Publisher Health

Our nervous systems are naturally wired to sense fear. Whether prompted by the eerie noises we hear alone in the dark or the approaching growl of a threatening animal, our fear response is a survival mechanism that tells us to remain alert and avoid dangerous situations.
But if fear arises in the absence of tangible threats, it can be harmful to our well-being. Those who have suffered episodes of severe or life-threatening stress can later experience intense feelings of fear, even during situations that lack a real threat. Experiencing this generalization of fear is psychologically damaging and can result in debilitating long-term mental health conditions such as post-traumatic stress disorder (PTSD).
The stress-induced mechanisms that cause our brain to produce feelings of fear in the absence of threats have been mostly a mystery. Now, neurobiologists at the University of California San Diego have identified the changes in brain biochemistry and mapped the neural circuitry that cause such a generalized fear experience. Their research, published in the journal Science on March 15, 2024, provides new insights into how fear responses could be prevented.
In their report, former UC San Diego Assistant Project Scientist Hui-quan Li, (now a senior scientist at Neurocrine Biosciences), Atkinson Family Distinguished Professor Nick Spitzer of the School of Biological Sciences and their colleagues describe the research behind their discovery of the neurotransmitters — the chemical messengers that allow the brain’s neurons to communicate with one another — at the root of stress-induced generalized fear.
Studying the brains of mice in an area known as the dorsal raphe (located in the brainstem), the researchers found that acute stress induced a switch in the chemical signals in the neurons, flipping from excitatory “glutamate” to inhibitory “GABA” neurotransmitters, which led to generalized fear responses.
“Our results provide important insights into the mechanisms involved in fear generalization,” said Spitzer, a member of UC San Diego’s Department of Neurobiology and Kavli Institute for Brain and Mind. “The benefit of understanding these processes at this level of molecular detail — what is going on and where it’s going on — allows an intervention that is specific to the mechanism that drives related disorders.”
Building upon this new finding of a stress-induced switch in neurotransmitters, considered a form of brain plasticity, the researchers then examined the postmortem human brains of individuals who had suffered from PTSD. A similar glutamate-to-GABA neurotransmitter switch was confirmed in their brains as well.

The researchers next found a way to stop the production of generalized fear. Prior to the experience of acute stress, they injected the dorsal raphe of the mice with an adeno-associated virus (AAV) to suppress the gene responsible for synthesis of GABA. This method prevented the mice from acquiring generalized fear.
Further, when mice were treated with the antidepressant fluoxetine (branded as Prozac) immediately after a stressful event, the transmitter switch and subsequent onset of generalized fear were prevented.
Not only did the researchers identify the location of the neurons that switched their transmitter, but they demonstrated the connections of these neurons to the central amygdala and lateral hypothalamus, brain regions that were previously linked to the generation of other fear responses.
“Now that we have a handle on the core of the mechanism by which stress-induced fear happens and the circuitry that implements this fear, interventions can be targeted and specific,” said Spitzer.

