Intermittent fasting triggers surprising changes in the brain

 More than one billion people worldwide now live with obesity, a condition that raises the risk of cardiovascular disease, diabetes, and several types of cancer. Yet losing weight and keeping it off can be extremely difficult. The body does not simply respond to fewer calories in a straightforward way. Signals from the gut, hormones, metabolism, and the brain can all influence hunger, cravings, and weight regain.

One approach that has drawn growing interest is intermittent energy restriction (IER), a form of dieting in which periods of reduced calorie intake are followed by periods of more typical eating. Research published in 2023 suggests that this strategy may do more than reduce body weight. It may also shift the relationship between gut bacteria and brain activity in ways that are closely tied to appetite and food behavior.

"Here we show that an IER diet changes the human brain-gut-microbiome axis. The observed changes in the gut microbiome and in the activity in addition-related brain regions during and after weight loss are highly dynamic and coupled over time," said last author Dr. Qiang Zeng, a researcher at the Health Management Institute of the PLA General Hospital in Beijing.

Intermittent fasting and the brain

To explore what happens inside the body during weight loss, the researchers studied 25 adults with obesity in China. The volunteers, who were about 27 years old on average, had a BMI between 28 and 45.

The team used several tools to track changes over time. Stool samples were analyzed with metagenomics to measure the composition of the gut microbiome. Blood tests were used to monitor metabolic and physiological changes. The researchers also used functional magnetic resonance imaging (fMRI) to examine activity in brain regions involved in appetite, emotion, attention, learning, inhibition, and reward.

"A healthy, balanced gut microbiome is critical for energy homeostasis and maintaining normal weight. In contrast, an abnormal gut microbiome can change our eating behavior by affecting certain brain area involved in addiction," explained coauthor Dr. Yongli Li from the Department of Health Management of Henan Provincial People's Hospital in Henan, China.

A carefully controlled weight loss program

The study began with a 32 day high controlled fasting phase. During this period, participants received meals designed by a dietitian. Their calorie intake was gradually reduced in steps until it reached about one quarter of their basic energy needs.

This was followed by a 30 day low controlled fasting phase. During this stage, participants were given a list of recommended foods rather than fully prepared meals. Those who followed the plan exactly would consume 500 calories per day for women and 600 calories per day for men.

By the end of the intervention, participants had lost an average of 7.6 kilograms, equal to about 7.8% of their starting body weight. They also had reductions in body fat and waist circumference.

The metabolic improvements extended beyond weight. Blood pressure fell, as did fasting plasma glucose, total cholesterol, HDL, LDL, and the activity of key liver enzymes. According to the researchers, these changes suggest that intermittent energy restriction may help reduce obesity related problems such as hypertension, hyperlipidemia, and liver dysfunction.

Brain and gut changes moved together

The researchers found that the weight loss program was linked to lower activity in several brain regions involved in appetite and addiction related behavior. These changes may help explain why dieting affects not only body size, but also food cravings, self control, and the drive to eat.

At the same time, the gut microbiome shifted. The abundance of Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis rose sharply. Escherichia coli decreased.

Further analysis suggested that certain microbes were connected with activity in specific brain areas. The abundance of E. coli, Coprococcus comes, and Eubacterium hallii was negatively associated with activity in the brain's left orbital inferior frontal gyrus, a region involved in executive function and willpower during weight loss.

Other bacteria showed the opposite pattern. P. distasonis and Flavonifractor plautii were positively linked with brain regions involved in attention, motor inhibition, emotion, and learning.

These findings point to a striking possibility: as people lose weight, the gut microbiome and the brain may change together. The study cannot prove whether gut bacteria drive the brain changes, whether the brain drives microbial changes, or whether another factor influences both. Still, the results add to evidence that weight control is not just a matter of willpower or calories. It may involve a changing biological conversation between the gut and the brain.

Source: ScienceDaily

The forgotten organ that could predict how long you live

 Researchers at Mass General Brigham have uncovered evidence that the thymus, a small immune system organ long thought to lose its importance after childhood, may play a major role in adult health. Two new studies found that adults with healthier thymuses were more likely to live longer and less likely to develop serious diseases. The research also suggests that thymic health may influence how well cancer patients respond to immunotherapy.

The findings were published in two papers in the same issue of Nature and challenge decades of assumptions about the thymus. The results indicate that the organ remains important throughout adulthood and could eventually help guide disease prevention strategies and cancer treatment decisions.

