3] years). The largest gains in years of LE would be made by eating more legumes (females: 2.2 [1.0-3.4]; males: 2.5 [1.1-3.9]), more whole grains (females: 2.0 [0.7-3.3]; males: 2.3 [0.8-3.8]), and more nuts (females: 1.7 [0.8-2.7]; males: 2.0 [1.0-3.0]), less red meat (females: 1.6 [0.7-2.5]; males: 1.9 [0.8-3.0]) and less processed meat (females: 1.6 [0.7-2.5]; males: 1.9 [0.8-3.0]). Changing from a typical diet to the optimized diet at age 60 years could still increase LE by 8.0 (4.8-11.2) years for women and 8.8 (5.2-12.5) years for men, and 80-year-olds could gain 3.4 years (females: 2.1-4.7 and males: 2.1-4.8) from such dietary changes.

"Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains," the authors say. "The Food4HealthyLife calculator could be a useful tool for clinicians, policy makers, and lay-people to understand the health impact of dietary choices."

Fadnes adds, "Research until now have shown health benefits associated with separate food group or specific diet patterns but given limited information on the health impact of other diet changes. Our modeling methodology has bridged this gap."

https://www.sciencedaily.com/releases/2022/02/220208143307.htm

Wisdom engendered: Study finds men and women have different strengths

Women score higher on compassion-related items and self-reflection while men score higher on cognitive-related items and emotional regulation

February 3, 2022

Science Daily/University of California - San Diego

Previous studies have shown that wisdom is a personality trait underpinning mental health and well-being. Recently, researchers at University of California San Diego School of Medicine looked at gender differences relative to wisdom, using two different validated scales.

The study, publishing in the February 3, 2022, online edition of Frontiers in Psychology, assessed gender differences in wisdom and associated constructs, including depression, loneliness, well-being, optimism and resilience.

Six hundred and fifty-nine community-based participants, ages 27 to 103, participated in the study and completed both the San Diego Wisdom Scale (SD-WISE) and the 3-Dimensional Wisdom Scale (3D-WS).

The SD-WISE includes 24 items related to six defined components of wisdom: pro-social behaviors (empathy and compassion), emotional regulation, self-reflection, acceptance of uncertainty and diversity of perspectives, decisiveness and social advising. The 3D-WS contains 39 items covering three dimensions of wisdom: cognitive, affective or compassionate/and reflective.

The researchers found that, in general, women scored higher on compassion-related items and on self-reflection while men scored higher on cognitive-related items and on emotional regulation. Generally speaking, the total 3-D-WS score was higher in women than in men, but there was no gender difference in the total score on the SD-WISE.

In both women and men, wisdom was associated with greater mental well-being, optimism, and resilience and lower levels of depression and loneliness.

"We wanted to gain information on potential differences in wisdom between men and women that could impact well-being," said senior author Dilip V. Jeste, MD, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine. "We found women and men have different relative strengths in wisdom, likely driven by both sociocultural and biological factors."

"Our latest findings are only a piece of the overall puzzle. There are several paths toward achieving a wise life. People approach wisdom differently and looking at gender is one way to assess those potential differences," said Emily Treichler, PhD, first author of the study and assistant professor in the Department of Psychiatry at UC San Diego School of Medicine and a research psychologist in the Desert Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) at the VA San Diego Healthcare System.

"Having a better understanding of wisdom and how to improve it has health benefits and value for individuals and society. Other studies have shown that the levels of certain components of wisdom like empathy/compassion and emotional regulation can be increased with appropriate psycho-social and behavioral interventions. Studies such as ours may help tailor wisdom interventions to individuals based on specific characteristics."

The researchers emphasize there were limitations of the study: It was cross-sectional rather than longitudinal. And it did not look at wisdom profiles of non-binary people or ask people whether they identify as transgender, and that should be one of the next steps.

"More work needs to be done, but we can take what we have learned and apply it to future studies to make the results applicable to different groups, with the ultimate goal of promoting healthier lives," said Jeste.

https://www.sciencedaily.com/releases/2022/02/220203083610.htm

Living in a walkable neighborhood lowers risk of excessive weight gain during pregnancy

February 2, 2022

Science Daily/Columbia University's Mailman School of Public Health

In one of the first studies to examine the link between neighborhood characteristics and weight gain during pregnancy, Columbia University Mailman School of Public Health researchers find that pregnant people who live in walkable neighborhoods in New York City have lower odds of excessive gestational weight gain (GWG) than those who live elsewhere in the city. They also found that living in a neighborhood with high rates of poverty increased the odds of excessive GWG. The findings are published in the journal Obesity.

