Category: News

Family physicians who report feeling burned out are nearly 1.5 times more likely to change practices or stop practicing medicine entirely than their peers who don’t report burnout, a study by Weill Cornell Medicine researchers found. Physician burnout can include emotional exhaustion, detachment from patients and colleagues, and feeling that work is no longer meaningful.

The findings, published March 30 in JAMA Internal Medicine, also highlight the consequences for patients: people who lose their family physician may be more likely to visit the emergency room, spend more on health care and be less satisfied with their care than those who keep their doctors.

“To our knowledge, this is the first national-level study examining the association between physician burnout and turnover,” said Dr. Amelia Bond, associate professor of population health sciences at Weill Cornell Medicine, who co-led the study.

To quantify burnout, Dr. Bond and her colleagues turned to the 2016-2020 American Board of Family Medicine surveys, which family physicians must complete to obtain and maintain board certification. As part of the survey, physicians are asked whether they feel burned out or callous.

The researchers then determined whether physicians changed practices or stopped practicing altogether in the subsequent year, based on billing patterns in de-identified Medicare data.

Of the nearly 20,000 physicians in the study, 43.5% reported burnout. Doctors under the age of 55 were more likely to report burnout than older doctors, and women were more likely to report burnout than men.

The research suggests that workplace stress may reduce physician retention. Among physicians who reported burnout, 4.8% changed practices versus 3.4% of physicians who did not report burnout; 5.4% of physicians with burnout stopped practicing entirely compared to 3.7% of physicians without burnout.

“These findings highlight the urgent need to address work conditions and professional satisfaction for both the stability of the physician workforce and the well-being of patients,” said Dr. Dhruv Khullar, associate professor of population health sciences at Weill Cornell Medicine and co-lead on the study.

Physician burnout and turnover have clinical, organizational and economic implications. “The issue definitely warrants more attention,” Dr. Bond said.

Further investigation could identify practices, systems and policy factors that may reduce rates of physician burnout and turnover. While this study found a correlation, additional work will be needed to establish a causal link between burnout and turnover.

Childhood obesity has been increasing in recent years. According to the U.S. Centers for Disease Control, about one in five children and teenagers in the United States met the clinical definition of obesity in 2024.

Midwives across the world are under growing pressure, with many reporting exhaustion, stress and a desire to leave the profession.

Australia is no exception. A 2024 national review commissioned by the Nursing and Midwifery Board of Australia found the country’s midwifery workforce is in “crisis,” and revealed that one in three midwives are considering leaving due to burnout, stress and low job satisfaction.

In light of these pressures, new research from the University of Technology Sydney (UTS) has found that regular Group Clinical Supervision (GCS) can meaningfully reduce burnout among midwives working in public maternity services.

The study titled, The effect of group clinical supervision on the burnout levels among midwives: A cluster randomised controlled trial was recently published in the journal BMC Pregnancy and Childbirth.

Lead author Professor Christine Catling said the findings arrive at a critical moment for the profession.

“Midwives carry a significant emotional and physical load,” she said.

“Support that allows them time to pause and reflect on the challenges they face can make the daily pressures more manageable.”

The UTS‑led trial followed almost 2000 midwives across 12 public maternity services in NSW over more than two years.

Midwives at intervention sites were offered monthly, hour‑long GCS sessions facilitated by trained senior midwifery academics.

Each session provided a confidential setting where small groups could reflect on their experiences and develop strategies for managing the emotional demands of their work.

After adjusting for key demographic and workplace factors, the study showed that access to GCS led to lower overall burnout, with a statistically significant reduction in work‑related burnout.

“The improvement was modest yet meaningful, demonstrating that structured, reflective support can help midwives manage the pressures of their work,” said Professor Catling.

The benefits of the program also extended beyond individual sessions.

“Midwives told us that simply knowing the support was available made them feel more valued, creating a sense that their wellbeing mattered to the organization.”

Previous research has shown that early‑career midwives are the most likely to leave the profession, reporting higher burnout and stronger intentions to leave than experienced colleagues.

At the same time, many older midwives have accelerated their retirement plans following the COVID‑19 pandemic. This combination has created skill-mix gaps and increased workloads.

“Burnout can lead to depersonalization and compassion fatigue, which makes it harder for midwives to offer the level of care they want to provide.”

