In a study published in Nature Neuroscience, researchers from Inserm and the University of Bordeaux at the NeuroCentre Magendie, working with scientists at the Université de Moncton in Canada, reported a major step forward in understanding dementia. Their results showed a direct cause and effect link between faulty mitochondrial activity and cognitive symptoms associated with neurodegenerative disease.

Brain Energy and Memory Loss

The team created a highly specific tool that allowed them to temporarily increase mitochondrial activity in animal models of neurodegenerative disease. When they boosted the brain’s energy machinery, memory problems improved.

Although the findings are still early and were observed in animal models, they point to an intriguing possibility: mitochondria may not simply break down after brain disease begins. Instead, their failure may help drive the symptoms that appear as dementia develops.

That idea could reshape how scientists think about future treatments. If brain cell energy failure contributes to memory loss, then restoring mitochondrial function may one day become a strategy for slowing or reducing symptoms.

Why Mitochondria Matter in the Brain

A mitochondrion is a small structure inside the cell that helps generate the energy required for normal function. This matters especially in the brain, which consumes a large amount of the body’s energy.

Neurons depend on that energy to send signals to one another. When mitochondrial activity drops, neurons may no longer have enough power to work properly. Over time, that energy shortage could weaken communication in the brain and contribute to memory and thinking problems.

Neurodegenerative diseases involve the gradual decline of neuronal function, followed by the death of brain cells. In Alzheimer’s disease, researchers have long observed that mitochondrial problems appear alongside neuronal degeneration, often before cells die. Until recently, however, it was difficult to determine whether mitochondrial dysfunction helped cause the disease process or merely appeared as a result of it.

A Tool Designed to Recharge Mitochondria

To explore that question, the researchers developed a tool that can temporarily stimulate mitochondrial activity. Their reasoning was simple but powerful. If increasing mitochondrial activity improved symptoms in animals, that would suggest mitochondrial impairment can come before neuron loss and contribute directly to cognitive decline.

Earlier work by the research teams had already identified a role for G proteins, which have the specific role of enabling the transfer of information within cells, in regulating mitochondrial activity in the brain. In the 2025 study, they built an artificial receptor called mitoDreadd-Gs. This receptor was designed to activate G proteins directly inside mitochondria, which in turn stimulated mitochondrial activity.

When mitoDreadd-Gs was activated in the brain, mitochondrial activity returned to normal levels. Memory performance also improved in mouse models of dementia.

A Possible New Target for Dementia Research

“This work is the first to establish a cause-and-effect link between mitochondrial dysfunction and symptoms related to neurodegenerative diseases, suggesting that impaired mitochondrial activity could be at the origin of the onset of neuronal degeneration,” explains Giovanni Marsicano, Inserm research director and co-senior author of the study.

The results do not mean that a treatment is ready for patients. The work was performed in animal models, and much more research is needed to determine whether similar approaches could be safe, durable, and effective in humans.

Still, the findings add momentum to a growing shift in dementia research. Scientists are increasingly looking beyond the familiar hallmarks of Alzheimer’s disease, such as amyloid plaques and tau tangles, to examine how energy production, metabolism, inflammation, and cellular stress may shape the disease from its earliest stages.

Recent research has continued to strengthen that broader view. A recent Mayo Clinic study linked disruptions in mitochondrial complex I, a key part of the cell’s energy system, to Alzheimer’s disease progression and potential treatment response. Reviews published afterward have also described mitochondrial failure as an early and potentially central feature of Alzheimer’s biology, not merely a late consequence of brain damage.

“These results will need to be extended, but they allow us to better understand the important role of mitochondria in the proper functioning of our brain. Ultimately, the tool we developed could help us identify the molecular and cellular mechanisms responsible for dementia and facilitate the development of effective therapeutic targets,” explains Étienne Hébert Chatelain, professor at the Université de Moncton and co-senior author of the study.

What Comes Next

The next major question is whether longer term stimulation of mitochondrial activity can do more than improve memory symptoms. Researchers now want to know whether restoring mitochondrial function could slow neuron loss, delay disease progression, or possibly help prevent damage before it becomes irreversible.