A large analysis in Canada finds that teenagers who had babies were twice as likely to die before age 31.Teen pregnancy increases the chances that a young woman will drop out of school and struggle with poverty, research has shown. Teenagers are also more likely to develop serious medical complications during pregnancy.Now a large study in Canada reports another disturbing finding: Women who were pregnant as teenagers are more likely to die before their 31st birthday. The trend was observed among women who had carried teen pregnancies to term, as well as among those who had miscarried.“The younger the person was when they became pregnant, the greater their risk was of premature death,” said Dr. Joel G. Ray, an obstetric medicine specialist and epidemiologist at St. Michael’s Hospital in Toronto and the first author of the study. It was published in JAMA Network Open on Thursday.“Some people will argue that we shouldn’t be judgmental about this, but I think we’ve always known intuitively that there’s an age that is too young for pregnancy,” he added.The study made use of a provincial health insurance registry to analyze pregnancy outcomes among some 2.2 million teenagers in Ontario, Canada, including all girls who were 12 years old between April 1991 and March 2021.Even after the researchers accounted for pre-existing health problems the girls may have had, and for income and education disparities, teenagers who carried pregnancies to term were more than twice as likely to suffer premature death later in life.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Early childhood is an important time for learning about nutrition and establishing healthy eating behaviors. Young children rely on parents to provide food options, and the availability of food in the home affects their dietary choices. A new study from the University of Illinois Urbana-Champaign looks at changes in home food availability and nutrient intake for children from 2 to 4 years old.
“It’s important to understand how the environments that children are in can influence their diet and nutrition. What types of foods and beverages are available in the home, and how accessible are those items for the young child? It’s about the likelihood of exposure to foods and having the opportunity to try foods, and also whether they may be able to access or grab foods themselves,” said lead author Jennifer Barton, now an assistant research professor at Pennsylvania State University. Barton conducted the research as a postdoctoral research associate at the Family Resiliency Center in the Department of Human Development and Family Studies (HDFS), part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at Illinois.
Barton and her colleagues used the Home Food Inventory (HFI) to measure food availability at 24, 36, and 48 months of age. The HFI is a comprehensive checklist of food categories administered by a research assistant visiting the homes of participating families. The researchers correlated the HFI data with surveys of the children’s food consumption completed by their mothers.
“We found significant changes in several food categories over time. Food items such as non-whole grains, processed meats, savory snacks, candy, and microwavable or quick-cook foods were more commonly available in the home at 48 months compared to 24 and 36 months,” Barton said.
The study included 468 mothers and children who were participants in STRONG Kids 2, an ongoing research project at Illinois that looks at nutrition and healthy habits from infancy through 10 years of age. STRONG Kids 2 co-directors Barbara Fiese, professor emerita of HDFS, and Sharon Donovan, professor of food science and human nutrition at Illinois, also contributed to the study.
The HFI includes an obesogenic score, which indicates the obesity risk of different foods. However, the scores are based on dietary recommendations for older children and include regular-fat dairy products such as milk, yogurt, and cheese. Toddlers have different energy and nutrient needs, and dairy products are considered as part of a healthy diet for young children, necessary for growth and development.
The researchers tested three obesogenic scores, two of which were developmentally sensitive scores that excluded milk, yogurt, and cheese. Even with the modified categories, they found that obesogenic scores increased significantly from 24 to 48 months.

“It makes sense that as children get older, the presence of more energy-dense and high-fat foods tends to grow. Children may request these foods more often, and outside influences, such as the opinions of peers, are starting to become more apparent. I do want to point out that we found some positive changes. Vegetables also become more available in the home at 48 months,” Barton said.
“The point is not to label certain foods as being good or bad. We likely all have food items in our home that are not ‘recommended.’ It’s really about trying to make sure that we get enough nutritious, recommended foods and eat the non-recommended items in moderation.”
A second research goal was to test the validity of the HFI measure for young children, as the method has been developed for adolescents. Barton and her colleagues conducted comprehensive tests of associations between food availability and nutrient intake, overall finding the expected results.
For example, the availability of processed meats such as lunch meat and hot dogs was correlated with higher saturated fat intake. Sweetened beverages, candy, desserts, and savory snacks were correlated with higher intake of those foods. A higher presence of fruit and vegetables in the home was also a consistent indicator of nutrients. These findings indicate that HFI is a reliable measure of home food availability and has demonstrated associations with food and nutrient intake for children ages 24, 36, and 48 months, the researchers conclude.
It’s important to support parents in making healthy decisions for their families, but food choice is much more than individual behavior, Barton stated.
“There are complex factors affecting parents’ decisions. Children may ask for certain foods, which may stem from the influence of media and advertising. We should also consider who else lives in the home such as siblings, and the parents may experience work demands and financial stressors that can spill over into their family life. Many people struggle with distance to food stores and access to fresh foods as well as food insecurity. I believe we need a food systems approach to ensure people have access to nutritious food and that parents feel supported in making decisions to promote the health and well-being of themselves and their children,” she concluded.
The paper, “Longitudinal Changes in Home Food Availability and Concurrent Associations with Food and Nutrient Intake Among Children at 24 to 48 Months” is published in Public Health Nutrition. Authors include Jennifer M. Barton, Arden L. McMath, Stewart P. Montgomery, Sharon M. Donovan. and Barbara H. Fiese.
This research was funded by grants from the National Dairy Council, the Gerber Foundation, the Christopher Family Foundation, Hatch ILLU 793-330 from the US Department of Agriculture, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (grant no. R01 DK107561) to Sharon Donovan. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Researchers have found a new way to potentially treat one of the most common forms of acute lymphoblastic leukaemia.
The study, led by WEHI and the Peter MacCallum Cancer Centre, was able to kill leukaemia cells in the lab and stop cancer cells from growing, after identifying two new proteins critical for the development of the aggressive disease.
The findings could lead to enhanced treatment options in the future, with plans underway to develop a clinical trial based on the research.
Around 5200 people are diagnosed with a form of leukaemia in Australia each year. An estimated 1500 of these cases are acute — meaning the blood cancer appears suddenly and grows quickly.
Blood cancers like leukaemia are notoriously difficult to treat in adults, with 50% of Australian patients relapsing after the first round of chemotherapy and subsequently becoming resistant to further treatments.
Associate Professor Ashley Ng, a corresponding author on the paper, said this presented a unique treatment challenge for these blood cancers and highlighted the urgent need for new therapeutics.
“About 135,000 people live with a blood cancer or blood disorder in Australia, with 16 people dying every day from the disease,” Assoc Prof Ng, a WEHI researcher and clinical haematologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, said.

