Pinpointing the cells that keep the body's master circadian clock ticking
A new mouse model helps researchers study the roles of cell types in keeping time inside the body
August 7, 2020
Science Daily/UT Southwestern Medical Center
UT Southwestern scientists have developed a genetically engineered mouse and imaging system that lets them visualize fluctuations in the circadian clocks of cell types in mice. The method, described online in the journal Neuron, gives new insight into which brain cells are important in maintaining the body's master circadian clock. But they say the approach will also be broadly useful for answering questions about the daily rhythms of cells throughout the body.
"This is a really important technical resource for advancing the study of circadian rhythms," says study leader Joseph Takahashi, Ph.D., chair of the department of neuroscience at UT Southwestern Medical Center, a member of UT Southwestern's Peter O'Donnell Jr. Brain Institute, and an investigator with the Howard Hughes Medical Institute (HHMI). "You can use these mice for many different applications."
Nearly every cell in humans -- and mice -- has an internal circadian clock that fluctuates on a roughly 24-hour cycle. These cells help dictate not only hunger and sleep cycles, but biological functions such as immunity and metabolism. Defects in the circadian clock have been linked to diseases including cancer, diabetes, and Alzheimer's, as well as sleep disorders. Scientists have long known that a small part of the brain -- called the suprachiasmatic nucleus (SCN) -- integrates information from the eyes about environmental light and dark cycles with the body's master clock. In turn, the SCN helps keep the rest of the cells in the body in sync with each other.
"What makes the SCN a very special kind of clock is that it's both robust and flexible," says Takahashi. "It's a very strong pacemaker that doesn't lose track of time, but at the same time can shift to adapt to seasons, changing day lengths, or travel between time zones."
To study the circadian clock in both the SCN and the rest of the body, Takahashi's research group previously developed a mouse that had a bioluminescent version of PER2 -- one of the key circadian proteins whose levels fluctuate over the course of a day. By watching the bioluminescence levels wax and wane, the researchers could see how PER2 cycled throughout the animals' bodies during the day. But the protein is present in nearly every part of the body, sometimes making it difficult to distinguish the difference in circadian cycles between different cell types mixed together in the same tissue.
"If you observe a brain slice, for instance, almost every single cell has a PER2 signal, so you can't really distinguish where any particular PER2 signal is coming from," says Takahashi.
In the new work, the scientists overcame this problem by turning to a new bioluminescence system that changed color -- from red to green -- only in cells that expressed a particular gene known as Cre. Then, the researchers could engineer mice so that Cre, which is not naturally found in mouse cells, was only present in one cell type at a time.
To test the utility of the approach, Takahashi and his colleagues studied two types of cells that make up the brain's SCN -- arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) cells. In the past, scientists have hypothesized that VIP neurons hold the key to keeping the rest of the SCN synchronized.
When the research team looked at VIP neurons -- expressing Cre in just those cells, so that PER2 luminesced green in VIP cells, while red elsewhere -- they found that removing circadian genes from the neurons had little overall effect on the circadian rhythms of the VIP neurons, or the rest of the SCN. "Even when VIP neurons no longer had a functioning clock, the rest of the SCN behaved essentially the same," explains Yongli Shan, Ph.D., a UTSW research scientist and lead author of the study. Nearby cells were able to signal to the VIP neurons to keep them in sync with the rest of the SCN, he says.
When they repeated the same experiment on AVP neurons, however -- removing key clock genes -- not only did AVP neurons themselves show disrupted rhythms, but the entire SCN stopped synchronously cycling on its usual 24-hour rhythm.
"What this showed us was that the clock in AVP neurons is really essential for the synchrony of the whole SCN network," says Shan. "That's a surprising result and somewhat counterintuitive, so we hope it leads to more work on AVP neurons going forward."
Takahashi says other researchers who study circadian rhythms have already requested the mouse line from his lab to study the daily cycles of other cells. The mice might allow scientists to hone in on the differences in circadian rhythms between cell types within a single organ, or how tumor cells cycle differently than healthy cells, he says.
"In all sorts of complex or diseased tissues, this can let you see which cells have rhythms and how they might be similar or different from the rhythms of other cell types."
https://www.sciencedaily.com/releases/2020/08/200807111938.htm
Vitamin D twice a day may keep vertigo away
August 5, 2020
Science Daily/American Academy of Neurology
Taking vitamin D and calcium twice a day may reduce your chances of getting vertigo again, according to a study published in the August 5, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.
"Our study suggests that for people with benign paroxysmal positional vertigo, taking a supplement of vitamin D and calcium is a simple, low-risk way to prevent vertigo from recurring," said Ji-Soo Kim, M.D., Ph.D., of Seoul National University College of Medicine in Korea. "It is especially effective if you have low vitamin D levels to begin with."
Benign paroxysmal positional vertigo happens when a change in head position gives you a sudden spinning sensation. It's one of the most common types of vertigo. Treatment includes a doctor performing a series of head movements that shift particles in the ears that cause the vertigo, but the condition tends to recur frequently. About 86% of people with this form of vertigo find that it interrupts their daily life or causes them to miss days at work.
The study looked at 957 people in Korea with benign paroxysmal positional vertigo who were treated successfully with the head movements. The participants were separated into two groups, intervention and observation.
The 445 people in the intervention group had their vitamin D levels taken at the start of the study. The 348 people with vitamin D levels below 20 nanograms per milliliter (ng/mL) were started on supplements with 400 international units of vitamin D and 500 milligrams of calcium twice daily, while those with vitamin D levels equal to or greater than 20 ng/mL were not given supplements.
The 512 people in the observation group did not have their vitamin D levels monitored and they did not get supplements.
Those in the intervention group who took the supplements had a lower recurrence rate for vertigo episodes after an average of one year than those in the observation group. People taking supplements had an average recurrence rate of 0.83 times per person-year, compared to 1.10 times per person-year for those in the observation group, or a 24% reduction in the annual recurrence rate.
There appeared to be greater benefit for those who were more deficient in vitamin D at the start of the study. Those who started with vitamin D levels lower than 10 ng/mL saw a 45% reduction in annual recurrence rate, while those starting with vitamin D levels at 10 to 20 ng/mL saw only a 14% reduction. A total of 38% of the people in the interventional group had another episode of vertigo, compared to 47% of those in the observation group.
"Our results are exciting because so far, going to the doctor to have them perform head movements has been the main way we treat benign paroxysmal positional vertigo," said Kim. "Our study suggests an inexpensive, low-risk treatment like vitamin D and calcium tablets may be effective at preventing this common, and commonly recurring, disorder."
A limitation of the study is that a large number of participants did not complete the entire study, with more people assigned to take the supplements dropping out of the study than in the observation group.
https://www.sciencedaily.com/releases/2020/08/200805160933.htm
REM sleep tunes eating behavior
August 6, 2020
Science Daily/University of Bern
Despite our broad understanding of the different brain regions activated during rapid-eye-movement sleep, little is known about what this activity serves for. Researchers at the University of Bern and the Inselspital have now discovered that the activation of neurons in the hypothalamus during REM sleep regulates eating behaviour: suppressing this activity in mice decreases appetite.
