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19 minutes agoShareSaveChloe HaywardShareSaveShutterstock”We just wanted a relaxing conversation with our dad and we weren’t able to have one,” says Jack Blumenthal. “It was horrible. And it was constant.”Raw pain is etched on Jack’s father’s face as he finally realises how his undiagnosed mental illness – and erratic manic behaviour – hurt the ones he loves the most.In a new BBC documentary, celebrity chef Heston Blumenthal is talking to his son for the first time about how he became impossible to live with.”We’d plan it three weeks in advance, getting prepared just to see you for half an hour,” says Jack, who now runs a restaurant himself. “And there was nothing I could do to help you.”Heston wipes a tear away. “I’m sorry,” he says.’Wired differently’At the height of his fame in the 2000s, Heston Blumenthal was a culinary icon. Known for bacon-and-egg ice cream, snail porridge, and theatrical dining, he was a big brand worth big bucks. But behind the molecular gastronomy and Michelin stars, his mind was increasingly in turmoil.For years, he thought he was simply “wired differently”.Heston had long believed his emotional highs and lows were just part of who he was – part of the creative chaos that fuelled his culinary genius. In the early years, his imagination ran riot in a positive way, he says.But gradually, the depression worsened. The highs became higher and the lows much darker.He recalls having to “lie on the floor to cope” during the filming of a cooking programme several years ago. At one point, he felt as though his new ideas were like thousands of sweets falling from the sky – and he could only catch a few.But in late 2023, a manic episode escalated into psychosis. Heston was hallucinating guns and had become obsessed with death.He was admitted to hospital for the first time – and finally diagnosed with bipolar disorder. “How did I get to 57 years-old before I was diagnosed?” he asks.Peter Dench/Getty ImagesI recently sat down with world-renowned psychiatrist Prof John Geddes to watch a new BBC new documentary I’d been collaborating on – “Heston: My Life with Bipolar”.In the programme there’s a clip of Heston being interviewed by the BBC in 2020 about using robots in the kitchen. He uses surreal, nonsensical metaphors: “I want to put the shadow back into the sunlight, I want to put the inside out back into the outside in… I want to put the being back into the human.”Watching the interview, Prof Geddes says it’s clear Heston was “in the midst of mania” at the time. “If I’d seen that then I would have immediately thought, ‘That is a sick man’,” he says.The high-octane celebrity chef’s environment allowed his erratic behaviour to thrive. His eccentricity wasn’t only accepted, but celebrated. His brand flourished, nurturing the capricious genius, and he was supported by a team that kept him functioning. But at home there was no such infrastructure – no such buffer.Research from Bipolar UK suggests that for every person with bipolar disorder, a further five family members – like Heston’s son Jack – are profoundly affected.”Families fall apart because of the mania more than the depression,” says Prof Geddes.Lithium lifelineDuring six months of filming, Heston’s psychiatrists wean him off the cocktail of pills prescribed to him after his hospital visit, and he is moved onto the mood-stabilising medicine, lithium.This isn’t an easy process. Changing medications can offer trigger extreme reactions, so to do it on camera is brave.Initially, Heston is subdued. He says the antipsychotics and antidepressants make him feel “zombified” and his memories are clouded.But as time passes his mood lifts, his energy returns, and he regains some of his old swagger. Lithium is working for him – and you start to recognise the Heston of years gone by.Towards the end of filming the documentary, Heston is keen to ask me about my own research into bipolar care in the UK.The man I speak to is definitely still Heston – obsessing over the perfect peppercorn ratio – but now he’s calm, focused, and self-aware.Prof Geddes isn’t surprised.”Lithium is the gold standard of care, but in the UK we don’t use it enough,” he says. “It requires careful