One protein may decide whether brain chemistry heals or harms

Tryptophan is widely known for its connection to sleep, but its importance goes much further. The compounds produced from tryptophan help build proteins, generate cellular energy (NAD+), and create essential brain chemicals such as serotonin and melatonin. Together, these processes support mood, learning, and healthy sleep patterns.

As the brain ages or develops neurological disease, this system begins to break down. Scientists have repeatedly observed disruptions in how tryptophan is processed in aging brains, with even stronger effects seen in neurodegenerative and psychiatric disorders. These changes are linked to worsening mood, impaired learning, and disturbed sleep. Until now, however, researchers did not know what caused the brain to shift how it uses tryptophan in the first place.

SIRT6 Identified as a Key Regulator of Brain Chemistry

Prof. Debra Toiber and her research team at Ben-Gurion University of the Negev have now uncovered a clear biological explanation. Their work points to the loss of a longevity-related protein called Sirtuin 6 (SIRT6) as the driving factor behind this metabolic imbalance.

Using experiments in cells, Drosophila (fly), and mouse models, the researchers showed that SIRT6 plays an active role in controlling gene expression (e.g., TDO2, AANAT). When SIRT6 levels drop, this control is lost. As a result, tryptophan is redirected toward the kynurenic pathway, which produces neurotoxic compounds, while the production of protective neurotransmitters such as serotonin and melatonin declines.

Published Evidence and a Reversible Effect

The findings were recently published in Nature Communications.

Importantly, the researchers also found that the damage caused by this shift is not permanent. In a SIRT6 knockout fly model, blocking the enzyme TDO2 led to a significant improvement in movement problems and reduced the formation of vacuoles, which are signs of brain tissue damage. These results suggest that there may be a meaningful window for therapeutic intervention.

"Our research positions SIRT6 as a critical, upstream drug target for combating neurodegenerative pathology," says Prof. Toiber.

Research Team and Funding Support

Additional researchers include: Shai Kaluski-Kopatch, Daniel Stein, Alfredo Garcia Venzor, Ana Margarida Ferreira Campos, Melanie Planque, Bareket Goldstein, Estefanía De Allende-Becerra, Dmitrii Smirnov, Adam Zaretsky, Dr Ekaterina Eremenko -- Sgibnev, Miguel Portillo, Monica Einav, Alena Bruce Krejci, Uri Abdu, Ekaterina Khrameeva, Daniel Gitler, and Sarah-Maria Fendt.

The study was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 849029), the David and Inez Myers foundation, the Israeli Ministry of Science and Technology (MOST), the High-tech, Bio-tech and Negev fellowships of Kreitman School of Advanced Research of Ben-Gurion University and The Israel Science Foundation (Grant no. 422/23). The RNA-seq data analysis was supported by the Russian Science Foundation (grant number 25-71-20017). 

 

Journal Reference:

1. Shai Kaluski-Kopatch, Daniel Stein, Alfredo Garcia Venzor, Ana Margarida Ferreira Campos, Melanie Planque, Bareket Goldstein, Estefanía De Allende-Becerra, Dmitrii Smirnov, Adam Zaretsky, Ekaterina Eremenko, Miguel Portillo, Monica Einav, Alena Bruce Krejci, Uri Abdu, Ekaterina Khrameeva, Daniel Gitler, Sarah-Maria Fendt, Debra Toiber. Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration. Nature Communications, 2025; 17 (1) DOI: 10.1038/s41467-025-67021-y 

Courtesy:

Ben-Gurion University of the Negev. "One protein may decide whether brain chemistry heals or harms." ScienceDaily. ScienceDaily, 15 January 2026. <www.sciencedaily.com/releases/2026/01/260115022811.htm>. 

Statins may help almost everyone with type 2 diabetes live longer

 

A large long-term study has found that statins, a widely used class of cholesterol-lowering medications, significantly reduce the risk of death and serious heart-related problems in adults with type 2 diabetes. Importantly, these benefits were seen even in people who were considered to have a low chance of developing heart disease within the next 10 years. This challenges a long-standing debate over whether preventive statin treatment is worthwhile for patients who appear to be at lower cardiovascular risk.

Statins are commonly prescribed to lower LDL cholesterol, what many people know as bad cholesterol. High LDL levels are linked to clogged arteries, heart attacks, and strokes. People with type 2 diabetes already face a higher risk of cardiovascular disease, but doctors have not always agreed on whether statins are necessary for those whose short-term heart risk appears minimal. The new findings suggest that statins may offer protective effects for a much wider group of diabetes patients than previously believed. The study was published in Annals of Internal Medicine.

The research team, led by scientists from the University of Hong Kong, examined health records from the IQVIA Medical Research Data (IMRD)-UK database. Their goal was to assess both the effectiveness and safety of starting statin therapy for primary prevention. Primary prevention refers to preventing a first heart attack or stroke before any such event has occurred.

The study focused on adults in the United Kingdom with type 2 diabetes between the ages of 25 and 84. Participants were followed for as long as 10 years. At the start of the study, none of the individuals had serious heart disease or significant liver problems, allowing researchers to more clearly assess the effects of statins without interference from existing severe conditions.

Statins Reduced Death and Heart Events at Every Risk Level

Researchers compared people who began taking statins with those who did not, grouping them based on their predicted 10-year risk of developing cardiovascular disease. This risk estimate is commonly used in clinical practice to guide treatment decisions.