While we are asleep, we transition between different phases of sleep each of which may contribute differently to us feeling rested. During (rapid eye movement) REM sleep, a peculiar sleep stage also called paradoxical sleep during which most dreaming occurs, specific brain circuits show very high electrical activity, yet the function of this sleep-specific activity remains unclear.
Among the brain regions that show strong activation during REM sleep are areas that regulate memory functions or emotion, for instance. The lateral hypothalamus, a tiny, evolutionarily well conserved brain structure in all mammals also shows high activity during REM sleep. In the awake animals, neurons from this brain region orchestrate appetite and the consumption of food and they are involved in the regulation of motivated behaviours and addiction.
In a new study, researchers headed by Prof. Dr. Antoine Adamantidis at the University of Bern set out to investigate the function of the activity of hypothalamic neurons in mice during REM sleep. They aimed at better understanding how neural activation during REM sleep influences our day-to-day behaviour. They discovered that suppressing the activity of these neurons decreases the amount of food the mice consume. "This suggests that REM sleep is necessary to stabilize food intake," says Adamantidis. The results of this study have been published in the journal Proceedings of the National Academy of Sciences (PNAS).
Long-lasting effect on neuronal activity and feeding behavior
The researcher discovered that specific activity patterns of neurons in the lateral hypothalamus that usually signal eating in the awake mouse are also present when the animals were in the stage of REM sleep. To assess the importance of these activity patterns during REM sleep the research group used a technique called optogenetics, with which they used light pulses to precisely shut down the activity of hypothalamic neurons during REM sleep. As a result, the researchers found that the activity patterns for eating were modified and that the animals consumed less food.
"We were surprised how strongly and persistently our intervention affected the neural activity in the lateral hypothalamus and the behaviour of the mice," says Lukas Oesch, the first author of the study. He adds: "The modification in the activity patterns was still measurable after four days of regular sleep." These findings suggest that electrical activity in hypothalamic circuits during REM sleep are highly plastic and essential to maintain a stable feeding behaviour in mammals.
It is a question of quality
These findings point out that sleep quantity alone is not solely required for our well-being, but that sleep quality plays a major role in particular to maintain appropriate eating behaviour. "This is of particular relevance in our society where not only sleep quantity decreases but where sleep quality is dramatically affected by shift work, late night screen exposure or social jet-lag in adolescents," explains Adamantidis.
The discovered link between the activity of the neurons during REM sleep and eating behaviour may help developing new therapeutical approaches to treat eating disorders. It might also be relevant for motivation and addiction. "However, this relationship might depend on the precise circuitry, the sleep stage and other factors yet to be uncovered," adds Adamantidis.
https://www.sciencedaily.com/releases/2020/08/200806111820.htm
Gut feelings help promote positive body image
Study finds association between feeling full and positive body image
July 30, 2020
Science Daily/Anglia Ruskin University
New research has found that paying greater attention to internal bodily sensations can increase our appreciation of our own bodies.
The study, led by Jennifer Todd of Anglia Ruskin University (ARU) and published in the journal Body Image, focused on gastric interoception, which are the feelings of hunger or fullness that originate in the gut.
The researchers carried out an experiment involving 191 adults in the UK and Malaysia fasting and then consuming water.
They measured both the quantity of water consumed in relation to stomach capacity, and the feelings and experiences of the adults during the task. This included completing questionnaires examining different aspects of body image, such as appreciation of the body and appreciation of the body's functionality.
Body image refers to appearance-related thoughts and feelings, and positive body image refers specifically to an active love, respect, and appreciation for one's body.
The study found that a greater change in the intensity of feelings in the gut after consuming water was associated with significantly higher levels of appreciation of the body and appreciation of the body's functionality for adults in both the UK and Malaysia.
Lead author Jennifer Todd, a Psychology PhD student at Anglia Ruskin University (ARU), said: "Our study shows a clear link between bodily awareness, in this case the feeling of fullness, and body image. In other words, people who are more in tune with their body's internal workings have a greater appreciation of their body in general. Interestingly, we found that this link exists in two very different countries.
"We think that greater sensitivity to gastric signals might increase awareness of the positive functions the body performs and improve the ability to respond to the body's needs, both of which promote positive body image.
"Individuals who are less in tune with internal stimuli, such as feeling full, could be more at risk of developing negative body image, due to an over-reliance on external, appearance-related characteristics such as shape and size.
"It is possible that body image can be promoted by encouraging people to be more aware of internal sensations, such as feeling full. Gut feelings can be good for you!"
https://www.sciencedaily.com/releases/2020/07/200730205826.htm
Major depressive episodes far more common than previously believed
July 30, 2020
Science Daily/Yale School of Public Health
The number of adults in the United States who suffer from major depressive episodes at some point in their life is far higher than previously believed, a new study by the Yale School of Public Health finds.
National survey data currently shows that approximately 17% of women and 10% of men report having a history of major depressive episodes (MDEs) in their lifetimes. But these data are subject to "recall error," or the tendency of people to forget or misreport their health histories when taking a survey.
Researchers led by Jamie Tam, Ph.D., assistant professor in the Department of Health Policy and Management, created a simulation model to generate corrected estimates of lifetime depression. They found that the proportion of U.S. adults who have had MDEs is actually closer to 30% of women and 17% of men after factoring in recall error.
"Major depressive episodes are far more common than we thought," said Tam. "Our model shows that the probability of someone having a first major depressive episode is especially high during adolescence. We also know from other research that having a first major depressive episode increases the likelihood you'll have a second one. This means that anything we can do to prevent or treat episodes among young people could lead to larger health benefits over the course of their life."
The findings are published in the American Journal of Preventive Medicine.
A major depressive episode is defined as a period of two weeks or longer in which a person experiences feelings of intense sadness and hopelessness, fatigue, weight gain or weight loss, changes in sleeping habits, loss of interest in activities and thoughts of suicide or attempts at suicide. These persistent symptoms cannot be easily changed, even if they are contradictory to a person's circumstances. Depressive episodes typically recur periodically in people diagnosed with major depression.
The study shows that mental health programs that screen for, prevent and treat depression could benefit a much larger segment of the population than previously thought, Tam said.
"If you think about chronic health conditions like heart disease, we do a lot to identify people who might be at risk for additional health events like heart attacks because that group would benefit from maintenance treatment and clinical monitoring," Tam said. "We don't do such a great job when it comes to mental health conditions. So, if we're able to assess how many people actually have histories of depression, that also tells us that more people are at risk of experiencing more depressive episodes."
The researchers also found that older adults are especially likely to under-report their history of having depressive symptoms. Among adults 65 years and older, underreporting for depression was as high as 70%. Older adults often experience what is referred to as "minor depression," where they still report significant depressive symptoms but don't always meet clinical requirements for major depression. Tam said there may be a tendency for older adults to downplay negative experiences of depression from when they were younger, classifying them as "growing pains" rather than major depression.