management from GPs and psychiatrists. In the NHS, the system simply can’t keep up – that’s probably one of the reasons why lithium use is falling in the UK, when it should be rising.”The UK has a stark shortage of psychiatrists and mental health professionals so patients face waits that often stretch over years. On average it takes someone more than nine years to be diagnosed with bipolar disorder from first contact with a GP.During my many interviews about the disorder, I heard psychiatrists describe bipolar patients as “ghosts in the system”, “the ones that fell through the cracks” and simply as “forgotten” or “let down”.Lithium use, and timely access to psychiatrists are both directly linked to a reduction in suicidal thoughts in people with bipolar disorder. In the UK, death by suicide is rising for people living with the illness. This bucks all other downward trends for suicide.Learning to live with the fireHeston’s diagnosis came only after he became a danger to himself – hallucinations, paranoia, and eventually a call from his wife to emergency services.Despite weeks spent in a mental health clinic, and a year of medication and rebuilding his mind, given the choice Heston says he wouldn’t turn off his bipolar disorder if he could. It is a part of him. This answer captures the essence of his journey – of learning to live with the fire, not extinguish it.”Someone living with bipolar cannot be separated from it – their personality is entirely and intrinsically connected to the condition,” says Prof Geddes. “Treatment doesn’t erase it, but it does make the mood changes manageable and helps a person function within their ecosystem – with their family, friends and job.”Heston’s journey mirrors that of many: misunderstood mood swings, delayed diagnosis, and the long road to balance. But it’s also a story of identity, resilience, and the power of clarity after chaos.The culinary world once masked his illness. Now, it gives him a platform to speak out – and he’s using it.If you have been affected by any issues in this report, help and support is available at BBC Action Line.

After firing an influential panel that sets U.S. vaccine policies, some of Mr. Kennedy’s picks to replace them have filed statements in court flagging concerns about vaccines.Three of the new advisers appointed by Health Secretary Robert F. Kennedy Jr. to guide the government on immunization policy took part in lawsuits casting doubt on the safety or efficacy of vaccines, public records show.In dismissing all 17 members of an influential Centers for Disease Control and Prevention advisory panel on Monday, Mr. Kennedy cited what he said was a history of conflicts of interest that he claimed made those experts a “rubber stamp” on approving vaccines. But adding members who assisted in legal cases that were either against vaccine makers or that suggested widespread vaccine-caused harm raises questions about a different form of potential bias.While the legal involvement of the three new panelists does not appear to violate the rules, critics of Mr. Kennedy said it created the appearance of a conflict.“He’s invoking the language of ethics and integrity to get rid of these experts and now is installing people who may have their own biases — that he apparently does not want to recognize,” said Kathleen Clark, a law professor and ethics expert at Washington University in St. Louis.One of Mr. Kennedy’s appointees, Vicky Pebsworth, is a nurse who serves on the board of a nonprofit dedicated to raising awareness about vaccine injuries. She certified to a court that, in her professional opinion, a survey of families of unvaccinated children supported the hypothesis that a rise in the number of recommended childhood vaccines explained an epidemic of chronic disease. Mr. Kennedy has espoused the same theory.Another, Dr. Robert Malone, a physician and biochemist whose criticism of mRNA Covid-19 vaccines catapulted him into the spotlight during the pandemic, was a paid expert witness on behalf of company whistle-blowers who claimed that Merck, one of the nation’s largest vaccine manufacturers, had covered up evidence casting doubt on the effectiveness of the mumps vaccine.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.

