Publisher Health

Plant based diets support health in several ways, including benefits for the gut, immune system, metabolism, and cardiovascular system. Part of that effect comes from encouraging a diverse population of bacteria in the intestines. Scientists have long known that dietary fiber contributes to these benefits because gut microbes help break it down. Plants also contain colorful “phytochemicals” that help protect them from environmental threats and may influence human health. Even so, researchers are still working to understand exactly how gut bacteria process the many components of plant foods and how those interactions produce beneficial effects.
Two studies led by Ludwig Princeton’s Jenna AbuSalim and Director Joshua Rabinowitz offer new insight into that process. One appears in the current issue of the Proceedings of the National Academy of Sciences, while the other was published in Nature Metabolism in June. The first study found that plant fiber and certain plant proteins can change microbial metabolism in ways that increase beneficial metabolites while reducing harmful ones. The second showed that several biologically important metabolites usually credited to gut microbes can also be produced in substantial amounts by mammalian metabolism.
“There’s growing interest across medical disciplines in manipulating the human microbiome or using its metabolic products themselves for therapy,” said Rabinowitz. “Diet holds great promise for controlling the microbiome and its outputs. But to devise effective therapeutic interventions, we need to understand what aspects of the diet control which microbial outputs.”
How Plant Foods Shift Gut Metabolites
In the PNAS study, Rabinowitz, AbuSalim and their colleagues examined how plant based foods influence phenol metabolites. Gut bacteria create these compounds when they digest the amino acids tyrosine and phenylalanine, but the resulting metabolites can have very different effects on health.
Phenylpropionate and hippuric acid are produced when bacteria process phenylalanine, and they are associated with gut health and healthy body weight. By contrast, p-cresol sulfate and phenol sulfate come from tyrosine and have been linked to worse outcomes in cancer patients as well as systemic toxicity in people with kidney disease.
“Our studies showed that both the fiber and indigestible proteins from plants — which we call ‘proteins imitating fiber,’ or Prif — shift the balance of phenol metabolites from the harmful kind made from tyrosine to the healthful variety derived from phenylalanine,” said AbuSalim.

Fiber has long been recognized as an important part of a healthy diet, but indigestible plant proteins have received far less attention. AbuSalim, Rabinowitz and their colleagues found that these proteins are processed by gut microbes and can alter both the makeup of the microbiome and the host’s metabolism. Working together with indigestible plant fiber, they can also change the metabolic activity of gut bacteria in ways that favor the production of beneficial phenols.
When Gut Bacteria Turn to the Gut Lining
To trace where these compounds came from, the researchers labeled proteins with stable (non-radioactive) isotopes and followed their digestion in the mouse gut. They found that the “bad” phenols were produced when bacteria consumed proteins from the host, including proteins found in the mucus lining of the gut. The good phenols, in contrast, came almost entirely from indigestible proteins in the diet (Prif).
Fiber reduced the bacterial breakdown of the gut’s mucus lining, which in turn lowered production of the harmful phenols. Prif increased the amount of dietary protein that reached gut microbes, giving them more material to produce the beneficial phenols.
“We think Prifs represent an emerging class of dietary nutrients that shape the composition of the gut microbiome and could have a far-reaching influence on metabolic health,” said AbuSalim.
“Food packaging may eventually list Prif right below fiber,” said Rabinowitz.

Rethinking Where Gut Metabolites Come From
The Nature Metabolism study focused on the origins of phenol metabolites as well as indole metabolites, which are produced from the amino acid tryptophan. Like phenols, indoles are being studied for their possible therapeutic value.
Indole metabolites have been connected to a wide range of diseases, including inflammatory bowel disease, neurodegenerative disorders, and cancer. In cancer research, they have been found to affect processes that include cancer metastasis and anti-tumor immune responses.
Scientists had generally assumed that phenols and indoles were produced only by gut bacteria. AbuSalim, Rabinowitz and their colleagues decided to test that assumption. Researchers have been especially interested in dietary and probiotic approaches that might increase beneficial indole metabolites. But those strategies may need to be reconsidered if mammalian metabolism, rather than microbes, is responsible for much of what circulates in the body.
Using isotope tracing in mice, rats and human cells, the researchers found that mammalian metabolism can produce many indole and phenol metabolites on its own. These included important compounds such as indole-3-lactate and indole-3-acetate.
In mice, circulating levels of these metabolites remained high even after antibiotic treatment disrupted the microbiome. A similar pattern appeared in samples from patients taking antibiotics, including cancer patients. At the same time, metabolites made exclusively by microbes, including indole-3-propionate and p-cresol sulfate, declined after antibiotic treatment.
New Clues for Diet and Microbiome Therapies
Together, the two studies provide a clearer picture of where phenol and indole metabolites come from and how they are produced. The findings could influence the development of therapies designed to raise or lower specific metabolites.
They also add important detail to scientists’ understanding of how diet interacts with the microbiome. Knowing which foods influence particular microbial products could eventually help researchers design more precise dietary, probiotic, or metabolic interventions.
“Beyond that,” said Rabinowitz, “a clearer picture of how different foods interact with the microbiome to modulate the production of bacterial metabolites will help sharpen the guidance nutritionists and doctors can give to people for disease prevention and therapy.”
These studies were funded by the Ludwig Institute for Cancer Research, the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, the Princeton Alliance for Collaborative Research and Innovation, Princeton University.
Aside from his post as Director of the Princeton Branch of the Ludwig Institute for Cancer Research, Joshua Rabinowitz is Professor in the Department of Chemistry & Lewis-Sigler Institute for Integrative Genomics and a member of the Rutgers Cancer Institute.