"Unfortunately, many people with depression or with histories of depression don't access, or don't have access to, treatment or support," Tam said. "There's a broader problem in our society of mental health not receiving the same attention and investment of resources compared to physical health conditions."
https://www.sciencedaily.com/releases/2020/07/200730132813.htm
Laughter acts as a stress buffer -- and even smiling helps
July 30, 2020
Science Daily/University of Basel
People who laugh frequently in their everyday lives may be better equipped to deal with stressful events -- although this does not seem to apply to the intensity of laughter. These are the findings reported by a research team from the University of Basel in the journal PLOS ONE.
It is estimated that people typically laugh 18 times a day -- generally during interactions with other people and depending on the degree of pleasure they experience. Researchers have also reported differences related to time of day, age, and gender -- for example, it is known that women smile more than men on average. Now, researchers from the Division of Clinical Psychology and Epidemiology of the Department of Psychology at the University of Basel have recently conducted a study on the relationship between stressful events and laughter in terms of perceived stress in everyday life.
Questions asked by app
In the intensive longitudinal study, an acoustic signal from a mobile phone app prompted participants to answer questions eight times a day at irregular intervals for a period of 14 days. The questions related to the frequency and intensity of laughter and the reason for laughing -- as well as any stressful events or stress symptoms experienced -- in the time since the last signal.
Using this method, the researchers working with the lead authors, Dr. Thea Zander-Schellenberg and Dr. Isabella Collins, were able to study the relationships between laughter, stressful events, and physical and psychological symptoms of stress ("I had a headache" or "I felt restless") as part of everyday life. The newly published analysis was based on data from 41 psychology students, 33 of whom were women, with an average age of just under 22.
Intensity of laughter has less influence
The first result of the observational study was expected based on the specialist literature: in phases in which the subjects laughed frequently, stressful events were associated with more minor symptoms of subjective stress. However, the second finding was unexpected. When it came to the interplay between stressful events and intensity of laughter (strong, medium or weak), there was no statistical correlation with stress symptoms. "This could be because people are better at estimating the frequency of their laughter, rather than its intensity, over the last few hours," says the research team.
https://www.sciencedaily.com/releases/2020/07/200730110114.htm
Hedonism leads to happiness
July 27, 2020
Science Daily/University of Zurich
Relaxing on the sofa or savoring a delicious meal: Enjoying short-term pleasurable activities that don't lead to long-term goals contributes at least as much to a happy life as self-control, according to new research from the University of Zurich and Radboud University in the Netherlands. The researchers therefore argue for a greater appreciation of hedonism in psychology.
We all set ourselves long-term goals from time to time, such as finally getting into shape, eating less sugar or learning a foreign language. Research has devoted much time to finding out how we can reach these goals more effectively. The prevailing view is that self-control helps us prioritize long-term goals over momentary pleasure and that if you are good at self-control, this will usually result in a happier and more successful life.
"It's time for a rethink," says Katharina Bernecker, researcher in motivational psychology at the University of Zurich. "Of course self-control is important, but research on self-regulation should pay just as much attention to hedonism, or short-term pleasure." That's because Bernecker's new research shows that people's capacity to experience pleasure or enjoyment contributes at least as much to a happy and satisfied life as successful self-control.
Distraction disrupts pleasure
Bernecker and her colleague Daniela Becker of Radboud University developed a questionnaire to measure respondents' capacity for hedonism, i.e. their ability to focus on their immediate needs and indulge in and enjoy short-term pleasures. They used the questionnaire to find out whether people differ in their capacity to pursue hedonic goals in a variety of contexts, and whether this ability is related to well-being.
They found that certain people get distracted by intrusive thoughts in moments of relaxation or enjoyment by thinking about activities or tasks that they should be doing instead. "For example, when lying on the couch you might keep thinking of the sport you are not doing," says Becker. "Those thoughts about conflicting long-term goals undermine the immediate need to relax." On the other hand, people who can fully enjoy themselves in those situations tend to have a higher sense of well-being in general, not only in the short term, and are less likely to suffer from depression and anxiety, among other things.
More isn't always better
"The pursuit of hedonic and long-term goals needn't be in conflict with one another," says Bernecker. "Our research shows that both are important and can complement each other in achieving well-being and good health. It is important to find the right balance in everyday life."
Unfortunately, simply sitting about more on the sofa, eating more good food and going to the pub with friends more often won't automatically make for more happiness. "It was always thought that hedonism, as opposed to self-control, was the easier option," says Bernecker. "But really enjoying one's hedonic choice isn't actually that simple for everybody because of those distracting thoughts."
Conscious planning of downtime
This is currently a topical issue with more people working from home, as the environment where they normally rest is suddenly associated with work. "Thinking of the work you still need to do can lead to more distracting thoughts at home, making you less able to rest," says Bernecker.
So what can you do to enjoy your downtime more? More research is needed, but the researchers suspect that consciously planning and setting limits to periods of enjoyment could help to separate them more clearly from other activities, allowing pleasure to take place more undisturbed.
https://www.sciencedaily.com/releases/2020/07/200727114739.htm
Wealthier men are more likely to develop high blood pressure
July 26, 2020
Science Daily/European Society of Cardiology
Working men with higher incomes are more likely to develop high blood pressure, reports a study presented at the 84th Annual Scientific Meeting of the Japanese Circulation Society (JCS 2020).
JCS 2020 takes place online from 27 July to 2 August in conjunction with the Asian Pacific Society of Cardiology Congress 2020 (APSC 2020). Joint scientific sessions are being held by the European Society of Cardiology (ESC) and JCS as part of the ESC Global Activities programme.
"Men with higher incomes need to improve their lifestyles to prevent high blood pressure," said study author Dr. Shingo Yanagiya of the Hokkaido University Graduate School of Medicine, Sapporo, Japan. "Steps include eating healthily, exercising, and controlling weight. Alcohol should be kept to moderate levels and binge drinking avoided."
More than one billion people have high blood pressure worldwide.2 Around 30-45% of adults are affected, rising to more than 60% of people over 60 years of age. High blood pressure is the leading global cause of premature death, accounting for almost 10 million deaths in 2015. Of those, 4.9 million were due to ischaemic heart disease and 3.5 million were due to stroke.
Japan alone has more than 10 million people with high blood pressure, and the number continues to rise. Dr. Yanagiya said: "High blood pressure is a lifestyle-related disease. As a physician seeing these patients I wanted to know if risk varies with socioeconomic class, to help us focus our prevention efforts."
This analysis of the J-HOPE3 study examined the relationship between household income and high blood pressure in Japanese employees. A total of 4,314 staff (3,153 men and 1,161 women) with daytime jobs and normal blood pressure were enrolled in 2012 from 12 workplaces.