“When midwives don’t get the support they need, this can affect the quality of care they give to parents, which makes structured workplace support more important than ever” she said.

“Group Clinical Supervision offers consistent support that quick‑fix wellbeing activities like lunchtime yoga sessions simply can’t provide.”

The researchers suggest that scaling up GCS across maternity services and offering more frequent sessions or consistent closed groups could deepen the benefits observed.

While the program was effective, Professor Catling emphasized that broader reforms are also essential.

“We need safer staffing levels, improved skill mix and workplace culture, as well as flexible models of care.

“But while those changes are developed, we cannot ignore the everyday realities facing midwives. Programs like GCS offer a clear and achievable way to support the workforce now,” said Professor Catling.

“Midwives play an irreplaceable role in ensuring safe, high‑quality maternity care.

“It’s time to provide them with the same level of care and compassion they give others every day.”

A new study has found that a prebiotic fiber supplement reduced pain, improved grip strength, and lowered pain sensitivity in people with knee osteoarthritis (OA) – with far fewer dropouts than a digital physiotherapy program.

The INSPIRE clinical trial, led by experts at the University of Nottingham, showed that taking a daily supplement of inulin- a natural dietary fiber found in chicory root, Jerusalem artichokes and other vegetables – significantly reduced pain in people with OA.

The results, which are published in the journal Nutrients, suggest that improving gut health could be a promising new approach to managing one of the most common and debilitating chronic conditions in older adults.

Knee OA affects hundreds of millions of people worldwide and is a leading cause of pain and disability, particularly in older adults. Current treatment options rely heavily on pain medications, which carry risks of side effects, or exercise program’s, which many patients struggle to maintain.

“This study raises the exciting possibility that a simple dietary change – adding a fiber supplement to your breakfast or yogurt – could meaningfully reduce pain and improve physical function,” said Dr. Afroditi Kouraki, lead author of the study from the School of Medicine at the University of Nottingham.

The gut microbiome – the trillions of bacteria living in our digestive system, plays a wide-ranging role in people’s health, including how we experience pain. Inulin acts as a prebiotic, meaning it feeds beneficial gut bacteria. This leads to the production of short-chain fatty acids (SCFAs), particularly a compound called butyrate, which can influence inflammation and pain pathways throughout the body.

In the INSPIRE trial, participants who took inulin showed increased levels of both butyrate and glucagon-like peptide-1 (GLP-1) — a hormone released by the gut that has been linked to pain regulation and muscle health. Higher GLP-1 levels were associated with improved grip strength, pointing to a possible gut-muscle connection that could open up exciting new avenues of research.

The six-week randomized controlled trial involved 117 adults with knee OA and tested four groups: inulin alone, digital physiotherapy-supported exercise (PSE) alone, a combination of both, and a placebo. Both inulin and physiotherapy independently reduced knee pain. However, inulin uniquely improved grip strength and reduced pain sensitivity, measures linked to how the nervous system processes pain, while physiotherapy did not.

Strikingly, the dropout rate for the inulin group was just 3.6%, compared to 21% for those in the physiotherapy group – suggesting that a daily dietary supplement may be easier for people to stick with than an exercise program.

Dr Kouraki said: “Our findings suggest that targeting gut health with a prebiotic supplement is a safe, well-tolerated, and effective way to reduce pain in people with knee osteoarthritis. The very low dropout rate compared to the exercise group is also encouraging from a public health perspective — people were able to fit this supplement easily into their daily lives.”

Senior author Professor Ana Valdes from the School of Medicine added: “The link we observed between GLP-1 and grip strength is particularly intriguing and points to a broader gut-muscle-pain axis that warrants further investigation. This could have implications not just for osteoarthritis, but for understanding how gut health influences ageing and physical resilience more broadly.”

Professor Lucy Donaldson, Director of Research at Arthritis UK said: “The pain of arthritis can severely impact quality of life. Our recent lived experience survey showed that six  in ten people are living in pain most or all of the time due to their arthritis.

“Researchers are starting to explore the role of the gut microbiome in our experience of pain. This exciting preliminary research highlights how diet and physiotherapy can act in different ways to have benefits for people with arthritis. We know a variety and balance of healthy foods, including fiber, and regular physical activity matter, and we’re glad to be supporting research that explores how they work to help people with arthritis.”