A chemical commonly used to preserve food has been linked to a recent increase in suicide deaths in the UK, with young people and boys and men accounting for a disproportionately large share of cases. The findings come from a comprehensive analysis of available data from 2019-24 published in the open-access journal BMJ Public Health.
Researchers say the findings point to an urgent public health need to reconsider unrestricted access to the chemical in an effort to prevent further avoidable deaths.
Suicide death rates across the UK have generally declined since the early 1990s. More recently, however, there are signs that the numbers may be increasing. At the same time, reports from around the world have documented a growing number of suicides associated with sodium nitrite poisoning.
Researchers Examine Sodium Nitrite Poisoning Cases
To investigate whether sodium nitrite poisoning may be contributing to suicide deaths in the UK, researchers conducted a retrospective analysis of cases submitted to the country’s primary laboratory for postmortem testing of nitrite and its oxidized metabolite, nitrate.
The cases were submitted by coroners, forensic pathologists, and police forces between March 2019 and August 2024.
Over that period, the laboratory received 274 samples connected to 201 suspected cases of either deliberate or accidental poisoning across the UK, Ireland, and Gibraltar.

Most cases originated in Greater London, South East England, Ireland, and the Midlands. However, the researchers caution that this geographic pattern could reflect differences in coroner awareness and testing practices rather than the actual distribution of cases.
The number of cases increased substantially after 2019, which was the first year the laboratory began receiving samples for nitrite/nitrate assessment.
For the final analysis, researchers used only cases for which coroners had approved the use of the data. That represented 82% (164) of the cases received between 2019 and 2024.
Young People and Men Accounted for Most Cases
The average age among the cases was 28. Ages ranged from 14-74 for males and 17-82 for females.
Nearly three-quarters (71%) of all cases involved younger generations. Gen Z accounted for 33% (born 1981- 96), while Millennials accounted for 38% (born 1997- 2012, but listed up to 2005 to account for a separate category of minors, as 4% of cases were among those under the age of 18).

Men substantially outnumbered women overall, with (109) male cases compared with (52) female cases. Men made up more than half of cases in every generation except the oldest classified generation (Silent, born 1928-45), which included only one case, involving a woman.
Blood testing also revealed unusually high concentrations of nitrite and nitrate. In 87% of cases, levels were 100 times higher than would normally be expected physiologically. Researchers say this finding suggests that ingestion of the chemical was intentional.
True Number of Deaths May Be Higher
The researchers note several important limitations to the findings. Nitrite and nitrate testing is not routinely required in every suspected suicide, making it difficult to determine exactly how many deaths are associated with the chemical.
“It is therefore likely that the cases included here represent a substantial underestimate of the actual incidence. Secondly, the interval between death and sample receipt varied considerably, introducing the possibility that delays may have affected the accuracy of the biochemical measurements,” they say.
Despite those limitations, researchers say the increase in cases involving predominantly young people is particularly concerning because younger generations tend to have greater digital literacy.
“Intentional poisoning has contributed to these recent increases, and at least in the USA, this rise has been partly attributed to the use (and availability) of sodium nitrite,” they point out.
Researchers also highlighted the role that online information may be playing.
“This trend has emerged alongside freely accessible online information detailing how sodium nitrite can be obtained and used, disseminated both under the guise of providing mental health support and for more explicitly harmful purposes,” they explain.
Researchers Call for Urgent Action
The team says the findings support taking immediate steps to address access to sodium nitrite and the circulation of harmful information online.
“Collectively, these findings establish unequivocally that use of sodium nitrite in the UK as a method of suicide is both substantial and concerning,” they write.
The researchers also suggest that younger people’s greater familiarity with digital technology may make it easier for them to encounter harmful online material.
“Our data provide strong support for the suggestion that the improved digital literacy of younger people enables access to illicit online material promoting suicide practices and lends further support for calls for tighter legislation to prevent availability of such information in online forums,” they add.
Alongside efforts to restrict access and harmful information, the researchers suggest that emergency services could take additional steps to reduce the consequences of sodium nitrite poisoning. Providing an antidote (methylthioninium chloride kits) in ambulances, they say, would be “a simple and cost-effective, timely method to prevent the devastating consequences of ingestion.”
Lead researcher, Professor Amrita Ahluwalia, comments: “This is an extremely difficult subject to talk about, and we appreciate the impact that this might have on all those affected by suicide.
“What our research shows is deeply upsetting. But it makes clear why urgent steps are needed to regulate access to this chemical and to reduce the spread of harmful information about it online.”