Workers were divided into four groups according to annual household income: less than 5 million, 5 to 7.9 million, 8 to 9.9 million, and 10 million or more Japanese yen per year. The researchers investigated the association between income and developing high blood pressure over a two-year period.
Compared to men in the lowest income category, men in the highest income group were nearly twice as likely to develop high blood pressure. Men in the 5 to 7.9 million and 8 to 9.9 million groups had a 50% higher risk of developing high blood pressure compared to men with the lowest incomes, although the positive association did not reach statistical significance in the 8 to 9.9 million group.
The findings were consistent regardless of age, and were independent of baseline blood pressure, worksite, occupation, number of family members, and smoking. The relationships were slightly weakened after accounting for alcohol consumption and body mass index (BMI; kg/m2), both of which were higher for men in the higher income groups.
In women, there was no significant link between income and blood pressure. However, women with higher household income tended to have a lower risk of developing high blood pressure.
"Some previous Japanese surveys have reported that higher household income is associated with more undesirable lifestyles in men, but not in women," said Dr. Yanagiya. "Our study supports this: men, but not women, with higher household incomes were more likely to be obese and drink alcohol every day. Both behaviours are major risk factors for hypertension."
He concluded: "Men with high-paying daytime jobs are at particular risk of high blood pressure. This applies to men of all ages, who can greatly decrease their chance of a heart attack or stroke by improving their health behaviours."
Dr. Yusuke Yoshikawa, public relations coordinator for JCS 2020, said: "Hypertension is one of the most important risk factors of cardiovascular disease in Japan, because the average daily salt intake in Japan (approx. 10 g/day) is much higher than desired. As the current guidelines2 strongly recommend healthy lifestyle to control high blood pressure, this study suggests a potential key to successful intervention for those who are at risk of heart disease and stroke."
https://www.sciencedaily.com/releases/2020/07/200726214837.htm
Remember the first time you...? Mysterious brain structure sheds light on addiction
Cocaine-addicted mice shed light on claustrum's role in associating reward with context
July 23, 2020
Science Daily/The Hebrew University of Jerusalem
Do you remember where you were when you first heard that two planes had crashed into New York's Twin Towers? Or where you had your first kiss? Our brains are wired to retain information that relates to the context in which highly significant events occurred. This mechanism also underlies drug addiction and is the reason why hanging out in an environment or with people associated with memories of drug use often leads to relapse.
How our brains create this strong association, however, is less clear. Now, new research by Professor Ami Citri and PhD student Anna Terem at Hebrew University of Jerusalem (HU)'s Edmond and Lily Safra Center for Brain Sciences and the Alexander Silberman Institute of Life Science, shows that a relatively obscure brain region known as the claustrum plays a significant role in making these connections. They published their findings in the latest edition of Current Biology.
The researchers' findings fit the idea of "incentive salience," the process that determines the desirability of an otherwise neutral stimulus. For example, a candy store façade becomes very attractive to kids after repeated associations with the rewarding treats that lie within. In time, children unconsciously learn to "want" to see the store stimulus, which is separate from their "liking" the actual candy reward. Taking a closer look at how context becomes associated with cocaine, the researchers found a group of neurons within the claustrum that lit up during cocaine use. Further, these neurons are pivotal in the formation of an incentive salience that links context with the pleasure of cocaine.
To determine when and how the claustrum participates in incentive salience, Citri and his team employed a conditioned-place preference (CPP) test for a group of lab mice. During this test, the mice learned to associate reward with context. The researcher administered cocaine to the mice and placed them in an area with distinctive flooring (rugged) and wall patterns (dots), ones that a mouse would notice, as the drug started to kick in. After a few times of this, when placed in a room where the mice could choose either to hang out in a region similar to the one paired with cocaine (rugged floors and dots wall) or a neutral area (smooth floor and striped walls), the mice would quickly congregate in the area where their drug high had played out.
To test the claustrum's involvement in how a context becomes associated with a given reward, Citri and his team observed the changes in mice behavior when they inhibited these claustral neurons. They found that the inhibition of these neurons inhibited the mice's behavioral responses to cocaine, meaning they no longer preferred hanging out in the cocaine-paired environment. On the other hand, activating these neurons -- even in the absence of any cocaine -- caused the mice to develop a preference for this context.
Importantly, the team found that the activity of the claustrum was not necessary for retrieval of the cocaine memory. Once the mice had been placed in a cocaine-paired context several times to enjoy their cocaine high, the memory for this context was encoded and inhibition of the claustrum had no effect on their preference for the cocaine-paired context. "These findings boosted our confidence that the claustrum is indeed integral to incentive salience, heightening the awareness of the mouse to the context in which it experienced the drug high" shared Citri.
As the number of deaths caused by drug overdose increases from year to year, this new study has wide-ranging implications towards a better understanding of the nature of addiction and the importance of breaking contextual cues before they develop. "By recognizing that the claustrum plays a pivotal role in creating a context association for reward, it becomes a structure of interest for the field of addiction. We hope this knowledge will lead to the development of new diagnostic tools to identify populations susceptible to addiction, as well as new therapeutic approaches," concluded Terem.
https://www.sciencedaily.com/releases/2020/07/200723115904.htm
When it comes to happiness, what's love got to do with it?
July 23, 2020
Science Daily/Michigan State University
How accurate was William Shakespeare when he said, "'Tis better to have loved and lost than never to have loved at all"? Researchers from Michigan State University conducted one of the first studies of its kind to quantify the happiness of married, formerly married and single people at the end of their lives to find out just how much love and marriage played into overall well-being.
The study -- published in the Journal of Positive Psychology -- examined the relationship histories of 7,532 people followed from ages 18 to 60 to determine who reported to be happiest at the end of their lives.
"People often think that they need to be married to be happy, so we asked the questions, 'Do people need to be in a relationship to be happy? Does living single your whole life translate to unhappiness? What about if you were married at some point but it didn't work out?,'" said William Chopik, MSU assistant professor of psychology and co-author of the paper. "Turns out, staking your happiness on being married isn't a sure bet."
Chopik and Mariah Purol, MSU psychology master's student and co-author, found that participants fell into one of three groups: 79% were consistently married, spending the majority of their lives in one marriage; 8% were consistently single, or, people who spent most of their lives unmarried; and 13% had varied histories, or, a history of moving in and out of relationships, divorce, remarrying or becoming widowed. The researchers then asked participants to rate overall happiness when they were older adults and compared it with the group into which they fell.
"We were surprised to find that lifelong singles and those who had varied relationship histories didn't differ in how happy they were," said Purol. "This suggests that those who have 'loved and lost' are just as happy towards the end of life than those who 'never loved at all.'"
While married people showed a slight uptick in happiness, Purol said the margin was not substantial -- nor what many may expect. If the consistently married group answered a 4 out of 5 on how happy they were, consistently single people answered a 3.82 and those with varied history answered a 3.7.