Excessive or inadequate weight gain during pregnancy poses numerous health risks for both pregnant individuals and children. Excessive GWG is associated with a higher risk of pregnancy complications, including pregnancy-related hypertension and greater long-term postpartum weight retention. Excessive GWG is also associated with the risk for childhood asthma and obesity. Earlier research by Columbia Mailman researchers found that GWG was linked with a three-fold increased risk of childhood obesity at age 7 and excessive maternal weight gain.

Neighborhood walkability refers to urban form characteristics that support and favor walking and is defined by criteria including population density, land-use mix, density of public transit infrastructure, and street connectivity. Residents of walkable neighborhoods have been shown to engage in more walking, greater overall physical activity, and to have lower body mass index (BMI). Walkable neighborhoods are associated with better control of blood sugar among people with Type II diabetes. The most walkable areas of New York City include Battery Park City, Greenwich Village, NoHo, SoHo, Little Italy, and the West Village (Manhattan CBs 1 and 2). The least walkable areas include neighborhoods in eastern Queens and parts of Staten Island (Queens CB13 and Staten Island CB2).

"Given the long-lasting benefits of healthy pregnancies for parental and child health, this research provides further impetus for the use of urban design and poverty reduction to support healthy weight and reduce the risk of excessive gestational weight gain and related health risks," says the study's first author, Eliza Kinsey, PhD, formerly a postdoctoral research scientist in the Department of Epidemiology, now an assistant professor at the University of Pennsylvania Perelman School of Medicine.

The current study was conducted in partnership with researchers at the New York City Department of Health and Mental Hygiene (DOHMH) Bureau of Vital Statistics and used de-identified birth record data for the year 2015 to examine neighborhood-level influences on GWG. Using medical record data, the DOHMH compiles data on all live births in the city, including basic health and demographic information for the pregnant individual and birth outcome statistics (e.g., birth weight, gestational age).

Among the sample of 106,285 births, 42 percent of the pregnant individuals experienced excessive GWG, and 26 percent had inadequate GWG. Pregnant people living in neighborhoods ranking among the poorest quarter of the city had an additional 17 percent greater odds of excessive GWG. Pregnant people living in the top quarter of neighborhoods ranked for walkability had 13 percent lower odds of excessive GWG. These findings align with prior studies in New York City that have found that both neighborhood poverty and walkability predict BMI in the general population.

Adjustment for pre-pregnancy BMI attenuated the association between neighborhood poverty and excessive GWG but had little impact on the association between neighborhood walkability and excessive GWG.

Senior author Andrew Rundle, DrPH, professor of epidemiology, noted: "Neighborhood walkability is likely associated with GWG due to differences in behavior during pregnancy, presumably walking for exercise and daily activities -- not solely by influences on pre-pregnancy BMI. A significant amount of the exercise pregnant people get comes from low-impact activities like walking. Making neighborhoods more walkable has a host of health benefits, both for those currently living there and future generations."

https://www.sciencedaily.com/releases/2022/02/220202134706.htm

Social isolation and loneliness increase heart disease risk in senior women

February 2, 2022

Science Daily/University of California - San Diego

During the current pandemic, social distancing has been one tool used to reduce the spread of COVID-19. But data from a new study point to as much as a 27% increase in heart disease risk in postmenopausal women who experience both high levels of social isolation and loneliness.

The findings of the prospective study, published in the February 2, 2022 online issue of JAMA Network Open, reveal that social isolation and loneliness independently increased cardiovascular disease risk by 8% and 5% respectively. If women experienced high levels of both, their risk rose 13% to 27% compared to women who reported low levels of social isolation and low levels of loneliness.

"We are social beings. In this time of COVID-19, many people are experiencing social isolation and loneliness, which may spiral into chronic states," said first author Natalie Golaszewski, Ph.D., a postdoctoral scholar at the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego. "It is important to further understand the acute and long-term effects these experiences have on cardiovascular health and overall well-being."

Importantly, social isolation and loneliness are mildly correlated and can occur at the same time, but they are not mutually exclusive. A socially isolated person is not always lonely and conversely a person experiencing loneliness is not necessarily socially isolated.

"Social isolation is about physically being away from people, like not touching or seeing or talking to other people. Loneliness is a feeling, one that can be experienced even by people who are regularly in contact with others," said senior author John Bellettiere, Ph.D., M.P.H., assistant professor of epidemiology at the Herbert Wertheim School of Public Health.

Social isolation and loneliness are a growing public health concern as they are associated with health conditions that increase the risk of cardiovascular disease including obesity, smoking, physical inactivity, poor diet, high blood pressure and high cholesterol.

When researchers included all of these health behaviors and conditions in their study and adjusted for diabetes and depression, high social isolation and loneliness remained strongly linked with increased risk for heart disease, supporting the importance of studying these social conditions.