Across all risk categories, statin use was linked to lower rates of death from any cause and fewer major cardiovascular events such as heart attacks and strokes. Even participants classified as low risk experienced measurable benefits, which directly challenges the assumption that statins only help people already at high risk of heart disease.

Safety Findings and What They Mean for Patients

In terms of safety, the researchers observed a very small increase in myopathy in one risk group. Myopathy refers to muscle-related side effects, which can include weakness or soreness and are a known but uncommon concern with statin use. No increase in liver-related problems was found, addressing another common worry among patients and clinicians.

Based on these results, the authors concluded that doctors should carefully consider the advantages of statin therapy for all adults with type 2 diabetes, even when a person's short-term predicted risk of cardiovascular disease is low. The findings suggest that relying solely on short-term risk estimates may cause some patients to miss out on treatments that could help them live longer and avoid serious heart complications.

Journal Reference:

1. Vincent Ka Chun Yan, Joseph Edgar Blais, John-Michael Gamble, Esther Wai Yin Chan, Ian Chi Kei Wong, Eric Yuk Fai Wan. Effectiveness and Safety of Statins in Type 2 Diabetes According to Baseline Cardiovascular Risk. Annals of Internal Medicine, 2025; DOI: 10.7326/ANNALS-25-00662 

Courtesy:

American College of Physicians. "Statins may help almost everyone with type 2 diabetes live longer." ScienceDaily. ScienceDaily, 15 January 2026. <www.sciencedaily.com/releases/2026/01/260115022812.htm>. 

 

 

Scientists reverse Alzheimer’s in mice and restore memory

 

A study reveals that restoring the brain's energy balance may not just slow Alzheimer's -- but actually reverse it.

• For more than a century, Alzheimer's disease has been widely viewed as permanent and untreatable once it begins. As a result, most research has focused on preventing the disease or slowing its progression rather than attempting to reverse it.
• By studying multiple mouse models of Alzheimer's alongside human Alzheimer's brain tissue, researchers identified a critical biological problem at the center of the disease. They found that the brain's inability to maintain healthy levels of a vital cellular energy molecule called NAD+ plays a major role in driving Alzheimer's.
• In animal models, maintaining normal brain NAD+ levels prevented Alzheimer's from developing. Even more striking, restoring NAD+ balance after the disease was already advanced allowed the brain to repair damage and fully restore cognitive function.
• These results suggest that treatments aimed at restoring the brain's energy balance could potentially move Alzheimer's therapy beyond slowing decline and toward meaningful recovery.
• The findings also open the door to further research, including the exploration of complementary strategies and carefully designed clinical trials to determine whether these results can translate to patients.

A Longstanding View of Alzheimer's Is Being Questioned

For more than 100 years, Alzheimer's disease (AD) has been widely viewed as a condition that cannot be undone. Because of this belief, most scientific efforts have focused on preventing the disease or slowing its progression, rather than attempting to restore lost brain function. Even after decades of research and billions of dollars in investment, no drug trial for Alzheimer's has ever been designed with the goal of reversing the disease and recovering cognitive abilities.

That long-held assumption is now being challenged by researchers from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center. Their work set out to answer a bold question: can brains already damaged by advanced Alzheimer's recover?

New Study Targets Brain Energy Failure

The research was led by Kalyani Chaubey, PhD, of the Pieper Laboratory and published on December 22 in Cell Reports Medicine. By examining both human Alzheimer's brain tissue and multiple preclinical mouse models, the team identified a key biological failure at the center of the disease. They found that the brain's inability to maintain normal levels of a critical cellular energy molecule called NAD+ plays a major role in driving Alzheimer's. Importantly, maintaining proper NAD+ balance was shown to not only prevent the disease but also reverse it in experimental models.

NAD+ levels naturally decline throughout the body, including the brain, as people age. When NAD+ drops too low, cells lose the ability to carry out essential processes needed for normal function and survival. The researchers discovered that this decline is far more severe in the brains of people with Alzheimer's. The same pattern was seen in mouse models of the disease.

How Alzheimer's Was Modeled in the Lab

Although Alzheimer's occurs only in humans, scientists study it using specially engineered mice that carry genetic mutations known to cause the disease in people. In this study, researchers used two such models. One group of mice carried multiple human mutations affecting amyloid processing, while the other carried a human mutation in the tau protein.

Amyloid and tau abnormalities are among the earliest and most significant features of Alzheimer's. In both mouse models, these mutations led to widespread brain damage that closely mirrors the human disease. This included breakdown of the blood-brain barrier, damage to nerve fibers, chronic inflammation, reduced formation of new neurons in the hippocampus, weakened communication between brain cells, and extensive oxidative damage. The mice also developed severe memory and cognitive problems similar to those seen in people with Alzheimer's.

Testing Whether Alzheimer's Damage Could Be Reversed

After confirming that NAD+ levels dropped sharply in both human and mouse Alzheimer's brains, the team explored two possibilities. They tested whether maintaining NAD+ balance before symptoms appeared could prevent Alzheimer's, and whether restoring that balance after the disease had already progressed could reverse it.

This approach built on the group's earlier work published in Proceeding of the National Academy of Sciences USA, which showed that restoring NAD+ balance led to both structural and functional recovery after severe, long-lasting traumatic brain injury. In the current study, the researchers used a well-characterized pharmacologic compound called P7C3-A20, developed in the Pieper laboratory, to restore NAD+ balance.

