They’re tiny particles — with potentially huge human consequences. Researchers at Aarhus University have uncovered a flaw in how cells form what are known as exosomes, and this defect is associated with a mutation found in some people living with dementia. The discovery may offer new insight into how Alzheimer’s develops — and potentially point toward future treatment strategies.
Exosomes are extraordinarily small. Millions of them could sit on the tip of a grain of rice. Despite their size, new findings from the Department of Biomedicine at Aarhus University suggest they may play a central role in Alzheimer’s disease. Assistant Professor Kristian Juul-Madsen is part of the team behind the study, which recently appeared in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“Exosomes are used to communicate with and activate surrounding cells, and we have now identified a defect in both the production and the quality of exosomes in cells that we know are predisposed to Alzheimer’s.”
SORLA Mutation Weakens Exosome Production
Scientists have identified four primary genes tied to inherited forms of Alzheimer’s. One of these is Sorl1, which contains the instructions for making the protein SORLA. When the SORLA-protein carries a mutation, a person’s risk of developing Alzheimer’s increases. According to Kristian Juul-Madsen and his colleagues, defects in this protein disrupt the ability of brain cells to produce healthy exosomes.
“We found that cells with this mutation produced 30% fewer exosomes, and those that were produced were significantly worse at stimulating the growth and maturation of surrounding cells — in fact, up to 50% less effective than in cells where the SORLA-protein is not mutated.”
Why Exosome Quality Matters for the Brain
This discovery could be an important step forward for Alzheimer’s research, he explains.

“It tells us that exosomes produced particularly by the brain’s immune cells play an important role in maintaining brain health — and that mutations leading to fewer and poorer quality exosomes are associated with increased risk of Alzheimer’s.”
Kristian Juul-Madsen believes these insights may eventually contribute to advances in Alzheimer’s treatment.
“The potential is very clear. We now have the opportunity to investigate new treatments for Alzheimer’s — either by stimulating the function of SORLA so that the cells produce more and better exosomes, or by targeting other known receptors that can enhance exosome production.”
A Growing Need for New Alzheimer’s Therapies
Alzheimer’s is the most common form of age-related dementia in Denmark. An estimated 55,000 Danes live with the disease, and effective treatment options are still lacking.

Ludwig Maximilian University of Munich (LMU) researchers have uncovered how ribosomes are able to alert the cell when something is wrong.
Ribosomes are best known as the cell’s protein builders. They attach to mRNA and travel along it, interpreting the genetic code and linking amino acids to form new proteins. Their role, however, extends beyond basic protein production. Ribosomes also help detect cellular stress and can trigger protective actions when the cell encounters harmful conditions. An international team led by Professor Roland Beckmann from LMU’s Gene Center Munich has now identified the key steps that launch this stress signaling process. The results were published in Nature.
How Stress Disrupts Protein Production
Protein synthesis is extremely sensitive to disruptions such as limited amino acids, damaged mRNA, or viral infections. These forms of stress interfere with normal mRNA reading and can cause ribosomes to stall and run into one another. When collisions occur, they set off what is known as the ribotoxic stress response (RSR). This response activates pathways that either repair the damage or, if necessary, initiate programmed cell death.
Investigating ZAK With Biochemistry and Cryo-Electron Microscopy
The protein ZAK — a so-called kinase, that is, an enzyme which activates other molecules by transferring a phosphate group to them — plays a central role in controlling this stress response. Until now, it had been unclear how ZAK detects ribosomes that have collided and uses that information to activate signaling pathways. By combining biochemical experiments with cryo-electron microscopy, the research group demonstrated that ribosome collisions serve as the main activation cue for ZAK.
The scientists identified how ZAK attaches to ribosomes and which structural features of the collided ribosomes are necessary for its activation. They found that ZAK interacts with specific ribosomal proteins, causing particular regions of ZAK to dimerize, meaning that two copies of the protein pair up. This pairing initiates the cellular signaling cascade.
Why Understanding ZAK Matters
“A deeper understanding of these mechanisms is important for several reasons,” says Beckmann. According to him, ZAK functions at one of the earliest stages of the stress response, so learning how it recognizes ribosome collisions offers valuable insight into how cells detect disturbances with remarkable speed. It also helps explain how ribosomal quality control, downstream signaling networks, and the immune system coordinate their responses.
ZAK is also of medical relevance, as abnormal ZAK activity is linked to inflammatory diseases and persistent ribosomal stress. “Our findings thus illuminate a central principle of eukaryotic stress biology,” says Beckmann. “The translation machinery itself serves here as a surveillance platform from which global stress signals are initiated.”