16 minutes agoShareSavePhilippa Roxby and Smitha MundasadHealth reportersShareSaveGetty ImagesPollen levels are forecast to be high or very high in many parts of the UK over the next five days.The fine powder released by certain grasses, trees and plants is causing chaos for the many who’re allergic to pollen.Itchy eyes, sneezing, dripping noses, scratchy throats and headaches are a common complaint.So what can you do to feel better?Why are my eyes streaming?If you’re sneezing hundreds of times day, your eyes are watering and you’re sleeping badly then it’s probably hay fever.You’re not alone – around one in five people are allergic to pollen and the culprit is usually grass, although trees can also trigger symptoms. Early summer is often peak pollen season, when the number of grains of pollen in the air multiplies.This year the warm weather in the UK, plus last year’s too, means conditions have been ideal for birch tree pollen – a major hay fever trigger. Recent warm, dry days in some parts of the UK have helped spread pollen through the air, creating what’s been dubbed a ‘pollen bomb’.Cities often have lower pollen counts than rural areas, but pollution in urban areas can make symptoms worse.In the long term, it’s likely that a changing climate will have an impact on hay fever.Changing temperatures and rainfall could make the pollen season longer and increase the concentration of pollen in the air.What are the best hay fever treatments?Getty ImagesThere’s no cure for hay fever, but there are medicines you can take to feel a bit better.Allergy expert Professor Stephen Till, from Guy’s and St Thomas’ Hospitals in London, recommends “a cocktail approach”.That means taking: antihistamine tablets or drops that don’t tend to make you feel sleepy and are long actingplus a steroid nasal sprayand eye drops”They all work in different ways and are all very safe for most people – just go to a pharmacy for advice,” Prof Till says. These products can all be bought over the counter in your local chemist. Some types work better for some people than others, and prices vary, so it’s important to try lots of different ones.Antihistamine medicines help dampen down your body’s allergic reaction to pollen. You can start taking them three or four days beforehand.One idea is to keep a diary of symptoms and medicines, so you can tell the pharmacist what you’ve already tested out.What else can I do to reduce symptoms?Avoiding hay fever triggers is essential too, says pharmacist Ashley Cohen from Leeds.”I always say it’s about good hygiene – pollen sits on your face and arms when you go outside, so have a shower and change your clothes when you come in.”And he warns that pets are “brilliant vehicles” for bringing pollen into your house.Other things the NHS says you can do include:putting nasal balms or jelly around you nostrils to trap pollenwearing sunglasses, mask or a cricket hat to stop pollen getting into your nose and eyesvacuuming and dusting your home regularlytrying out a pollen filter in the air vents of your carAlso, try to avoid:cut grass or walking on grasskeeping fresh flowers in the housesmoking or being around smokersdrying clothes outsideGetty ImagesWhat if my hay fever gets really bad?”Ninety percent of people with hay fever can be managed with over-the-counter medication,” says pharmacist Ashley Cohen.If your hay fever becomes really debilitating, then you’ll need to see your GP who can refer you to specialist – but that will mean waiting for a while.Immunotherapy treatment might be available for the worst affected. That’s when tiny amounts of pollen are injected into the body over time to get it used to the substance, so that it no longer overreacts.The NHS stopped offering the steroid injection Kenalog years ago for hay fever because of the risk of serious side-effects. The charity Allergy UK does not recommend anyone use it either, and private clinics are no longer allowed to advertise the drug.Does local honey help hay fever?Afraid not. Bees don’t pollinate grass and trees – they pollinate flowers, which don’t cause hay fever.So there’s no evidence that spreading local honey on your toast will help hay fever caused by grass and tree pollens.

With two extraordinary moves, Health Secretary Robert F. Kennedy Jr. has upended the certainty that American children will always have cost-free access to lifesaving vaccines.For decades, a little-known scientific panel at the Centers for Disease Control and Prevention has recommended which shots Americans should get and when. The group’s endorsement means insurance companies must cover the costs and helps states decide which vaccines to mandate for school-age children.The panel, the Advisory Committee on Immunization Practices, also determines which shots are provided for free through the Vaccines for Children program, which serves about half of the children in the United States.On Monday, Mr. Kennedy, long a vaccine skeptic, fired all 17 members of A.C.I.P., claiming that the group was rife with conflicts of interest and that a clean sweep was needed to restore public trust. Mr. Kennedy also reassigned C.D.C. staff scientists who oversee the panel’s work and vet its members.On X, he promised not to replace the panel’s experts with “ideological anti-vaxxers.” On Wednesday, Mr. Kennedy named eight new members, at least half of whom have expressed skepticism of certain vaccines. Only one was a widely recognized expert in vaccines.For years, Mr. Kennedy has argued that American children receive too many shots and has falsely claimed that vaccines are not tested in placebo-controlled studies. Critics fear he is now setting the stage for a rollback of federal recommendations.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.