“Our work now consists of trying to measure the effects of continuous stimulation of mitochondrial activity to see whether it impacts the symptoms of neurodegenerative diseases and, ultimately, delays neuronal loss or even prevents it if mitochondrial activity is restored,” added Luigi Bellocchio, Inserm researcher and co-senior author of the study.

For now, the discovery offers a striking message: memory loss may be tied not only to dying brain cells, but also to living neurons that are running short on energy. By learning how to recharge those tiny engines, scientists may be opening a new path in the fight against dementia.

The discovery offers a rare direct look at one of the largest structures in existence and could help researchers better understand how galaxies grow and evolve over cosmic time.

The Universe’s Hidden Structure

Modern cosmology suggests that dark matter makes up roughly 85% of all matter in the Universe. Although invisible, dark matter is believed to shape a gigantic web-like framework made of long filaments. At the points where these filaments intersect, galaxies form and shine brightly.

Scientists think these filaments also act as intergalactic highways, channeling gas into galaxies and fueling the birth of new stars. Learning how this gas moves through the cosmic web is considered essential for understanding how galaxies develop.

But detecting that gas has been extremely difficult. Most intergalactic gas has only been observed indirectly by measuring how it absorbs light from bright objects behind it. Hydrogen, the most abundant element in the cosmos, emits only a very faint glow, making direct observations nearly impossible for older instruments.

Hundreds of Hours of Telescope Observations

The new observations were carried out by researchers from the University of Milano-Bicocca together with scientists from the Max Planck Institute for Astrophysics (MPA). The team used MUSE (Multi-Unit Spectroscopic Explorer), a powerful instrument mounted on the European Southern Observatory’s Very Large Telescope in Chile.

Even with such advanced technology, the project required one of the most ambitious MUSE observing campaigns ever conducted in a single region of the sky. Researchers gathered data over hundreds of hours to detect the faint filament clearly enough for detailed analysis.

The study, led by Davide Tornotti, PhD student at the University of Milano-Bicocca, produced the sharpest image ever captured of a cosmic filament stretching roughly 3 million light-years. The structure connects two galaxies that each contain an active supermassive black hole.

The findings were published in Nature Astronomy and provide a new way to study the physical properties of gas inside intergalactic filaments.

A 12-Billion-Year Journey Across Space

“By capturing the faint light emitted by this filament, which traveled for just under 12 billion years to reach Earth, we were able to precisely characterize its shape,” explains Davide Tornotti. “For the first time, we could trace the boundary between the gas residing in galaxies and the material contained within the cosmic web through direct measurements.”

To better interpret the observations, the researchers compared the data with supercomputer simulations of the Universe created at MPA. These simulations predicted what such filamentary structures should look like under current cosmological models.

“When comparing to the novel high-definition image of the cosmic web, we find substantial agreement between current theory and observations,” Tornotti adds.

New Clues About Galaxy Formation

The successful match between observations and simulations gives scientists greater confidence in their understanding of how gas is distributed around galaxies and how galaxies receive the material needed to continue forming stars.

Researchers now hope to identify many more of these faint structures in order to build a broader picture of how matter flows through the cosmic web.

Fabrizio Arrigoni Battaia, MPA staff scientist involved in the study, concludes: “We are thrilled by this direct, high-definition observation of a cosmic filament. But as people say in Bavaria: ‘Eine ist keine’ — one doesn’t count. So we are gathering further data to uncover more such structures, with the ultimate goal to have a comprehensive vision of how gas is distributed and flows in the cosmic web.”

Research from UC Davis Health found that people diagnosed with anxiety disorders had lower levels of choline in the brain than people without anxiety. The finding comes from a study published in Molecular Psychiatry, a Nature journal, and offers a rare look at the chemistry that may be connected to anxiety across several different diagnoses.

The researchers reviewed data from 25 previous studies that measured neurometabolites, the chemicals involved in brain metabolism. Altogether, the analysis included 370 people with anxiety disorders and 342 people without anxiety.

A Consistent Chemical Signal in the Brain

The standout finding was choline. People with anxiety disorders had about 8% lower levels of this nutrient in the brain compared with those in the control groups. The pattern was especially clear in the prefrontal cortex, a brain region that helps regulate thought, emotion, decision making, and behavior.