Cambridge researchers have uncovered why both activating and blocking the same brain receptor can promote weight loss. The findings may help scientists develop obesity treatments that are more effective and potentially work better in combination.
The mouse study, published in Nature Metabolism, found that the outcome depends on which part of the brain is targeted. Activating the receptor in the brainstem reduced appetite, while blocking the same receptor in the hypothalamus produced a similar weight loss effect through a different mechanism.
More than a billion people around the world are living with obesity, a condition that raises the risk of diseases including type 2 diabetes, cardiovascular disease and cancer. Losing weight can reduce some of these risks, but achieving substantial weight loss through diet and exercise alone can be difficult.
How Modern Weight Loss Drugs Target the Brain
A new generation of weight loss medications has emerged in recent years that act on specific receptors involved in appetite. By influencing these receptors, the drugs can reduce food intake, promote weight loss, and help regulate blood sugar.
Several widely used medications, including Wegovy and Ozempic, activate a protein receptor called the glucagon-like peptide 1 receptor (GLP-1R).
Other obesity treatments act on both GLP-1R and another receptor known as the glucose-dependent insulinotropic polypeptide receptor (GIPR). This second target has presented scientists with an unusual puzzle.

Some medications, including Mounjaro and Zepbound, activate GIPR. Others, such as MariTide, block it. Despite producing opposite effects on the same receptor, both approaches can help promote weight loss.
Researchers at the Institute of Metabolic Science, University of Cambridge, set out to understand why. Their experiments in mice revealed that the two types of GIPR drugs work through different regions of the brain. The researchers also found that these approaches can increase weight loss when paired with certain GLP-1-based weight loss medicines.
Tracking GIPR Activity in Different Brain Regions
To identify the brain regions responsible for these effects, the team used genetically engineered mice in which GIPR had been selectively removed from specific areas.
One group lacked GIPR in the brainstem, the region at the base of the brain just above the spinal cord that is involved in appetite and nausea. Another group lacked the receptor in the hypothalamus, an important brain region involved in regulating hunger and body weight. A third group consisted of normal, unmodified mice that served as controls.
The scientists treated the animals with different combinations of a GIPR agonist (which activates the receptor), a GIPR antagonist (which blocks the receptor) and a GLP-1 drug. They then monitored food consumption, body weight, fat mass, blood sugar control and brain activity.

Comparing the different groups allowed the team to pinpoint where each treatment was acting.
The results showed that GIPR agonists primarily work through the brainstem. Activating GIPR in this region reduced appetite and led to lower body weight.
Blocking a Brain Brake on Fullness
GIPR antagonists followed a different route.
Instead of acting primarily through the brainstem, the researchers found that blocking GIPR promoted weight loss through the hypothalamus. In this region, GIPR appears to function as a kind of ‘brake’ that limits how strongly the brainstem responds to signals indicating that the body is full.
Blocking the receptor effectively releases that ‘brake’, allowing fullness signals to have a stronger effect.
The researchers also found evidence that blocking GIPR could enhance the effects of emerging medicines that target the amylin receptor. This suggests that GIPR antagonists might eventually be useful for strengthening several different classes of obesity treatments.
Clues to More Powerful Obesity Drug Combinations
The results help explain why treatments such as MariTide can be effective. MariTide, currently in phase 3 clinical trials, combines GIPR antagonism with GLP-1 receptor agonism.
Understanding how these separate pathways interact could also help researchers design more effective combinations of obesity medicines in the future.
Dr. Jo Lewis, the study’s first author from the Institute of Metabolic Science at the University of Cambridge, said: “Understanding which brain circuits respond to these medications – and how they do so – could help us design better drugs that produce more weight loss with fewer side effects, and which might work in combination with other obesity medicines to even greater effect.
“Our work also strengthens the idea that the brain is central to obesity treatment. Obesity drugs are not acting simply on the gut or pancreas. Instead, they have important effects on specific, identifiable brain circuits that regulate appetite and food intake.”
The research was funded by the Medical Research Council and Wellcome.

For decades, scientists have generally viewed the brain’s immune system as largely separate from the immune defenses operating throughout the rest of the body. The brain has its own specialized immune cells, along with the blood-brain barrier, which restricts many substances and cells from entering brain tissue.
New research from Stanford is challenging that picture. Scientists found that large numbers of immune cells from elsewhere in the body enter the human brain as people age. The discovery could reshape scientists’ understanding of brain aging and may eventually create new possibilities for treating neurological diseases. The work, supported in part by the Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, was published recently in the journal Nature.
“We usually think of the brain as a closed system,” said Julia Belk, a postdoctoral scholar in pathology at Stanford Medicine and first author on the new study. “What we found is that actually a lot of immune cells enter the human brain during aging.”
An Unexpected Path Into Brain Research
Belk’s interest in neuroscience began while she was a graduate student in the Department of Computer Science at Stanford Humanities and Sciences. During that time, she also trained through Sarafan ChEM-H’s Chemistry/Biology Interface Predoctoral Training Program. She has described that experience as important in shaping an interdisciplinary approach that combines basic science, computer science, and medicine.
That training eventually led to a collaboration with Siddhartha Jaiswal, a senior author of the new study, an associate professor of pathology at Stanford Medicine, and a member of the Institute for Stem Cell Biology and Regenerative Medicine.
In earlier work, the researchers examined genetic information from thousands of people, including some who had been followed for decades. The team showed that people carrying certain clones of immune cells produced by mutated blood stem cells were much less likely to develop Alzheimer’s. That result raised the possibility that these unusual immune cells might somehow be interacting with the brain.