“Despite the medical advancements made in the cancer field over the years, the incidence of blood cancer has grown by 47% in the past decade.
“The best way to enhance treatment options for patients is to continually improve our understanding of how leukaemia cancers behave and what drives their growth.
“Our new research has identified two proteins that are critical for the development of B-cell acute lymphoblastic leukaemia, expanding our knowledge into how these cancers can form.
“By uncovering this new vulnerability in leukaemia formation, we hope to exploit the findings for therapeutic benefit and also apply them to other forms of the disease.”
The research is published in the journal Science Advances.
Master regulators
Assoc Prof Ng has spent over a decade researching a protein that regulates gene activity in the cell nucleus, known as ERG. Imbalances in this protein can lead to blood cancers, like acute lymphoblastic leukaemia.

His previous research uncovered the protein’s critical role in Down syndrome associated blood disease and normal blood cell function, including how B cells — which are essential for producing antibodies to fight against infections — develop.
First author Dr Kira Behrens said the research team wanted to understand what other types of proteins ERG works with to fuel leukaemia development.
“We looked at the proteins that control how specific genes switch ‘on’ or ‘off’ to analyse how normal B-cells — and critically — B-cell acute lymphoblastic leukaemia — can develop,” Dr Behrens said.
“After analysing the genes regulated by ERG and another protein, c-MYC, we discovered that these proteins were actually the master regulators of several important pathways and processes within the leukaemia cell.”
Researchers then narrowed the list down to focus on one pathway essential for making proteins, known as ribosome biogenesis.
This led the team to focus on targeting a key gene essential to this pathway, POL I, which is also controlled by these master regulator proteins.
The gene helps direct an important cell growth and division process that can lead to the development of cancer if it goes awry.
Dr Behrens said: “By targeting POL I with inhibitors, we were able to kill leukaemia cells and stop their growth in our pre-clinical and human tissue models.”
“This was a surprising, yet remarkable discovery, as we were able to unravel a new pathway and potential drug target that can hopefully be used in the fight against leukaemia in the future.”
The study also involved a collaboration with Associate Professor Elaine Sanij (St. Vincent’s Institute of Medical Research) whose work focuses on targeting POL I and ribosome biogenesis in cancer therapy.
“The findings show that a subset of aggressive acute lymphoblastic leukaemia exhibit a form of addiction to producing of ribosomes, the protein making molecular machinery,” Assoc Prof Sanij said.
“They render this aggressive leukaemia sensitive to POL I inhibitors which target ribosome production.
“Altogether, our work highlights the importance of developing this new approach to cancer therapy to treat oncogene-driven cancers.”
Collaborative power
One of the drugs used in the study to target POL I was an agent developed by the Peter MacCallum Cancer Centre.
Professor Rick Pearson, former Associate Director of Laboratory Research at Peter Mac, said the team hopes to mimic the study in a future clinical trial to help patients with acute lymphoblastic leukaemia.
“We worked with WEHI researchers to confirm our agent is effective in targeting POL I activity and demonstrated its potency in impeding the leukaemia cell growth and division.
“These findings highlight the power of collaboration and the remarkable results that can be achieved when bringing together experts from across various areas.
“We hope this research will translate into successful clinical trials and potentially offer doctors a new treatment option for patients with acute lymphoblastic leukaemia,” Professor Pearson said.
This research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft), the National Health and Medical Research Council (NHMRC), Cancer Council Victoria, National Stem Cell Foundation of Australia, the Leukaemia Foundation and Victorian Cancer Agency.
The study, “ERG and c-MYC Regulate a Critical Gene Network in BCR::ABL1-Driven B-cell Acute Lymphoblastic Leukaemia,” is published in Science Advances.