“This is the first meta-analysis to show a chemical pattern in the brain in anxiety disorders,” said Jason Smucny, co-author and an assistant professor in the Department of Psychiatry and Behavioral Sciences. “It suggests nutritional approaches — like appropriate choline supplementation — may help restore brain chemistry and improve outcomes for patients.”

Choline (pronounced kō-lēn) plays several important roles in the body. It helps form cell membranes and supports brain functions involved in memory, mood regulation, and muscle control. Although the body can make a small amount on its own, most choline must come from food.

Why Anxiety Disorders Matter

Anxiety disorders are among the most common mental health conditions in the United States. Richard Maddock, senior author of the study, is a psychiatrist and research professor in the Department of Psychiatry and Behavioral Sciences. He is also a researcher at the UC Davis Imaging Research Center, where scientists use magnetic resonance imaging (MRI) methods to study brain health.

Maddock has spent decades treating people with anxiety disorders and studying how these conditions affect the brain.

“Anxiety disorders are the most common mental illness in the United States, affecting about 30% of adults. They can be debilitating for people, and many people do not receive adequate treatment,” Maddock said.

Anxiety disorders include generalized anxiety disorder, panic disorder, social anxiety disorders, and phobias.

How the Brain Processes Fear and Stress

Anxiety disorders are connected to the way the brain responds to stress, danger, and uncertainty. Two key regions are often involved: the amygdala, which helps shape the sense of safety or threat, and the prefrontal cortex, which supports planning, decision making, and emotional control.

When this system is working well, the brain can usually separate manageable problems from serious threats. In anxiety disorders, that balance can shift. Everyday concerns may feel overwhelming, and the body’s stress response can become difficult to calm.

Brain chemistry also plays a role. Anxiety disorders have been linked to changes in neurotransmitters, including norepinephrine, which is part of the body’s “fight-or-flight” response. Norepinephrine is often elevated in anxiety disorders, and the UC Davis researchers suggest that this heightened arousal may increase the brain’s demand for choline.

In generalized anxiety disorder, for example, people may worry excessively about ordinary events and struggle to control nervousness or fear.

Measuring Brain Chemicals Without Surgery

Maddock and Smucny have long studied how brain chemistry is connected to mental illness using proton magnetic resonance spectroscopy, also known as 1H-MRS.

This technique is noninvasive and is performed with an MRI machine. Instead of producing a standard image of brain structure, 1H-MRS uses magnetic fields and radio waves to measure chemical levels in tissue.

Maddock had previously seen low choline levels in studies of people with panic disorder. That earlier work helped lead to the larger meta-analysis with Smucny. Even though the researchers expected to see reduced choline, the consistency of the result stood out.

“An 8% lower amount doesn’t sound like that much, but in the brain it’s significant,” Maddock said.

The study also found reduced levels of cortical NAA across brain regions after some exclusions. NAA is often considered a marker related to neuronal health and function. However, the clearest and most consistent signal was the reduction in choline-containing compounds across anxiety disorders.

Choline, Diet, and Mental Health

The researchers think that chronic fight-or-flight activity may raise the brain’s need for choline. If the brain cannot take in enough to meet that demand, choline levels may drop.

That does not mean choline supplements are a proven treatment for anxiety. Maddock emphasized that the question remains open.

“We don’t know yet if increasing choline in the diet will help reduce anxiety. More research will be needed,” Maddock said. He cautions that people with anxiety should not self-medicate with excessive choline supplements.

Still, the finding adds to growing interest in the relationship between nutrition and mental health. Choline is already known to be important for the brain and nervous system, and many people in the United States do not get the recommended daily amount.

“Someone with an anxiety disorder might want to look at their diet and see whether they are getting the recommended daily amount of choline. Previous research has shown that most people in the U.S., including children, don’t get the recommended daily amount,” Maddock said. “Some forms of omega-3 fatty acids, like those found in salmon, may be especially good sources for supplying choline to the brain.”