"When it comes to happiness, whether someone is in a relationship or not is rarely the whole story," Chopik said. "People can certainly be in unhappy relationships, and single people derive enjoyment from all sorts of other parts of their lives, like their friendships, hobbies and work. In retrospect, if the goal is to find happiness, it seems a little silly that people put so much stock in being partnered."
If someone longs for a lifelong partner to start a family and build a happy life together, Chopik and Purol's research suggests that if that individual isn't completely happy to begin with, getting married won't likely dramatically change it all.
"It seems like it may be less about the marriage and more about the mindset," Purol said. "If you can find happiness and fulfillment as a single person, you'll likely hold onto that happiness -- whether there's a ring on your finger or not."
https://www.sciencedaily.com/releases/2020/07/200723115833.htm
Health and happiness depend on each other
July 22, 2020
Science Daily/Association for Psychological Science
Good health and a happy outlook on life may seem like equally worthy yet independent goals. A growing body of research, however, bolsters the case that a happy outlook can have a very real impact on your physical well-being.
New research published in the journal Psychological Scienceshows that both online and in-person psychological interventions -- tactics specifically designed to boost subjective well-being -- have positive effects on self-reported physical health. The online and in-person interventions were equally effective.
"Though prior studies have shown that happier people tend to have better cardiovascular health and immune-system responses than their less happy counterparts," said Kostadin Kushlev, a professor in Georgetown University's Department of Psychology and one of the authors of the paper, "our research is one of the first randomized controlled trials to suggest that increasing the psychological well-being even of generally healthy adults can have benefits to their physical health."
Intervention for Healthy Outcomes
Over the course of six months, Kushlev and his colleagues at the University of Virginia and the University of British Columbia examined how improving the subjective well-being of people who were not hospitalized or otherwise undergoing medical treatment affected their physical health.
A group of 155 adults between the ages of 25 and 75 were randomly assigned either to a wait-list control condition or a 12-week positive psychological intervention that addressed three different sources of happiness: the "Core Self," the "Experiential Self," and the "Social Self."
The first 3 weeks of the program focused on the Core Self, helping individuals identify their personal values, strengths, and goals. The next 5 weeks focused on the Experiential Self, covering emotion regulation and mindfulness. This phase also gave participants tools to identify maladaptive patterns of thinking. The final 4 weeks of the program addressed the Social Self, teaching techniques to cultivate gratitude, foster positive social interactions, and engage more with their community.
The program, called Enduring Happiness and Continued Self-Enhancement (ENHANCE), consisted of weekly modules either led by a trained clinician or completed individually using a customized online platform. None of the modules focused on promoting physical health or health behaviors, such as sleep, exercise, or diet.
Each module featured an hour-long lesson with information and exercises; a weekly writing assignment, such as journaling; and an active behavioral component, such as guided meditation.
"All of the activities were evidence-based tools to increase subjective well-being," Kushlev noted.
When the program concluded, the participants were given individual evaluations and recommendations of which modules would be most effective at improving their happiness in the long term. Three months after the conclusion of the trial, researchers followed up with the participants to evaluate their well-being and health.
A Happy Future
Participants who received the intervention reported increasing levels of subjective well-being over the course of the 12-week program. They also reported fewer sick days than control participants throughout the program and 3 months after it ended.
The online mode of administering the program was shown to be as effective as the in-person mode led by trained facilitators.
"These results speak to the potential of such interventions to be scaled in ways that reach more people in environments such as college campuses to help increase happiness and promote better mental health among students," Kushlev said.
https://www.sciencedaily.com/releases/2020/07/200722170142.htm
Meditation linked to lower cardiovascular risk
Survey data from more than 61,000 people points to heart benefits
July 15, 2020
Science Daily/Veterans Affairs Research Communications
Meditation was linked to lower cardiovascular risk in a data analysis by Veterans Affairs researchers and colleagues.
The results appeared online June 30 in the American Journal of Cardiology.
Previous studies have suggested that meditation may have beneficial effects on a number of conditions. A 2017 American Heart Association scientific statement suggests that meditation may be of benefit for cardiovascular risk reduction. Data show that it may help with blood pressure, cholesterol level, quitting smoking, and overall cardiovascular health. However, this connection is far from definitive. By using a large national database with many participants, the authors of the new study sought further evidence on how meditation impacts cardiovascular risk.
Lead researcher Dr. Chayakrit Krittanawong -- of the Michael E. DeBakey VA Medical Center, Baylor College of Medicine, and the Icahn School of Medicine at Mount Sinai -- and his colleagues studied data from the National Health Interview Survey, conducted annually by the National Center for Health Statistics. It collects information on a wide range of health topics from a nationally representative sample.
The researchers looked at data on more than 61,000 survey participants. Of those, almost 6,000 (nearly 10%) said they participated in some form of meditation.
The researchers found that people who meditated had lower rates of high cholesterol, high blood pressure, diabetes, stroke, and coronary artery disease, compared with those who did not meditate.
The greatest difference was in coronary artery disease. Those who meditated were 51% as likely as those who didn't to have the disease. The prevalence of other cardiovascular risks in the meditation group compared with the non-meditation group was 65% for high cholesterol, 70% for diabetes, 76% for stroke, and 86% for high blood pressure.
The researchers controlled for other factors connected to cardiovascular risk, such as age, sex, cigarette smoking, and body mass index. After adjusting for these factors, the effect of meditation was still significant.
Many types of meditation exist. Most focus on attention and awareness. Meditation has been shown to increase physical and mental relaxation. "I believe in meditation, as it can give us a sense of calm, peace, and stress reduction, leading to improvement of our emotional well-being," explained Krittanawong.
Practicing meditation has been linked to decreased stress, greater mindfulness, and improved psychological health. It may even lead to long-term functional and anatomical changes in the brain. Meditation is also simple, cost-effective, and low-risk.
Krittanawong and colleagues did note several limitations to the study. First, the survey did not capture what type of meditation people were using. Some types of meditation may offer more cardiovascular benefit than others, say the researchers. The survey also did not ask about the duration or intensity of that meditation. It is possible that those who practice longer and more frequently will get more benefit, but the study cannot measure these effects.
Also, the researchers cannot definitively say that meditation directly decreases cardiovascular risk. It could be that people who are in better cardiovascular health to begin with are more likely to practice meditation, rather than the other way around.
Other life activities might also obscure the link between meditation and cardiovascular health. The researchers found factoring in alcohol consumption and physical activity lowered the significance of the relationship between meditation and cardiovascular risk.
Considering all these factors, the researchers concluded that meditation is "probably" associated with lower prevalence of cardiovascular risk. Krittanawong notes that, while the results suggest that meditation can improve cardiovascular health, "we would need a powerful study such as a clinical trial to determine whether meditation could benefit cardiovascular health in veterans."
Meanwhile, the study adds to a growing body of research on the potential benefits of meditation, they say.
https://www.sciencedaily.com/releases/2020/07/200715135734.htm
Apathy not depression helps to predict dementia
July 13, 2020
Science Daily/University of Cambridge
Apathy offers an important early warning sign of dementia in individuals with cerebrovascular disease, but depression does not, new research led by the University of Cambridge suggests.