Researchers from University of Tsukuba investigated the propulsion mechanism by visualizing water flow around a swimmer during underwater dolphin-kick swimming in a water channel via particle image velocimetry. Their findings revealed that swimmers can utilize water flow and vortexes more effectively as their speed increases.
The swimming motion imparts momentum to water, a fluid, thereby generating a propulsive force. Thus, we can understand the propulsion mechanism by examining the water flow generated by a swimmer’s motion. However, observing colorless, transparent water with the naked eye or a camera is challenging. To address this issue, researchers employed particle image velocimetry, a technique utilized in fluid dynamics, to visualize water-flow patterns. They investigated how water flow changes as swimmers change their speed while executing the dolphin-kick swimming technique. This investigation was conducted in an experimental circulating-water channel (a pool with flowing water).
The results revealed that the water-flow velocity increased with increasing swimming speed during the underwater dolphin-kick lower-limb action, generating a strong vortex during the kicking action. This phenomenon possibly contributes to the increased propulsive force. Additionally, recycling of the flow generated during the downward-kick phase was observed during the transition to the upward-kick phase, with the effect becoming more pronounced as the swimming speed increased. This study marks the first observation of water-flow changes during dolphin-kick swimming at varying speeds.
This study is expected to advance research on water flow, a critical topic in swimming research. It offers scientific evidence for instructors to adopt kick-swimming techniques.
This work was supported by Japan Science and Technology Agency, Grant Number 22 K19725.

It is known that large amounts of liquorice cause high blood pressure. A study by researchers at Linköping University, Sweden, now shows that even small amounts of liquorice raise blood pressure. The individuals who react most strongly also show signs of strain on the heart.
Liquorice is produced from the root of plants of the Glycyrrhiza species and has long been used as a herbal remedy and flavouring. However, it is known that eating liquorice can also raise blood pressure. This is mainly due to a substance called glycyrrhizic acid that affects the body’s fluid balance through effects on an enzyme in the kidney. High blood pressure, in turn, increases the risk of cardiovascular disease.
Both the European Union and the World Health Organization have concluded that 100 mg of glycyrrhizic acid per day is probably safe to eat for most individuals. But some people eat more liquorice than that. The Swedish Food Agency has estimated that 5 per cent of Swedes have an intake higher than this level.
In the current study, published in The American Journal of Clinical Nutrition, researchers at Linköping University wanted to test whether the limit stated as likely safe actually is so or not.
It is not easy to know how much glycyrrhizic acid is in the liquorice you eat, as its concentration in different liquorice products varies greatly. This variation may depend on factors such as origin, storage conditions and liquorice root species. In addition, the amount of glycyrrhizic acid is not indicated on many products. The Linköping University study is the first to have carefully measured the amount of glycyrrhizic acid in the liquorice that was tested, while being randomised and having a control group.
In the study, 28 women and men aged 18-30 were instructed to eat liquorice, or a control product that did not contain any liquorice, over two periods of time. The control product instead contained salmiak, which gives salty liquorice its flavour. The liquorice weighed 3.3 grammes and contained 100 mg of glycyrrhizic acid, that is, the amount indicated as likely safe for most people to eat daily. Participants were randomly assigned to eat either liquorice or the control product for two weeks, take a break for two weeks, and then eat the other variety for two weeks. This enabled the researchers to compare the effect of both varieties in the same person. The study participants were asked to measure their blood pressure at home every day. At the end of each intake period, the researchers measured levels of various hormones, salt balance, and heart workload.
“In the study, we found that a daily intake of liquorice containing 100 mg glycyrrhizic acid raised blood pressure in young healthy people. This hasn’t previously been shown for such small amounts of liquorice,” says Peder af Geijerstam, doctoral student at the Department of Health, Medicine and Caring Sciences at Linköping University, general practitioner, and lead author of the study.
When the participants ate liquorice, their blood pressure increased by an average of 3.1 mmHg. The researchers also measured two hormones that are affected by liquorice and that regulate fluid balance: renin and aldosterone. The levels of both of these decreased when eating liquorice. The quarter of the study participants who were most sensitive, based on their levels of the hormones renin and aldosterone decreasing the most after eating liquorice, also gained slightly in weight, most likely due to an increased amount of fluid in the body. This group also had elevated levels of a protein that the heart secretes more of when it needs to work harder to pump around the blood in the body, N-terminal pro-brain natriuretic peptide (NT-proBNP). This suggests increased fluid volume and heart workload in the individuals most sensitive to the effects of liquorice.
“Our results give reason to be more cautious when it comes to recommendations and labelling for food containing liquorice,” says Fredrik Nyström, professor at the same department, who was responsible for the study.
The study was funded with support from, among others, The Strategic Research Network in Circulation and Metabolism (LiU-CircM) at Linköping University, The National Research School in General Practice at Umeå University, King Gustaf V and Queen Victoria Freemason Foundation and Region Östergötland.

