The research, led by Haruka Nagaya of Hirosaki University in Japan, was published on June 10, 2026, in the open access journal PLOS One.

Vitamin C and Brain Structure

Earlier studies have suggested that people who consume more vitamin C are less likely to experience cognitive impairment as they get older. However, relatively little research has examined whether vitamin C levels measured directly in the blood are associated with physical changes in the brain.

To investigate that question, the researchers analyzed magnetic resonance imaging (MRI) scans and blood plasma samples from 2,044 Japanese adults over the age of 64.

Using the MRI scans, they measured the volume of gray matter and white matter in each participant’s brain while accounting for differences in overall brain size. They also examined connectivity within the default mode network, a group of interconnected brain regions that plays an important role in attention, autobiographical memory, and other cognitive functions.

Lower Vitamin C Linked to Smaller Gray Matter

After adjusting for factors that can also influence brain health, including age, education level, and physical activity, the researchers found a consistent pattern. Participants with lower plasma vitamin C levels tended to have reduced gray matter volume and weaker connectivity within the default mode network.

The results suggest that maintaining healthy vitamin C levels could potentially help support cognitive function and healthy brain aging. However, the researchers emphasize that this was an observational study, meaning it cannot determine whether vitamin C directly causes these differences in brain structure or function. More research will be needed to uncover the biological mechanisms behind these statistical associations.

Future studies could strengthen the evidence by measuring vitamin C levels repeatedly over time, considering additional lifestyle and dietary factors, and including participants from a wider range of ethnic and socioeconomic backgrounds.

Everyday Diet and Brain Health

Tomohiro Shintaku adds: “Our study demonstrates that higher plasma vitamin C levels are associated with better preserved structural connectivity of the default mode network (DMN), a key brain network involved in cognitive function. This finding generates the exciting hypothesis that a diet rich in vitamin C might play a supportive role in maintaining brain health and mitigating age-related cognitive decline in older adults.”

He continued: “What I found most fascinating about this research is that we were able to detect these subtle but significant associations between a single nutritional factor and large-scale brain networks by utilizing a robust, community-based cohort of over 2,000 older adults. It truly highlights the potential impact of our everyday dietary habits on our brain structures.”

Funding: The KAGOME CO., LTD. provided support in the form of salaries for authors D.K. and Y.U., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Additionally, this research was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP16dk0207025 and JP21dk0207053.

Writing this week in Science, Jonathan Alder, Ph.D., and colleagues describe a combination of genetic changes that allows melanoma cells to dramatically extend their lifespan while fueling rapid tumor growth. The discovery could reshape how researchers understand melanoma and may point to new treatment strategies.

“We did something that was, in essence, obvious based on previous basic research and connected back to something that is happening in patients,” said Alder, assistant professor in the Division of Pulmonary, Allergy and Critical Care Medicine at Pitt’s School of Medicine.

Telomeres Help Control a Cell’s Lifespan

Telomeres are protective caps located at the ends of chromosomes that help keep DNA from breaking down. Every time a healthy cell divides, its telomeres become a little shorter. Eventually, they shrink to the point where the cell can no longer divide.

Keeping telomeres at the proper length is critical for health. Telomeres that become too short can cause disorders linked to premature aging and early death. On the other hand, unusually long telomeres are often associated with cancer.

Scientists have long known that melanoma tumors contain exceptionally long telomeres, especially compared with many other types of cancer.

“There’s some special link between melanoma and telomere maintenance,” said Alder. “For a melanocyte to transform into cancer, one of the biggest hurdles is to immortalize itself. Once it can do that, it’s well on its way to cancer.”

The Missing Genetic Link Behind Melanoma

The enzyme telomerase lengthens telomeres, helping protect chromosomes and preventing cells from dying. In most healthy cells, telomerase remains inactive. Many cancers, however, activate the enzyme through mutations in the telomerase gene known as TERT, allowing cancer cells to keep dividing.

Melanoma is particularly dependent on this strategy. Roughly 75% of melanoma tumors carry TERT mutations that increase telomerase production and activity.