New findings from the University of Birmingham suggest that regularly eating foods rich in flavanols, including tea, berries, apples, and cocoa, may help protect men’s blood vessels from the negative effects that occur during long periods of sitting.
Sedentary habits are widespread in modern life. Young adults spend an estimated six hours a day seated, and extended sitting is known to reduce how well blood vessels function.
Earlier research has shown that even a small 1% drop in vascular function, measured through brachial Flow-mediated dilatation (FMD), corresponds to a 13% rise in the risk of cardiovascular conditions such as heart disease, strokes, and heart attacks.
Researchers in the new study set out to determine whether specific dietary choices, particularly foods high in flavanols, could help offset the decline in vascular health that occurs during uninterrupted sitting.
What Flavanols Are and Why They Matter
Flavanols are naturally occurring polyphenols found in various fruits, tea, nuts, and cocoa beans. They have previously been linked to cardiovascular benefits, including support for the vascular system during psychological stress.
The study, which has been published in the Journal of Physiology, builds on this earlier evidence.

Dr. Catarina Rendeiro, Assistant Professor in Nutritional Sciences at the University of Birmingham and lead author, explained: “Whether we are sitting at desks, behind the wheel of a car, on a train, or on the sofa reading a book or watching TV, we all spend a lot of time seated. Even though we are not moving our bodies, we are still putting them under stress. Finding ways to mitigate the impact that sitting for uninterrupted periods has on our vascular system could help us cut the risk of developing cardiovascular diseases.”
Cardiovascular disease continues to rise. According to the British Heart Foundation, deaths among working-aged adults in the UK increased by 18% to 21,975 in 2023 compared to 2019. Recent analyses also estimate that cardiovascular diseases cost the UK approximately £29 billion.
Testing Whether Flavanols Protect the Body During Sitting
To explore whether flavanols could help preserve vascular function, the researchers examined the effects of these compounds during a two-hour sitting period. Forty healthy young men took part. Twenty had higher fitness levels and twenty had lower fitness levels. Each participant consumed either a high-flavanol cocoa drink (695 mg of total flavanols per beverage) or a low-flavanol cocoa drink (5.6 mg of total flavanols per beverage) before beginning the sitting session.
Women were not included in the study because fluctuations in estrogen during the menstrual cycle may influence how flavanols affect vascular function. The researchers note that this should be explored in future trials.
Before and after the sitting period, the team measured several indicators of vascular health, including: FMD in the superficial femoral artery and the brachial artery arterial resting shear rate and blood flow systolic and diastolic blood pressure leg muscle oxygenationHigh-Flavanol Cocoa Prevents Declines in Blood Vessel Function