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death for women in the United States, responsible for 1 in every 5 deaths.

As social networks shrink, older adults are more at risk for social isolation and loneliness, wrote the authors. One-fourth of adults 65 and older report social isolation and one-third of adults 45 or older report being lonely.

"We do not yet know whether the increased risk of cardiovascular disease is due to acute exposure to social isolation and loneliness or whether prolonged exposure accumulated over a lifetime is the culprit. Further studies are needed to better understand that," said Bellettiere.

Previous research indicates women experience more social isolation than men.

For this study, 57,825 postmenopausal women living in the United States who had previously participated in the Women's Health Initiative study responded to questionnaires assessing social isolation from 2011 to 2012. They were sent a second questionnaire assessing loneliness and social support in 2014 to 2015.

Participants were followed from the time of the questionnaire completion through 2019 or when they were diagnosed with cardiovascular disease. A total of 1,599 women experienced cardiovascular disease.

"Measures of social isolation and loneliness -- even with brief questions as was done in our study -- should be incorporated into standard care," said Golaszewski. "We monitor our patients' blood pressure, weight and temperature, and it might also be beneficial to capture the social needs that individuals may be lacking to better understand cardiovascular risk and develop solutions."

Individuals who feel lonely or socially isolated can find information about steps to help reduce these feelings from the National Institute on Aging.

https://www.sciencedaily.com/releases/2022/02/220202111730.htm

Paternal alcohol use increases frequency of fetal development issues

February 1, 2022

Science Daily/Texas A&M University

Prenatal visits have traditionally focused almost exclusively on the behavior of mothers, but new research from the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVMBS) continues to suggest that science should be looking more closely at the fathers' behavior as well.

Dr. Michael Golding, an associate professor in the CVMBS' Department of Veterinary Physiology & Pharmacology (VTPP), has spent years investigating the father's role, specifically as it relates to drugs and alcohol, in fetal development.

Golding says a number of publications have shown that males pass down more than just their genetics, but exactly how that process works and the consequences of it remain largely unknown.

"When you look at the data from throughout human history, there's clear evidence that there's something beyond just genetics being inherited from the male," Golding said. "So, if that data is solid, we've got to start looking more at male behavior.

"Say you had a parent who was exposed to starvation -- they could pass on what you might call a 'thriftiness,' where their kids can derive more nutrition from less food," he said. "That could be a positive if they grow up in a similar environment, or they could grow up in a time when starvation isn't an issue and they might be more prone to obesity or metabolic syndromes. That kind of data is clearly present in clinical data from humans."

Golding's study of how things beyond genes, such as behavior and environment, affect development is called epigenetics, and one of the big questions in the search for answers on how male prenatal behavior can impact fetal growth has been how exactly these epigenetic factors manifest.

Now, there is at least one answer.

In a November publication in the FASEB Journal, Golding's team showed that the epigenetic factor of prenatal exposure to alcohol in males can manifest in the placenta.

According to Kara Thomas, VTPP graduate student and the lead author on the paper, their data shows that in mice, offspring of fathers exposed to alcohol have a number of placenta-related difficulties, including increased fetal growth restriction, enlarged placentas, and decreased placental efficiency.

"The placenta supplies nutrients to the growing fetus, so fetal growth restriction can be attributed to a less efficient placenta. This is why placental efficiency is such an important metric; it tells us how many grams of fetus are produced per gram of placenta," Thomas said. "With paternal alcohol exposure, placentas become overgrown as they try to compensate for their inefficiency in delivering nutrients to the fetus."

However, the mystery also deepened.

While these increases happened frequently in male offspring, the frequency varied greatly based on the mom; however, the same increases were far less frequent in female offspring. Golding believes this suggests that although that information is passed from the father, the mother's genetics and the offspring's sex also play a role.

"This is a novel observation because it says that there's some complexity here," Golding said. "Yes, men can pass things on to their offspring beyond just genetics, but the mom's genetics can interpret those epigenetic factors differently, and that ultimately changes the way that the placenta behaves."

These results don't draw a clear line in how human male drinking prior to conception impacts fetal development, but they continue to at least point to it being a question that needs to be explored.

Golding is hoping that soon doctors, and society at large, will begin to ask more questions about male prenatal behavior so that there's more data from which to work.

"The thing that I want to ultimately change is this stigma surrounding the development of birth defects," Golding said. "There's information coming through in sperm that is going to impact the offspring but is not tied to the genetic code; it's in your epigenetic code, and this is highly susceptible to environmental exposures, so the birth defects that we see might not be the mother's fault; they might be the father's or both, equally.

https://www.sciencedaily.com/releases/2022/02/220201161046.htm