Monthly Archives: May 2026

Why Older Adults Face Higher Risks from COVID-19 and Flu

Older adults are significantly more likely to develop severe illness from influenza or COVID-19, and new research suggests that ageing lung cells may play a central role in this vulnerability. A study led by scientists at the University of California, San Francisco, has found that structural cells in the lungs can trigger exaggerated immune responses as people age. These findings offer new insight into why infections that might cause only mild symptoms in younger individuals can escalate into serious, even life-threatening conditions in older adults.

The research sheds light on the broader phenomenon of age-related inflammation, often referred to as “inflammaging.” This process helps explain how what begins as a relatively minor respiratory symptom, such as a cough, can rapidly progress into a condition requiring hospital care in older individuals. Rather than simply being a consequence of weaker immunity, the study suggests that ageing lungs may actively contribute to harmful inflammatory responses.

To investigate what goes wrong in ageing lungs, the research team focused on fibroblasts—structural cells responsible for maintaining the integrity of lung tissue. In laboratory experiments, scientists engineered these cells in young mice to activate an age-associated distress signal. This manipulation caused the lungs to develop clusters of inflamed cells, mimicking patterns typically seen in older individuals. Among these were immune cells marked by the GZMK gene, previously identified in severe cases of COVID-19.

The study revealed that these fibroblasts do not act in isolation. Instead, they appear to work closely with immune cells, amplifying inflammatory processes. According to senior author Tien Peng, this interaction was unexpected and suggests new possibilities for early intervention. By identifying how these cells collaborate to drive inflammation, researchers may be able to develop therapies that interrupt this process before it escalates to severe disease requiring interventions such as mechanical ventilation.

At the molecular level, the distress signal observed in the study is linked to the NF-κB pathway, a well-known regulator of inflammation that becomes more active with age. Activation of this pathway prompted macrophages—key immune cells in the lungs—to initiate a broader immune response. This, in turn, attracted additional immune cells from the bloodstream, including those expressing GZMK. Although these cells were not effective at combating infection, they contributed to tissue damage and worsened lung function.

When these inflammatory cell clusters formed, the lungs of otherwise young and healthy mice began to respond to infection as though they were much older. However, when researchers removed the GZMK-marked cells using genetic techniques, the mice showed a markedly improved ability to withstand infection. This finding suggests that the ageing lung environment itself, rather than infection alone, plays a decisive role in driving severe inflammatory responses.

To validate these findings in humans, the team analysed lung tissue from older patients hospitalised with COVID-related acute respiratory distress syndrome (ARDS). They observed similar clusters of inflamed cells, with more extensive clustering associated with more severe illness. In contrast, lung tissue from healthy individuals showed no such patterns. These results point to a self-reinforcing cycle between ageing lung tissue and the immune system, highlighting a potential target for future therapies aimed at reducing harmful inflammation in older adults.

More information: Nancy Allen et al, NF-κB-activated fibroblasts orchestrate inflammaging and emergence of pro-inflammatory granzyme K+ T cells, Immunity. DOI: 10.1016/j.immuni.2026.02.016

Journal information: Immunity Provided by University of California – San Francisco

Mediterranean-style eating could strengthen mitochondrial pathways supporting cardiovascular and cognitive health

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A new study from researchers at the USC Leonard Davis School of Gerontology suggests that some of the well-known health benefits of the Mediterranean diet may be explained by tiny proteins found inside our cells’ mitochondria. These small proteins, called mitochondrial microproteins, appear to play an important role in how diet influences ageing and the risk of disease. The findings offer a fresh perspective on how what we eat can affect the body at a very fundamental, cellular level.

The research, led by Roberto Vicinanza, found that people who closely follow a Mediterranean-style diet tend to have higher levels of two specific microproteins, humanin and SHMOOSE. Both have been linked to protection against heart disease and conditions affecting the brain. According to the researchers, these microproteins may act as messengers, helping to translate dietary habits into changes in how cells function and age. This could help explain why the Mediterranean diet has such a strong reputation for supporting long-term health.

The Mediterranean diet, which emphasises foods such as olive oil, fish, legumes, fruits, and vegetables, has long been associated with lower risks of cardiovascular disease, diabetes, and cognitive decline. However, the biological mechanisms behind these benefits have not been fully understood. In this study, researchers analysed blood samples from older adults with different levels of adherence to the diet. Those who followed the diet most closely had higher levels of humanin and SHMOOSE, along with lower levels of oxidative stress, which is a key contributor to ageing and chronic illness.

The study also found that specific foods within the diet may have distinct effects. For example, olive oil, fish, and legumes were linked to higher levels of humanin. In comparison, olive oil combined with a lower intake of refined carbohydrates was associated with higher levels of SHMOOSE. These findings suggest that not just the overall dietary pattern, but also particular food choices, may directly influence mitochondrial function and overall health.