Both the higher and lower fitness groups who consumed the low-flavanol drink showed declines in FMD in the arteries of their arms and legs. These participants also experienced increases in diastolic blood pressure, reductions in shear rate and blood flow, and lower leg muscle oxygenation. The results indicate that simply being more physically fit does not protect against the vascular effects of prolonged sitting.
In contrast, participants in both fitness groups who consumed the high-flavanol cocoa did not show declines in FMD in either the arm or leg arteries. This is the first study to demonstrate that flavanols can prevent sitting-induced vascular dysfunction in healthy young men.
Dr. Sam Lucas, Professor of Cerebrovascular, Exercise & Environmental Physiology at the University of Birmingham and co-author, said: “Our experiment indicates that higher fitness levels do not prevent the temporary impairment of vascular function induced by sitting when only drinking low-flavanol cocoa. Importantly, after the high-flavanol drink, both fitter and less-fit participants kept their FMD the same as it was before sitting for two hours.”
The results also show for the first time that baseline cardiorespiratory fitness does not change how the body responds to flavanol intake. This suggests that flavanols may help support vascular health regardless of someone’s fitness level.
Adding Flavanol-Rich Foods to Daily Routines
Alessio Daniele, PhD student at the University of Birmingham, noted: “It is actually quite easy to add high flavanol foods to your diet. There are cocoa products available in supermarkets and health stores which are processed through methods that preserve flavanol levels. If cocoa isn’t your thing, fruits like apples, plums and berries, nuts, and black and green tea are all common kitchen staples and are readily available.”
Dr. Catarina Rendeiro added: “Our research shows that consuming high-flavanol foods and drinks during periods spent sitting down is a good way to reduce some of the impact of inactivity on the vascular system.
“Given how common sedentary lifestyles have become and the increased risk this can have to vascular health, using flavanol-rich food and drink, especially in combination with breaking up periods of inactivity by going for a short walk or standing up, could be a good way to enhance long-term health, no matter the individual’s fitness level.”

Tatiana Schlossberg, granddaughter of former US President John F Kennedy, moved many Americans over the weekend with her emotional essay about being diagnosed with terminal cancer shortly after giving birth to her second child. In The New Yorker, the 35-year-old stunned readers, writing that she was battling acute myeloid leukaemia (AML), an aggressive blood cancer, and had less than a year to live. Doctors and researchers say the essay helped raise awareness about the deadly illness and critical need for more funding and research to tackle treatment-resistant cancers. “It’s such an obviously moving and courageous essay,” said Vijay Sankaran, a physician with Dana-Farber Cancer Institute. “She comes from a very prominent family, and yet anybody can be affected by cancer, even people who are young, who are seemingly healthy.”In the essay, titled A Battle With My Blood, Schlossberg said she was diagnosed after doctors noticed an abnormally high white-blood cell count after giving birth to her daughter in May 2024. The daughter of designer Edwin Schlossberg and diplomat Caroline Kennedy, she said she was shocked by the diagnosis, as she considered herself “one of the healthiest people I knew”. One of the dangers of acute myeloid leukaemias is that they can emerge suddenly, going from being undetactable to affecting hundreds of cells in a matter of days, said Dr Sankaran. The cancer – affecting both the bone marrow and blood – is rare, sickening four in 100,000 adults each year. Schlossberg’s subtype of leukaemia – a chromosomal abnormality formerly called Inversion 3 – is even rarer, affecting only 1% to 2% of people with acute myeloid leukaemia. The rare genetic mutation makes Schlossberg’s cancer even more dangerous. It is one of the few subsets of acute myeloid leukaemia for which there are few effective therapies – meaning remissions or cures “are the minority”, said Courtney DiNardo, professor of leukaemia at University of Texas MD Anderson Cancer Center. The most common treatments involve bone marrow transplants, chemotherapy and clinical trials. Schlossberg tried them all.She described in her essay the transplant doctors drained from her sister’s arms and chemotherapy that made her once “great hair” fall out. She joined a clinical trial for CAR-T-cell therapy, a type of immunotherapy for certain blood cancers, in which she said scientists “engineered my sister’s T-cells, directing them to attack my cancer cells”. Though the therapy has been revolutionary for other types of leukaemia, it is less so for acute myeloid leukaemia, Dr Sankaran said. In the last clinical trial, her doctor told Schlossberg that he could “keep me alive for a year, maybe”. She also discussed battling cancer while watching her cousin, Health Secretary Robert F Kennedy Jr, make massive cuts to research funding, including for cancers. She and other family members are ardent critics of Kennedy since his unsuccessful presidential campaign and nomination for the health role. “As I spent more and more of my life under the care of doctors, nurses, and researchers striving to improve the lives of others, I watched as Bobby cut nearly a half billion dollars for research into mRNA vaccines, technology that could be used against certain cancers,” Schlossberg wrote. Kennedy, a vaccine sceptic, announced in August that he was pulling the funding over claims that “mRNA technology poses more risks than benefits” for certain respiratory viruses. He also revoked funding for hundreds of research grants through the National Institutes of Health (NIH).Even though cuts to mRNA funding were only for respiratory viruses, they have had a chilling effect in the entire mRNA research community, said Jeff Coller, a Bloomberg Distinguished Professor at Johns Hopkins University focused on RNA therapeutics. “We’ve seen that researchers are, quite frankly, afraid to put together proposals for clinical trials that would be using mRNAs. And we call these cancer vaccines,” he said. The NIH was once a global leader in funding for biomedical research, but that has changed this year, Dr Sankaran said. “That’s been limiting, because you could just imagine you need to take more shots on goal to actually have research that will successfully lead to therapies,” he said. Schlossberg’s battle – while having access to the best care as a member of a prominent American family – highlights the need for more funding to develop better screening tools and treatments for all patients, physicians said. “[Schlossberg] continues to have a poor prognosis with even the best available tools that we have, and so I think it just really emphasizes our need to do better for many of our patients,” Dr Sankaran said.