Depression is often thought to be a risk factor for dementia but this may be because some depression scales used by clinicians and researchers partially assess apathy, say scientists from the universities of Cambridge, King's College London, Radboud and Oxford.
The study, published on 11 July in the Journal of Neurology, Neurosurgery & Psychiatry is the first to examine the relationships between apathy, depression, and dementia in individuals with cerebral small vessel disease (SVD). SVD may occur in one out of three elderly individuals, causes about a quarter of all strokes, and is the most common cause of vascular dementia.
The team studied two independent cohorts of SVD patients, one from the UK and the other from the Netherlands.* Across both cohorts, they found that individuals with higher baseline apathy, as well as those with increasing apathy over time, had a greater risk of dementia. In contrast, neither baseline depression nor change in depression had any detectable influence on dementia risk.
These findings were consistent despite variation in the severity of participants' symptoms, suggesting that they could be generalised across a broad spectrum of SVD cases. The relationship between apathy and dementia remained after controlling for other well-established risk factors for dementia including age, education, and cognition.
Lead author, Jonathan Tay, from Cambridge's Department of Clinical Neurosciences said: "There has been a lot of conflicting research on the association between late-life depression and dementia. Our study suggests that may partially be due to common clinical depression scales not distinguishing between depression and apathy."
Apathy, defined as a reduction in 'goal-directed behaviour', is a common neuropsychiatric symptom in SVD, and is distinct from depression, which is another symptom in SVD. Although there is some symptomatic overlap between the two, previous MRI research linked apathy, but not depression, with white matter network damage in SVD.
Jonathan Tay said: "Continued monitoring of apathy may be used to assess changes in dementia risk and inform diagnosis. Individuals identified as having high apathy, or increasing apathy over time, could be sent for more detailed clinical examinations, or be recommended for treatment."
Over 450 participants -- all with MRI-confirmed SVD -- recruited from three hospitals in South London and Radboud University's Neurology Department in the Netherlands, were assessed for apathy, depression and dementia over several years.
In the UK cohort, nearly 20% of participants developed dementia, while 11% in the Netherlands cohort did, likely due to the more severe burden of SVD in the UK cohort. In both datasets, patients who later developed dementia showed higher apathy, but similar levels of depression at baseline, compared to patients who did not.
The study provides the basis for further research, including the mechanisms that link apathy, vascular cognitive impairment, and dementia. Recent MRI work suggests that similar white matter networks underlie motivation and cognitive function in SVD. Cerebrovascular disease, which can be caused by hypertension and diabetes, can lead to network damage, resulting in an early form of dementia, presenting with apathy and cognitive deficits. Over time, SVD-related pathology increases, which is paralleled by increasing cognitive and motivational impairment, eventually becoming severe enough to meet criteria for a dementia state.
Jonathan Tay says: "This implies that apathy is not a risk factor for dementia per se, but rather an early symptom of white matter network damage. Understanding these relationships better could have major implications for the diagnosis and treatment of patients in the future."
https://www.sciencedaily.com/releases/2020/07/200713120022.htm
Long-studied protein could be a measure of traumatic brain injury
Cathepsin B in brain and cerebral spinal fluid is a biomarker for traumatic brain injury
July 13, 2020
Science Daily/Walter Reed Army Institute of Research
Scientists at the Walter Reed Army Institute for Research (WRAIR) have recently demonstrated that cathepsin B, a well-studied protein important to brain development and function, can be used as biomarker, or indicator of severity, for traumatic brain injury.
Traumatic brain injury (TBI) or brain trauma results from blows to the head, leading to life-changing disruption of the brain and a cascade of long-term health conditions. A leading cause of disability and death worldwide, TBI may occur due to an open-skull injury, like a gunshot wound, a fall, or an automobile accident. Athletes, the elderly, children, and military service members are particularly vulnerable.
Biomarkers are a source of great interest to researchers due to their potential to dramatically improve both the diagnosis and categorization of severity of TBI. Furthermore, they have the potential to validate treatment strategies by indicating whether drugs have reached their proposed targets and achieved therapeutic benefits.
In their publication in the Journal of Neurotrauma, the researchers showed that levels of cathepsin B were increased in areas of the injured brain relevant to controlling the senses, language, memory and other critical executive functions. In healthy cells, cathepsin B has a range of roles, including helping to eliminate damaged cells, maintaining metabolic homeostasis, and degrading improperly produced proteins. When the level of cathepsin B is not tightly controlled, it is linked to inflammation and tissue death. This publication reports the first results demonstrating the ability to use cathepsin B as a blood-based biomarker to capable of identifying TBI severity within different brain regions as well as cerebral spinal fluid.
"Biomarker tests that accurately reflect the extent and severity of injury can dramatically improve the standard of care, minimizing the need for resource-intensive diagnostics like CT or MRI scans in favor of more portable tests," said Dr. Angela Boutte, lead author and section chief of molecular biology and proteomics within the Brain Trauma Neuroprotection Branch at WRAIR. "This would allow for early, accurate detection of TBI, whether at the side of the road after an accident or, most importantly, on the battlefield to help guide medical decisions."
https://www.sciencedaily.com/releases/2020/07/200713154950.htm
Does eating fish protect our brains from air pollution?
July 15, 2020
Science Daily/American Academy of Neurology
Older women who eat more than one to two servings a week of baked or broiled fish or shellfish may consume enough omega-3 fatty acids to counteract the effects of air pollution on the brain, according to a new study published in the July 15, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.
Researchers found that among older women who lived in areas with high levels of air pollution, those who had the lowest levels of omega-3 fatty acids in their blood had more brain shrinkage than women who had the highest levels.
"Fish are an excellent source of omega-3 fatty acids and easy to add to the diet," said study author Ka He, M.D., Sc.D., of Columbia University in New York. "Omega-3 fatty acids have been shown to fight inflammation and maintain brain structure in aging brains. They have also been found to reduce brain damage caused by neurotoxins like lead and mercury. So we explored if omega-3 fatty acids have a protective effect against another neurotoxin, the fine particulate matter found in air pollution."
The study involved 1,315 women with an average age of 70 who did not have dementia at the start of the study. The women completed questionnaires about diet, physical activity, and medical history.
Researchers used the diet questionnaire to calculate the average amount of fish each woman consumed each week, including broiled or baked fish, canned tuna, tuna salad, tuna casserole and non-fried shellfish. Fried fish was not included because research has shown deep frying damages omega-3 fatty acids.
Participants were given blood tests. Researchers measured the amount of omega-3 fatty acids in their red blood cells and then divided the women into four groups based on the amount of omega-3 fatty acids in their blood.
Researchers used the women's home addresses to determine their three-year average exposure to air pollution. Participants then had brain scans with magnetic resonance imaging (MRI) to measure various areas of the brain including white matter, which is composed of nerve fibers that send signals throughout the brain, and the hippocampus, the part of the brain associated with memory.