Full Cognitive Recovery Observed in Advanced Disease

The results were striking. Preserving NAD+ balance protected mice from developing Alzheimer's, but even more surprising was what happened when treatment began after the disease was already advanced. In those cases, restoring NAD+ balance allowed the brain to repair the major pathological damage caused by the genetic mutations.

Both mouse models showed complete recovery of cognitive function. This recovery was also reflected in blood tests, which showed normalized levels of phosphorylated tau 217, a recently approved clinical biomarker used to diagnose Alzheimer's in people. These findings provided strong evidence of disease reversal and highlighted a potential biomarker for future human trials.

Researchers Express Cautious Optimism

"We were very excited and encouraged by our results," said Andrew A. Pieper, MD, PhD, senior author of the study and Director of the Brain Health Medicines Center, Harrington Discovery Institute at UH. "Restoring the brain's energy balance achieved pathological and functional recovery in both lines of mice with advanced Alzheimer's. Seeing this effect in two very different animal models, each driven by different genetic causes, strengthens the idea that restoring the brain's NAD+ balance might help patients recover from Alzheimer's."

Dr. Pieper also holds the Morley-Mather Chair in Neuropsychiatry at UH and the CWRU Rebecca E. Barchas, MD, DLFAPA, University Professorship in Translational Psychiatry. He serves as Psychiatrist and Investigator in the Louis Stokes VA Geriatric Research Education and Clinical Center (GRECC).

A Shift in How Alzheimer's Is Viewed

The findings suggest a fundamental change in how Alzheimer's could be approached in the future. "The key takeaway is a message of hope -- the effects of Alzheimer's disease may not be inevitably permanent," said Dr. Pieper. "The damaged brain can, under some conditions, repair itself and regain function."

Dr. Chaubey added, "Through our study, we demonstrated one drug-based way to accomplish this in animal models, and also identified candidate proteins in the human AD brain that may relate to the ability to reverse AD."

Why This Approach Differs From Supplements

Dr. Pieper cautioned against confusing this strategy with over the counter NAD+-precursors. He noted that such supplements have been shown in animal studies to raise NAD+ to dangerously high levels that promote cancer The method used in this research relies instead on P7C3-A20, a pharmacologic agent that helps cells maintain healthy NAD+ balance during extreme stress, without pushing levels beyond their normal range.

"This is important when considering patient care, and clinicians should consider the possibility that therapeutic strategies aimed at restoring brain energy balance might offer a path to disease recovery," said Dr. Pieper.

Next Steps Toward Human Trials

The research also opens the door to additional studies and eventual testing in people. The technology is currently being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by Dr. Pieper.

"This new therapeutic approach to recovery needs to be moved into carefully designed human clinical trials to determine whether the efficacy seen in animal models translates to human patients," Dr. Pieper explained. "Additional next steps for the laboratory research include pinpointing which aspects of brain energy balance are most important for recovery, identifying and evaluating complementary approaches to Alzheimer's reversal, and investigating whether this recovery approach is also effective in other forms of chronic, age-related neurodegenerative disease."

Journal Reference:

1. Kalyani Chaubey, Edwin Vázquez-Rosa, Sunil Jamuna Tripathi, Min-Kyoo Shin, Youngmin Yu, Matasha Dhar, Suwarna Chakraborty, Mai Yamakawa, Xinming Wang, Preethy S. Sridharan, Emiko Miller, Zea Bud, Sofia G. Corella, Sarah Barker, Salvatore G. Caradonna, Yeojung Koh, Kathryn Franke, Coral J. Cintrón-Pérez, Sophia Rose, Hua Fang, Adrian A. Cintrón-Pérez, Taylor Tomco, Xiongwei Zhu, Hisashi Fujioka, Tamar Gefen, Margaret E. Flanagan, Noelle S. Williams, Brigid M. Wilson, Lawrence Chen, Lijun Dou, Feixiong Cheng, Jessica E. Rexach, Jung-A Woo, David E. Kang, Bindu D. Paul, Andrew A. Pieper. Pharmacologic reversal of advanced Alzheimer’s disease in mice and identification of potential therapeutic nodes in human brain. Cell Reports Medicine, 2025; 102535 DOI: 10.1016/j.xcrm.2025.102535 

Courtesy:

University Hospitals Cleveland Medical Center. "Scientists reverse Alzheimer’s in mice and restore memory." ScienceDaily. ScienceDaily, 24 December 2025. <www.sciencedaily.com/releases/2025/12/251224032354.htm>.

This AI spots dangerous blood cells doctors often miss

 

A new artificial intelligence system that examines the shape and structure of blood cells could significantly improve how diseases such as leukemia are diagnosed. Researchers say the tool can identify abnormal cells with greater accuracy and consistency than human specialists, potentially reducing missed or uncertain diagnoses.

The system, known as CytoDiffusion, relies on generative AI, the same type of technology used in image generators such as DALL-E, to analyze blood cell appearance in detail. Rather than focusing only on obvious patterns, it studies subtle variations in how cells look under a microscope.

Moving Beyond Pattern Recognition

Many existing medical AI tools are trained to sort images into predefined categories. In contrast, the team behind CytoDiffusion demonstrated that their approach can recognize the full range of normal blood cell appearances and reliably flag rare or unusual cells that may signal disease. The work was led by researchers from the University of Cambridge, University College London, and Queen Mary University of London, and the findings were published in Nature Machine Intelligence.

Identifying small differences in blood cell size, shape, and structure is central to diagnosing many blood disorders. However, learning to do this well can take years of experience, and even highly trained doctors may disagree when reviewing complex cases.