Mitochondrial microproteins are a relatively new area of scientific interest. Unlike most proteins, which are produced from DNA in the cell nucleus, these are encoded within the mitochondria themselves. Some regions of mitochondrial DNA were once thought to have no real function, but scientists now know they can produce important molecules like humanin. This microprotein has already been linked to improved insulin sensitivity, cardiovascular protection, and better cognitive function. SHMOOSE, discovered more recently, has been connected to brain health, with certain genetic variations linked to a higher risk of Alzheimer’s disease.

Another important finding from the study is that higher levels of humanin were associated with lower activity of an enzyme called Nox2, which produces harmful molecules that contribute to oxidative stress. This suggests that the Mediterranean diet may protect the heart through multiple pathways, both by reducing harmful processes and by boosting protective ones. Although the study was relatively small and observational, it points towards the possibility of using these microproteins as biomarkers to guide personalised nutrition strategies. Future research will explore whether changing diet can directly increase these protective proteins and whether that leads to measurable improvements in health and longevity.

More information: Roberto Vicinanza et al, Mediterranean diet adherence is associated with mitochondrial microproteins Humanin and SHMOOSE; potential role of the Humanin–Nox2 interaction in cardioprotection, Frontiers in Nutrition. DOI: 10.3389/fnut.2025.1727012

Journal information: Frontiers in Nutrition Provided by University of Southern California

The Brain’s Internal Compass Stability May Hold the Key to Memory Longevity

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A discovery by McGill University researchers sheds light on how memories can endure over time, even as brain activity is constantly in flux. Published in Nature, the preclinical study found that the brain’s internal compass remains remarkably stable, suggesting that this persistent sense of direction may act as a reliable anchor for memory.

“This has been a long-standing puzzle: if the brain’s memory systems are continually changing, how do our memories remain so stable?” said senior author Adrien Peyrache, Associate Professor in the Department of Neurology and Neurosurgery at McGill and director of the Peyrache Lab at The Neuro (Montreal Neurological Institute-Hospital). The brain’s internal compass, known as the head-direction system, is a network of neurons that tracks orientation as we move and links the hippocampus—the brain’s key memory centre—to broader neural circuits.

Using miniature head-mounted microscopes, the researchers followed the same brain cells in mice over several months. They found that while the hippocampus reorganised its activity over time, the head-direction system remained structurally stable. When mice explored a new environment, this internal compass quickly established a directional reference point—effectively defining “north” and “south”—and preserved that orientation when the space was revisited weeks later.

“These findings reveal a striking contrast,” Peyrache noted. “While the hippocampus may reorganise, the head-direction system provides a stable foundation for interpreting spatial information.” The results may also have implications for Alzheimer’s disease, as disorientation is often one of the earliest warning signs. Understanding how spatial stability is normally maintained could help explain why these abilities deteriorate and support new approaches to early detection and future therapies.

More information: Sofia Skromne Carrasco et al, Months-long stability of the head-direction system, Nature. DOI: 10.1038/s41586-025-10096-w

Journal information: Nature Provided by McGill University

Data-Driven Platform Reveals Alzheimer’s Pathways, Offering a New Approach to Predicting Risk

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A powerful new real-world data platform could change how scientists understand and predict Alzheimer’s disease and related dementias (AD/ADRD), according to a study led by researchers at Columbia University Mailman School of Public Health and their collaborators. The initiative, known as the M3AD Study and Real-World Data Metaplatform, brings together expertise from multiple institutions to advance research on ageing, dementia prevention, and care. The findings are published in Alzheimer’s & Dementia.

The platform uses electronic health records collected from three major U.S. cities and includes data from around 60,000 individuals living with Alzheimer’s disease or related dementias. By combining these records, researchers can follow how health conditions, behaviours, and social factors interact over time to influence dementia risk. This creates one of the most comprehensive datasets ever assembled for studying dementia in real-world settings.

Unlike traditional research that often focuses on a single disease, this platform takes a broader approach. It examines how multiple chronic conditions, lifestyle factors, and social environments work together and change over time. This allows scientists to capture the complexity of ageing better and to improve predictions about who may develop dementia and how the disease may progress.

The need for this kind of approach is increasing as populations age. In the United States, more than 7.2 million older adults are living with Alzheimer’s disease, including a significant share of those aged 85 and older. At the same time, most older adults are managing more than one chronic illness. This pattern, known as multimorbidity, makes both diagnosis and care more challenging and highlights the limits of studying diseases in isolation.

Researchers stress that dementia does not occur on its own. Instead, it develops through complex interactions between health conditions, behaviours, and life circumstances over many years. By analysing long-term clinical histories, the platform may help identify early warning signs of dementia that have previously been overlooked, creating opportunities for earlier detection and intervention.