In a compelling Genomic Press Interview published today in Brain Medicine, Sophia Shi, PhD, unveils her pioneering research that fundamentally changes our understanding of brain aging and opens revolutionary therapeutic pathways for Alzheimer’s disease and related neurodegenerative conditions.
Uncovering the Brain’s Hidden Shield
Dr. Shi’s groundbreaking work focuses on the glycocalyx, a complex “forest” of sugar molecules coating blood-brain barrier endothelial cells. Her research, recently published in Nature, demonstrates that this protective layer deteriorates dramatically with age, leading to blood-brain barrier dysfunction and neuroinflammation, key drivers of cognitive decline and neurodegenerative diseases.
“The glycocalyx acts like a protective shield for the brain’s blood vessels,” Dr. Shi explains. “When we restored these critical sugar molecules in aged mice, we saw remarkable improvements in both barrier integrity and cognitive function.” This discovery represents the first time scientists have successfully reversed age-related blood-brain barrier dysfunction through glycocalyx restoration.
From Puzzles to Proteins: A Scientific Journey
Dr. Shi’s path to this breakthrough began with childhood fascinations with puzzles and pattern recognition, skills that would later prove invaluable in decoding the complex language of glycosylation. Working under the mentorship of Nobel laureate Carolyn Bertozzi and renowned neurobiologist Tony Wyss-Coray at Stanford, she bridged two distinct fields, glycobiology and neuroscience, to tackle questions others had overlooked.
Her interdisciplinary approach faced significant challenges. How do you study molecules so structurally complex that they’ve resisted traditional analysis methods? What techniques can capture the dynamic nature of glycosylation in living brain tissue? Dr. Shi’s innovative solutions to these problems exemplify the power of cross-disciplinary thinking in modern biomedical research.

Recognition and Research Excellence
The impact of Dr. Shi’s work extends far beyond the laboratory. Her research garnered the prestigious David S. Miller Young Scientist Award at the Cerebral Vascular Biology Conference, recognizing her as one of the field’s most promising young investigators. Perhaps more remarkably, she is launching her independent laboratory at Harvard’s prestigious Rowland Institute directly from doctoral training — a rare achievement that speaks to the transformative potential of her discoveries.
“Post-translational modifications like glycosylation have been understudied for too long,” Dr. Shi notes. “These modifications can completely transform protein function, yet we’re only beginning to understand their role in brain health and disease.” Her work positions glycoscience at the forefront of neurodegeneration research, challenging long-held assumptions about therapeutic targets.
Therapeutic Implications and Future Directions
The therapeutic implications of Dr. Shi’s findings are profound. By identifying specific mucin-type O-glycans as critical for blood-brain barrier integrity, her research provides concrete molecular targets for drug development. This precision approach could lead to treatments that address the root causes of neurodegeneration rather than merely managing symptoms.
Intriguing questions emerge from this work: Can glycocalyx restoration prevent or slow Alzheimer’s disease progression in humans? How early in the aging process do these protective molecules begin to deteriorate? What environmental or genetic factors influence glycocalyx health throughout the lifespan? These questions will drive the next phase of Dr. Shi’s research program at Harvard.

Building an Inclusive Scientific Future
Beyond her scientific contributions, Dr. Shi is committed to fostering diversity in science. “It’s easy to feel isolated or like you don’t belong in science, especially without early exposure or role models,” she reflects. Her dedication to mentoring and creating inclusive research environments promises to amplify her impact by inspiring the next generation of interdisciplinary scientists.