What Later Research Adds

Since the UC Davis work was published, the broader research picture has remained intriguing but not settled. Related dietary research in adults has suggested that higher choline intake may be linked with lower odds of depression, but the same study did not find a significant adjusted association with anxiety or psychological distress.

That makes the UC Davis brain imaging result especially interesting. It points to a measurable chemical difference inside the brain, but it does not prove that low dietary choline causes anxiety or that increasing choline will relieve symptoms. Controlled trials would be needed to test whether changing choline intake can alter brain chemistry or improve anxiety outcomes.

For now, the findings support a practical but cautious message: nutrition may be one piece of the anxiety puzzle, but it is not a substitute for professional mental health care.

Foods That Provide Choline

Choline is found in several common foods. Rich sources include beef liver, eggs (particularly the yolk), beef, chicken, fish, soybeans and milk, among others.

The study highlights a possible biological link between anxiety and a nutrient the brain depends on every day. It also raises a larger question for future research: whether improving choline status could help restore brain chemistry in people with anxiety disorders.

For now, researchers say the answer is not yet known. But the discovery gives scientists a clearer chemical target to investigate and gives people another reason to pay attention to the nutrients that support brain health.

Eloise Theisen never expected to become a specialist in medical cannabis. Now a geriatric nurse practitioner focused on cannabis therapy at Stanford Medicine, she first turned to cannabis herself after a severe car accident left her with chronic pain that other treatments failed to relieve.

When she later returned to work in an oncology clinic, she noticed many patients were already using cannabis or considering it, often without guidance from medical professionals.

“I found that our patients were going to use it whether their providers approved of it or not,” Theisen said. “Many of our patients were older, and they had risks that needed to be evaluated and addressed before they started using cannabis.”

Cannabis Use Is Rising Among Older Adults

Both medical and recreational cannabis use continue to increase across the United States, including among adults over 65. Yet researchers still have major unanswered questions about how cannabis affects the body and brain, partly because marijuana remains federally illegal, making some kinds of research difficult.

Many older adults use cannabis in hopes of easing chronic pain, insomnia, or anxiety. However, Smita Das, MD, PhD, clinical associate professor of psychiatry and behavioral sciences at Stanford Medicine, said there is still no broad medical agreement that cannabis effectively treats these conditions.

Experts say older adults face unique risks from regular cannabis use. These include higher chances of heart disease, certain cancers, addiction, cognitive problems, and dangerous medication interactions. Today’s cannabis products are also much stronger than the marijuana many people encountered decades ago, increasing the risk of accidental overuse.

Stanford Medicine specialists shared five important things older adults should know before using cannabis.

1. Today’s Cannabis Is Much Stronger Than It Used To Be

Medical marijuana is legal in 40 states and the District of Columbia, while recreational cannabis is legal in 24 states and D.C. Although regular use among seniors remains relatively uncommon, it is rising quickly. According to the National Survey on Drug Use and Health, 7% of adults over 65 reported recent cannabis use in 2023, compared with less than 5% in 2021.

Many older adults may not realize how dramatically cannabis potency has changed. In the 1970s, marijuana typically contained between 1% and 4% tetrahydrocannabinol (THC), the compound responsible for the drug’s psychoactive effects. Today, legal cannabis flower averages around 20% THC, and some strains contain as much as 35%.

Other cannabis products can be even more concentrated. Oils, edibles, and concentrates may contain THC levels approaching 90%. Synthetic marijuana products such as spice or K2 are even stronger and have been linked to heart problems. These products are illegal in California and many other states.

“We’re trying to catch up in our understanding of how that drastic of an increase in the psychoactive ingredient is impacting the brain and the body,” said Claudia Padula, PhD, assistant professor of psychiatry and behavioral sciences.

The increased strength of cannabis products may also help explain a rise in accidental overconsumption among older adults. A Canadian study comparing emergency room visits before and after nationwide legalization found that cannabis poisoning cases among adults over 65 nearly tripled.

“There are so many different formulations and so many different strengths,” Das said. “This is really not the cannabis of the ’70s.”

2. Cannabis May Raise Risks for Heart Disease and Cognitive Problems

Although cannabis research is still developing, several studies have linked regular cannabis use to cardiovascular disease.

Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute and the Simon H. Stertzer, MD, Professor of Medicine & Radiology, said this is especially concerning for older adults because heart disease remains the leading cause of death in the United States.

Wu’s research team found that THC triggers inflammation in blood vessels in animal studies. Epidemiological research has also connected cannabis use with several forms of heart disease in humans. According to these studies, regular cannabis use is associated with a 29% increase in heart attacks and a 20% increase in stroke risk.

While those risks are lower than the risks linked to heavy tobacco or alcohol use, Wu noted that many cannabis users also smoke cigarettes, drink alcohol, or both. Combining these substances may further increase cardiovascular danger. Smoking cannabis has also been associated with lung cancer and cancers of the head and neck.

Wu said smoking and vaping cannabis appear to promote more inflammation than edible products, although edibles are not risk free.

“There is no safe amount of cannabis. Low doses and occasional use are still associated with vascular inflammation,” he said. “Abstinence is the safest option for heart health.”

Theisen also watches for other complications in older patients using cannabis, including dizziness, confusion, falls, and worsening cognitive issues such as dementia.

Older adults metabolize cannabis more slowly than younger people, meaning the drug can stay in the body longer and its effects may last longer than expected. Slower metabolism also increases the chances of interactions with prescription medications.

One example involves cannabidiol (CBD), a non-intoxicating cannabis compound. CBD can interfere with enzymes responsible for breaking down medications such as blood thinners. This may raise drug levels in the body and increase the danger of bleeding after an injury or fall. In some cases, cannabis may also reduce the effectiveness of medications.

3. Cannabis Can Be Addictive

A widespread belief about cannabis is that it is not addictive, but Das said research suggests otherwise.

Studies indicate that roughly 30% of regular cannabis users may develop cannabis use disorder. Like other substance use disorders, the condition is diagnosed based on how strongly the drug affects a person’s daily life. Signs may include withdrawal symptoms, needing larger doses over time, or cannabis interfering with relationships and responsibilities.

Even though cannabis addiction rates are lower than those for alcohol, Das said many health care providers may not routinely ask older adults about cannabis use.

“I’m noticing that older adults may not necessarily be disclosing cannabis use to their providers unless specifically asked. This isn’t a population we traditionally think about in terms of using cannabis,” Das said. “If someone comes to me for another reason such as depression or alcohol use disorder, I might be the first person who has asked them about their cannabis use.”

For people struggling to cut back or quit, Das said speaking openly with a doctor or addiction specialist is important. Treatments such as cognitive behavioral therapy have been shown to help.

“Empowering individuals by helping them understand the criteria of a substance use disorder can then help them decide, ‘Is this something I want to talk about?'” Das said. “On the clinician side, we can do a lot to make substance use part of the conversation. What are they using the cannabis for? And if somebody wants to stop using, we need to stick with them through the difficult part of stopping.”

Padula is also studying how the brain reacts to environmental cues in people with cannabis use disorder and other addictions. Using functional MRI scans, her research has found that people who relapse after treatment often show heightened sensitivity to drug-related signals in their surroundings.

4. Cannabis May Help Some Conditions, but Research Remains Limited

Research suggests that different age groups use cannabis for different reasons.

In a 2017 study led by Padula involving medically licensed cannabis users at a San Francisco dispensary, adults ages 18-30 were more likely to use cannabis for boredom or social situations. Middle-aged users commonly reported insomnia as a reason for use, while adults ages 51-72 often used cannabis for cancer, chronic pain, or other long-term medical conditions.

The Food and Drug Administration has not approved cannabis itself for medical treatment. However, it has approved two cannabis-related compounds for specific uses. CBD is approved for certain forms of childhood epilepsy, while dronabinol, a synthetic cannabis compound, is used to treat nausea and appetite loss in patients with cancer or HIV/AIDS.

Cannabis compounds have also shown benefits for muscle spasms caused by multiple sclerosis. Some countries approve cannabis for that purpose, although the United States does not.

CBD products are now widely marketed for pain, sleep problems, anxiety, and substance use disorders, but evidence supporting many of these uses remains limited.