Drug maker Novo Nordisk says semaglutide, the active ingredient for the weight loss jab Wegovy, does not slow Alzheimer’s – despite initial hopes that it might help against dementia.Researchers began two large trials involving more than 3,800 people after reports the medicine was having an impact in the real world.But the studies showed the GLP-1 drug, which is already used to manage type 2 diabetes and obesity, made no difference compared to a dummy drug. The disappointing results are due to be presented at an Alzheimer’s disease conference next month and are yet to be published in a peer-reviewed journal.Martin Holst Lange, chief scientific officer and executive vice president of research and development at Novo Nordisk, said: “Based on the significant unmet need in Alzheimer’s disease as well as a number of indicative data points, we felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success.”While semaglutide did not demonstrate efficacy in slowing the progression of Alzheimer’s disease, the extensive body of evidence supporting semaglutide continues to provide benefits for individuals with type 2 diabetes, obesity, and related comorbidities,” he said. Dr Susan Kohlhaas from Alzheimer’s Research UK said the results would come as a blow for people affected by Alzheimer’s.The patients who took part in the Evoke trials were aged between 55 and 85 and had mild cognitive impairment or mild dementia due to Alzheimer’s disease.Dementia progression was monitored and measured through tests and interviews. Treatment with semaglutide resulted in improvement of Alzheimer’s disease-related biomarkers, but this did not translate into delaying progression of the disease.Dr Kohlhaas said: “These trial results are another reminder that Alzheimer’s is driven by several different biological processes. No single approach is likely to be enough. “The field now needs to focus on understanding those processes in much greater detail and developing treatments that can be used together to tackle the disease from multiple angles.”She added that the growing use of GLP-1 medicines through private prescriptions, largely for weight loss, offers an opportunity to gather better real-world data on their longer-term effects.Fiona Carragher, chief policy and research officer at Alzheimer’s Society, said while it was “very disappointing” that these eagerly awaited results were not what everyone had hoped for, “no trial is wasted”.”Every investigation helps us develop better drugs and design better trials in the future.”She said there were currently more than 130 Alzheimer’s drugs in clinical trials of which around 30 are in late-stage trials – the final step before they are considered by regulators.