"We've all got many different types of blood cells that have different properties and different roles within our body," said Simon Deltadahl from Cambridge's Department of Applied Mathematics and Theoretical Physics, the study's first author. "White blood cells specialize in fighting infection, for example. But knowing what an unusual or diseased blood cell looks like under a microscope is an important part of diagnosing many diseases."

Handling the Scale of Blood Analysis

A standard blood smear can contain thousands of individual cells, far more than a person can realistically examine one by one. "Humans can't look at all the cells in a smear -- it's just not possible," Deltadahl said. "Our model can automate that process, triage the routine cases, and highlight anything unusual for human review."

This challenge is familiar to clinicians. "The clinical challenge I faced as a junior hematology doctor was that after a day of work, I would face a lot of blood films to analyze," said co-senior author Dr. Suthesh Sivapalaratnam from Queen Mary University of London. "As I was analyzing them in the late hours, I became convinced AI would do a better job than me."

Training on an Unprecedented Dataset

To build CytoDiffusion, the researchers trained it on more than half a million blood smear images collected at Addenbrooke's Hospital in Cambridge. The dataset, described as the largest of its kind, includes common blood cell types, rare examples, and features that often confuse automated systems.

Instead of simply learning how to separate cells into fixed categories, the AI models the entire range of how blood cells can appear. This makes it more resilient to differences between hospitals, microscopes, and staining techniques, while also improving its ability to detect rare or abnormal cells.

Detecting Leukemia With Greater Confidence

When tested, CytoDiffusion identified abnormal cells associated with leukemia with much higher sensitivity than existing systems. It also performed as well as or better than current leading models, even when trained with far fewer examples, and was able to quantify how confident it was in its own predictions.

"When we tested its accuracy, the system was slightly better than humans," said Deltadahl. "But where it really stood out was in knowing when it was uncertain. Our model would never say it was certain and then be wrong, but that is something that humans sometimes do."

Co-senior author Professor Michael Roberts from Cambridge's Department of Applied Mathematics and Theoretical Physics said the system was evaluated against real-world challenges faced by medical AI. "We evaluated our method against many of the challenges seen in real-world AI, such as never-before-seen images, images captured by different machines and the degree of uncertainty in the labels," he said. "This framework gives a multi-faceted view of model performance which we believe will be beneficial to researchers."

When AI Images Fool Human Experts

The team also found that CytoDiffusion can generate synthetic images of blood cells that look indistinguishable from real ones. In a 'Turing test' involving ten experienced hematologists, the specialists were no better than random chance at telling real images apart from those created by the AI.

"That really surprised me," Deltadahl said. "These are people who stare at blood cells all day, and even they couldn't tell."

Opening Data to the Global Research Community

As part of the project, the researchers are releasing what they describe as the world's largest publicly available collection of peripheral blood smear images, totaling more than half a million samples.

"By making this resource open, we hope to empower researchers worldwide to build and test new AI models, democratize access to high-quality medical data, and ultimately contribute to better patient care," Deltadahl said.

Supporting, Not Replacing, Clinicians

Despite the strong results, the researchers emphasize that CytoDiffusion is not intended to replace trained doctors. Instead, it is designed to assist clinicians by quickly flagging concerning cases and automatically processing routine samples.

"The true value of healthcare AI lies not in approximating human expertise at lower cost, but in enabling greater diagnostic, prognostic, and prescriptive power than either experts or simple statistical models can achieve," said co-senior author Professor Parashkev Nachev from UCL. "Our work suggests that generative AI will be central to this mission, transforming not only the fidelity of clinical support systems but their insight into the limits of their own knowledge. This 'metacognitive' awareness -- knowing what one does not know -- is critical to clinical decision-making, and here we show machines may be better at it than we are."

The team notes that additional research is needed to increase the system's speed and to validate its performance across more diverse patient populations to ensure accuracy and fairness.

The research received support from the Trinity Challenge, Wellcome, the British Heart Foundation, Cambridge University Hospitals NHS Trust, Barts Health NHS Trust, the NIHR Cambridge Biomedical Research Centre, NIHR UCLH Biomedical Research Centre, and NHS Blood and Transplant. The work was carried out by the Imaging working group within the BloodCounts! consortium, which aims to improve blood diagnostics worldwide using AI. Simon Deltadahl is a Member of Lucy Cavendish College, Cambridge.

Journal Reference:

1. Simon Deltadahl, Julian Gilbey, Christine Van Laer, Nancy Boeckx, Mathie P. G. Leers, Tanya Freeman, Laura Aiken, Timothy Farren, Matthew Smith, Mohamad Zeina, Stephen MacDonald, Daniel Gleghorn, Martijn Schut, Folkert Asselbergs, Sujoy Kar, Sophie Williams, Mickey Koh, Yvonne Henskens, Norbert de Wit, Umberto D’Alessandro, Bubacarr Bah, Ousman Secka, Rajeev Gupta, Sara Trompeter, Christine van Laer, Gordon A. Awandare, Kwabena Sarpong, Lucas Amenga-Etego, Willem H. Ouwehand, James H. F. Rudd, James HF Rudd, Concetta Piazzese, Joseph Taylor, Nicholas Gleadall, Carola-Bibiane Schönlieb, Suthesh Sivapalaratnam, Michael Roberts, Parashkev Nachev. Deep generative classification of blood cell morphology. Nature Machine Intelligence, 2025; 7 (11): 1791 DOI: 10.1038/s42256-025-01122-7 

Courtesy:

University of Cambridge. "This AI spots dangerous blood cells doctors often miss." ScienceDaily. ScienceDaily, 13 January 2026. <www.sciencedaily.com/releases/2026/01/260112214317.htm>. 