Researchers led by Hiroshi Ohno at the RIKEN Center for Integrative Medical Sciences in Japan have discovered a link between gut bacteria and the success of milk-allergy oral immunotherapy. Published in the scientific journal Allergology International, the study found that Bifidobacterium — a genus of beneficial bacteria in the gut — was associated with a higher chance of successful treatment. The finding may help in the development of more effective oral immunotherapies, perhaps by combining them with probiotic supplements.
Many children have allergic reactions to cow’s milk, specifically to certain milk proteins. Although most grow out of it, for some it becomes a life-long challenge to avoid all foods that include milk, especially when the allergic reactions are severe and include anaphylactic shock. Researchers have found that milk allergy is improved by oral immunotherapy, a treatment in which patients purposely drink small amounts of milk. Unfortunately, while allergic reactions are controlled during treatment, in most cases, tolerance disappears soon after the treatment ends.
Gut bacteria are thought to help reduce allergic reactions to some foods, but little is known about the link between these bacteria and oral immunotherapy for milk allergy. Therefore, the RIKEN IMS team examined 32 children with cow’s milk allergy who received oral immunotherapy, with the first month being conducted in a hospital. “Oral immunotherapy is not without risk,” explains Ohno. “We closely monitored the children in the hospital, and in fact 4 children had such severe reactions to the milk that we could not allow them to continue the treatment.”
The remaining 28 children then completed an additional 12 months of treatment at home. Next, they avoided milk for two weeks, and were then tested on a double-blind, placebo-controlled food challenge to see if they could still tolerate milk without any allergic reactions. During the food challenge, children were initially given a tiny amount of placebo or milk — only 0.01 ml — which was gradually increased every 20 minutes until they had an allergic reaction or until they could drink the final 30 ml without a reaction.
The researchers focused their analyses on immunological and bacterial changes during the treatment and the relationship between gut bacteria and successful treatment — which was defined as showing milk tolerance that lasted beyond the treatment period by passing the food challenge. They found that during treatment, immunological markers for cow’s milk allergy improved, and bacteria in the gut changed. Nevertheless, after two weeks of avoiding milk, only 7 of the 28 children passed the food challenge, even though they had been able to drink milk safely at the end of the treatment.
To understand why the treatment worked for these seven children but not the others, the team looked for the clinical factors and types of gut bacteria that were related to successful treatment. Of the clinical factors, unsuccessful treatment was more likely in children who were being treated for eczema or asthma and in children who initially had higher levels of milk-protein antibodies. Among the gut bacteria, the presence of Bifidobacterium, a genus of beneficial bacteria in the Bifidobacteriaceae family was related to a higher chance of successful treatment. In fact, only children who passed the final food challenge showed an increasing trend in these bacteria over the course of treatment. When considering ways to improve oral immunotherapy, this is good news because while the first two factors are difficult to change, the types of bacteria in one’s gut are not set in stone.
“With this study, we have identified gut environmental factors that help establish immune tolerance against cow’s milk allergy via oral immunotherapy,” says Ohno. “The next step is to examine the mechanisms underlying this phenomenon and to develop ways to improve the effectiveness of oral immunotherapy, such as the addition of probiotic supplements.”