The interview reveals how personal experiences shape scientific pursuits. Dr. Shi’s appreciation for hiking and trail running mirrors her approach to research: seeking new perspectives from challenging vantage points. This blend of rigorous science with human experience characterizes the new generation of biomedical researchers.Implications for Brain Medicine
Dr. Shi’s discoveries raise fundamental questions about how we approach brain aging and disease. If glycocalyx deterioration is a common pathway in multiple neurodegenerative conditions, could targeting these molecules provide a unified therapeutic strategy? How might lifestyle factors influence glycocalyx health? These considerations could reshape preventive medicine approaches for brain health.
The transition from viewing the blood-brain barrier as a simple wall to understanding it as a dynamic, sugar-coated interface represents a paradigm shift in neuroscience. This new perspective demands innovative research approaches and may explain why previous therapeutic strategies targeting the barrier have shown limited success.
Dr. Sophia Shi’s Genomic Press interview is part of a larger series called Innovators & Ideas that highlights the people behind today’s most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that explore the scientist’s impact on the field, while also touching on broader human themes.

Your breath is one of a kind. A study published June 12 in the Cell Press journal Current Biology demonstrated that scientists can identify individuals based solely on their breathing patterns with 96.8% accuracy. These nasal respiratory “fingerprints” also offer insights into physical and mental health.
The research stemmed from the lab’s interest in olfaction, or the sense of smell. In mammals, the brain processes odor information during inhalation. This link between the brain and breathing led researchers to wonder: since every brain is unique, wouldn’t each person’s breathing pattern reflect that?
To test the idea, the team developed a lightweight wearable device that tracks nasal airflow continuously for 24 hours using soft tubes placed under the nostrils. Most breathing tests last just one to 20 minutes, focusing on evaluating lung function or diagnosing disease. But those brief snapshots aren’t enough to capture subtle patterns.
“You would think that breathing has been measured and analyzed in every way,” says author Noam Sobel of the Weizmann Institute of Science, Israel. “Yet we stumbled upon a completely new way to look at respiration. We consider this as a brain readout.”
Sobel’s team fitted 100 healthy young adults with the device and asked them to go about their daily lives. Using the collected data, the team identified individuals using only their breathing patterns with high accuracy. This high-level accuracy remained consistent across multiple retests conducted over a two-year period, rivaling the precision of some voice recognition technologies.
“I thought it would be really hard to identify someone because everyone is doing different things, like running, studying, or resting,” says author Timna Soroka of the Weizmann Institute of Science. “But it turns out their breathing patterns were remarkably distinct.”
Moreover, the study found that these respiratory fingerprints correlated with a person’s body mass index, sleep-wake cycle, levels of depression and anxiety, and even behavioral traits. For example, participants who scored relatively higher on anxiety questionnaires had shorter inhales and more variability in the pauses between breaths during sleep. Soroka noted that none of the participants met clinical diagnostic criteria for mental or behavioral conditions. The results suggest that long-term nasal airflow monitoring may serve as a window into physical and emotional well-being.
“We intuitively assume that how depressed or anxious you are changes the way you breathe,” says Sobel. “But it might be the other way around. Perhaps the way you breathe makes you anxious or depressed. If that’s true, we might be able to change the way you breathe to change those conditions.”
The current device still faces real-world challenges. A tube that runs under the nose is often associated with illness and may deter adoption. The device also doesn’t account for mouth breathing and can slip out of place when sleeping. The team aims to design a more discreet and comfortable version for everyday use.
Soroka and Sobel are already investigating whether people can mimic healthy breathing patterns to improve their mental and emotional states. “We definitely want to go beyond diagnostics to treatment, and we are cautiously optimistic,” says Sobel.

A new study to be presented at the SLEEP 2025 annual meeting found that teens who get moderate — but not excessive — catch-up sleep on weekends have fewer symptoms of anxiety.
Results show that teens who got up to two more hours of sleep on weekends than on weekdays exhibited fewer anxiety symptoms compared with those who did not sleep longer on weekends. However, longer durations of catch-up sleep on weekends were associated with slightly more internalizing symptoms.