Yet there was a mystery. Even after researchers introduced TERT mutations into melanocytes, they still could not recreate the unusually long telomeres found in melanoma tumors. That suggested another important factor was missing.

Pattra Chun-on, M.D., an internist pursuing her Ph.D. in Alder’s lab, set out to uncover that missing link. Drawing on her background in cancer biology and growing interest in telomeres, she investigated why TERT mutations alone were not enough.

“The fun part of this story is when Pattra joined my lab,” Alder said. “She contacted me and told me that she was interested in studying cancer. I told her that I study short telomeres and not long telomeres. This went on until I realized that Pattra would never take ‘no’ for an answer.”

TPP1 Completes the Puzzle

Earlier work from Alder’s laboratory had identified frequent mutations in a telomere binding protein called TPP1 while analyzing cancer mutation databases.

Chun-on discovered that these TPP1 mutations closely resembled the TERT mutations. They occurred in the newly annotated promoter region of TPP1 and boosted production of the protein. That finding immediately caught Alder’s attention because scientists had already shown that TPP1 enhances telomerase activity.

“Biochemists more than a decade before us showed that TPP1 increases the activity of telomerase in a test tube, but we never knew that this actually happened clinically,” he said.

Chun-on, who is also enrolled in a Ph.D. program in the Department of Environmental and Occupational Health at Pitt’s School of Public Health, then introduced the mutated forms of both TERT and TPP1 into cells. Working together, the two proteins produced the exceptionally long telomeres that characterize melanoma tumors.

The results revealed that TPP1 was the long sought missing factor, one that had been hidden in plain sight.

New Target for Future Melanoma Treatments

The findings offer a new explanation for how melanoma develops and survives. They also identify a cancer specific telomere maintenance system that could become a promising target for future therapies.

Additional authors of the study are Angela M. Hinchie, Agustin A. Gil Silva, Ph.D., Elizabeth Rush, Cindy Sander, Brittani K.N. Seynnaeve, M.D., M.S., John M. Kirkwood, M.D., all of Pitt, UPMC or both; Holly C. Beale, Ph.D., and Olena M. Vaske, Ph.D., both of the University of California, Santa Cruz; Carla J. Connelly, of Johns Hopkins University; and Carol W. Greider, Ph.D., of the University of California, Santa Cruz and Johns Hopkins University.

The research was supported by National Institutes of Health grants R35CA209974 and R01HL135062.

The research, led by PhD candidate Ton Sharoni and Prof. Yehu Moran at the Hebrew University of Jerusalem in collaboration with scientists from the University of North Carolina at Charlotte, was published in Nature Ecology & Evolution. It challenges the long standing idea that animals inherited a single core antiviral system from a common ancestor and instead points to multiple evolutionary solutions for resisting viral infections.

An Ancient Animal Offers New Clues About Immunity

Viruses have threatened living organisms throughout evolutionary history. In humans and other vertebrates, one of the body’s key antiviral defenses depends on a protein called MAVS. When a virus is detected, MAVS helps trigger the immune system so it can respond to the infection.

To investigate how old this defense system might be, the researchers studied sea anemones. These ancient marine animals split from the evolutionary line that eventually led to humans more than 600 million years ago. Because they are close relatives of corals and jellyfish, sea anemones provide scientists with a valuable glimpse into the early evolution of animal immunity.

During the study, the team discovered a previously unknown protein they named CARDIB (CARD Inhibitor Binding protein). At first, CARDIB looked remarkably similar to MAVS, leading researchers to believe it might perform the same antiviral role found in humans.

That assumption quickly fell apart.

“Everything about CARDIB suggested it should function like MAVS,” said Prof. Yehu Moran, head of the Department of Ecology, Evolution and Behavior at the Hebrew University. “Instead, we discovered that it does the exact opposite. Rather than activating antiviral defenses, CARDIB normally suppresses them.”

A Surprising Protein That Protects by Slowing the Immune System

The discovery immediately raised an important question. Why would an animal deliberately suppress its own immune response?