Viral infections trigger more cases of intussusception, the common cause of bowel blockages in young children, than previously thought, according to a new study.
The research, led by Murdoch Children’s Research Institute (MCRI) and published in Clinical Infectious Diseases, found during the COVID-19 lockdowns hospital admissions for intussusception, a medical emergency involving obstruction of the intestine, among young children significantly decreased.
For the study, 12 years of data was analysed across Victoria, NSW and Queensland. A total of 5,589 intussusception cases were recorded between January, 2010 and April, 2022. Of those, 3,179 were children under the age of two.
During the lockdown periods, Victoria and NSW experienced a decline in hospital admissions for intussusception among children under two by 62.7 per cent and 40.1 per cent, respectively. The rate of intussusception cases has now returned to normal levels.
MCRI and Monash University researcher Dr Ben Townley said the magnitude of the decline supported that common respiratory diseases such as colds, the flu and respiratory syncytial virus (RSV), were behind a significant proportion of intussusception cases.
“Reductions in intussusception hospital admissions were seen in all age groups, however most occurred in children less than two years of age,” he said.
“Intussusception is the leading cause of acute bowel obstruction in infants and young children and without prompt diagnosis and management, can be fatal.

“Countries with prolonged COVID-19 lockdowns and suppression strategies saw reductions in common respiratory viruses, which influenced the drop in intussusception admissions.”
Victoria experienced the greatest lockdown duration, with Melbourne having six lockdown periods, for a total of 263 days. Greater Sydney had 159 days and Brisbane had 18 days in lockdown.
MCRI Professor Jim Buttery said the decrease in intussusception cases was greater than expected given previous research into the causes of the condition.
“Our analysis found commons viruses play a larger role than previously recognised in triggering intussusception,” he said. Infectious triggers were thought to comprise only a minority, about 30 per cent, of cases.”
Professor Buttery said the findings raised the possibility that emerging vaccines like the new RSV vaccines may help prevent intussusception.
“When a new vaccine against common childhood respiratory viruses is introduced, we may find there are some unexpected benefits, like protecting more children from intussusception,” he said. We last saw this in 2007, when introducing the rotavirus vaccine against gastroenteritis, also reduced febrile convulsions in young children.”
Researchers fromSydney Children’s Hospital Network, University of Melbourne and Queensland Health also contributed to the findings.

A healthier diet is associated with a reduced dementia risk and slower pace of aging, according to a new study at Columbia University Mailman School of Public Health and The Robert Butler Columbia Aging Center. The findings show that a diet-dementia association was at least partially facilitated by multi-system processes of aging. While literature had suggested that people who followed a healthy diet experienced a slowdown in the processes of biological aging and were less likely to develop dementia, until now the biological mechanism of this protection was not well understood. The findings are published in the Annals of Neurology.
“Much attention to nutrition in dementia research focuses on the way specific nutrients affect the brain” said Daniel Belsky, PhD, associate professor of Epidemiology at Columbia School of Public Health and the Columbia Aging Center, and a senior author of the study. “We tested the hypothesis that healthy diet protects against dementia by slowing down the body’s overall pace of biological aging.”
The researchers used data from the second generation of the Framingham Heart Study, the Offspring Cohort. Originating in 1971, participants in the latter were 60 years of age or older, were free of dementia, and also had available dietary, epigenetic, and follow-up data. The Offspring Cohort were followed-up at nine examinations, approximately every 4 to 7 years. At each follow-up visit, data collection included a physical examination, lifestyle-related questionnaires, blood sampling, and, starting in 1991, neurocognitive testing.
Of 1,644 participants included in the analyses, 140 of the participants developed dementia. To measure the pace of aging, the researchers used an epigenetic clock called DunedinPACE developed by Belsky and colleagues at Duke University and the University of Otago. The clock measures how fast a person’s body is deteriorating as they grow older, “like a speedometer for the biological processes of aging,” explained Belsky.
“We have some strong evidence that a healthy diet can protect against dementia,” said Yian Gu, PhD, associate professor of Neurological Sciences at Columbia University Irving Medical Center and the other senior author of the study, “But the mechanism of this protection is not well understood.” Past research linked both diet and dementia risk to an accelerated pace of biological aging.
“Testing the hypothesis that multi-system biological aging is a mechanism of underlying diet-dementia associations was the logical next step,” explained Belsky. The research determined that higher adherence to the Mediterranean-Dash Intervention for Neurodegenerative Delay diet (MIND) slowed the pace of aging as measured by DunedinPACE and reduced risks for dementia and mortality. Furthermore, slower DunedinPACE accounted for 27 percent of the diet-dementia association and 57 percent of the diet-mortality association.
“Our findings suggest that slower pace of aging mediates part of the relationship of healthy diet with reduced dementia risk, and therefore, monitoring pace of aging may inform dementia prevention,” said first author Aline Thomas, PhD, a Postdoc at the Columbia Department of Neurology and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. “However, a portion of the diet-dementia association remains unexplained, therefore we believe that continued investigation of brain-specific mechanisms in well-designed mediation studies is warranted.”
“We suggest that additional observational studies be conducted to investigate direct associations of nutrients with brain aging, and if our observations are also confirmed in more diverse populations, monitoring biological aging, may indeed, inform dementia prevention,” noted Belsky.
Co-authors are Calen Ryan and Jiayi Zhou, Columbia Aging Center; and Avshalom Caspi, Terrie Moffitt, and Karen Sugden, Duke University.
The study was supported by the National Institute on Aging grants R01AG061378, R01AG073402, R01AG059013, R01AG061008, R01AG073207 and R01AG049789.