A new analysis from the Physicians Committee for Responsible Medicine, published in Frontiers in Nutrition, reports that people who follow a vegan diet tend to eat more plant-based foods, even those labeled as “unhealthy” by the plant-based diet index. This shift in eating patterns was associated with more weight loss compared to individuals following the Mediterranean diet.
Weight loss was linked to several factors: avoiding animal products; eating items such as potatoes and refined grains, which are categorized as “unhealthy” by the plant-based diet index; and limiting added oils and nuts, which the same index classifies as “healthy.”
“Our research shows that even when a low-fat vegan diet includes so-called unhealthy plant-based foods — as defined by the plant-based diet index — like refined grains and potatoes, it’s better than the Mediterranean diet for weight loss, because it avoids animal products and added oils,” says Hana Kahleova, MD, PhD, director of clinical research at the Physicians Committee for Responsible Medicine and lead author of the study.
How the Diets Were Compared
This analysis builds on a previous Physicians Committee study that directly compared a low-fat vegan diet with a Mediterranean diet. In that trial, 62 adults with excess weight were randomly assigned to one of the two eating patterns for 16 weeks. The vegan plan included fruits, vegetables, grains, and beans, while the Mediterranean plan featured fruits, vegetables, legumes, fish, low-fat dairy, and extra-virgin olive oil. No calorie restrictions were placed on either group.
After the first 16 weeks, participants returned to their usual diets for a four-week break and then switched to the opposite plan for another 16 weeks. Results from the original study showed that the vegan diet led to greater weight loss and improvements in body composition, insulin sensitivity, and cholesterol levels.
Understanding the Plant-Based Diet Index
In the secondary analysis, researchers examined participants’ dietary logs to explore how three scoring systems within the plant-based diet index (PDI, hPDI, and uPDI) related to weight changes on both diets. The PDI system labels foods in the following way:

“Healthful” plant-based foods include fruits, vegetables, whole grains, nuts, legumes, oils, coffee, and tea. “Unhealthful” plant-based foods include fruit juice, sugar-sweetened beverages, refined grains, potatoes, and sweets.
The index assigns scores as follows: PDI: Score increases with more plant-based foods overall. hPDI: Score increases with more “healthful” plant-based foods and fewer “unhealthful” plant-based foods. uPDI: Score increases with more “unhealthful” plant-based foods and fewer “healthful” plant-based foods.What the Scores Reveal About Weight Loss
The analysis showed that PDI scores rose significantly among participants on the vegan diet but stayed the same among those on the Mediterranean diet. The hPDI score increased in both groups, while the uPDI score rose in the vegan group and decreased among those eating the Mediterranean diet.
Only the increases in PDI and uPDI scores, seen exclusively on the low-fat vegan diet, were linked to weight loss. The rise in hPDI scores did not correspond with changes in body weight in either group.
Why the Vegan Diet Produced These Effects
Most of the increase in PDI, hPDI, and uPDI scores on the vegan diet came from removing animal products. Cutting back on oils and nuts also contributed to higher uPDI scores. Together, these patterns indicate that replacing animal-based foods with plant-based options, along with reducing oils and nuts, may be effective strategies for weight management.

Some tumors remain extremely difficult to treat, and carcinomas are among the most challenging. Unlike many other cancers, these tumors can behave unpredictably. Some even shift their appearance and begin to resemble entirely different types of cells found in the human body, such as those in the skin. This unusual ability makes many current treatments far less effective.
“The tumors are notoriously plastic in their cellular identity,” says Cold Spring Harbor Laboratory (CSHL) Professor Christopher Vakoc. In some cases, this shifting identity helps the cancer avoid therapies designed to destroy it.
New Research Reveals Hidden Weaknesses
Recent studies from the Vakoc lab provide important insights into two of these difficult carcinomas. According to Vakoc, the new work exposes weaknesses that could “tee up targets for therapy.”
In research published in Nature Communications, CSHL scientists identified a protein that determines whether pancreatic cancer cells retain their traditional appearance or begin to adopt features similar to skin cells. In a separate study in Cell Reports, the team mapped the crystal structure of another group of proteins that is essential in tuft cell lung cancer.
Linking Past Discoveries to New Therapeutic Possibilities
Vakoc describes this latest development as a full-circle moment for the lab. When tuft cell lung cancer was first identified in 2018, he and his colleagues were searching for epigenetic influences that promote tumor growth. They focused on the mechanisms of transcription and gene regulation rather than the genes themselves. Now, working with CSHL Director of Research Leemor Joshua-Tor, the researchers have uncovered a finding that may eventually lead to an epigenetic therapy capable of halting cancer growth.