To find out, the researchers used CRISPR gene editing to remove the CARDIB gene from sea anemones before exposing them to viruses.

The results were unexpected. Sea anemones without CARDIB became much more susceptible to infection. Viruses multiplied more rapidly, the animals failed to properly activate their antiviral defenses, and their ability to fight infection dropped dramatically.

“The results were completely counterintuitive,” said Sharoni. “Although CARDIB acts as a brake on the immune system under normal conditions, that brake turns out to be essential for mounting an effective antiviral response.”

Overall, the experiments showed that sea anemones rely on an antiviral pathway that is fundamentally different from the one used by humans, even though both systems contain molecular components that look strikingly alike.

Natural Environment Confirms the Discovery

The researchers also wanted to determine whether this newly identified immune pathway mattered outside carefully controlled laboratory conditions.

To answer that question, genetically modified sea anemones were moved from laboratory aquaria into outdoor marine mesocosms supplied with natural estuarine water in South Carolina. This exposed the animals to the wide variety of viruses and microorganisms found in their normal environment.

The difference became obvious within days. Sea anemones lacking CARDIB and related antiviral genes accumulated substantially more viruses than unmodified animals. Researchers also found that one immune gene that appeared only moderately important in laboratory tests became clearly important under natural environmental conditions.

“This demonstrated that the pathway we discovered is not simply a laboratory phenomenon,” said Moran. “It plays a crucial role in helping these animals cope with the viral challenges they face in nature.”

Multiple Evolutionary Solutions to Fighting Viruses

The findings suggest that evolution did not settle on a single universal antiviral strategy. Instead, different groups of animals may have independently developed distinct molecular systems for detecting viruses and preventing them from spreading.

“Humans and sea anemones both need protection from viruses, but this work shows that evolution can organize those defenses in fundamentally different ways,” Moran added.

The research also underscores the importance of looking beyond traditional laboratory animals. Ancient organisms such as sea anemones can preserve evolutionary innovations that would remain hidden if scientists focused only on humans, mice, and other commonly studied species.

As researchers continue exploring the remarkable diversity of life, discoveries like this are revealing that evolution has repeatedly found unexpected ways to solve some of biology’s most fundamental challenges.

Now, researchers have uncovered an unexpected player in that process. In a study of mice, they found that a brain protein called Arc, which normally helps neurons communicate, also appears to help toxic Tau spread from diseased brain cells to healthy ones.

The discovery points to a possible new strategy for slowing Alzheimer’s disease. Rather than trying to eliminate Tau entirely, future treatments might stop it from reaching healthy brain cells in the first place.

“I’m excited by the fact that we’ve identified a new way of potentially stopping the progression of Alzheimer’s disease,” says Jason Shepherd, PhD, professor of neurobiology at University of Utah Health and senior author of the study.

The findings were published in the journal Cell.

How Arc Helps Toxic Tau Travel

To investigate how Alzheimer’s spreads, the researchers compared mouse models of the disease with and without the Arc protein. Their experiments showed that Arc is essential for moving toxic Tau between neurons.

Under normal conditions, Arc plays an important role in brain function. The protein packages itself inside tiny membrane bound sacs known as extracellular vesicles (EVs), which travel from one neuron to another carrying important cellular signals.

The researchers found that toxic Tau can exploit this natural communication system. By attaching itself to Arc inside these microscopic vesicles, Tau is able to travel from an unhealthy neuron into a healthy one, where it can continue spreading disease.

Tau Turns Healthy Brain Cells Toxic

Every neuron contains Tau, but in Alzheimer’s disease the protein begins clumping into large, sticky tangles that interfere with the cell’s internal transport system before eventually killing the neuron.

Mitali Tyagi, PhD, postdoctoral research associate at Washington University in St. Louis and first author of the study, who conducted the research while a neuroscience graduate student in the Shepherd Lab at U of U Health, compares these tangles to “glue monsters.”

“They glue together and block transportation within the neuron,” Tyagi explains. “But they can break down into smaller glue monsters, called Tau seeds, which can then get transferred to a new neuron. And once this Tau seed comes into contact with healthy Tau, it is able to corrupt it. So, the pathology starts all over again in a healthy neuron.”