The researchers later found evidence that some of the mutant cells could enter the brain itself. The mutations involved are associated with clonal hematopoiesis of indeterminate potential, a condition found in only a minority of people. Even so, the discovery led the team to ask a broader question: Could immune cells from the blood routinely enter the brains of people as they grow older?
“Unlike most immune cells, which are continuously replenished by blood stem cells from the bone marrow, immune cells in the brain were presumed to renew themselves throughout the lifespan without contribution from outside the brain,” said Jaiswal. “Our first study showed that this might not always be the case.”
Challenging a Longstanding View of Microglia
For years, many researchers believed that the brain’s specialized immune cells, known as microglia, were established at birth and remained a self-sustaining population throughout life. Under that model, immune cells from elsewhere in the body were not expected to migrate into the brain and become part of this population.
Belk and her colleagues began to consider a different possibility. If outside immune cells could enter the brain in some people, perhaps the process was not rare at all. It might instead be a regular feature of human aging.
The idea that blood-based immune cells could play a role in Alzheimer’s was both unusual and controversial. In 2022, Jaiswal and colleagues sought support from the Knight Initiative for Brain Resilience, which funds research intended to rethink how scientists study brain resilience and neurodegenerative disease.

With support in part from a Knight Initiative Innovation Award, Belk, Jaiswal, and co-senior author Howard Chang, the Virginia and D. K. Ludwig Professor of Cancer Research and a professor of genetics at Stanford Medicine, began investigating why peripheral immune cells appeared to increase resilience to Alzheimer’s. Before addressing that question, however, they first needed to determine whether immune cells from the blood truly could replenish microglia in the brain.
Tracing Immune Cells From Blood to Brain
To investigate, the researchers studied human brain tissue. They used samples from the Stanford Rapid Autopsy Center, which is led by co-author Jody Hooper, a professor of pathology at Stanford Medicine, as well as samples from the University of Washington’s Alzheimer’s Disease Sequencing Project.
These programs collect both blood and post-mortem brain tissue from people with and without Alzheimer’s. That combination gave the team an unusual chance to directly compare immune cells found in the bloodstream with those present in brain tissue after death.
The challenge was determining exactly where the immune cells inside the brain had originated. Because immune cells divide continuously, the scientists needed to trace their cellular family trees. Their goal was to distinguish cells descended from the original population of microglia that had been present since birth from cells descended from blood stem cells in the bone marrow later in life.
The researchers found a way to do this by comparing DNA from immune cells in the blood with DNA from immune cells in the brain. They used shared mutations as biological markers of ancestry, somewhat like a consumer ancestry testing service.
Random mutations gradually accumulate in blood stem cells as people age. Immune cells produced by those stem cells inherit the same mutations. As a result, if two groups of immune cells carry matching mutations, they are highly likely to share the same origin.
“If we see the same mutations in the blood and in the brain’s microglia, then we can be very confident that immune cells in the brain are descendants of those immune cells in the blood,” she said.
Using that approach and techniques developed during their 2023 research, Belk and her colleagues compared immune cells from paired blood and brain samples. The genetic signatures matched. The results showed that immune cells from the body had entered the brain, with the process occurring as early as middle age.
Further experiments revealed another striking development. Once the peripheral immune cells entered the brain, they transformed into specialized microglia. The researchers noted that this process does not appear to occur in other species such as mice or non-human primates.
A Possible New Route for Brain Immunotherapy
Beyond challenging established ideas about brain immunity, the finding could eventually provide a new strategy for developing treatments aimed at the brain.
“Now that we know that these immune cells actually can get into the brain, we can think about all kinds of new engineering strategies to have those peripheral immune cells do useful things.”
One possibility would be to engineer immune cells so they could target and break down amyloid and tau aggregates associated with neurodegenerative diseases. Such cells might eventually be given to people preventively, before those damaging aggregates begin accumulating.
The discovery could also broaden research into how the health and history of blood stem cells affect the brain. Because many microglia in aging humans appear to originate from blood stem cells, anything that changes cells in the blood or bone marrow could potentially influence the brain as well.
“Our findings suggest that the life history of blood stem cells could influence the risk of brain diseases by altering the microglia,” Jaiswal said.
For Belk, the results are also notable because they reveal an aspect of brain aging that appears to be distinctly human.
“I think this is exciting because this is also a uniquely human feature of aging that we had no idea about.”

New research from the University of East Anglia and the Norfolk and Norwich University Hospital suggests that something as simple as choosing the stairs could contribute to a longer life.
The large study found that people who regularly climbed stairs had a substantially lower risk of dying from cardiovascular disease. Frequent stair climbers were 39% less likely to die from heart-related causes and 24% less likely to die from any cause compared with people who climbed stairs less often.
Regular stair climbing was also associated with a lower likelihood of developing serious cardiovascular conditions, including heart attack, stroke, and heart failure.
Prof Vassilios Vassiliou, from UEA’s Norwich Medical School, said: “Cardiovascular disease is the leading cause of death worldwide — with cases nearly doubling between 1990 and 2019. But it is largely preventable through a healthy lifestyle — including regular physical activity, a heart-healthy diet, not smoking, maintaining a healthy weight, and managing blood pressure, cholesterol, and diabetes.
“Taking the stairs is a practical and often overlooked way to build physical activity into daily life.
“We wanted to better understand how this everyday activity could have life-saving potential.”
Large Study Links Stair Climbing to Lower Death Risk
Researchers set out to determine whether regularly climbing stairs might help reduce the risk of cardiovascular disease and premature death.