The data come from three major health systems: NewYork-Presbyterian Hospital, the University of Chicago, and the University of Miami. Together, they provide decades of patient information covering millions of individuals. The dataset also reflects a diverse population, including people from different racial and ethnic backgrounds, allowing researchers to study dementia risk across a wide range of communities.

In addition to its scale, the platform uses advanced analytical tools, including machine learning, to identify patterns in complex data. It also relies on a federated system that allows institutions to work together while keeping patient data secure. Over time, the platform can be expanded to include additional sources of information, such as imaging, genetic data, and new biomarkers.

Beyond improving risk prediction, the platform will help researchers test prevention strategies in real-world populations. It can be used to study how factors like smoking, healthy weight, and blood pressure in midlife influence later cognitive decline. By linking clinical data with social and environmental information, the initiative also supports a more holistic understanding of dementia, helping to guide better care and future research.

More information: Moise Desvarieux et al, Accelerating real-world prediction and research in Alzheimer’s: The M3AD study, Alzheimer’s & Dementia. DOI: 10.1002/alz.71174

Journal information: Alzheimer’s & Dementia Provided by Columbia University’s Mailman School of Public Health

The Moving Body, the Hydraulic Brain: Exploring Fluid Shifts in the Brain

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The brain is more mechanically connected to the body than previously understood, according to new research published on 27 April in Nature Neuroscience. Using experiments in mice alongside computational simulations, scientists identified a potential biological explanation for why physical activity is beneficial for brain health. They found that contractions of the abdominal muscles can compress blood vessels linked to the spinal cord and brain, allowing the brain to shift subtly within the skull. This gentle movement appears to encourage the circulation of cerebrospinal fluid around the brain, which may help clear away waste that could otherwise impair neurological function.

Patrick Drew, a professor of engineering science and mechanics, neurosurgery, biology, and biomedical engineering at Penn State, explained that the findings build on earlier work showing how sleep and neuronal loss influence the timing and flow of cerebrospinal fluid. The new study suggests that everyday bodily motion itself plays a direct physiological role in maintaining brain health. According to Drew, even simple movements may contribute to processes that support the brain’s ability to cleanse itself.

“Our research helps explain how ordinary movement can act as a key mechanism for promoting brain health,” Drew noted. He described how abdominal muscle contractions push blood from the abdomen into the spinal cord in a manner similar to a hydraulic system. This action creates pressure that causes the brain to move slightly, which in turn drives fluid flow in and around it. Such fluid movement is thought to be essential for removing metabolic waste and may help reduce the risk of neurodegenerative conditions. The findings suggest that even modest physical activity could play a meaningful role in supporting these processes.

Drew further explained that, much like a pump in a hydraulic system generates pressure to move fluid, the “pump” in this case is the contraction of abdominal muscles. These contractions can be very subtle, such as those that occur before standing up or taking a step. When the muscles tighten, they apply pressure to the vertebral venous plexus—a network of veins connecting the abdomen to the spinal cavity—causing the brain to shift position within the skull.

To observe this mechanism, the research team used advanced imaging techniques in moving mice, including two-photon microscopy for detailed views of living tissue and microcomputed tomography for high-resolution three-dimensional imaging. They detected brain movement occurring just before the animals initiated motion, immediately following the abdominal muscle contractions that precede movement. Additional experiments confirmed the role of abdominal pressure by applying controlled force to the abdomens of lightly anaesthetised mice. Even in the absence of other movement, this localised pressure caused the brain to shift, demonstrating that abdominal contraction alone can drive the effect.

The researchers then turned to computational modelling to better understand how this motion influences fluid flow. Led by Francesco Costanzo, the team developed simplified models treating the brain as a sponge-like structure, allowing them to simulate how fluid moves through its complex spaces. By comparing the process to cleaning a sponge—running water through it while squeezing—they showed how small mechanical movements could help circulate fluid and remove waste. While further research is needed to determine how these findings translate to humans, the study points to a compelling link between everyday movement and the brain’s ability to maintain its own health.

More information: C. Spencer Garborg et al, Brain motion is driven by mechanical coupling with the abdomen, Nature Neuroscience. DOI: 10.1038/s41593-026-02279-z

Journal information: Nature Neuroscience Provided by Penn State

Lingering Effects: How Early Substance Use Leaves Its Mark on the Brain

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Young adults who frequently use substances may face lasting consequences for memory later in life, according to new research from the University of Michigan. The study found that patterns of heavy use in early adulthood could be linked to significantly poorer memory decades down the line.

Researchers examined how often participants engaged in binge drinking and daily—or near-daily—use of alcohol, cannabis, and cigarettes between the ages of 18 and 30. They then compared these behaviours with participants’ self-reported memory performance between the ages of 50 and 65. By following individuals across such a long period, the study provides insight into how early-life habits may shape cognitive health in midlife.