In the Alzheimer’s mouse model, the team found extracellular vesicles containing both Arc and “sticky” Tau in brain tissue. These vesicles were capable of entering healthy cells and triggering the formation of new Tau tangles.

The picture changed dramatically when Arc was removed. Mice lacking the protein had extracellular vesicles containing very little Tau, and the disease could no longer spread effectively to neighboring brain cells.

“When we removed Arc, we saw that the transfer of Tau was severely, severely reduced,” Tyagi says. “It was almost gone.”

Arc Has Both Harmful and Helpful Effects

Although blocking Arc might sound like an obvious treatment strategy, the researchers discovered that the protein also performs an important protective role during the early stages of disease.

By helping neurons expel excess toxic Tau, Arc appears to allow damaged cells to survive longer. In mice without Arc, toxic Tau remained trapped inside neurons, causing those already sick cells to die more quickly.

“When Arc is absent, Tau becomes trapped inside neurons and accumulates to toxic levels. When Arc is present, Tau can be released in extracellular vesicles. While this helps reduce Tau buildup within the original neuron, the released Tau can be taken up by neighboring healthy neurons, promoting the spread of pathology,” Tyagi says.

These findings suggest that the most effective treatment may not be preventing diseased cells from releasing Tau. Instead, it may be better to stop those toxic extracellular vesicles from entering healthy neurons.

A Potential New Target for Alzheimer’s Therapies

The researchers also found extracellular vesicles containing both Arc and Tau in human brain tissue, suggesting the same mechanism could exist in people. However, they stress that much more research is needed before any potential therapy reaches patients.

“Most of the work we’ve been doing is in mice, not in humans,” Shepherd says. “We have some clues that whatever is happening in these mice could also be happening in humans, but we don’t know that yet. And we’re far away from saying that we’re developing a treatment for anything. But it could open new avenues to get to that point.”

One promising possibility would be to intercept Tau containing extracellular vesicles after they leave diseased neurons but before they reach healthy ones. While such an approach would not reverse existing brain damage, it could potentially slow or prevent further spread of Alzheimer’s disease.

“If we could target these particular EVs, that would be a really useful therapy strategy,” Shepherd says. “For someone with early-onset Alzheimer’s or dementia, if we could stop the spread, then we could prevent further damage and cognitive decline.”

The study, titled “Arc mediates intercellular tau transmission via extracellular vesicles,” was published in Cell.

The research was supported by the National Institutes of Health, including the Director’s Office Transformative Research Award (R01 NS115716), the National Institute of Neurological Disorders and Stroke (DSPAN F99), and the National Institute on Aging (AG073236), the Chan-Zuckerberg Initiative Ben Barres Early Acceleration Award, the Alzheimer’s Association, the McKnight Brain Disorders Award, the Jon M. Huntsman Presidential Endowed Chair fund, the Max Planck Society, AIRC IG 26229, PRIN 2022EMZJL4, the Rainwater Foundation, the JPB Foundation, and the Cure Alzheimer Fund. The Massachusetts Alzheimer’s Disease Research Center, supported by the National Institute on Aging (P30AG062421) provided human samples.

Shepherd is a co-founder of VNV, LLC and holds stock in and is a consultant for Aera Therapeutics, Inc., which licenses intellectual property and patents that include Arc capsids.

The findings offer cautious optimism, but they also highlight how much remains unknown. While some clinical trials reported meaningful improvements in depression symptoms, others found no benefit at all, leaving scientists with an intriguing question rather than a clear answer.

Reviewing the Clinical Evidence

Instead of conducting a new experiment, researchers led by Bassam Jeryous Fares of the University of Ottawa analyzed existing research. After reviewing the available literature, they identified six published reports covering five randomized controlled trials, in which participants received either creatine or a placebo without knowing which treatment they were taking.

The studies were carried out in South Korea, the United States, Brazil, Israel, and India. Together, they included 238 participants at the start of the trials, with 126 receiving creatine and 112 receiving placebo. Participants averaged 36 years of age, and most were women. Two of the studies enrolled only women.