After adjusting for age, education, smoking and other factors that could affect brain shrinkage, researchers found that women who had the highest levels of omega-3 fatty acids in the blood had greater volumes of white matter than those with the lowest levels. Those in the highest group had 410 cubic centimeters (cm3) white matter, compared to 403 cm3 for those in the lowest group. The researchers found that for each quartile increase in air pollution levels, the average white matter volume was 11.52 cm3 smaller among people with lower levels of omega-3 fatty acids and 0.12 cm3 smaller among those with higher levels.
Women with the highest levels of omega-3 fatty acids in the blood also had greater volumes of the hippocampus.
"Our findings suggest that higher levels of omega-3 fatty acids in the blood from fish consumption may preserve brain volume as women age and possibly protect against the potential toxic effects of air pollution," said He. "It's important to note that our study only found an association between brain volume and eating fish. It does not prove that eating fish preserves brain volume. And since separate studies have found some species of fish may contain environmental toxins, it's important to talk to a doctor about what types of fish to eat before adding more fish to your diet."
A limitation of the study was that most participants were older white women, so the results cannot be generalized to others. Also, researchers were only able to examine exposures to later-life air pollution, not early or mid-life exposures, so future studies should look at exposures to air pollution across a person's lifespan.
https://www.sciencedaily.com/releases/2020/07/200715163555.htm
High-fat diet with antibiotic use linked to gut inflammation
Combining Western diet and antibiotic use is a pre- IBD risk factor
July 15, 2020
Science Daily/University of California - Davis Health
UC Davis researchers have found that combining a Western-style high-fat diet with antibiotic use significantly increases the risk of developing pre-inflammatory bowel disease (pre-IBD). The study, published July 14 in Cell Host and Microbe, suggests that this combination shuts down the energy factories (mitochondria) in cells of the colon lining, leading to gut inflammation.
Irritable bowel syndrome (IBS) affects approximately 11% of people worldwide. It is characterized by recurring episodes of abdominal pain, bloating and changes in bowel habits. IBS patients with mucosal inflammation and changes in the gut's microbial composition are considered pre-IBD.
Antibiotic usage with high-fat diet is a risk factor
The study included 43 healthy adults and 49 adult patients diagnosed with IBS. The researchers measured fecal calprotectin, a biomarker for intestinal inflammation, of participants. Elevated levels of fecal calprotectin indicated a pre-IBD condition. The study identified 19 patients with IBS as pre-IBD.
The researchers found that all participants who consumed high-fat diet and used antibiotics were at 8.6 times higher risk for having pre-IBD than those on low-fat diet and no recent history of antibiotic use. Participants with the highest fat consumption were about 2.8 times more likely to have pre-IBD than those with the lowest fat intake. A history of recent antibiotic usage alone was associated with 3.9 times higher likelihood of having pre-IBD.
"Our study found that a history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD," said Andreas Bäumler, professor of medical microbiology and immunology and lead author on the study. "Until now, we didn't appreciate how different environmental risk factors can synergize to drive the disease."
Shutting the cell's powerhouse promotes gut microbial growth
Using mouse models, the study also tested the effect of high-fat diet and antibiotics use on the cells in the intestinal lining. It found that high-fat diet and antibiotics cooperate to disrupt the work of the cell's mitochondria, shutting its ability to burn oxygen. This disruption causes reduction in cell's oxygen consumption and leads to oxygen leakage into the gut.
The body's beneficial bacteria thrive in environments lacking oxygen such as the large intestine. Higher oxygen levels in the gut promote bacterial imbalances and inflammation. With the disruption in the gut environment, a vicious cycle of replacing the good bacteria with potentially harmful proinflammatory microbes that are more oxygen tolerant begins. This in turn leads to mucosal inflammation linked to pre-IBD conditions.
The study also identified 5-aminosalicylate (mesalazine), a drug that restarts the energy factories in the intestinal lining, as a potential treatment for pre-IBD.
"The best approach to a healthy gut is to get rid of the preferred sustenance of harmful microbes," Lee said. "Our study emphasized the importance of avoiding high fat food and abuse of antibiotics to avoid gut inflammation."
https://www.sciencedaily.com/releases/2020/07/200715142400.htm
Regular physical activity seems to enhance cognition in children who need it most
July 15, 2020
Science Daily/University of Tsukuba
Researchers re-analyzed data from three experiments that tested whether physical activity interventions lead to improved cognitive skills in children. They found that (1) the benefits of regular exercise on cognition were greater in children who have poor cognitive performance before the intervention and (2) spending time on physical activity did not hinder cognition in children who already had good cognitive performance before the intervention.
A common school-age stereotype is that smart kids are unathletic. However, as a recent study lead by Associate Professor Keita Kamijo at the University of Tsukuba and Assistant Professor Toru Ishihara at Kobe University shows, physical activity is linked to better cognitive ability, which is in turn related to academic performance in school. Understanding the effects of physical activity on cognition has been difficult for several reasons. "Previous studies looked at the issue too broadly," explains Professor Kamijo, "When we broke down the data, we were able to see that physical activity helps children the most if they start out with poor executive function."
Executive functions refer to three types of cognitive skills. The first is the ability to suppress impulses and inhibit reflex-like behaviors or habits. To assess this ability, children were asked to indicate the color in which words like "red" and "blue" were displayed on a computer screen. This is easy when the words and colors match ("red" displayed in red font), but often requires inhibition of a reflex response when they don't ("red" displayed in blue font). The second skill is the ability to hold information in working memory and process it. This was evaluated by testing how well children could remember strings of letters that vary in length. The third cognitive skill is mental flexibility. This was measured by asking children to frequently switch the rules for categorizing colored circles and squares from shape-based to color-based.
Professor Kamijo and Professor Ishihara, and their colleagues re-analyzed the data from previous experiments in which executive function was assessed in children before and after several months of daily intervention with physical activity, such as aerobic activities, ball games, and playing tag. They looked at a factor that was missed in the initial analyses. That is, they considered whether the effectiveness of the intervention depended on the initial baseline scores.
The researchers found that cognitive skills, which have been shown to closely associate with academic performance, improved most in children whose skills were initially poor. The team also found that increased time spent doing regular physical activity did not negatively affect cognitive function in children who started out with better cognitive functions.
The finding that daily physical activity can improve executive function in children who might need it the most has some practical implications. "Because the cognitive functions evaluated in our study are related to academic performance," says Professor Kamijo, "we can say that daily physical activity is critical for school-aged children. Our findings can help educational institutions design appropriate systems for maximizing the effects of physical activity and exercise."
https://www.sciencedaily.com/releases/2020/07/200715111421.htm
Early life stress is associated with youth-onset depression for some types of stress but not others
July 15, 2020
Science Daily/Elsevier
A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that individuals exposed to early life stress (ELS) were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.
Examining the association between eight different types of ELS and youth-onset depression, the authors found that while some types of ELS (e.g., poverty) were not associated with MDD, other types of stress, including emotional abuse, were associated more strongly with MDD than a broader assessment of ELS.