Research on cannabis for chronic pain has produced mixed findings. Some studies report pain relief, but researchers have also observed large placebo effects. Das helped develop a statement from the American Psychiatric Association opposing cannabis as a psychiatric treatment because there is currently no evidence showing it effectively treats psychiatric disorders.

Theisen sees the issue somewhat differently in her work with palliative care patients facing life-limiting illnesses. Many of these patients use cannabis to manage cancer-related symptoms, including pain, and often want alternatives to opioid medications, which can cause serious side effects and addiction. Research has shown that chronic pain patients who use cannabis sometimes reduce their opioid use.

Theisen also said many patients appreciate the sense of well-being cannabis can provide.

“THC has gotten a bad rap over the years, but in very small doses it can be therapeutic,” she said. “There’s also a lot of stigma around its effects of euphoria. In our patients who may have months to a few years to live, still being able to experience joy is really important.”

5. Doctors Say Honest Conversations Matter Most

While experts may disagree about how medically useful cannabis is, they agree on one thing: older adults should talk openly with health care providers before using it.

Theisen said she would rather patients discuss cannabis with a medical professional than rely on advice from dispensary staff or experiment on their own.

During the early years of legalization, she frequently heard stories of patients accidentally consuming extremely high doses of THC edibles because they did not receive proper instructions.

“Patients would sometimes end up in the emergency department, or they would not want to take it again because they thought, ‘This isn’t going to work for me,'” she said.

Reliable information about cannabis can still be difficult to find. Doctors can help patients evaluate whether cannabis is appropriate, discuss possible alternatives, and identify risks related to existing medical conditions or medications.

“Your primary care physician will know the constellation of your medical conditions and other medications you might be on,” Padula said. “Talking to your doctor and letting them know not only what you’re prescribed, but what you’re using recreationally, will help formulate a way to do it in as safe a manner as possible.”

Also known as riboflavin, vitamin B2 cannot be produced by the body and must come from food sources such as dairy products, eggs, meat, and green vegetables. Once absorbed, the vitamin is converted into molecules that help protect cells from oxidative damage and support other important biological functions.

Scientists at the Rudolf Virchow Centre (RVZ) at Julius-Maximilians-Universität Würzburg (JMU) have now discovered that this protective effect may come with a serious drawback. Their findings show that vitamin B2 metabolism can also shield cancer cells from destruction.

“Vitamin B2 plays a crucial role in protecting cancer cells from ferroptosis, a special form of programmed cell death,” says PhD student Vera Skafar. She is part of the research team led by José Pedro Friedmann Angeli, Professor of Translational Cell Biology. The study was published in Nature Cell Biology.

How Vitamin B2 Helps Cancer Cells Survive

Programmed cell death is one of the body’s natural defense systems. It allows damaged or dangerous cells to die in a controlled way without triggering inflammation in nearby tissue. Ferroptosis is one type of this process and has been linked to cancer, neurodegenerative diseases, and other serious conditions.

Ferroptosis occurs when iron-driven damage to cell membranes overwhelms a cell’s antioxidant defenses. Cancer cells often avoid this fate by strengthening systems that protect them from oxidative stress.

The new study found that vitamin B2 metabolism plays an important role in these protective defenses. According to the researchers, this means that blocking riboflavin-related pathways could make tumors more vulnerable to ferroptosis and easier to destroy.

Researchers Test a Possible Cancer Therapy Strategy

A protein called FSP1 was central to the team’s investigation. The protein helps healthy cells avoid unwanted cell death, and vitamin B2 supports its activity.

Using genome editing and cancer cell models, the researchers found that cancer cells became much more sensitive to ferroptosis when vitamin B2 was limited.

The team believes this process could eventually be used as a cancer treatment by shutting down vitamin B2 metabolism in tumors and triggering cancer cell death. However, there is currently no inhibitor specifically designed for that purpose.

To explore the idea further, the researchers tested roseoflavin, a naturally occurring compound produced by bacteria that has a structure similar to vitamin B2.

Roseoflavin Successfully Triggered Ferroptosis

In laboratory experiments using cancer cell models, the researchers found that roseoflavin was able to trigger ferroptosis even at low concentrations.