The full study can be found here.

As the use of injectable GLP-1 drugs continues to rise, questions persist about what happens after patients stop taking them in real-world settings.

A new Cleveland Clinic analysis of nearly 8,000 patients suggests that discontinuing semaglutide and tirzepatide, on average, does not lead to significant weight regain in clinical practice, as many patients later restart the original medication or try an alternative obesity treatment.

New Cleveland Clinic study reveals real world insights

In one of the largest real-world studies to date examining obesity treatment use and long-term weight changes after GLP-1 discontinuation, researchers at Cleveland Clinic found that many patients successfully stabilized their weight after one year through alternative treatments and therapeutic lifestyle interventions.

The findings, published in the journal Diabetes, Obesity and Metabolism, provide real-world context to previous randomized clinical trials indicating that patients who stopped semaglutide (sold under the brand names Ozempic/Wegovy) and tirzepatide (sold under the brand names Mounjaro/Zepbound) regained more than half of the weight they lost within 12 months.

Hamlet Gasoyan, DS, Ph.D., MPH, a researcher with Cleveland Clinic’s Center for Value-Based Care Research, led the study.

“Our real-world data show that many patients who stop semaglutide or tirzepatide restart the medication or transition to another obesity treatment, which may explain why they regain less weight than patients in randomized trials,” Dr. Gasoyan said.

This retrospective cohort study included 7,938 adult patients with obesity or overweight in Ohio and Florida.  All patients initiated injectable semaglutide or tirzepatide for obesity or type 2 diabetes and stopped the medication within three to 12 months. Dr. Gasoyan and his research team analyzed what treatments patients pursued next and how their weight changed over time.

While patients in the study achieved meaningful weight loss, individual results varied:

• Those treated for obesity lost an average of 8.4% of body weight before discontinuation, and regained an average of 0.5% one year later.
• Those treated for type 2 diabetes lost an average of 4.4% of body weight before discontinuation, and lost an additional 1.3% of body weight one year later.
• In the obesity group, 55% gained weight in the year after discontinuation, while 45% kept losing or stayed the same.
• In the diabetes group, 44% gained weight, while 56% kept losing or stayed the same.

The research group earlier documented two primary drivers that contributed to patients stopping their medication: cost or insurance coverage limitations and side effects, with the former being the dominant reason. Individuals taking the drugs for diabetes were more likely to restart the medication compared with those using them for obesity, a difference associated with more consistent insurance coverage for diabetes-related prescriptions.

Overall, many patients in both groups explored other weight-management treatment options within 12 months of stopping their initial GLP-1 injectable:

•  27% switched to a different medication (including older-generation obesity medications or switching between semaglutide and tirzepatide)
• 20% restarted their original medication
• 14% continued their obesity treatment via lifestyle modification visits with healthcare professionals such as dietitians or exercise specialists.
• Less than 1% transitioned to undergoing metabolic and bariatric surgery.

Researchers say the findings underscore the importance of personalized, ongoing support for patients seeking obesity treatment – even when they stop medication.

“Many patients do not give up on their obesity treatment journey, even if they need to stop their initial medication,” said Dr. Gasoyan. “In our future work, we will examine the comparative effectiveness of alternative treatment options for obesity in patients who discontinue semaglutide or tirzepatide, to help patients and their clinicians make informed decisions.”

Designs for Health®, the practitioner-recommended and preferred brand for high-quality, research-backed supplements, today welcomed a recent decision from the U.S. District Court for the District of Delaware in the matter involving Kaneka Corporation.

The Court’s decision confirms that Designs for Health’s CoQnol 100™ and CoQnol 200™ CoQ10 products currently sold in market do not infringe on a competitive patent and reinforces the company’s science-first approach to developing clinically relevant formulations.

“We are pleased with the Court’s decision, which reinforces the strength of our science-first approach and the rigor behind our formulations,” said Chris Tedesco, Chief Executive Officer of Designs for Health. “Our team has a long-standing commitment to developing high-quality, clinically relevant solutions that practitioners can trust, and this outcome reflects the integrity of that work.”

The outcome underscores Designs for Health’s continued commitment to innovation, quality, and scientific integrity—principles that guide its work in supporting healthcare practitioners and their patients. Through its practitioner-first model, integrated clinical education, and portfolio of 350+ Science-First™ formulations, Designs for Health remains focused on translating innovation into real-world clinical outcomes.