 

 

 

 

Doctors discover the source of mysterious intoxication

Scientists have identified specific gut bacteria and biological pathways that cause alcohol to be produced inside the body in people with auto-brewery syndrome (ABS). This rare and frequently misunderstood condition causes individuals to experience intoxication even though they have not consumed alcohol. The research was conducted by a team at Mass General Brigham in collaboration with researchers from the University of California San Diego and was published on January 7 in Nature Microbiology.

Auto-brewery syndrome develops when certain microbes in the gut break down carbohydrates and convert them into ethanol (alcohol), which then enters the bloodstream. While normal digestion can create trace amounts of alcohol in anyone, people with ABS can produce levels high enough to cause noticeable intoxication. Although the condition is extremely rare, experts believe it is often missed because of limited awareness, difficulties with diagnosis, and social stigma.

Long Delays and Serious Consequences

Many people with ABS spend years without an accurate diagnosis. During that time, they may face social strain, medical complications, and even legal problems linked to unexplained intoxication. Confirming the condition is also challenging because the gold-standard diagnostic approach requires carefully supervised blood alcohol testing, which is not easily accessible in many settings.

To investigate the biological roots of the disorder, researchers studied 22 people diagnosed with ABS, along with 21 unaffected household partners and 22 healthy control participants. The team compared the makeup and activity of gut microbes across these groups to identify meaningful differences.

Laboratory testing showed that stool samples collected from patients during active ABS flare-ups produced far more ethanol than samples from household partners or healthy controls. This finding highlights the possibility of developing a stool-based test that could make diagnosing the condition easier and more reliable in the future.

Identifying the Microbes and Pathways Involved

Until now, scientists had limited information about which specific gut microbes (yeasts or bacteria) were responsible for auto-brewery syndrome. Detailed stool analysis pointed to several bacterial species as key contributors, including Escherichia coli and Klebsiella pneumoniae. During symptom flare-ups, some patients also showed much higher levels of enzymes involved in fermentation pathways compared to control participants. The researchers note that identifying the exact causative microbes in individual patients remains a complex and time-consuming task.

The research team also followed one patient whose symptoms improved after receiving a fecal microbiota transplantation when other treatments had not worked. Periods of relapse and recovery closely matched changes in specific bacterial strains and metabolic activity in the gut, offering additional biological evidence for the condition. After a second fecal transplant, using a different antibiotic pretreatment, the patient remained symptom-free for more than 16 months.

Hope for Better Diagnosis and Care

"Auto-brewery syndrome is a misunderstood condition with few tests and treatments. Our study demonstrates the potential for fecal transplantation," said co-senior author Elizabeth Hohmann, MD, of the Infectious Disease Division in the Mass General Brigham Department of Medicine. "More broadly, by determining the specific bacteria and microbial pathways responsible, our findings may lead the way toward easier diagnosis, better treatments, and an improved quality of life for individuals living with this rare condition."

Hohmann is currently working with colleagues at UC San Diego on a study evaluating fecal transplantation in eight patients with ABS.

Authorship: In addition to Hohmann, Mass General Brigham authors include Valeria Magallan. Additional authors include Cynthia L. Hsu, Shikha Shukla, Linton Freund, Annie C. Chou, Yongqiang Yang, Ryan Bruellman, Fernanda Raya Tonetti, Noemí Cabré, Susan Mayo, Hyun Gyu Lim, Barbara J. Cordell, Sonja Lang, Peter Stärkel, Cristina Llorente, Bernhard O. Palsson, Chitra Mandyam, Brigid S. Boland, Elizabeth Hohmann, and Bernd Schnabl.

Disclosures: Schnabl has been consulting for Ambys Medicines, Boehringer Ingelheim, Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, Surrozen and Takeda. Schnabl's institution UC San Diego has received research support from Axial Biotherapeutics, BiomX, CymaBay Therapeutics, Intercept, NGM Biopharmaceuticals, Prodigy Biotech and Synlogic Operating Company. Schnabel is founder of Nterica Bio. Hohman has received research support from Seres Therapeutics, MicrobiomeX/Tend.

Funding: This work was supported by the National Institutes of Health (grants K99 AA031328 and T32 DK007202), the American Association for the Study of Liver Diseases Foundation (Grant #CTORA23-208366), and a Pilot and Feasibility Award from the Southern California Research Center for ALPD and Cirrhosis funded by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health P50AA011999 (to C.L.H), in part by NIH grants R01 AA024726, R01 AA020703, U01 AA026939, by Award Number BX004594 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (to B.S.) and services provided by NIH centers P50 AA011999 and the San Diego Digestive Diseases Research Center (SDDRC) P30 DK120515. This study was supported in part by NIH grants R01 AA029106, 1R21 AA030654, P30 AR073761 the D34 HP31027 UC San Diego's Hispanic Center of Excellence, and by the Isenberg Endowed Fellowship jointly awarded by the Pilot/Feasibility Program of the San Diego Digestive Diseases Research Center (SDDRC), the Hellman Family Foundation (P30 DK120515) (to C.L.). This work was also supported by the Joint BioEnergy Institute, U.S. Department of Energy, Office of Science, Biological and Environmental Research Program under Award Number DE-AC02-05CH11231. This publication includes data generated at the UC San Diego IGM Genomics Center utilizing an Illumina NovaSeq X Plus that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).