These two studies support a long-standing mission in Vakoc’s research program. “We aim to identify the master regulators of cellular identity,” he says. Scientists hope that these “master regulators” could one day serve as the basis for new treatments, similar to the hormone therapies now used for breast and prostate cancers that were once much harder to manage. Although promising, Vakoc notes that this goal will require more time and continued study.
Toward Safer and More Precise Cancer Treatments
If future medicines emerge from these findings, Vakoc hopes they will be designed to target cancer cells while protecting the rest of the body. That principle is reflected in the lab’s current work. In both the pancreatic cancer and lung cancer mouse models they tested, the researchers found no signs of toxicity or harm to major organs. “We’re setting a higher bar for specificity when it comes to new cancer targets and treatments,” Vakoc says.
Their efforts extend beyond developing future therapies. By revealing how cellular identity is controlled and altered in cancer, the team is contributing to a deeper scientific understanding that could help shape a more precise and effective standard of care in the years ahead.
Research Funding: National Cancer Institute, Pershing Square Sohn Cancer Research Alliance, CSHL-Northwell Health Affiliation, Treeline Biosciences, National Institutes of Health, U.S. Department of Defense, Howard Hughes Medical Institute

A new preclinical study from investigators at Weill Cornell Medicine reports that hypertension disrupts blood vessels, neurons and white matter in the brain long before blood pressure rises to detectable levels. These early disruptions may help explain why hypertension is strongly associated with cognitive disorders, including vascular cognitive impairment and Alzheimer’s disease.
The study, published Nov. 14 in Neuron, shows that hypertension can trigger early shifts in gene expression within individual brain cells. Such changes may impair thinking and memory, opening the door to treatments that could simultaneously control blood pressure and protect brain health.
People with hypertension are known to have a 1.2 to 1.5-fold greater risk of developing cognitive problems compared to those without the condition, yet the biological reason for this link has remained unclear. Common hypertension medications can successfully bring high blood pressure under control but often show little benefit for cognition. This pattern suggests that damage to brain blood vessels may occur independently of elevated pressure.
“We found that the major cells responsible for cognitive impairment were affected just three days after inducing hypertension in mice — before blood pressure increased,” said senior author Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute, professor of neuroscience and Anne Parrish Titzell Professor of Neurology at Weill Cornell. “The bottom line is something beyond the dysregulation of blood pressure is involved.”
Dr. Anthony Pacholko, postdoctoral associate in neuroscience at Weill Cornell, co-led the research.
Cellular Vulnerability Revealed Through Advanced Techniques
Earlier work from Dr. Iadecola’s team showed that hypertension can globally disrupt neuronal function. New single-cell analysis tools have now enabled the researchers to examine, in detail, how different brain cell types respond at the molecular level.