About Designs for Health, Inc.

Family-owned Designs for Health, Inc. offers high-quality nutritional supplements and functional foods to health-care professionals and their patients. Guided by its founding philosophy of “Science-First™,” the company is unwaveringly committed to creating research-driven formulations with meaningful quantities of functional ingredients that maximize the potential for successful health outcomes. For over 36 years, Designs for Health has been many healthcare professionals’ trusted source not only for product innovation but also for leadership in clinical education and practice development solutions. https://www.designsforhealth.com/our-story

Researchers from the University of California San Diego have found that a novel blood-based biomarker can predict a woman’s risk of developing dementia as many as 25 years before symptoms appear. The study, published on March 10, 2026 in JAMA Network Open, shows that higher levels of phosphorylated tau 217 (p-tau217) — a protein linked to the brain changes seen in Alzheimer’s disease — were strongly associated with future mild cognitive impairment and dementia among older women who were cognitively healthy at baseline, meaning at the start of the study before any memory or thinking problems were detected.

“Our study suggests we may be able to identify women at elevated risk for dementia decades before symptoms emerge,” said Aladdin H. Shadyab, PhD, MPH, first author of the study and UC San Diego associate professor of public health and medicine at the Herbert Wertheim School of Public Health and Human Longevity Science and the School of Medicine. “That kind of long lead time opens the door to earlier prevention strategies and more targeted monitoring, rather than waiting until memory problems are already affecting daily life.”

The findings are based on data from 2,766 participants in the Women’s Health Initiative Memory Study, a large national study that enrolled women ages 65 to 79 in the late 1990s and followed them for up to 25 years. All women were cognitively unimpaired when they entered the study. Blood samples collected at baseline were analyzed years later to measure p-tau217, a form of tau protein that reflects early brain changes associated with Alzheimer’s disease.

Over the years of follow-up, researchers identified women who developed memory or thinking problems, including dementia. Those who had higher levels of p-tau217 in their blood at the start of the study were much more likely to develop dementia later in life. In fact, as levels of this biomarker increased, so did dementia risk. Women with the highest p-tau217 levels faced the greatest likelihood of developing dementia over the long term.

However, the researchers also found that risk of cognitive impairment or dementia associated with higher levels of p-tau217 was not the same for everyone. For example, higher p-tau217 levels were more strongly associated with poorer cognitive outcomes among women over age 70 than those younger than 70 years at baseline and among those with the APOE ε4 genetic risk factor for Alzheimer’s disease. The study also found that p-tau217 was more predictive of dementia among women who had been randomized to estrogen plus progestin hormone therapy versus placebo. The strength of the association also differed between white and Black women, but combining p-tau217 with age improved dementia prediction similarly in both groups.

“Blood-based biomarkers like p-tau217 are especially promising because they are far less invasive and potentially more accessible than brain imaging or spinal fluid tests,” said Linda K. McEvoy, PhD, senior author of the study, senior investigator at Kaiser Permanente Washington Health Research Institute and professor emeritus at the Herbert Wertheim School of Public Health. “This is important for accelerating research into the factors that affect risk of dementia and for evaluating strategies that may reduce risk.”

Currently, blood-based biomarkers are not recommended for clinical use in people without symptoms of cognitive impairment. The authors note that additional studies are needed to determine how p-tau217 testing might be used in routine clinical care and whether early identification can meaningfully change outcomes. Future research will also explore how factors such as hormone therapy, genetics and age-related health conditions interact with plasma p-tau217 over the course of someone’s life to affect dementia risk.

“Ultimately, the goal is not just prediction,” Shadyab added, “but using that knowledge to delay or prevent dementia altogether.”