Journal Reference:

1. Cynthia L. Hsu, Shikha Shukla, Linton Freund, Annie C. Chou, Yongqiang Yang, Ryan Bruellman, Fernanda Raya Tonetti, Noemí Cabré, Susan Mayo, Hyun Gyu Lim, Valeria Magallan, Barbara J. Cordell, Sonja Lang, Münevver Demir, Peter Stärkel, Cristina Llorente, Bernhard O. Palsson, Chitra Mandyam, Brigid S. Boland, Elizabeth Hohmann, Bernd Schnabl. Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort. Nature Microbiology, 2026; DOI: 10.1038/s41564-025-02225-y 

Courtesy:

Mass General Brigham. "Doctors discover the source of mysterious intoxication." ScienceDaily. ScienceDaily, 13 January 2026. <www.sciencedaily.com/releases/2026/01/260113220920.htm>. 

 

 

 

Common food preservatives linked to higher risk of type 2 diabetes

People who consume higher amounts of food preservatives may face a greater risk of developing type 2 diabetes, according to a large new study. Preservatives are commonly added to processed foods and beverages to extend shelf life. The research was conducted by scientists from Inserm, INRAE, Sorbonne Paris Nord University, Paris Cité University and Cnam as part of the Nutritional Epidemiology Research Team (CRESS-EREN). The findings are based on health and diet data from more than 100,000 adults enrolled in the NutriNet-Santé cohort and were published in the journal Nature Communications.

Preservatives are part of the broader category of food additives and are widely used throughout the global food supply. Their presence is extensive. In 2024, the Open Food Facts World database listed around three and a half million food and beverage products. More than 700,000 of those products contained at least one preservative.

wo Major Types of Preservative Additives

In their analysis, Inserm researchers divided preservative additives into two main groups. The first group includes non-antioxidant preservatives, which slow spoilage by limiting microbial growth or slowing chemical reactions in food. The second group consists of antioxidant additives, which help preserve foods by reducing or controlling exposure to oxygen in packaging.

On ingredient labels, these additives typically appear under European codes between E200 and E299 (for preservatives in the strict sense) and between E300 and E399 (for antioxidant additives).

Why Researchers Are Investigating Preservatives

Earlier experimental research has raised concerns that some preservatives may harm cells or DNA and interfere with normal metabolic processes. However, direct evidence linking preservative intake to type 2 diabetes in large human populations has been limited until now.

To better understand this potential connection, a research team led by Mathilde Touvier, Inserm Research Director, examined long-term exposure to food preservatives and the incidence of type 2 diabetes using detailed data from the NutriNet-Santé study.

Tracking Diet and Health Over More Than a Decade

The study followed more than 100,000 French adults between 2009 and 2023. Participants regularly provided information about their medical history, socio-demographic background, physical activity, lifestyle habits, and overall health.

They also submitted detailed food records covering multiple 24-hour periods. These records included the names and brands of industrial food products they consumed. Researchers cross-referenced this information with several databases (Open Food Facts, Oqali, EFSA) and combined it with measurements of additives in foods and beverages. This allowed the team to estimate each participant's long-term exposure to preservatives.

Measuring Preservative Consumption

Across all food records, researchers identified a total of 58 preservative-related additives. This included 33 preservatives in the strict sense and 27 antioxidant additives. From this group, 17 preservatives were analyzed individually because they were consumed by at least 10% of the study participants.

The analysis accounted for many factors that could influence diabetes risk, including age, sex, education, smoking, alcohol use, and overall diet quality (calories, sugar, salt, saturated fats, fibre, etc.).

Diabetes Cases and Risk Increases

Over the study period, 1,131 cases of type 2 diabetes were identified among the 108,723 participants.

Compared with people who consumed the lowest levels of preservatives, those with higher intake showed a markedly increased risk of developing type 2 diabetes. Overall preservative consumption was linked to a 47% higher risk. Non-antioxidant preservatives were associated with a 49% increase, while antioxidant additives were linked to a 40% higher risk.

Specific Preservatives Associated With Risk

Among the 17 preservatives examined individually, higher intake of 12 was associated with an increased risk of type 2 diabetes. These included widely used non-antioxidant preservatives (potassium sorbate (E202), potassium metabisulphite (E224), sodium nitrite (E250), acetic acid (E260), sodium acetates (E262) and calcium propionate (E282)) as well as antioxidant additives (sodium ascorbate (E301), alpha-tocopherol (E307), sodium erythorbate (E316), citric acid (E330), phosphoric acid (E338) and rosemary extracts (E392)).

What the Researchers Say

"This is the first study in the world on the links between preservative additives and the incidence of type 2 diabetes. Although the results need to be confirmed, they are consistent with experimental data suggesting the harmful effects of several of these compounds," explains Mathilde Touvier, Inserm research director and coordinator of this work.

"More broadly, these new data add to others in favor of a reassessment of the regulations governing the general use of food additives by the food industry in order to improve consumer protection," adds Anaïs Hasenböhler, a doctoral student at EREN who conducted these studies.

"This work once again justifies the recommendations made by the National Nutrition and Health Programme to consumers to favor fresh, minimally processed foods and to limit unnecessary additives as much as possible," concludes Mathilde Touvier.