"The thymus has been overlooked for decades and may be a missing piece in explaining why people age differently, and why cancer treatments fail in some patients," said Hugo Aerts, PhD, corresponding author on the papers and director of the Artificial Intelligence in Medicine (AIM) Program at Mass General Brigham. "Our findings suggest thymic health deserves much more attention and may open new avenues for understanding how to protect the immune system as we age."

What the Thymus Does

Located in the chest, the thymus helps train T cells, a type of immune cell that helps defend the body against infections and disease. Because the organ gradually shrinks after puberty and produces fewer new T cells over time, many scientists assumed it played only a limited role in adult health.

As a result, the thymus has received relatively little attention in large population studies. Earlier research connected T cell diversity to aging and declining immune function, but those studies were typically small and focused on blood samples.

The new research took a much broader approach. Investigators analyzed data from more than 25,000 adults participating in a national lung cancer screening trial, along with more than 2,500 people enrolled in the Framingham Heart Study, a long-running study that tracks the health of generally healthy adults.

AI Reveals Links to Longevity and Disease Risk

Using artificial intelligence (AI) to evaluate routine CT scans, the researchers measured the size, structure, and composition of the thymus. From those measurements, they created a "thymic health" score.

People with higher thymic health scores experienced significantly better outcomes. Compared with individuals who had poorer thymic health, they had about a 50% lower risk of death from any cause, a 63% lower risk of death from cardiovascular disease, and a 36% lower risk of developing lung cancer. These relationships remained strong even after accounting for age and other health factors.

The researchers believe that declines in thymic health may reduce T cell diversity, making it harder for the immune system to recognize and respond to new threats such as cancer and other diseases.

Their analysis also identified several factors associated with poorer thymic health, including chronic inflammation, smoking, and higher body weight. These findings suggest that lifestyle factors and ongoing inflammation may affect the immune system's ability to remain resilient over time.

Thymus Health and Cancer Immunotherapy

In a separate study, the team examined CT scans and clinical outcomes from more than 1,200 cancer patients treated with immunotherapy.

The results showed that patients with healthier thymuses tended to respond better to treatment. They faced about a 37% lower risk of cancer progression and a 44% lower risk of death, even after researchers adjusted for differences in patients, tumors, and treatment approaches.

According to the researchers, these findings highlight a potentially important but previously underrecognized role for the thymus in determining how effectively modern cancer immunotherapies work.

More Research Needed

The scientists emphasize that additional studies will be needed to confirm the results. They also note that the imaging technique used to measure thymic health is not yet ready for routine use in clinical practice.

Although lifestyle factors were associated with thymic health, the studies did not investigate whether changing those factors can directly improve thymus function.

The research team is continuing to explore other influences on thymic health. One ongoing study is examining whether unintended radiation exposure to the thymus during lung cancer treatment could affect patient outcomes.

"Improving our understanding and monitoring of thymic health could eventually help physicians better assess disease risk and guide treatment decisions," said Aerts.

Source: ScienceDaily

Your brain starts making social decisions before you do

 Why do we decide to approach other people? According to new research from the Hebrew University of Jerusalem, the answer may begin unfolding in the brain several seconds before any movement takes place.

The study found that social behavior is preceded by a distinctive pattern of activity that spreads across the brain. Researchers also discovered that the strength of this neural pattern is linked to how socially motivated an individual is.

The work was led by Dr. Lilah Avitan and carried out by PhD student Imri Lifshitz and other members of Avitan's laboratory at the Edmond and Lily Safra Center for Brain Sciences (ELSC) at the Hebrew University of Jerusalem.

Tracking Social Decisions in Real Time

To investigate how the brain turns social information into action, the researchers used zebrafish, a model organism that allows scientists to monitor brain activity at the level of individual cells.

The team created a new experimental system in which one fish watched and responded to another fish that was swimming nearby. While this happened, researchers recorded activity throughout the observer fish's entire brain in real time.

This setup allowed them to examine the neural events leading up to a social decision and follow the process as it unfolded moment by moment.

A Brain-Wide Signal Appears Before Social Behavior

The researchers found that when a fish was about to swim toward another fish, changes in brain activity began several seconds before the movement itself.

Instead of relying on a single brain region dedicated to social behavior, the process involved coordinated changes across multiple parts of the brain.

Activity increased in the pallium, a higher brain region associated with complex behaviors. At the same time, activity decreased in other brain areas.