“It turned out that roseoflavin triggers ferroptosis in low concentrations,” says the group leader, “our experiments show the feasibility of this concept.”

The findings suggest that targeting vitamin B2 metabolism could become a promising new approach for future cancer therapies based on ferroptosis.

Next, the RVZ research team plans to develop more effective inhibitors of vitamin B2 metabolism and test them in preclinical cancer models.

Potential Implications Beyond Cancer

Friedmann Angeli says the importance of ferroptosis extends beyond oncology.

“Ferroptosis is not only relevant to cancer. Increasing evidence suggests that it also contributes to pathological processes in neurodegenerative diseases and in tissue damage following organ transplantation or ischemia-reperfusion injury.”

Because of this, understanding how vitamin B2 metabolism influences ferroptosis could eventually help scientists better understand a wide range of diseases involving excessive or insufficient cell death.

The research was supported by the German Research Foundation (DFG) through the priority program “Ferroptosis: from Molecular Basics to Clinical applications” (SPP2306).

The work was also conducted as part of the DeciFerr (Deciphering and exploiting ferroptosis regulatory mechanism in cancer) project led by Professor Friedmann Angeli. Since May 2024, the project has received funding from the European Research Council (ERC) through an ERC Consolidator Grant worth nearly two million euros.

Tinnitus can range from mildly irritating to severely distressing. For some people, the nonstop noise creates anxiety and disrupts daily life. Researchers estimate that as many as 14% of people globally experience the condition, with many cases considered severe.

A team from Oregon Health & Science University and Anhui University in China studied mice and found that increasing serotonin levels in the brain also increased behaviors associated with tinnitus.

Serotonin and Tinnitus Connection

The findings could have important implications for people living with tinnitus, especially those taking antidepressants that affect serotonin levels, said co-senior author Laurence Trussell, Ph.D., professor of otolaryngology in the OHSU School of Medicine and a scientist at the OHSU Vollum Institute and Oregon Hearing Research Center.

“People with tinnitus should work with their prescribing physician to find a drug regimen that gives them a balance between relief of psychiatric symptoms like depression and anxiety, while minimizing the experience of tinnitus,” Trussell said. “This study highlights the importance of clinicians recognizing and validating patient reports of medication-associated increases in tinnitus.”

The medications discussed in the study include selective serotonin reuptake inhibitors, commonly known as SSRIs. These antidepressants are widely prescribed for moderate to severe depression and anxiety because they raise serotonin levels in the brain.

Researchers have long suspected serotonin played a role in tinnitus, but the exact mechanism remained unclear.

“We’ve suspected that serotonin was involved in tinnitus, but we didn’t really understand how,” said co-author Zheng-Quan Tang, Ph.D., of Anhui University in China. “Now, using mice, we’ve found a specific brain circuit involving serotonin that goes straight to the auditory system, and found that it can induce tinnitus-like effects. When we turned that circuit off, we were able to ameliorate the tinnitus significantly.

“This gives us a much clearer picture of what’s going on in the brain — and points toward new possibilities for treatment.”

Tang began the project while working as a postdoctoral scholar in Trussell’s laboratory.

Brain Circuit Linked to Ringing Ears

The new work builds on earlier research published in 2017.

In the latest study, scientists used optogenetics, a technique that uses fiber optics and light to activate specific brain cells. By targeting neurons that produce serotonin, the researchers were able to trigger activity in regions of the brain involved in hearing. They then measured how the mice responded using a modified auditory startle test.

“When you stimulate these serotonergic neurons, we can see that it stimulates activity in the auditory region in the brain,” Trussell said. “We also saw that animals then behaved as if they were hearing tinnitus. In other words, it’s producing symptoms that we would expect to be experienced as tinnitus in humans.”

According to the researchers, the findings match reports from some patients who say their tinnitus becomes more intense while taking serotonin-boosting medications such as SSRIs.

Future Tinnitus Treatments

“Our study suggests a delicate balance,” Trussell said. “It may be possible to develop cell- or brain region-specific drugs that steer the elevation of serotonin in some brain regions but not others. In that way, it may be possible to separate the beneficial and important effects of the antidepressant from the potentially harmful effects on hearing.”