To model hypertension in mice, the team used the hormone angiotensin, which raises blood pressure in a manner similar to the condition in humans. They analyzed changes in various brain cells after three days (before blood pressure increased) and after 42 days (when blood pressure was high and cognitive problems were apparent).
Within the first three days, pronounced gene expression changes appeared in endothelial cells, interneurons and oligodendrocytes. Endothelial cells, which line blood vessels, showed signs of accelerated aging, including reduced energy metabolism and increased senescence markers. The team also observed the early weakening of the blood-brain barrier, which normally regulates nutrient flow into the brain and prevents harmful substances from entering. Interneurons, which help balance excitatory and inhibitory nerve signals, were also damaged. This imbalance resembled early patterns seen in Alzheimer’s disease.
Oligodendrocytes, the cells that produce myelin to insulate nerve fibers, expressed fewer genes required for maintaining and regenerating the myelin sheath. When this support declines, neurons eventually lose the ability to communicate efficiently. By day 42, even more gene expression changes had emerged, corresponding with measurable cognitive decline.
“The extent of the early alterations induced by hypertension was quite surprising,” Dr. Pacholko said. “Understanding how hypertension affects the brain at the cellular and molecular levels during the earliest stages of the disease may provide clues to finding ways that can potentially block neurodegeneration.”
Possible Protective Effects of Current Blood Pressure Medication
One medication already used to treat hypertension, losartan, inhibits the angiotensin receptor. “In some human studies, the data suggest that the angiotensin receptor inhibitors may be more beneficial to cognitive health than other drugs that lower blood pressure,” Dr. Iadecola said. In their experiments, losartan reversed early hypertension-related damage in endothelial cells and interneurons in the mouse model.
“Hypertension is a leading cause of damage to the heart and the kidneys, that can be prevented by antihypertensive drugs. So independent of cognitive function, treating high blood pressure is a priority,” Dr. Iadecola said.
Dr. Iadecola’s team is now studying how the accelerated aging of small blood vessels caused by hypertension might lead to dysfunction in interneurons and oligodendrocytes. Ultimately, they hope to find the most effective strategies to prevent or reverse the long-term cognitive consequences associated with the condition.

At the cellular scale, the way muscle tissue repairs itself becomes surprisingly complex. The body does not respond the same way to all forms of damage. A sudden muscle tear from a sports injury differs greatly from the slow decline in muscle strength seen in conditions such as muscular dystrophy.
A research team at Cincinnati Children’s has uncovered a shared and unexpected repair process that may help the body recover from several kinds of muscle damage. The findings were published online on Nov. 21, 2025, in Current Biology. The project was led by first author Gyanesh Tripathi, PhD, and corresponding author Michael Jankowski, PhD, who oversees the Research Division in Cincinnati Children’s Department of Anesthesia and serves as Associate Director of Basic Science Research for the Pediatric Pain Research Center.
The newly identified mechanism involves macrophages, a type of immune cell. These cells are usually known for acting like tiny cleanup crews that remove bacteria, dead cells, and other unwanted material.
A Neuron-Like Repair Signal
“The biggest surprise about this was finding that a macrophage has a synaptic-like property that delivers an ion to a muscle fiber to facilitate its repair after an injury,” Jankowski says. “It’s literally like the way a neuron works, and it’s working in an extremely fast synaptic-like fashion to regulate repair.”
Scientists have long known that macrophages respond to muscle injury by releasing cytokines and chemokines that create inflammation, influence pain, and help drive the growth and regeneration of muscle fibers.
Searching for Pain Relief Leads to a Different Breakthrough
The research team originally aimed to uncover ways to ease pain during recovery after surgery. They were looking for clues that could eventually reduce the need for pain medications that carry significant side effects.

Although they did not find a new approach for pain relief, they identified a process that makes muscle repair occur more quickly. This discovery may support the development of future treatments for muscle wasting and acute injuries. The findings also suggest that macrophages might eventually serve as specialized “delivery vehicles” for cell-based therapies targeting a wider range of medical conditions.
“These are infiltrating macrophages, a very specific type. They’re not ones already residing in the tissue. These come in after damage occurs,” Jankowski says.
Real-Time Evidence of Rapid Muscle Activation
In experiments that used mouse models of two different injury types, researchers examined how macrophages interact with the myofibers that form muscle tissue. They were even able to capture key moments of this activity as it occurred.
By using brief bursts of a designer chemical to activate the macrophages, the team observed these immune cells forming synaptic-like contacts with myofibers. The macrophages then released calcium ions directly to the muscle fibers, accelerating early stages of healing. Within 10 to 30 seconds, the researchers measured bursts of electrical activity inside the damaged muscle.
“This occurs in a very rapid fashion. You can activate the macrophage and make the muscle twitch subtly almost immediately,” Jankowski says.