Together, these changes created what researchers describe as a neural "pre-decision state." This brain-wide pattern signaled that a social action was about to occur and could be used to predict the behavior before it happened.

Brain Activity Linked to Social Drive

The study also revealed that the strength of this neural signature varied among individuals.

Fish that showed a stronger brain-wide pattern tended to be more social overall, suggesting that the neural signal reflects an individual's underlying social drive.

The findings further highlighted the importance of the pallium. Results suggest that this brain region plays a central role in generating the motivation to approach others and engage in social interactions.

"This study identifies a brain-wide neural signature of social approach that emerges before movement begins," said Dr. Avitan. "This signature predicts not only whether an upcoming action will be social, but also how strongly socially driven the individual is."

What the Findings Could Mean

Understanding how the brain generates social behavior may help researchers better explain why some individuals are naturally more social than others.

Because similar brain structures contribute to social behavior across many species, the findings could also offer clues about human social function and conditions in which social behavior is altered or disrupted.

Source: ScienceDaily

A single protein may be holding back CAR T cancer therapy

 Researchers from Columbia University and University Hospital Tübingen have discovered a protein that appears to play a major role in weakening CAR T cells over time. By disabling the protein, known as NFIL3, the scientists found that these engineered immune cells remained active longer and were better able to attack tumors. The findings, published in Cancer Discovery, could help improve CAR T-cell therapy, particularly against solid tumors that have proven difficult to treat.

CAR T-cell therapy is one of the most advanced forms of personalized cancer treatment. The approach involves collecting a patient's own immune cells, genetically modifying them to recognize cancer, and then returning them to the body to seek out and destroy tumor cells.

The therapy has produced remarkable results for some blood cancers. However, it has been far less successful against solid tumors. An international team led by Prof. Michel Sadelain, MD, PhD, of Columbia University, working with Prof. Judith Feucht, MD, of University Hospital Tübingen, set out to better understand why. Sadelain is widely recognized as one of the pioneers of CAR T-cell therapy and has played a key role in its development and clinical use.

NFIL3 Linked to CAR T-Cell Exhaustion

To identify factors that limit CAR T-cell performance, the researchers conducted a large-scale analysis of roughly 400 transcription factors, proteins that control which genes are switched on or off inside cells.

Their investigation pointed to NFIL3 as a major contributor to CAR T-cell exhaustion, a process in which the cells gradually lose their ability to function effectively. When the researchers removed NFIL3, the CAR T cells stayed active for longer periods, multiplied more efficiently, and maintained stronger anti-tumor effects.

The team used CRISPR/Cas9 gene-editing technology to disable the gene responsible for producing NFIL3. Often described as genetic scissors, CRISPR allows scientists to precisely cut and modify DNA.

"Switching off NFIL3 could be a decisive step toward significantly improving the long-term potency of CAR T cells," explains Prof. Feucht.

Stronger Tumor Control in Animal Studies

The benefits of removing NFIL3 were demonstrated across several mouse models. CAR T cells lacking the protein were more effective at controlling tumors and helped extend survival.

The results suggest a possible path toward improving treatment for cancers that currently respond poorly to CAR T-cell therapy, particularly solid tumors.

"Our goal is to improve the effectiveness of CAR T cells in solid tumors as well," says Celina May, co-first author of the study and a member of Prof. Feucht's research group. "We expect this to open up new possibilities in the treatment of cancer patients," adds Feucht.

Bridging Laboratory Research and Patient Care

Prof. Feucht combines cancer research with hands-on clinical care. She conducts research within Germany's only Cluster of Excellence in oncology, iFIT (Image Guided and Functionally Instructed Tumor Therapies), while also treating children and adolescents at the Department of Pediatrics at University Hospital Tübingen.

Her work follows the "bench-to-bedside" approach, which focuses on translating scientific discoveries into treatments that can directly benefit patients. Although additional research will be needed before this strategy can be tested and used in people, the findings provide encouraging evidence that targeting NFIL3 could strengthen CAR T-cell therapy and potentially expand its usefulness against a wider range of cancers.

Source: ScienceDaily

The secret to pigeons’ incredible navigation was hiding in their liver

 How pigeons can travel hundreds of miles and still find their way home has puzzled scientists for decades. New research suggests the answer may lie in an unexpected place: the liver.

According to a study published in Science, pigeons may use specialized immune cells in their livers to detect Earth's magnetic field, providing them with an internal navigation system.