The research, funded by the National Institute on Drug Abuse and published in the Journal of Aging and Health, highlights both immediate and long-term effects of substance use. According to Megan Patrick, a research professor at the Institute for Social Research and principal investigator of the Monitoring the Future Longitudinal Panel Study, memory problems are often an early indicator of dementia. The study set out to determine whether substance use during young adulthood is associated with these kinds of cognitive concerns later in life.

Young adulthood represents a crucial phase for brain development, making it a particularly sensitive period for behaviours that can influence long-term health. This study is among the first to show a connection between cumulative substance use during these years and self-rated cognitive function decades later. Longitudinal data from the Monitoring the Future study allowed researchers to trace these associations across multiple stages of adulthood.

The findings suggest that different substances may affect later memory through distinct pathways. Binge drinking and frequent cannabis use were not directly associated with poor memory in later life. Instead, they increased the likelihood of developing substance use disorders in participants’ 30s, which in turn were linked to poorer memory outcomes. This indicates that addressing substance use disorders in midlife may help mitigate some of the longer-term cognitive risks.

Cigarette smoking, however, followed a different pattern. Daily smoking in young adulthood was directly associated with poorer memory in early midlife, regardless of whether individuals continued smoking later on. This underscores the importance of preventing smoking early, as its effects on brain health may persist even if the behaviour changes later in life.

Overall, the study reinforces the idea that behaviours in early adulthood can have far-reaching implications. Even when immediate health effects are not apparent, heavy substance use may contribute to cognitive decline many years later. The findings point to the value of early prevention and timely intervention, suggesting that reducing substance use among young adults could play a meaningful role in protecting long-term brain health.

More information: Megan Patrick et al, Young Adult Substance Use as a Predictor of Poor Self-Rated Memory Decades Later in Midlife, Journal of Aging and Health. DOI: 10.1177/08982643261431

Journal information: Journal of Aging and Health Provided by University of Michigan

Blood-Based Test Could Guide More Precise Breast Cancer Therapy for Older Women

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For women aged 70 and older diagnosed with a common form of breast cancer, identifying the most appropriate level of treatment remains a persistent challenge. Clinicians often lack sufficiently precise tools to tailor care to individual needs, making it difficult to strike the right balance between effective treatment and avoiding unnecessary interventions. This uncertainty is particularly relevant for patients with oestrogen receptor–positive breast cancer who may be considering less aggressive approaches, such as endocrine (hormone-blocking) therapy, instead of surgery and radiation.

A study published in Clinical Cancer Research by investigators at UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine suggests that a blood-based test could help guide these complex decisions. The research focused on a carefully selected group of women aged 70 and older who were evaluating endocrine therapy as their primary treatment option while opting to forgo surgery and radiation. The findings point to the potential of a minimally invasive test to support more individualised care strategies in this population.

At the centre of the study is the analysis of circulating tumour DNA (ctDNA), which consists of small fragments of genetic material shed by cancer cells into the bloodstream. By examining blood samples, researchers assessed whether the presence or absence of ctDNA could help identify which patients were less likely to respond to endocrine therapy alone. This approach offers a promising way to monitor tumour behaviour without relying solely on imaging or more invasive procedures.

The results indicated that patients with negative ctDNA tests—either at the start of treatment or shortly after beginning endocrine therapy—were more likely to experience stable disease or tumour shrinkage. For these individuals, avoiding surgery and radiation may not compromise outcomes, sparing them from potential side effects such as scarring, chronic swelling, infection, or nerve damage. Conversely, patients whose ctDNA remained detectable during treatment were more likely to show tumour progression, suggesting that additional interventions, including surgery, might still be necessary.

Importantly, the study did not aim to compare the effectiveness of different treatments. Instead, it sought to identify an early decision-making window that could help clinicians determine which patients are unlikely to benefit from hormone therapy alone. Because ctDNA testing can be performed through simple blood draws, many participants were able to provide samples from home. This reduced the need for frequent hospital visits and enabled broader participation across regional oncology sites, improving accessibility for patients outside major academic centres.

The study also incorporated perspectives from both patients and caregivers, groups whose experiences are often underrepresented in clinical research. More than 80% of patients reported that ctDNA results helped them feel better informed about their treatment decisions, particularly during the initial months of care. Caregivers highlighted the significant demands associated with supporting loved ones through treatment, often requiring them to reprioritise work and personal responsibilities. While the findings are encouraging, researchers emphasise that the study involved fewer than 50 participants and is not yet ready to inform standard clinical practice. Larger studies will be essential to confirm these results and determine how best to integrate this approach into routine care.

More information: Neil Carleton et al, Use of ctDNA in Older Women with ER+ Breast Cancer to Facilitate Surgical De-escalation: A Prospective, Hybrid-Decentralized Trial with Correlative Studies, Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-25-4079

Journal information: Clinical Cancer Research Provided by University of Pittsburgh