Healing Effects Seen in Both Injury and Disease Models
The same type of macrophage-driven signaling also helped mice with disease-like muscle damage. After recognizing the injury, the immune cells gathered at the site and triggered waves of activity in the muscle fibers. After 10 days, mice that received this treatment had substantially more new muscle fibers than mice in the control group.
“A similar synaptic-like response worked in both scenarios,” Jankowski says.
Next Research Steps
More work is needed to determine whether human macrophages behave the same way when muscle is injured. If they do, researchers will still need to learn how to guide or control the process in ways that could be safely used as therapy.
The team is also interested in an unexpected outcome: although the infiltrating macrophages sped up healing, they did not appear to reduce acute pain. Understanding why this occurs may help explain why about 20% of children who undergo surgery continue to experience lingering pain afterward.
Looking ahead, the researchers want to explore whether macrophages can deliver other helpful signals or materials to muscle cells.
Cincinnati Children’s co-authors include Adam Dourson, PhD, Fabian Montecino-Morales, PhD, Jennifer Wayland, MS, Sahana Khanna, Megan Hofmann, Hima Bindu Durumutla, MS, Thirupugal Govindarajan, PhD, Luis Queme, MD, PhD, and Douglas Millay, PhD. The Bioanalysis and Imaging Facility at Cincinnati Children’s also contributed to the work.
Funding for this research came from grants provided by the National Institutes of Health (R01NS105715, R01NS113965, R61/R33AR078060, R01AR068286, R01AG082697) and the Cincinnati Children’s Hospital Research Foundation.

Chronic constipation becomes more common with age. Researchers from Mass General Brigham conducted a new study examining whether five widely followed diets could help prevent chronic constipation in middle- and older-age adults. The team monitored more than 96,000 participants for several years to see how long-term eating habits influenced the likelihood of developing this persistent gastrointestinal issue. Their analysis showed that people who routinely ate a Mediterranean or plant-based diet experienced a lower incidence of constipation. The findings appear in Gastroenterology.
“Chronic constipation affects millions of people and can significantly impact a patient’s quality of life,” said senior author Kyle Staller, MD, MPH, of the Division of Gastroenterology at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system. “Our findings suggest that as we age, certain healthy diets may provide benefits to our gut beyond the known cardiovascular benefits.”
Healthy Eating Patterns and Risk Reduction
Previous research has demonstrated that healthy diets can ease constipation symptoms, but this study is the first to show that some diets may actually prevent chronic constipation from developing. “We have always assumed that the benefits of eating a healthy diet would be driven by fiber, but our analyses showed the benefit of these healthy diets on constipation were independent of fiber intake,” said Staller.
Using information from the Nurses’ Health Study, Nurses’ Health Study II and the Health Professionals Follow-Up Study, the investigators evaluated long-term dietary patterns in middle- and older-age adults and identified who later experienced chronic constipation, which was defined as symptoms lasting at least 12 weeks within a year. The study assessed five diets: the Mediterranean diet, plant-based diet, low-carb diet, Western diet and inflammatory diet. Participants who consistently consumed a Western or inflammatory diet were more likely to develop chronic constipation, while those who followed a low-carb diet did not show a strong effect on constipation risk.
Key Dietary Takeaways
“Our findings suggest a diet rich in vegetables, nuts and healthy fats may help prevent chronic constipation in middle- and older-age adults,” said Staller.
Authorship: In addition to Staller, Mass General Brigham authors include Braden Kuo, Madeline Berschback and Andrew T. Chan.
Disclosures: Andrew T. Chan served as a consultant for Pfizer Inc., and Boehringer Ingelheim. Kyle Staller has received research funding from Ardelyx and ReStalsis and has served as a consultant to Ardelyx, Gemelli Biotech, Laborie, Mahana, ReStalsis, Salix, and Takeda. Braden Kuo has been a consultant to Ironwood, Takeda, Atmo, Restalsis, Pahthom. No other disclosures were reported.
Funding: This work was supported by the National Institutes of Health (U01 CA167552, UM1 CA186107, P01 CA87969, U01 CA176726, K23DK120945).