"Researchers have documented that early life stress increases the risk for developing depression in adulthood. We wanted to know the degree to which it was associated with depression earlier in life -- specifically during childhood or adolescence," said lead author Joelle LeMoult, PhD, a researcher at the University of British Columbia, Vancouver, Canada. "Given that earlier onsets of depression often mean a more recurrent course across the lifespan. We found that exposure to early life stress more than doubled the likelihood someone will develop youth-onset depression.
"These findings indicate that there is a narrow window between adversity and depression during which we have the opportunity to intervene."
The findings are based on a meta-analysis of data from 62 journal articles and over 44,000 unique participants. Studies that assessed early life stress and the presence or absence of MDD before the age of 18 years were also included.
Compared to youth who were not exposed to ELS, youth who were exposed to ELS were 2.5 times more likely to develop MDD (OR=2.50; 95% CI [2.08, 3.00]).
The authors also conducted eight additional meta-analyses to examine the association between different types of ELS and a diagnosis of MDD during childhood or adolescence. Sexual abuse, physical abuse, death of a family member, domestic violence, and emotional abuse were associated with significantly higher risk for youth-onset MDD; in contrast, poverty, illness/injury, and exposure to a natural disaster were not.
Several variables moderated the association between ELS and youth-onset MDD. For example, studies that used interview-based assessments or included larger sample sizes reported stronger associations between ELS and depression.
Taken together, findings provide evidence that the adverse effects of ELS on risk for MDD manifests early in development, before adulthood, and varies by type of ELS. Further, findings support recommendations to use best-practice methods in early life stress research.
https://www.sciencedaily.com/releases/2020/07/200715142326.htm
Two paths of aging: New insights on promoting healthspan
Master aging circuit identified
July 16, 2020
Science Daily/University of California - San Diego
Molecular biologists and bioengineers at the University of California San Diego have unraveled key mechanisms behind the mysteries of aging. They isolated two distinct paths that cells travel during aging and engineered a new way to genetically program these processes to extend lifespan.
The research is described July 17 in the journal Science.
Our lifespans as humans are determined by the aging of our individual cells. To understand whether different cells age at the same rate and by the same cause, the researchers studied aging in the budding yeast Saccharomyces cerevisiae, a tractable model for investigating mechanisms of aging, including the aging paths of skin and stem cells.
The scientists discovered that cells of the same genetic material and within the same environment can age in strikingly distinct ways, their fates unfolding through different molecular and cellular trajectories. Using microfluidics, computer modeling and other techniques, they found that about half of the cells age through a gradual decline in the stability of the nucleolus, a region of nuclear DNA where key components of protein-producing "factories" are synthesized. In contrast, the other half age due to dysfunction of their mitochondria, the energy production units of cells.
The cells embark upon either the nucleolar or mitochondrial path early in life, and follow this "aging route" throughout their entire lifespan through decline and death. At the heart of the controls the researchers found a master circuit that guides these aging processes.
"To understand how cells make these decisions, we identified the molecular processes underlying each aging route and the connections among them, revealing a molecular circuit that controls cell aging, analogous to electric circuits that control home appliances," said Nan Hao, senior author of the study and an associate professor in the Section of Molecular Biology, Division of Biological Sciences.
Having developed a new model of the aging landscape, Hao and his coauthors found they could manipulate and ultimately optimize the aging process. Computer simulations helped the researchers reprogram the master molecular circuit by modifying its DNA, allowing them to genetically create a novel aging route that features a dramatically extended lifespan.
"Our study raises the possibility of rationally designing gene or chemical-based therapies to reprogram how human cells age, with a goal of effectively delaying human aging and extending human healthspan," said Hao.
The researchers will now test their new model in more complex cells and organisms and eventually in human cells to seek similar aging routes. They also plan to test chemical techniques and evaluate how combinations of therapeutics and drug "cocktails" might guide pathways to longevity.
"Much of the work featured in this paper benefits from a strong interdisciplinary team that was assembled," said Biological Sciences Professor of Molecular Biology Lorraine Pillus, one of the study's coauthors. "One great aspect of the team is that we not only do the modeling but we then do the experimentation to determine whether the model is correct or not. These iterative processes are critical for the work that we are doing."
https://www.sciencedaily.com/releases/2020/07/200716144732.htm
Blood iron levels could be key to slowing aging
July 16, 2020
Science Daily/University of Edinburgh
Genes linked to ageing that could help explain why some people age at different rates to others have been identified by scientists.
The international study using genetic data from more than a million people suggests that maintaining healthy levels of iron in the blood could be a key to ageing better and living longer.
The findings could accelerate the development of drugs to reduce age-related diseases, extend healthy years of life and increase the chances of living to old age free of disease, the researchers say.
Scientists from the University of Edinburgh and the Max Planck Institute for Biology of Ageing in Germany focused on three measures linked to biological ageing -- lifespan, years of life lived free of disease (healthspan), and being extremely long-lived (longevity).
Biological ageing -- the rate at which our bodies decline over time -- varies between people and drives the world's most fatal diseases, including heart disease, dementia and cancers.
The researchers pooled information from three public datasets to enable an analysis in unprecedented detail. The combined dataset was equivalent to studying 1.75 million lifespans or more than 60,000 extremely long-lived people.
The team pinpointed ten regions of the genome linked to long lifespan, healthspan and longevity. They also found that gene sets linked to iron were overrepresented in their analysis of all three measures of ageing.
The researchers confirmed this using a statistical method -- known as Mendelian randomisation -- that suggested that genes involved in metabolising iron in the blood are partly responsible for a healthy long life.
Blood iron is affected by diet and abnormally high or low levels are linked to age-related conditions such as Parkinson's disease, liver disease and a decline in the body's ability to fight infection in older age.
The researchers say that designing a drug that could mimic the influence of genetic variation on iron metabolism could be a future step to overcome some of the effects of ageing, but caution that more work is required.
The study was funded by the Medical Research Council and is published in the journal Nature Communications.
Anonymised datasets linking genetic variation to healthspan, lifespan, and longevity were downloaded from the publically available Zenodo, Edinburgh DataShare and Longevity Genomics servers.
Dr Paul Timmers from the Usher Institute at the University of Edinburgh, said: "We are very excited by these findings as they strongly suggest that high levels of iron in the blood reduces our healthy years of life, and keeping these levels in check could prevent age-related damage. We speculate that our findings on iron metabolism might also start to explain why very high levels of iron-rich red meat in the diet has been linked to age-related conditions such as heart disease."
Dr Joris Deelen from the Max Planck Institute for Biology of Ageing in Germany, said: "Our ultimate aim is to discover how ageing is regulated and find ways to increase health during ageing. The ten regions of the genome we have discovered that are linked to lifespan, healthspan and longevity are all exciting candidates for further studies."
https://www.sciencedaily.com/releases/2020/07/200716101548.htm