“The results show that both sleeping less on weekends than weekdays and sleeping substantially more on weekends were associated with higher anxiety symptoms,” said lead author Sojeong Kim, a doctoral candidate in the department of clinical psychology and psychology graduate advisor at the University of Oregon in Eugene. “In contrast, moderate catch-up sleep — defined as less than two hours — was associated with lower anxiety symptoms, suggesting that some weekend recovery sleep may be beneficial.”
The American Academy of Sleep Medicine recommends that teenagers 13 to 18 years of age should sleep 8 to 10 hours on a regular basis to promote optimal health. However, CDC data show that only 23% of high school students get sufficient sleep on an average school night.
“Many teens try to make up for lost sleep by sleeping in on weekends,” Kim said.
Consistently getting sufficient sleep is associated with better health outcomes including improved attention, behavior, learning, memory, emotional regulation, quality of life, and mental and physical health. In contrast, insufficient sleep in teenagers is associated with increased risks of problems such as depression and suicidal thoughts.
The study involved 1,877 adolescents with a mean age of 13.5 years. Sleep duration was estimated using Fitbit devices, while internalizing symptoms were assessed using the Child Behavior Checklist survey. Weekend catch-up sleep was calculated as the difference between weekend and weekday sleep duration.

Kim noted that it is important to identify the right amount of catch-up sleep that is beneficial to teens who restrict their sleep during the week.
“Too little or too much sleep variability from weekday to weekend may contribute to the symptoms someone is trying to combat, like physical or mental fatigue and feelings of anxiety,” she said.
The research abstract was published recently in an online supplement of the journal Sleep and will be presented Wednesday, June 11, during SLEEP 2025 in Seattle. SLEEP is the annual meeting of the Associated Professional Sleep Societies, a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.
Abstract Title: The Sweet Spot of Weekend Catch-Up Sleep: A Protective Factor Against Depressive Symptoms?
Abstract ID: 0263

Genetic material shed by tumors can be detected in the bloodstream three years prior to cancer diagnosis, according to a study led by investigators at the Ludwig Center at Johns Hopkins, Johns Hopkins Kimmel Cancer Center, the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health.
The study, partly funded by the National Institutes of Health, was published May 22 in Cancer Discovery.
Investigators were surprised they could detect cancer-derived mutations in the blood so much earlier, says lead study author Yuxuan Wang, M.D., Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine. “Three years earlier provides time for intervention. The tumors are likely to be much less advanced and more likely to be curable.”
To determine how early cancers could be detected prior to clinical signs or symptoms, Wang and colleagues assessed plasma samples that were collected for the Atherosclerosis Risk in Communities (ARIC) study, a large National Institutes of Health-funded study to investigate risk factors for heart attack, stroke, heart failure and other cardiovascular diseases. They used highly accurate and sensitive sequencing techniques to analyze blood samples from 26 participants in the ARIC study who were diagnosed with cancer within six months after sample collection, and 26 from similar participants who were not diagnosed with cancer.
At the time of blood sample collection, eight of these 52 participants scored positively on a multicancer early detection (MCED) laboratory test. All eight were diagnosed within four months following blood collection. For six of the eight individuals, investigators also were able to assess additional blood samples collected 3.1-3.5 years prior to diagnosis, and in four of these cases, tumor-derived mutations could also be identified in samples taken at the earlier timepoint.
“This study shows the promise of MCED tests in detecting cancers very early, and sets the benchmark sensitivities required for their success,” says Bert Vogelstein, M.D., Clayton Professor of Oncology, co-director of the Ludwig Center at Johns Hopkins and a senior author on the study.
“Detecting cancers years before their clinical diagnosis could help provide management with a more favorable outcome,” adds Nickolas Papadopoulos, Ph.D., professor of oncology, Ludwig Center investigator and senior author of the study. “Of course, we need to determine the appropriate clinical follow-up after a positive test for such cancers.”