The team reviewed nearly 1,900 studies before analyzing data from more than 480,000 people included in nine high-quality studies. Participants were followed for a median of 14 years.
The group included both healthy individuals and people with a previous history of heart problems. Participants ranged in age from 35 to 84, and 53% were women.
Dr. Sophie Paddock, also from UEA’s Norwich Medical School and a cardiology specialist registrar at the NNUH, said: “After pooling results from over 450,000 participants, we found a consistent association between stair climbing and lower risk of both cardiovascular death and overall mortality.
“Unlike going to the gym or doing a workout, climbing the stairs is something you can easily fit into your day at home, at work or when you’re out. It’s a good option for people who don’t have much time or easy access to exercise.
“So if you have the choice of taking the stairs or the lift, go for the stairs as it will help your heart.
“Even brief bursts of physical activity have beneficial health impacts, and short bouts of stair climbing should be an achievable target to integrate into daily routines.”
Even Short Bursts of Stair Climbing May Help

Earlier research cited by the researchers found that spending just a few minutes climbing stairs several times each week can improve cardiorespiratory fitness and reduce cholesterol levels.
One large cohort study included in the analysis indicated that climbing about six flights of stairs each day might provide the greatest benefit. However, researchers say more work is needed to determine the ideal “dose” of stair climbing.
Dr. Paddock said: “Some of the studies we looked at showed that the more stairs climbed, the greater the health benefits. But even small changes had a measurable impact.”
A Simple Way to Add More Physical Activity
The results add to growing evidence that even relatively short periods of physical activity can produce meaningful health benefits.
Prof Vassiliou said: “With more than a quarter of adults worldwide failing to meet recommended activity levels, choosing to take the stairs offers a realistic, scalable intervention.
“Encouraging people to take the stairs in workplaces, public buildings and homes could form part of a wider strategy to reduce cardiovascular disease at population level.”
Stair Climbing Is Not Suitable for Everyone
Despite the potential benefits, the researchers note that climbing stairs may not be appropriate for everyone, especially people with mobility limitations or joint conditions.
They also say future studies should use wearable technology to track physical activity more precisely and help determine the most effective amount of stair climbing to recommend.
‘Evaluating the Impact of Stair Climbing on Cardiovascular Risk Reduction: A Systematic Review and Meta-analysis’ is published in the American Journal of Cardiovascular Drugs.

When laboratory mice experience brain damage, e.g., from an injection, Jan Deussing repeatedly notices the same response. A particular group of cells appears and becomes active around the damaged area. Although Deussing, a research group leader and experienced neurobiologist, had observed the phenomenon many times, he did not know exactly what type of cells were involved.
The mystery became an ideal research question for a master’s student. Clemens Ries, who had recently joined the Max Planck Institute of Psychiatry for an internship as he approached the end of his biology degree, took on the challenge.
Identifying the Brain’s Repair Cells
Using a mouse model, Ries systematically tested markers for all known cell types. Only one produced a response: the marker for oligodendrocyte progenitor cells (OPCs).
These precursor cells can mature into oligodendrocytes, which produce the myelin sheath surrounding axons. Axons are extensions of nerve cells that allow neurons to communicate with one another. Myelin acts much like the insulating material around an electrical cable. It supports efficient information transmission along axons and also helps supply them with nutrients, making it vital to healthy brain function.
Damage to myelin can have serious consequences. In autoimmune diseases such as multiple sclerosis (MS), the protective coating breaks down. Physical injuries can also harm myelin, and in severe cases, the resulting damage can lead to the death of entire neurons. Restoring myelin around affected axons is therefore an important part of the brain’s response to injury.
A Surprising Stress Hormone Appears After Injury
Ries initially studied the newly identified cells for his master’s thesis. “The topic remained so exciting that it became my doctoral thesis,” says the biologist.

His subsequent research showed that these precursor cells multiply dramatically around the edges of brain wounds. Most then continue to mature, eventually becoming oligodendrocytes capable of producing new myelin.
But Ries and Deussing also uncovered something that had not been known before. Near the damaged tissue, about one third of the OPCs activate corticotropin-releasing hormone (CRH), a hormone that plays a central role in regulating the body’s stress response. Researchers had not previously known that OPCs could produce neuropeptides such as CRH. The findings have now been published in the renowned journal Cell Reports.
The CRH response begins remarkably quickly. Production can be detected within just a few hours after an injury, but it shuts down again after roughly three days. This short and rapid burst suggests that CRH has an important function during the earliest stages of the healing response.
CRH Helps Control the Timing of Myelin Repair
One of the two known receptors for CRH also appears to be central to this process. CRH receptor 1 is present on a different population of OPCs and allows those cells to respond to the CRH that has been released.
When CRHR1 is absent, OPCs multiply more rapidly after an injury. That initial increase, however, does not translate into better repair. Ultimately, fewer mature oligodendrocytes are produced and remain.