This work was funded by the European Research Council (ERC ADDITIVES), the National Cancer Institute, and the French Ministry of Health.

Story Source:

Materials provided by INSERM (Institut national de la santé et de la recherche médicale). Note: Content may be edited for style and length.

Courtesy:

INSERM (Institut national de la santé et de la recherche médicale). "Common food preservatives linked to higher risk of type 2 diabetes." ScienceDaily. ScienceDaily, 9 January 2026. <www.sciencedaily.com/releases/2026/01/260109080211.htm>. 

The 4x rule: Why some people’s DNA is more unstable than others

A large scale genetic analysis of more than 900,000 people has revealed that specific regions of DNA become increasingly unstable over time. These regions are made up of very short sequences that repeat again and again, and the study shows that they tend to grow longer as people age. Researchers also found that common inherited genetic differences can strongly influence how quickly this expansion occurs, speeding it up or slowing it down by as much as fourfold. In some cases, expanded DNA repeats were linked to serious health conditions, including kidney failure and liver disease.

Expanded DNA repeats are responsible for more than 60 inherited disorders. These conditions develop when repeating genetic sequences lengthen beyond normal limits and interfere with healthy cell function. Examples include Huntington's disease, myotonic dystrophy, and certain forms of ALS.

Although most people carry DNA repeats that slowly expand throughout life, scientists had not previously examined how widespread this instability is or which genes control it using large biobank datasets. This research shows that repeat expansion is far more common than previously recognized. It also identifies dozens of genes involved in regulating the process, creating new opportunities to develop treatments that could slow disease progression.

How Researchers Studied Nearly a Million Genomes

The research team, which included scientists from UCLA, the Broad Institute, and Harvard Medical School, analyzed whole genome sequencing data from 490,416 participants in the UK Biobank and 414,830 participants in the All of Us Research Program. To carry out the analysis, they developed new computational approaches capable of measuring DNA repeat length and instability using standard sequencing data.

Using these tools, the team examined 356,131 variable repeat sites across the human genome. They tracked how repeat lengths changed with age in blood cells and identified inherited genetic variants that affected the speed of expansion. The researchers also searched for associations between repeat expansion and thousands of disease outcomes in order to uncover previously unknown links to human illness.

Key Findings on DNA Repeat Instability

The study found that common DNA repeats in blood cells consistently expand as people get older. Researchers identified 29 regions of the genome where inherited genetic variants altered repeat expansion rates, with differences of up to fourfold between individuals with the highest and lowest genetic risk scores.

One surprising result was that the same DNA repair genes did not behave uniformly. Genetic variants that helped stabilize some repeats made other repeats more unstable. The researchers also identified a newly recognized repeat expansion disorder involving the GLS gene. Expansions in this gene, which occur in about 0.03% of people, were linked to a 14-fold increase in the risk of severe kidney disease and a 3-fold increase in the risk of liver diseases.

What the Findings Mean for Future Research

The results suggest that measuring DNA repeat expansion in blood could serve as a useful biomarker for evaluating future treatments designed to slow repeat growth in diseases such as Huntington's. The computational tools developed for this study can now be applied to other large biobank datasets to identify additional unstable DNA repeats and related disease risks.

Researchers note that further mechanistic studies will be needed to understand why the same genetic modifiers can have opposite effects on different repeats. These efforts will focus on how DNA repair processes differ across cell types and genetic contexts. The discovery of kidney and liver disease linked to GLS repeat expansion also suggests that additional, previously unrecognized repeat expansion disorders may be hidden within existing genetic data.

Expert Perspective on the Findings

"We found that most human genomes contain repeat elements that expand as we age," said Margaux L. A. Hujoel, PhD, lead author of the study and assistant professor in the Departments of Human Genetics and Computational Medicine at the David Geffen School of Medicine at UCLA. "The strong genetic control of this expansion, with some individuals' repeats expanding four times faster than others, points to opportunities for therapeutic intervention. These naturally occurring genetic modifiers show us which molecular pathways could be targeted to slow repeat expansion in disease."

Margaux L. A. Hujoel (UCLA and Brigham and Women's Hospital/Harvard Medical School), Robert E. Handsaker (Broad Institute and Harvard Medical School), David Tang (Brigham and Women's Hospital/Harvard Medical School), Nolan Kamitaki (Brigham and Women's Hospital/Harvard Medical School), Ronen E. Mukamel (Brigham and Women's Hospital/Harvard Medical School), Simone Rubinacci (Brigham and Women's Hospital/Harvard Medical School and Institute for Molecular Medicine Finland), Pier Francesco Palamara (University of Oxford), Steven A. McCarroll (Broad Institute and Harvard Medical School), Po-Ru Loh (Brigham and Women's Hospital/Harvard Medical School and Broad Institute).

What the Findings Mean for Future Research

The results suggest that measuring DNA repeat expansion in blood could serve as a useful biomarker for evaluating future treatments designed to slow repeat growth in diseases such as Huntington's. The computational tools developed for this study can now be applied to other large biobank datasets to identify additional unstable DNA repeats and related disease risks.

Researchers note that further mechanistic studies will be needed to understand why the same genetic modifiers can have opposite effects on different repeats. These efforts will focus on how DNA repair processes differ across cell types and genetic contexts. The discovery of kidney and liver disease linked to GLS repeat expansion also suggests that additional, previously unrecognized repeat expansion disorders may be hidden within existing genetic data.