# # #

Link to full study: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2846152

Additional co-authors on the study include: Bowei Zhang, MS; Andrea Z. LaCroix, PhD, MPH; and Steve Nguyen, PhD, from the Herbert Wertheim School of Public Health and Human and Human Longevity Science at UC San Diego. Caroline M. Nievergelt, PhD, and Adam X. Maihofer, PhD, from UC San Diego School of Medicine. Michelle M. Mielke, PhD, and Ramon Casanova, PhD, from Wake Forest University School of Medicine. Susan M. Resnick, PhD, and Luigi Ferrucci, MD, PhD, from the National Institute of Aging. Towia A. Libermann, PhD, from Beth Israel Deaconess Medical Center and Harvard Medical School. Long Ngo, PhD, from Beth Israel Deaconess Medical Center and Harvard T.H. Chan School of Public Health. Alexander P. Reiner, MD, from University of Washington. Danni Li, PhD, from University of Minnesota, Minneapolis. JoAnn E. Manson, MD, DrPH, from Brigham and Women’s Hospital, Harvard Medical School.

Disclaimer: Shadyab reports funding from R01AG079149. Mielke reports receiving funding from U24 AG082930; grants and contracts from NIH (RF1AG69052, RF1AG077386, RF1AG079397, U19 AG078109, U24 AG082930), DOD (W81XWH2110490), Alzheimer’s Association, and Davos Alzheimer’s Collaborative; consulting fees from Acadia, Althira, Beckman Coulter, Biogen, Cognito Therapeutics, Eisai, Lilly, Merck, Neurogen Biomarking, Novo Nordisk, Roche, Siemens Healthineers; payment from Roche, Novo Nordisk, Biogen, and Medscape; and payments for grant reviews. Resnick reports employment by the NIA Intramural Research Program during the study; support from the McKnight Foundation Annual Meeting as a keynote speaker; ISAB member of the Canadian Consortium on Neurodegeneration in Aging; External Advisory Board Member on the Adult Aging Brain Connectome Study; and ISAB member for Dementia Platforms UK. Ngyuen reports funding from 5K99AG082863-02. LaCroix reports funding from grant R01AG079149 and contract 75N92021D00001. Zhang reports funding from R01AG079149 and residual class settlement funds in the matter of April Krueger vs. Wyeth, Inc., Case No. 03-cv-2496 (US District Court, SD of California). McEvoy reports funding from R01AG079149. All other authors declare no competing interests.

Kyowa Hakko USA today announced that its branded postbiotic ingredient EYEMUSE^® powers the world’s first postbiotic eye gummy, featured in Zen Nutrients‘ THE EYE-MAZEN GUMMY products for adults, teens, and kids.

EYEMUSE^®, along with Cognizin^®, Kyowa Hakko USA’s branded citicoline ingredient, are among the premium‑quality components in both formulas.

“Quality and science come first, so our partners can formulate with confidence and communicate with care,” said Katie Emerson, Senior Manager of Scientific Affairs at Kyowa Hakko USA. “We are proud to be an ingredient partner behind new product innovation for consumers around the world.”

EYEMUSE^® is a heat-treated probiotic strain, also described as a postbiotic, identified as Lacticaseibacillus paracasei KW3110, discovered by its parent company, Kirin Holdings, Ltd. in Japan. EYEMUSE supports eye health and is known to help reduce digital stress-related eye fatigue and discomfort, and in vitro studies suggest it may help filter blue light.

Supported by patents and peer-reviewed studies from Japan in 2018 and 2020, EYEMUSE^™ features a unique, heat-inactivated form of Lacticaseibacillus paracasei KW3110 that has been shown in human trials to help reduce screen-related eye fatigue and support comfort during prolonged use of digital devices.

Research indicates that KW3110 helps maintain visual performance by improving measures such as critical flicker frequency—an indicator of eye fatigue—and offering cellular-level support against blue light-related stress. Laboratory studies conducted by Kyowa Hakko further suggest that EYEMUSE^™ helps the eyes filter blue light, keeping eyes more comfortable and resilient.

In a recent The Daily Caller article, which profiled pharmacist and father Devan Patel, who was working to ease his daughter’s screen-related eye strain, he developed The Eye Mazen Gummy concept, which combines EYEMUSE^® with ingredients including Cognizin^® citicoline and other nutrients in a gummy format for kids and adults.

“Today’s screen-heavy lifestyles bring new considerations for eye health,” Patel told The Daily Caller. “That inspired me to explore a more modern approach to nutritional support for families.”

The launch of THE EYE-MAZEN GUMMY marks a milestone in consumer innovation by bridging rigorous science with everyday wellness. Both formulas are available on the Zen Nutrients website. That is the same website where consumers can review ingredient details and directions for use by age, reflecting a shared commitment to helping families support eye health in today’s screen-filled world.