The study was supported in part by National Institutes of Health grant #s R21NS113016, RA37CA230400, U01CA230691, P30 CA 06973, DRP 80057309, and U01 CA164975. Additional funding was provided by the Virginia and D.K. Ludwig Fund for Cancer Research, the Commonwealth Fund, the Thomas M Hohman Memorial Cancer Research Fund, The Sol Goldman Sequencing Facility at Johns Hopkins, The Conrad R. Hilton Foundation, the Benjamin Baker Endowment, Swim Across America, Burroughs Wellcome Career Award for Medical Scientists, Conquer Cancer — Fred J. Ansfield, MD, Endowed Young Investigator Award, and The V Foundation for Cancer Research. The Atherosclerosis Risk in Communities study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contract numbers 75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, and 75N92022D00005.

Using advanced single-nuclei RNA sequencing (snRNA-seq) and a widely used preclinical model for Alzheimer’s disease, researchers from Mass General Brigham and collaborators at SUNY Upstate Medical University have identified specific brain cell types that responded most to exercise. These findings, which were validated in samples from people, shed light on the connection between exercise and brain health and point to future drug targets. Results are published in Nature Neuroscience.
“While we’ve long known that exercise helps protect the brain, we didn’t fully understand which cells were responsible or how it worked at a molecular level,” said senior author Christiane D. Wrann, DVM, PhD, a neuroscientist and leader of the Program in Neuroprotection in Exercise at the Mass General Brigham Heart and Vascular Institute and the McCance Center for Brain Health at Massachusetts General Hospital. “Now, we have a detailed map of how exercise impacts each major cell type in the memory center of the brain in Alzheimer’s disease.”
The study focused on a part of the hippocampus — a critical region for memory and learning that is damaged early in Alzheimer’s disease. The research team leveraged single-nuclei RNA sequencing, a relatively new technologies that allow researchers to look at activity at the molecular level in single cells for an in-depth understanding of diseases like Alzheimer’s.
The researchers exercised a common mouse model for Alzheimer’s disease using running wheels, which improved their memory compared to the sedentary counterparts. They then analyzed gene activity across thousands of individual brain cells, finding that exercise changed activity both in microglia, a disease-associated population of brain cells, and in a specific type of neurovascular-associated astrocyte (NVA), newly discovered by the team, which are cells associated with blood vessels in the brain. Furthermore, the scientist identified the metabolic gene Atpif1 as an important regulator to create new neurons in the brain. “That we were able to modulate newborn neurons using our new target genes set underscores the promise our study,” said lead author Joana Da Rocha, PhD, a postdoctoral fellow working in Dr. Wrann’s lab.
To ensure the findings were relevant to humans, the team validated their discoveries in a large dataset of human Alzheimer’s brain tissue, finding striking similarities.
“This work not only sheds light on how exercise benefits the brain but also uncovers potential cell-specific targets for future Alzheimer’s therapies,” said Nathan Tucker, a biostatistician at SUNY Upstate Medical University and co-senior of the study. “Our study offers a valuable resource for the scientific community investigating Alzheimer’s prevention and treatment.”
Authorship: In addition to da Rocha and Wrann, Mass General Brigham authors include Renhao Luo, Pius Schlachter, Luis Moreira, Mohamed Ariff Iqbal, Paula Kuhn, Sophia Valaris, Mohammad R. Islam, Gabriele M. Gassner, Sofia Mazuera, Kaela Healy, Sanjana Shastri, Nathaniel B. Hibbert, Kristen V. Moran-Figueroa, Erin B. Haley, Sema Aygar, and Ksenia V. Kastanenka. Additional authors include Michelle L. Lance, Robert S. Gardner, Ryan D. Pfeiffer, Logan Brase, Oscar Harari, Bruno A. Benitez, and Nathan R. Tucker.
Disclosures: Wrann is an academic co-founder and consultant for Aevum Therapeutics. Wrann has a financial interest in Aevum Therapeutics, a company developing drugs that harness the protective molecular mechanisms of exercise to treat neurodegenerative and neuromuscular disorders. Wrann’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies.