Expert Perspective on the Findings

"We found that most human genomes contain repeat elements that expand as we age," said Margaux L. A. Hujoel, PhD, lead author of the study and assistant professor in the Departments of Human Genetics and Computational Medicine at the David Geffen School of Medicine at UCLA. "The strong genetic control of this expansion, with some individuals' repeats expanding four times faster than others, points to opportunities for therapeutic intervention. These naturally occurring genetic modifiers show us which molecular pathways could be targeted to slow repeat expansion in disease."

Margaux L. A. Hujoel (UCLA and Brigham and Women's Hospital/Harvard Medical School), Robert E. Handsaker (Broad Institute and Harvard Medical School), David Tang (Brigham and Women's Hospital/Harvard Medical School), Nolan Kamitaki (Brigham and Women's Hospital/Harvard Medical School), Ronen E. Mukamel (Brigham and Women's Hospital/Harvard Medical School), Simone Rubinacci (Brigham and Women's Hospital/Harvard Medical School and Institute for Molecular Medicine Finland), Pier Francesco Palamara (University of Oxford), Steven A. McCarroll (Broad Institute and Harvard Medical School), Po-Ru Loh (Brigham and Women's Hospital/Harvard Medical School and Broad Institute)

Story Source:

Materials provided by University of California - Los Angeles Health Sciences. Note: Content may be edited for style and length.

Courtesy:

University of California - Los Angeles Health Sciences. "The 4x rule: Why some people’s DNA is more unstable than others." ScienceDaily. ScienceDaily, 9 January 2026. <www.sciencedaily.com/releases/2026/01/260109080214.htm>. 

Sleeping less than 7 hours could cut years off your life

Getting a full night of sleep may play a larger role in longevity than many people realize. New research from Oregon Health & Science University indicates that regularly getting too little sleep is linked to a shorter lifespan.

The findings were recently published in the journal SLEEP Advances.

Nationwide Data Reveal Patterns Across the U.S.

To reach their conclusions, researchers analyzed a large national database, examining survey patterns related to life expectancy across counties throughout the United States. They compared county-level life expectancy figures with detailed survey data collected by the Centers for Disease Control and Prevention between 2019 and 2025.

When researchers evaluated lifestyle factors tied to how long people live, sleep stood out clearly. Its association with life expectancy was stronger than that of diet, physical activity, or social isolation. Smoking was the only factor that showed a greater influence.

"I didn't expect it to be so strongly correlated to life expectancy," said senior author Andrew McHill, Ph.D., associate professor in the OHSU School of Nursing, the OHSU School of Medicine and OHSU's Oregon Institute of Occupational Health Sciences. "We've always thought sleep is important, but this research really drives that point home: People really should strive to get seven to nine hours of sleep if at all possible."

Researchers Surprised by the Strength of the Findings

Much of the work was carried out by graduate students in the Sleep, Chronobiology and Health Laboratory within the OHSU School of Nursing.

While scientists have long recognized that adequate sleep supports overall health, the authors said they were still struck by how closely sleep duration tracked with life expectancy. In the analysis, insufficient sleep outweighed diet and exercise as a predictor of lifespan.

"It's intuitive and makes a lot of sense, but it was still striking to see it materialize so strongly in all of these models," McHill said. "I'm a sleep physiologist who understands the health benefits of sleep, but the strength of the association between sleep sufficiency and life expectancy was remarkable to me."

First Study to Track Yearly State-by-State Trends

Previous studies have linked poor sleep to increased risk of death, but this research is the first to show year-by-year connections between sleep and life expectancy across every U.S. state. For their models, researchers used the CDC definition of sufficient sleep as at least seven hours per night, which aligns with recommendations from the American Academy of Sleep Medicine and the Sleep Research Society.

Across nearly all states and in each year analyzed, the data showed a clear relationship between sleep duration and life expectancy.

Why Sleep May Influence Longevity

The study did not examine the biological reasons behind the connection. However, McHill noted that sleep plays a critical role in heart health, immune function, and brain performance.

"This research shows that we need to prioritize sleep at least as much as we do to what we eat or how we exercise," he said. "Sometimes, we think of sleep as something we can set aside and maybe put off until later or on the weekend.

"Getting a good night's sleep will improve how you feel but also how long you live."

Study Authors and Funding

In addition to McHill, the research team included lead author Kathryn E. McAuliffe, B.S., Madeline R. Wary, B.S., Gemma V. Pleas, B.A., Kiziah E.S. Pugmire, B.S., Courtney Lysiak, B.A., Nathan F. Dieckmann, Ph.D., and Brooke M. Shafer, Ph.D.

Funding for the study came from the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award numbers R01HL156948, R01HL169317 and T32HL083808; the OHSU School of Nursing; and the Oregon Institute of Occupational Health Sciences through support from the Division of Consumer and Business Services of the state of Oregon (ORS 656.630).

Journal Reference:

1. Kathryn E McAuliffe, Madeline R Wary, Gemma V Pleas, Kiziah E S Pugmire, Courtney Lysiak, Nathan F Dieckmann, Brooke M Shafer, Andrew W McHill. Sleep insufficiency and life expectancy at the state-county level in the United States, 2019–2025. SLEEP Advances, 8 December 2025 [abstract]

Courtesy: 

Oregon Health & Science University. "Sleeping less than 7 hours could cut years off your life." ScienceDaily. ScienceDaily, 10 January 2026. <www.sciencedaily.com/releases/2026/01/260108231414.htm>.