Researchers found that these cells, called macrophages, accumulate iron while breaking down old red blood cells. The iron gives the cells unique magnetic properties that could allow them to respond to the planet's magnetic field. When the cells were removed, pigeons struggled to find their way home, pointing to a previously unknown role in navigation.

"We didn't expect immune cells to act like sensors for magnetic fields at all. Our results reveal a previously unknown mechanism for magnetic perception in animals," says Prof. Christian Kurts, Director at the Institute of Molecular Medicine and Experimental Immunology at the University Hospital Bonn, and one of the study's co-senior authors.

"What looks like a 'gut feeling' in bird navigation may actually have a physical basis," adds Prof. Martin Wikelski, Director at the Max Planck Institute of Animal Behavior and the other co-senior author of the study.

The Long Search for Birds' Magnetic Sense

Scientists have long known that homing pigeons and migratory birds use Earth's magnetic field as one of several tools for navigation. However, exactly how animals detect that field has remained one of biology's biggest mysteries.

Over the years, researchers proposed several possibilities. Some theories suggested birds could detect magnetic fields through light-sensitive molecules in their eyes. Others pointed to tiny magnetic particles in their beaks. Despite years of investigation, neither idea has received strong experimental confirmation.

The new study offers a different explanation, combining expertise from immunology, physics, and animal behavior. The research team included scientists from the University of Bonn, the University Hospital Bonn, the University of Duisburg-Essen, and the Max Planck Institute of Animal Behavior (MPI-AB).

Iron-Rich Liver Cells Show Strong Magnetic Properties

To determine where magnetic sensing might occur, the researchers examined multiple organs that have previously been linked to magnetoreception, including the eyes, beak, and brain. They also analyzed the liver and spleen using techniques known as "vibrating sample magnetometry" and "magnetic cell separation."

"We had some clues that the liver and spleen have magnetic properties, because they break down red blood cells and so store much iron in the body," says first author Dr. Clivia Lisowski, from the University of Bonn and the University Hospital Bonn, who led the immunological work.

The results were striking. Among all the tissues studied, the liver contained the highest concentration of iron and produced the strongest magnetic response.

"Iron is crystallized in oxide nanoparticles making the cells superparamagnetic and reactive to magnetic fields. We found by far the strongest magnetic response in liver tissue," adds Prof. Ulf Wiedwald, from the University of Duisburg-Essen.

Further investigation revealed that liver macrophages were responsible for these magnetic properties.

Navigation Experiments Reveal a Critical Role

The researchers then tested whether the macrophages actually influence navigation.

At the MPI-AB in Konstanz, Germany, pigeons had been trained to return to their aviary from locations more than twenty kilometers away. Scientists removed the liver macrophages and monitored how the birds performed.

The results depended on the weather. On overcast days, when the sun was hidden, pigeons that lacked the macrophages lost their sense of direction and had difficulty navigating home. On sunny days, however, they successfully returned, likely relying on the sun as a navigational cue instead of Earth's magnetic field.

These findings suggest that birds use magnetic information alongside solar cues to orient themselves during flight.

How Magnetic Signals May Reach the Brain

After establishing a link between the liver cells and navigation, the researchers looked for a way the information could travel to the brain.

Source: Sciencedaily

Why cancer spreads more in middle age than in old age

 Cancer becomes more common with age and is often harder to treat in older adults. Yet most cancer studies in mice do not reflect that reality. Fewer than 10% of mouse experiments use aged animals, with researchers typically relying on mice that roughly correspond to humans in their early 20s.

That gap may help explain why many cancer therapies that perform well in laboratory studies ultimately fail in human clinical trials.

New findings from Fox Chase Cancer Center, presented at the American Association for Cancer Research annual meeting, suggest that melanoma does not behave the same way throughout the aging process. Researchers found that cancer spread was lowest in young mice, reached its highest level in middle aged mice, and then declined again in very old mice.

"The vast majority of studies are done in these very young mice that have a healthy and intact immune system," said Mitchell Fane, PhD, a cancer biologist who specializes in aging and cancer, and lead investigator of the study. "Right now, it's easy to personalize care for someone who's young and fit, who's potentially not going to experience as many toxicities; understanding how therapies affect older patients would give us more and better treatment options."

Immune Cells May Hold the Key

The researchers believe a specialized group of immune cells known as gamma delta (γδ) T cells may help explain the surprising pattern.