Trussell’s research was supported by the National Institutes of Health through award RO1DC004450. The authors noted that the findings and conclusions are solely their responsibility and do not necessarily reflect the official views of the NIH.

Scientists have been exploring ways to remove or repair these harmful cells, but there has been a major obstacle. Researchers have struggled to reliably identify senescent cells hiding among healthy cells in living tissue.

DNA Aptamers Help Researchers Identify Senescent Cells

A team at Mayo Clinic now says it has found a promising new strategy. Writing in the journal Aging Cell, the researchers describe a technique that uses molecules called “aptamers” to tag senescent cells.

Aptamers are short strands of synthetic DNA that naturally fold into complex three dimensional shapes. Those shapes allow them to attach to specific proteins found on the surfaces of cells.

Working with mouse cells, the scientists screened more than 100 trillion random DNA sequences and identified several rare aptamers capable of binding to proteins associated with senescent cells. Once attached, the aptamers effectively flagged the cells for identification.

“This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones,” says biochemist and molecular biologist Jim Maher, III, Ph.D., a principal investigator of the study. “Though this study is a first step, the results suggest the approach could eventually apply to human cells.”

A Chance Conversation Sparked the Discovery

The project began with an unexpected idea shared during a casual conversation between graduate students at Mayo Clinic.

Keenan Pearson, Ph.D. — who recently earned his degree from Mayo Clinic Graduate School of Biomedical Sciences — had been studying how aptamers might be used against brain cancer or neurodegenerative diseases while working with Dr. Maher.

Elsewhere on campus, Sarah Jachim, Ph.D., — who was also completing graduate research at the time — was studying aging and senescent cells in the laboratory of Nathan LeBrasseur, Ph.D.

The two students crossed paths during a scientific event and started discussing their thesis projects. Dr. Pearson began wondering whether aptamer technology could be adapted to recognize senescent cells.

“I thought the idea was a good one, but I didn’t know about the process of preparing senescent cells to test them, and that was Sarah’s expertise,” says Dr. Pearson, who became lead author of the publication.

Researchers Pursue a “Crazy” Idea

The students presented the idea to their mentors as well as researcher Darren Baker, Ph.D., whose work focuses on therapies targeting senescent cells.

Dr. Maher says the concept initially sounded “crazy,” but intriguing enough to investigate further. The mentors ultimately embraced the collaboration.

“We frankly loved that it was the students’ idea and a real synergy of two research areas,” says Dr. Maher.

The research advanced quickly. Early experiments produced encouraging findings sooner than expected, leading the team to bring in additional students from several labs.

Then-graduate students Brandon Wilbanks, Ph.D., Luis Prieto, Ph.D., and M.D.-Ph.D. student Caroline Doherty contributed specialized techniques, including advanced microscopy and analysis of a wider variety of tissue samples.

“It became encouraging to expend more effort,” Dr. Jachim says, “because we could tell it was a project that was going to succeed.”

New Clues About the Biology of Zombie Cells

The study may offer more than just a new way to identify senescent cells. It also uncovered information about the cells themselves.

“To date, there aren’t universal markers that characterize senescent cells,” says Dr. Maher. “Our study was set up to be open-ended about the target surface molecules on senescent cells. The beauty of this approach is that we let the aptamers choose the molecules to bind to.”

Several of the aptamers attached to a variation of fibronectin, a protein found on the surface of mouse cells. Researchers do not yet understand exactly how this fibronectin variant relates to senescence, but the finding could help scientists better define what makes senescent cells unique.

Future Potential for Aging and Disease Treatments

The researchers caution that additional studies will be needed before aptamers can reliably identify senescent cells in humans.

Still, the technology could eventually become much more than a detection tool. Scientists believe aptamers might one day carry therapies directly to senescent cells, allowing highly targeted treatment approaches.

Dr. Pearson says aptamers are also less expensive and more adaptable than traditional antibodies, which are commonly used to distinguish different types of cells.

“This project demonstrated a novel concept,” says Dr. Maher. “Future studies may extend the approach to applications related to senescent cells in human disease.”