About EYEMUSE^®
EYEMUSE^® is a proprietary postbiotic ingredient for eye health made from heat-killed Lacticaseibacillus paracasei KW3110. Developed by Kirin Holdings Co., Ltd., EYEMUSE^® is supported by published in vitro, in vivo, and human clinical research exploring the connection between eye health and immune response. Studies suggest EYEMUSE^® stimulates immune cells that produce regulatory cytokines such as IL‑10, helping support a balanced immune response that may reduce the effects of blue light and occasional digital stress‑related eye fatigue and other ocular discomforts. As a postbiotic, EYEMUSE^® offers stability advantages versus live probiotics, including greater heat resistance and no refrigeration requirements. For more information, visit EYEMUSEhealth.com.

About Cognizin^®
Cognizin^® Citicoline, manufactured by Kyowa Hakko Bio Co., Ltd., is a clinically studied and branded form of citicoline, a natural substance made endogenously in the body and especially vital to brain health. Citicoline is a potent brain-health nutrient. A proprietary form of citicoline, Cognizin^®, has been clinically studied to support mental energy, focus, and attention. Cognizin^® is manufactured through a fermentation process to yield high-quality, high-purity products. Cognizin^® is also highly stable, GRAS, ultra-pure, and allergen-free. Cognizin^® can be sold as a dietary ingredient for supplements, foods, and beverages in the United States and is approved as a novel food ingredient in the EU for food supplements. For more information on Cognizin^®, visit Cognizin.com.

About Kyowa Hakko USA:
Kyowa Hakko USA is the North & South American office of Kyowa Hakko Bio Co., Ltd., an international health ingredients manufacturer and world leader in the development, manufacturing, and marketing of pharmaceuticals, nutraceuticals, and food & beverage products. Kyowa is the maker of branded ingredients, including Cognizin^®, Eyemuse^® Lacticaseibacillus paracasei KW3110, Citicoline, Pantesin^® Pantethine, Setria^® Glutathione, and L-Alanyl-L-Glutamine. For more information, visit http://www.kyowa-usa.com.

SOURCE Kyowa Hakko U.S.A

Researchers at the University of California San Diego have identified new genetic variants associated with autism spectrum disorder (ASD) by using long-read whole genome sequencing (LR-WGS), an emerging approach that reads large sections of the genome at once, making it easier for scientists to find new genetic variants and understand how genetic variants affect the function of a gene. The team found that compared to traditional short-read approaches, LR-WGS enhanced the discovery of several categories of genetic variants. The findings may pave the way for more accurate genetic tests and could enable new therapies targeting specific genetic mechanisms underlying ASD.

Despite significant progress in understanding the genetics of autism, a substantial portion of its genetic basis remains unexplained. This gap is what researchers call the “missing heritability.” In their latest study, the researchers show that long-read sequencing can discover new gene mutations that were hidden from view when they used more traditional short-read sequencing technologies. This is one of the first studies of autism to utilize this approach at scale.

“Long-read technologies are game changers in terms of the diverse functional information we can get from a single genome sequence,” said senior author Jonathan Sebat, professor of psychiatry and cellular and molecular medicine at the UC San Diego School of Medicine. “This technology can improve our understanding of the genetic basis of autism and other neurodevelopmental disorders, and may ultimately lead to better diagnostics and targeted therapies.”

Analyzing 267 genomes from families with autism, the study found:

• LR-WGS enhances the discovery of gene-disrupting structural variants (changes in genes) and tandem repeats (repeated sections of DNA) by 33% and 38%, respectively, compared to traditional short-read sequencing.
• Some of the new mutations found are complex rearrangements of genes, which can disrupt gene function and contribute to the development of autism.
• By analyzing data on genetic variants in tandem with DNA methylation — small chemical modifications that regulate the activity of a gene — the researchers could determine how mutations impact the function of a gene.

The researchers caution that though this study is the largest of its kind to date, even larger studies analyzing more genomes will be required to estimate exactly how much of the missing heritability can now be explained with long reads. Sebat hypothesizes that LR-WGS could double the amount of heritability explained by certain types of variants, such as tandem repeats and structural variants.

For now, the study offers new insights into the genetic origins of autism and highlights the potential of LR-WGS to reveal complex genetic variations and their functional consequences with a single test.