The findings indicate that CRH helps regulate the timing of OPC maturation. That timing appears to be essential for producing enough mature oligodendrocytes to properly restore the damaged myelin sheath.
The Same System Shapes the Developing Brain
OPCs are not only important after injury. They also have a major role in building myelin as the brain matures. Much of this myelination takes place after birth and continues until young adulthood.
Because CRH receptor 1 is found on OPCs even when no injury is present, Ries and Deussing began to wonder whether the receptor might also influence myelination during normal brain development. Working with other researchers, they examined myelin formation in additional mouse models using several different methods.
They found that mice lacking CRH receptor 1 produced more OPCs during the early stages of development. Those changes did not disappear with age. Instead, they had lasting effects on the structure of the brain.
In adult brains, the researchers detected changes in myelination that could be traced to thicker myelin sheaths, particularly around thin axons. The results suggest that CRH receptor 1 on OPCs plays an important role not only in repairing myelin after injury, but also in regulating how myelin develops in the first place.
Where Does CRH Come From During Development?
Following an injury, OPCs themselves respond by producing and releasing CRH. Brain development raises a different question: where does the stress hormone come from when the brain is maturing normally?
The scientists propose that neurons may provide the answer. Their hypothesis is that developing neurons release CRH, which then influences both the multiplication of OPCs and their maturation into oligodendrocytes that produce myelin.
A Possible Connection to Depression and Stress
Neurons are already known to release CRH, particularly during stressful conditions. Stress experienced during early childhood development is also recognized as a risk factor for psychiatric disorders.
The new results therefore raise the possibility that the CRH system operating in OPCs could have broader implications for mental health.
“Our current findings suggest that in stress-associated psychiatric disorders such as depression, the CRH system in OPCs may play a greater role than previously known,” Deussing speculates.
If future research confirms and expands on that connection, understanding how CRH signaling affects OPCs, myelin formation, and brain development could eventually point toward completely new therapeutic approaches.

A large study has found that women who used hormone therapy later in life had a lower risk of developing dementia. The findings were published August 12, 2026, in Neurology, the medical journal of the American Academy of Neurology.
Researchers emphasized that the results show an association and do not demonstrate that hormone therapy can prevent dementia.
“While these findings help us better understand the relationship between hormone therapy use and various markers of dementia, more research needs to be done before we can make recommendations to women about their use of these therapies in relation to their brain health,” said study author Jennifer Bruno, PhD, of Stanford Medicine in Stanford, California. “This study looked back at women who were using hormone therapy decades ago with the timing and type of use differing from what is current practice for most women today, so the results are informative, but they may not apply to today’s standards.”
More Than 21,000 Women Studied
Researchers analyzed medical information from two large data sets that together included 21,462 female participants who underwent clinical testing while they were alive. In one data set, 728 participants received brain scans or biomarker testing during life. In the other, 2,959 participants underwent autopsies after death, at an average age of 82, so researchers could look for evidence of Alzheimer’s disease.
Participants in the two data sets were followed for about three to five years, beginning at an average age of 71.
Among all participants, 1,953 used hormone therapy and 19,509 did not. On average, the women who received hormone therapy began using it after age 70.

The analysis focused only on estrogen-only therapy. Earlier studies had suggested that treatment combining estrogen with progestin may raise dementia risk. Under current medical practice, estrogen-only therapy is prescribed only to people who have undergone a hysterectomy because of the risk of endometrial cancer.
Fewer Signs of Alzheimer’s at Autopsy
Among participants whose brains were examined after death, those who had used hormone therapy were less likely to show evidence of Alzheimer’s disease.
Researchers evaluated three major features associated with Alzheimer’s disease: amyloid-beta plaques, tau tangles, and neuritic plaques, which are amyloid plaques surrounded by damaged nerve cells. These findings were combined into a single score used to assess the amount of Alzheimer’s related pathology in the brain.
Among women who had used hormone therapy, 18% showed no signs of Alzheimer’s disease at autopsy. That compared with 10% of women who had not used the therapy.
At the other end of the spectrum, 40% of hormone therapy users showed all three signs of Alzheimer’s disease, compared with 51% of women who had not used hormone therapy.

After researchers accounted for factors including age, education, genetics, race and hypertension, hormone therapy use was associated with 35% lower odds of showing signs of Alzheimer’s disease at autopsy.
Biomarkers Pointed to Less Amyloid Buildup
A separate analysis examined biomarker tests collected while participants were alive. Women who had used hormone therapy had amyloid biomarker levels in their blood and spinal fluid that were consistent with less amyloid accumulating in the brain than women who did not use hormone therapy.
Higher levels of amyloid-beta protein in blood and spinal fluid can indicate that less of the protein is being deposited in the brain as plaques.
Hormone therapy use was also associated with 39% lower odds of receiving a clinical dementia diagnosis. Women who used the therapy were also less likely to show memory problems or declines in their ability to carry out everyday functions.
Findings Differ From Current Hormone Therapy Use
An important limitation is that the women in the study used hormone therapy differently from how it is typically prescribed today. Bruno noted that participants who received hormone therapy had an average age of 70.
Current standard practice generally involves starting hormone therapy in the late 40s to early 50s and stopping treatment before age 60.
“Despite these limitations, our findings provide evidence of an association between use of estrogen-only hormone therapy during later life and better outcomes on dementia and brain health,” Bruno said.
The study was supported by the National Institute on Aging.