Galantamine is a common medication used by people with Alzheimer’s disease and other forms of dementia around the world to treat their symptoms. Unfortunately, synthesizing the active compounds in a lab at the scale needed isn’t commercially viable. The active ingredient is extracted from daffodils through a time-consuming process, and unpredictable factors, such as weather and crop yields, can affect supply and price of the drug.
Now, researchers at The University of Texas at Austin have developed tools — including an artificial intelligence system and glowing biosensors — to harness microbes one day to do all the work instead.
In a paper in Nature Communications, researchers outline a process using genetically modified bacteria to create a chemical precursor of galantamine as a byproduct of the microbe’s normal cellular metabolism. Essentially, the bacteria are programmed to convert food into medicinal compounds.
“The goal is to eventually ferment medicines like this in large quantities,” said Andrew Ellington, a professor of molecular biosciences and author of the study. “This method creates a reliable supply that is much less expensive to produce. It doesn’t have a growing season, and it can’t be impacted by drought or floods.”
Danny Diaz, a postdoctoral fellow with the Deep Proteins research group in UT’s Institute for Foundations of Machine Learning (IFML), developed an AI system called MutComputeX that is key to the process. It identifies how to mutate proteins inside the bacteria to improve their efficiency and operating temperature in order to maximize production of a needed medicinal chemical.
“This system helped identify mutations that would make the bacteria more efficient at producing the target molecule,” Diaz said. “In some cases, it was up to three times as efficient as the natural system found in daffodils.”
The process of harnessing microbes to produce useful byproducts is nothing new. Brewers use yeast to make alcohol, and bacteria help create cheese and yogurt. Microbial fermentation is currently used to make certain types of insulin for diabetes treatment, hormones and recombinant proteins used in several drugs such as autoimmune treatments, and even vaccines. But applying AI in the process is relatively new and expands what is possible with microbial fermentation.

The research team genetically modified E. coli to produce 4-O’Methyl-norbelladine, a chemical building block of galantamine. The complex molecule is in a family of compounds extracted from daffodils that have medicinal uses in treating conditions such as cancer, fungal infections and viral infections, but using microbial fermentation to create a chemical in this family is new.
The scientists also created a fluorescent biosensor to quickly detect and analyze which bacteria were producing the desired chemicals and how much. When the biosensor, a specially created protein, comes into contact with the chemical researchers wanted to create, it glows green.
“The biosensor allows us to test and analyze samples in seconds when it used to take something like five minutes each,” said Simon d’Oelsnitz, a postdoctoral researcher formerly at UT Austin and now at Harvard University, the first author of the paper. “And the machine learning program allows us to easily narrow candidates from tens of thousands to tens. Put together, these are really powerful tools.”
Wantae Kim, Daniel Acosta, Tyler Dangerfield, Mason Schechter, James Howard, Hannah Do, James Loy, Hal Alper and Y. Jessie Zhang of UT and Matthew Minus of Prairie View A&M University were also authors of the paper. The research was supported by the National Institute of Standards and Technology, the Air Force Office of Scientific Research and the National Institutes of Health, and the National Science Foundation supports IFML. Computing resources were provided by Advanced Micro Devices.
Those involved in this research have submitted required financial disclosure forms with the University, and Ellington, Diaz and d’Oelsnitz have filed a patent application on materials described in this text. Diaz and d’Oelsnitz are each involved with startups related to this research.