The study was published in Cell Genomics and funded, in part, by grants from the National Institute for Mental Health (MH113715, MH133899), the National Institute of Drug Abuse (U01DA051234), and the National Human Genome Research Institute (1R01HG010149). The authors declare no competing interests.

Bone repair is a tightly coordinated biological process that relies on stem and progenitor cells to rebuild damaged bone tissue. In younger individuals, these cells rapidly differentiate into osteoblasts—the bone-forming cells that generate new mineralized tissue. With aging, however, this process slows dramatically. Clinicians have long observed that fractures in older adults heal more slowly and are often associated with impaired recovery; however, the molecular signals driving this decline have remained unclear. Understanding why bone regeneration falters with age is critical amid global population aging and rising fracture-related disability.

Against this backdrop, in a new study, researchers have identified apolipoprotein E (ApoE), a protein produced primarily by the liver, as a key systemic inhibitor of bone repair during aging. The team found that circulating ApoE levels increase with age and interfere directly with signaling pathways required for osteoblast formation. By blocking ApoE activity, they were able to restore bone regeneration and significantly improve fracture healing in aged animal models. Their findings were made available online on January 22, 2026, in Volume 14 of the journal Bone Research.

The study was led by Associate Professor Gurpreet Singh Baht from the Department of Orthopaedic Surgery at Duke University, USA, along with Postdoctoral Associate Dr. Mingjian Huang and Ms. Kristin Molitoris, Research Technician, from the Duke Molecular Physiology Institute, USA.

To uncover how aging alters bone repair, the researchers used mouse models of fracture healing combined with molecular, cellular, and histological analyses. They compared young and aged mice to track differences in systemic factors, stem cell behavior, and bone regeneration outcomes. Their experiments revealed that elevated ApoE in older mice suppressed β-catenin signaling in bone marrow stromal cells—a pathway essential for osteoblast differentiation. Without this signal, progenitor cells failed to mature properly, stalling the repair process at an early stage.

Crucially, the researchers demonstrated that ApoE exerts its inhibitory effect by interacting with the Lrp4 receptor on bone marrow stromal cells. This interaction disrupts downstream β-catenin activity, effectively placing a molecular “brake” on bone formation. When ApoE-neutralizing antibodies were administered, β-catenin signaling was restored, osteoblast differentiation resumed, and fracture healing improved markedly. “Aging doesn’t just slow bone repair—it starts to turn it off through systemic signals,” explains Dr. Baht. “By blocking ApoE, we were able to release that brake and allow healing to proceed.”

The impact of ApoE neutralization was striking. Aged mice treated with ApoE-blocking antibodies formed larger, more robust calluses and showed improved bone bridging at fracture sites compared to untreated controls. Importantly, the regenerated bone more closely resembled healthy repair seen in younger animals, suggesting that the intervention did more than simply accelerate healing—it restored quality regeneration. “What surprised us was how reversible the process turned out to be,” notes Dr. Baht. “Even in aged animals, bone-forming cells retained their regenerative potential once the inhibitory signal was removed.”

Beyond fracture healing, the findings highlight the liver’s unexpected role in regulating skeletal repair. While bone biology has traditionally focused on local signals at the injury site, this study underscores the influence of circulating factors produced by distant organs. The identification of ApoE as a systemic suppressor of bone regeneration opens new avenues for treating age-related skeletal fragility. Therapies that target circulating inhibitors, rather than bone cells themselves, may offer safer and more effective strategies for older patients.

The researchers were motivated by a growing clinical challenge: fractures in elderly patients are associated with longer hospital stays, higher complication rates, and reduced independence. Current treatments focus largely on surgical fixation, with limited options to enhance biological healing. By revealing a modifiable molecular pathway that links aging, liver function, and bone repair, the study offers hope for therapies that actively restore regenerative capacity rather than simply managing its decline.

Together, these findings redefine how aging influences bone repair and identify ApoE as a promising therapeutic target. Neutralizing age-elevated systemic inhibitors could transform fracture care for older adults, reducing nonunion risk and improving recovery. As populations age worldwide, strategies that restore the body’s natural regenerative programs may play a critical role in preserving mobility and quality of life.

Source/Website: https://dmpi.duke.edu/