A large study involving more than 5,500 adults over age 50 has identified a potentially dangerous combination of health risks. People who had both abdominal obesity and vitamin D deficiency faced a 123% higher risk of death compared with those who had neither condition.
The findings, published in the journal Diabetes, Obesity and Metabolism, suggest that the two conditions may be especially harmful when they occur together. Although each was associated with a higher risk of death on its own, the combined effect was substantially greater.
“Abdominal obesity is a well-known risk factor because it’s associated with inflammation and metabolic problems. Vitamin D, on the other hand, is a hormone that acts on various organs, and its deficiency impairs several bodily functions. When these two conditions occur together, one amplifies the effects of the other, further increasing the risk of death,” explains Tiago Silva Alexandre, a professor in the Department of Gerontology at the Federal University of São Carlos (UFSCar) in Brazil, who coordinated the study. “For that reason, monitoring vitamin D levels and treating excess abdominal fat are essential measures to prevent premature death, especially after age 50,” he adds.
Tracking Health Risks Over Six Years
The research was carried out in collaboration with University College London (UCL) in the United Kingdom and funded by FAPESP. Researchers followed 5,520 people age 50 and older for six years. All of the participants were enrolled in the English Longitudinal Study of Ageing (ELSA), one of the world’s largest studies focused on aging.
The data showed that vitamin D deficiency (levels below 30 nmol/L) was associated with a greater risk of death on its own than abdominal obesity. Abdominal obesity was defined as a waist circumference greater than 102 centimeters for men and 88 centimeters for women.
People with abdominal obesity alone had a 47% higher risk of death, while vitamin D deficiency by itself was associated with an increase of up to 91%. When both conditions were present, however, the risk of death rose by more than twofold.

How Belly Fat May Reduce Available Vitamin D
Alexandre says abdominal obesity and vitamin D deficiency may reinforce one another in a harmful cycle. Abdominal fat can “sequester” vitamin D circulating in the body, storing it in adipocytes (fat cells) instead of leaving it available in the bloodstream.
“This means that although the body may have the vitamin stored in fat, it isn’t freely available in the blood to perform vital functions in other organs and systems,” he says.
Obesity may also interfere with the way the body processes vitamin D. People with obesity have lower expression of enzymes involved in vitamin D metabolism, further limiting how much of the vitamin is available for the body to use.
“Abdominal obesity reduces circulating vitamin D, and that deficiency impairs the immune system, exacerbating the chronic inflammation caused by excess fat and drastically increasing the risk of mortality,” Alexandre explains to Agência FAPESP.
Aging, Inflammation, and Vitamin D
The combination may be particularly important later in life because aging itself is associated with inflammaging, a state of low-grade chronic inflammation.

“Under normal conditions, vitamin D acts as a regulator of the immune system, preventing inflammation from getting out of control. When vitamin D levels are low and there’s excess abdominal fat, an unfavorable systemic environment develops that accelerates cardiovascular and metabolic diseases, as well as muscle loss,” he stresses.
Cascade Effect
The new findings are part of a broader series of studies examining how vitamin D affects health during aging.
“In previous studies, we identified a cascade effect. Vitamin D deficiency leads to a loss of strength, which results in reduced walking speed, causing a loss of independence and greater dependence in daily activities,” Alexandre explains.
The research group has also found in a separate study that vitamin D deficiency increases the risk of cognitive decline.
“Vitamin D is a hormone with various functions. It plays a role in regulating blood pressure, heart rate, the central nervous system, the immune system, and the endocrine system. Therefore, when its levels are low, several essential bodily functions are compromised,” he says.

Congenital heart disease is the most common birth defect, affecting about 1 in 100 babies born each year. The condition can have many causes, including changes involving TBX5, a gene that plays a critical role in building the heart. In some cases, a child has only one working copy of TBX5 rather than two healthy copies inherited from the parents.
For years, researchers have been trying to understand why losing the function of just one copy can have such a major effect on heart development, even when the second copy still works.
Researchers at Gladstone Institutes now report that TBX5 has another important role beyond controlling gene activity. It helps organize DNA into the physical three-dimensional structure that heart cells need to work properly. In a new study published in Science, the scientists found that losing even one copy of TBX5 can disrupt this organization, changing how many other genes are used inside heart cells.
The findings offer a new way to think about a long-standing question in genetics: why losing one copy of certain genes, a condition called haploinsufficiency, can cause severe problems during development.
“TBX5 is just one example of a broader class of genes that cause birth defects when only one copy is lost,” says Benoit Bruneau, PhD, director of the Gladstone Institute of Cardiovascular Disease and a senior author of the study. “What’s exciting about our findings is they suggest many different birth defects might happen for the same reason: the cell’s 3D instruction manual simply gets folded the wrong way.”
“We developed and used different computational models to analyze results from thousands of individual cells,” says Katie Pollard, PhD, director of the Gladstone Institute of Data Science and Biotechnology and the other senior author of the study. “That allowed us to finally see how losing this one protein causes the heart’s DNA structure to break down on every level.”
How DNA Folding Helps Cells Work
Packing DNA into a cell is a remarkable feat. It is similar to squeezing a miles-long instruction manual into the head of a pin. But DNA is not packed randomly. Each type of cell folds its genetic material into a distinct three-dimensional arrangement, allowing a heart cell to access a different set of instructions than a brain cell.