Four trials focused on people with major depressive disorder, while one involved participants with bipolar disorder who were experiencing a depressive episode. Because the studies differed substantially in their design and methods, the researchers did not combine the data into a single statistical analysis. Instead, they evaluated each study individually.

Mixed Results Across Depression Studies

The review revealed a divided picture.

Two of the five trials, both involving women with major depressive disorder, found that creatine provided additional benefits. In one study, participants who took five grams of creatine each day alongside the antidepressant escitalopram experienced greater reductions in depressive symptoms after eight weeks than those receiving escitalopram with a placebo. The improvement was considered large by conventional statistical standards, with a Cohen’s d of 1.13 on the Hamilton Depression Rating Scale, and more participants achieved remission.

Another study paired creatine with cognitive behavioral therapy. Participants receiving creatine showed a greater reduction in depression symptoms on a standard assessment than those receiving therapy with a placebo.

The remaining three trials, however, found no meaningful benefit.

One study reported that neither five nor ten grams of creatine per day improved symptoms in people whose depression had not responded to medication. Another found no advantage over placebo among adolescent girls, even when different doses were tested. A third trial involving people with bipolar disorder also showed no improvement.

Researchers also noted an important safety concern. Two participants with bipolar disorder who received creatine developed hypomania or mania, suggesting that creatine may affect people differently depending on their underlying condition.

Why Scientists Think Creatine Could Affect the Brain

The idea that creatine could influence depression is grounded in the brain’s enormous energy demands.

Although creatine is best known for helping muscles rapidly regenerate adenosine triphosphate, the molecule that powers cells, the brain also depends heavily on this energy system. Previous research has found changes in brain creatine metabolism among people with mood disorders, leading scientists to investigate whether disruptions in cellular energy production could contribute to depression.

Creatine may also influence dopamine and serotonin, two neurotransmitters that play important roles in mood regulation and are targeted by many antidepressant medications.

Still, the review’s authors emphasize that these connections remain theoretical. Existing studies show correlations rather than proof that altered creatine metabolism directly causes depression, and the disorder itself involves many biological pathways.

“The signal is interesting, but it is not a verdict,” said Bassam Jeryous Fares, first author of the review and a student in the Faculty of Medicine at the University of Ottawa. “Two trials pointed one way and three pointed another. That is not the kind of evidence on which you change clinical practice. It is the kind that tells you the question is worth further exploration.”

Nicholas Fabiano, corresponding author and a psychiatry resident at the University of Ottawa, also urged caution.

“Creatine appears to be a safe intervention. The adverse events we found were limited to mild gastrointestinal discomfort. We cannot yet reliably say that creatine helps with depressive symptoms or if the findings are generalizable to everyone.”

Larger Studies Are Still Needed

The researchers stress that the current evidence is too limited to support routine use of creatine for depression.

The clinical trials were relatively small, included disproportionately more women than men, and varied in quality. Two studies were judged to have a low risk of bias, while the remaining three raised some concerns, primarily related to participant assignment and missing data. As a result, the findings cannot yet be applied broadly.

The review calls for larger and longer clinical trials that extend beyond eight weeks. Researchers also recommend studying creatine alongside exercise and investigating whether different doses produce better outcomes, while recognizing that higher doses may not necessarily lead to greater benefits.

Animal studies may offer another clue. Experiments have shown that creatine can affect depression like behavior differently in male and female rodents, a finding that could help explain why the human studies involving mostly women produced the strongest positive results.

For now, creatine remains an intriguing possibility rather than a proven treatment. A supplement long associated with building muscle is now attracting growing interest from scientists searching for new ways to treat depression.

The peer-reviewed research article, “Creatine as a treatment for depression,” was published in Brain Medicine and is available through Open Access beginning June 30, 2026.

The research, published in The Lancet Digital Health, found that more than 98% of people identified by their general practitioners as eligible for statin therapy were at low predicted risk of developing a serious muscle disorder over the following 10 years. The findings suggest that fears about severe muscle related side effects may be overstated for most people who could benefit from treatment.