These cells act as an early defense system, helping prevent cancer from spreading throughout the body. Young mice and very old mice had higher levels of these protective immune cells, and their tumors were more likely to remain dormant or spread less aggressively.

Middle aged mice told a different story. They had fewer γδ T cells, and melanoma was much more likely to spread to organs such as the lungs and liver.

The team also discovered that melanoma cells can actively weaken the immune system as animals age. In middle aged mice, the cancer released molecules that suppressed or exhausted γδ T cells. As those defenses weakened, previously dormant cancer cells were able to become active and spread more aggressively.

Additional experiments reinforced the importance of these immune cells. When researchers removed γδ T cells from young and very old mice, melanoma spread increased significantly. Conversely, blocking the signals that suppress immune activity restored protection and reduced cancer spread in middle aged mice, although the same effect was not seen in the younger or older groups.

Why Researchers Need More Aged Mouse Models

One reason aging studies remain uncommon is practical. Young mice are easier and less expensive to obtain, while aged mice require long term care and breeding. Researchers must typically wait 18 to 24 months before mice reach an age suitable for aging research.

To address that challenge, Fane and colleague Yash Chabra, PhD, both Assistant Professors in the Cancer Signaling and Microenvironment Research Program, helped establish an aged mouse facility at Fox Chase Cancer Center.

The goal is to make older animal models more accessible and encourage scientists to test whether their findings hold true across different stages of life.

"Now we have a facility with established aged mouse colonies, which lowers the cost and time barriers to aging research," he said. "It allows us to tell colleagues, 'Your model is interesting, why not test it in aged mice?'"

Rethinking the Link Between Cancer and Aging

Understanding how aging affects cancer could lead to more effective treatments for older adults. Fane's laboratory is particularly interested in the observation that the relationship between age and cancer does not appear to follow a simple straight line.

Although cancer risk generally rises with age, rates unexpectedly decline among people over 80 to 85 years old.

"While risk increases steadily as people age, it abruptly decreases after ages 80-85," said Fane. "We want to explain the mechanism of why very old patients are getting less cancer, but middle-aged patients are getting more."

The new findings suggest that changes in the immune system over the course of aging may play an important role in determining when cancer is most likely to spread. They also highlight the importance of including older animals in cancer research to better reflect the patients most affected by the disease.

Source: ScienceDaily

Human organoids reveal how to reverse “irreversible” nerve damage

 Scientists at the University of Cambridge have created tiny lab-grown brain and spinal cord systems that mimic how movement signals travel through the human nervous system. Using this model, the team discovered that nerve damage once believed to be permanent may actually be reversible under certain conditions.

As the human body develops from an embryo into a fetus and eventually an infant, neurons form complex communication networks between the brain and spinal cord. These signals travel through axons, the long nerve fibers that allow neurons to send messages and control muscle movement.Over time, however, the central nervous system largely loses its ability to regrow damaged axons. As a result, injuries to the brain or spinal cord often become permanent, leading to serious disabilities such as paralysis or loss of movement. This loss of regenerative ability is also linked to neurological diseases including motor neurone disease and multiple sclerosis.

Mini Human Brain and Spinal Cord Models

In 2021, Dr. András Lakatos and his colleagues at the University of Cambridge developed miniature human brain models using stem cells taken from patients. These pea-sized "brain organoids" resembled parts of the cerebral cortex and allowed researchers to study molecular changes linked to motor neurone disease and explore ways to prevent them.

Now, in a new study published in Cell Reports, the researchers expanded on that work by building a miniature version of the connected human brain and spinal cord system.

Because the brain and spinal cord are separate but connected structures in the body, the team kept the organoids physically apart in the lab. They then observed axons from the brain tissue growing across the gap and connecting with the spinal cord tissue. The resulting neural circuit was functional enough to trigger contractions in tiny clusters of muscle cells.

Nerve Regrowth Declines During Development

The scientists maintained these miniature systems in the lab for more than a year. They discovered that until about day 150 of development, roughly corresponding to the middle stage of pregnancy, damaged axons could still regrow. After that point, the neurons showed a major decline in their ability to regenerate.

George Gibbons from the Department of Clinical Neurosciences at the University of Cambridge and first author of the study said: "Neurons taken from less mature organoids regrew long fibers after injury, but those from more mature organoids showed a sharp drop in their ability to regrow. In other words, poor regeneration is built into human neurons as they mature in the central nervous system."

Source: ScienceDaily