This 3D structure is arranged in multiple layers. It includes large compartments (like separate binders of the manual), domains (like paragraphs), and chromatin loops (like folding a page so two distant sentences touch). These loops allow distant genetic switches called enhancers to make physical contact with specific genes. Those contacts help cells activate the instructions they need.
Scientists already knew that TBX5 is one of the major regulators of heart development. The protein helps activate many of the genes required for heart cells to develop and function. Earlier work from Bruneau’s lab showed that losing one copy of TBX5 affects the levels of hundreds of other heart-specific genes. What remained unclear was exactly how that happened.
The researchers therefore set out to determine whether the physical folding of DNA influences how heart cells behave, and whether TBX5 helps control that process.
Mapping the Heart’s 3D Genome
To investigate, the team combined several advanced methods that allowed them to examine how individual cells respond to different amounts of TBX5. They guided human stem cells into becoming heart muscle cells. Some cells were healthy, some lacked one copy of TBX5, and others lacked both copies.
The scientists then used high-resolution 3D mapping to examine DNA loops at extremely fine detail.

Because the experiment produced millions of data points from thousands of individual cells, the researchers relied on computational models to analyze the enormous datasets.
“Using the custom computational approaches we developed, we were able to see for the first time how the loss of TBX5 triggers the total collapse of the heart’s 3D DNA organization,” says Shuzhen Kuang, PhD, a first author of the study and former bioinformatics fellow in Pollard’s lab. “Surprisingly, we discovered this collapse happens at every level of genome organization — compartments, domains, and chromatin loops.”
TBX5 Acts as an Architect for Heart DNA
As healthy stem cells developed into heart muscle cells, the researchers saw major changes in the organization of the genome. Large sections of DNA switched between active and inactive states as the cells matured.
TBX5 emerged as a central organizer of these structural changes.
The researchers found that TBX5 works like a GPS for a molecular motor called cohesin. TBX5 helps direct cohesin to the correct locations on DNA, where it creates chromatin loops that bring genes together with their enhancers.
When TBX5 levels fall too low, these loops do not form properly. DNA becomes incorrectly folded, and important genes involved in heart development may fail to switch on when they are needed.
“What was striking was how the amount of TBX5 matters immensely,” says Zoe Grant, PhD, a first author of the study and a postdoctoral researcher in Bruneau’s lab. “The more TBX5 you removed, the worse the disruption across every level of genome organization we looked at.”
The results showed that reducing TBX5 to half its normal amount is enough to disrupt DNA folding and directly contribute to heart defects.
The researchers also discovered that individual heart cells do not all respond in exactly the same way to the loss of TBX5. Clear differences appeared between two major types of heart cells, atrial and ventricular cells. Variation was also seen among individual cells of the same type.
“This could help explain why people with the same mutation can have different heart defects,” Grant says.
A Broader Mechanism for Developmental Disease
Although the findings provide new insight into congenital heart disease, the researchers believe the same basic mechanism could be involved in other developmental disorders.
“We believe we’ve uncovered a new mechanism of disease,” says Bruneau. “We showed that even a small decrease in a single protein can cause the DNA blueprint to fold incorrectly and lead to disease. So, many birth defects currently attributed to genetic mutations may actually be caused by the 3D misfolding of DNA.”
The findings suggest that some genetic mutations may cause disease not only by changing individual genetic instructions, but also by disturbing the physical arrangement of the genome itself.
Next, the team plans to determine when TBX5 first begins organizing the genome during early heart development. The researchers also want to learn whether other proteins associated with birth defects shape DNA in similar ways.
About the Study
The paper, “Dose-dependent sensitivity of human three-dimensional chromatin to a heart disease-linked transcription factor,” was published in the journal Science on July 23, 2026. The authors are Zoe L. Grant, Shuzhen Kuang, Shu Zhang, Abraham J. Horrillo, Zhe Chen, Kavitha S. Rao, Cemre Celen, Vasumathi Kameswaran, Carine Joubran, Deepak Srivastava, Katie Pollard, and Benoit Bruneau of Gladstone; Pik Ki Lau, Keyi Dong, Bing Yang, Weronika M. Bartosik, Nathan R. Zemke, and Bing Ren of UC San Diego; and Irfan S. Kathiriya of UC San Francisco.
The work was supported by the National Institutes of Health (NHLBI U01 HL157989, UM1HG011585, R01 HL155906), the California Institute for Regenerative Medicine, Additional Venture, Gladstone Institutes, the Roddenberry Foundation, the Younger Family Fund, UC San Francisco, the Saving tiny Hearts Society, and the National Science Foundation.

An eye surgeon says that fewer people have been seeking treatment for eye damage than after the UK’s last total solar eclipse in 1999.Millions across the UK on Wednesday witnessed the most significant solar eclipse in 27 years – which saw more than 90% of the Sun covered by the Moon.Speaking to the BBC, Mr Alexander Ionides from Moorfield Eye Hospital said hospitals were “inundated” with worried patients in 1999, but said it seemed warnings about looking directly at the sun with the naked eye were “getting through”.He added that symptoms of eye damage can include a spot in the centre of your vision, which may appear grey or yellow. Symptoms can develop within hours, but sometimes take days to develop.