Funding: This study was funded in part by the National Institutes of Health (NS117694, AG062904, AG064580, AG072054, HL140187, AG066171, AG057777, AG072464, NS118146, NS127211), Cure Alzheimer’s Fund, Alzheimer Association Research Grant, SPARC Award from the McCance Center for Brain Health, Hassenfeld Clinical Scholar Award, Claflin Distinguished Scholar Award, BIDMC 2023 Translational Research Hub Spark Grant Award, Massachusetts General Hospital Fund for Medical Discovery (2024A022508), ADDF-Harrington

Researchers at Johannes Gutenberg University Mainz (JGU), the Max Planck Institute for Polymer Research and the University of Texas at Austin have identified a form of molecular motion that has not previously been observed. When what are known as ‘guest molecules’ – molecules that are accommodated within a host molecule – penetrate droplets of DNA polymers, they do not simply diffuse in them in a haphazard fashion, but propagate through them in the form of a clearly-defined frontal wave. “This is an effect we did not expect at all,” points out Weixiang Chen of the Department of Chemistry at JGU, who played a major role in the discovery. The findings of the research team have today been published in an article in the prestigious journal Nature Nanotechnology. The new insights are not only fundamental to our understanding of how cells regulate signals, but they could also contribute to the development of intelligent biomaterials, innovative types of membranes, programmable carriers of active ingredients and synthetic cell systems able to imitate the organizational complexity of the processes in living beings. Molecular wave patterns instead of conventional diffusion
It is usually the case that molecules are distributed throughout liquids by means of simple diffusion. For instance, if you add a blue dye to a glass of water, the dye gradually disperses in the liquid, forming soft, blurry color gradients. However, the observed behavior of guest molecules in DNA droplets is quite different. “The molecules move in a structured and controlled manner that is contrary to the traditional models, and this takes the form of what appears to be a wave of molecules or a mobile boundary,” explains Professor Andreas Walther from JGU’s Department of Chemistry, who led the research project.
The research team used droplets made up of thousands of individual strands of DNA, structures that are also known as biomolecular condensates. What is of particular interest in this connection is the fact that the properties of the droplets can be precisely determined with the help of the DNA structures and other parameters, such as the concentration of salts. Moreover, these droplets have their counterparts in biological cells, which are able to employ similar condensates to arrange complex biochemical processes without the need for membranes. “Our synthetic droplets thus represent an excellent model system with which we can simulate natural processes and come to better understand them,” emphasizes Chen. Into their droplets, the researchers introduced specially designed ‘guest’ DNA strands that are able to specifically recognize the inner structure of the droplets and bind to them. According to the team, the intriguing motion of the guest molecules, that they have now detected for the first time, is in part attributable to the way that the added DNA and the DNA present in the droplets combine on the basis of the key-and-lock principle. This means that the surrounding material becomes less dense and no longer fixed in place, so that swollen, dynamic states develop locally. Chen adds: “The well-defined, highly concentrated front continues to move forward in a linear fashion over time, driven by chemical binding, material conversion and programmable DNA interactions. Something that is completely new when it comes to soft matter.”
New basis for understanding cellular processes
The findings are not only relevant to providing us with a better understanding of the physics of soft matter, but also to improving our knowledge of the chemical processes that occur in cells. “This might be one of the missing pieces of the puzzle that, once assembled, will reveal to us how cells regulate signals and organize processes on the molecular level,” states Walther. This would also be of interest when it comes to the treatment of neurodegenerative disorders in which proteins migrate from cell nuclei into the cytoplasm, forming condensates there. As these age, they transform from a dynamic to a more stable state and build the problematic fibrils. “It is quite conceivable that we may be able to find a way of influencing these aging processes with the aid of our new insights, so that, over the long term, an entirely new approach to the treatment of neurodegenerative diseases could emerge,” concludes Walther.