New Tool Aims To Personalize Statin Decisions

The researchers also uncovered a significant treatment gap. More than 60% of people who were eligible to take statins were not using them, even though some faced a high risk of heart attack or stroke. The team believes the new calculator could improve conversations between patients and clinicians by providing personalized estimates of risk instead of relying on general statistics or broad concerns about side effects.

The calculator, available through the Oxford University Innovation software store, is based on a clinical prediction model developed and tested using anonymized health records from more than 5.6 million people registered with GP practices across England. Researchers built the model using data from more than 1.7 million people and then validated its accuracy with records from another 3.9 million.

How the Statin Risk Calculator Works

The model analyzes 22 routinely collected health factors to estimate the likelihood of developing a serious muscle disorder over one, five, and 10 years. These factors include age, sex, ethnicity, body mass index, smoking status, existing medical conditions, previous muscle problems, vitamin D deficiency, medication use, and whether a person has been prescribed statins.

Researchers expect the calculator to be used alongside cardiovascular risk assessment tools such as QRISK. Together, these tools could help doctors and patients weigh both the benefits of lowering the risk of heart attacks and strokes and the potential risk of serious muscle complications when deciding whether statin treatment is appropriate.

Putting Statin Side Effects Into Perspective

Statins are among the most commonly prescribed medications for preventing cardiovascular disease. However, worries about muscle related side effects often discourage people from starting treatment or lead them to stop taking the medication, even when the potential benefits are substantial.

The researchers emphasized that their work focuses only on serious muscle disorders that result in hospital admission or death, not the milder muscle aches and pains that some people experience. Previous research has shown that many mild muscle symptoms reported during statin treatment are not actually caused by statins and should not prevent patients from beginning therapy. Although serious muscle disorders are much less common, understanding the possibility of these rare events remains important when balancing the risks and benefits of treatment.

Dr. Ting Cai, Research Fellow in the Nuffield Department of Primary Care Health Sciences, University of Oxford, and lead author of the study, said:

“Serious muscle disorders are one of the most widely discussed concerns about statins, but our findings suggest that the risk is very low for the vast majority of people who may benefit from treatment. Understanding a person’s risk can help put those concerns into perspective, support more informed treatment decisions and provide reassurance. For the small number of people at higher risk, it gives clinicians a clearer basis for discussing monitoring, checks or alternative treatment options.”

Personalized Risk Could Improve Treatment Decisions

Professor James Sheppard, Professor of Primary Care Research at the University of Oxford and a senior author of the study, said:

“Treatment decisions are often based on estimates of a person’s future cardiovascular risk, but much less information is available about their individual risk of adverse outcomes. This research helps address that gap by providing a way to estimate a person’s risk of serious muscle disorders alongside their cardiovascular risk. Bringing those two pieces of information together could support more personalized and better-informed decisions about statin treatment.”

Professor Constantinos Koshiaris, Assistant Professor of Medical Statistics at the University of Nicosia Medical School and a senior author of the study, said:

“Clinical decisions are often based on estimates of potential benefit, but understanding potential harms is equally important. This model provides a way to quantify that risk at an individual level, helping support more balanced discussion about treatment options.”

By offering personalized estimates of both potential benefits and risks, the researchers hope the calculator will help patients and healthcare providers make more confident, evidence based decisions about statin treatment and long term cardiovascular disease prevention.

The online calculator based on the model will be available through the Oxford University Innovation software store as the STRATIFY-StatinMD Risk Calculator — Academic use.

The study was funded by a British Heart Foundation PhD Scholarship (ref: FS/19/13/34235). James Sheppard and Constantinos Koshiaris were supported by the Wellcome Trust and the Royal Society (Sir Henry Dale Fellowship, ref: 211182/Z/18/Z) and the National Institute for Health and Care Research (NIHR) School for Primary Care Research. Richard McManus was supported by an NIHR Senior Investigator award. Richard Hobbs was partially supported by the NIHR Applied Research Collaboration Oxford and Thames Valley.