Monthly Archives: May 2025

Body Clocks, Muscle Function, and the Accelerated Ageing of Shift Workers

Muscle cells possess internal circadian clocks, finely tuned biological systems that regulate various cellular processes. According to recent research, disrupting these clocks, as often occurs with shift work, can significantly accelerate the ageing process. This study, published in the Proceedings of the National Academy of Sciences (PNAS), adds to a growing body of evidence linking irregular work schedules with long-term health impacts. The findings reveal that muscle clocks are crucial in maintaining muscle health by regulating protein turnover, a process critical for muscle growth, repair, and function. When this internal timing is disturbed, it can lead to premature muscle decline, echoing the effects of natural ageing.

The research, conducted by a team at King’s College London, highlights the critical function of these muscle clocks in coordinating the nightly breakdown and replenishment of defective proteins. During rest periods, muscle cells activate specific pathways to clear out damaged proteins that accumulate throughout the day due to physical stress and everyday wear. This nightly ‘housekeeping’ is essential for maintaining muscle strength and mass, as it clears cellular debris and ensures the continued function of muscle fibres. Disruption of this nocturnal process, as seen in shift workers, compromises this essential repair cycle, potentially accelerating the onset of sarcopenia – the age-related loss of muscle mass and strength.

To investigate this connection, the researchers turned to zebrafish, a popular model organism in biological studies. Zebrafish share about 70% of their genetic material with humans, making them an excellent choice for exploring fundamental biological processes. Their transparency as larvae allows for direct observation of muscle fibres under a microscope, providing a unique window into the cellular changes driving muscle health and decline. By impairing the muscle clocks in these fish through the overexpression of a malfunctioning clock protein, the researchers could simulate the long-term effects of circadian disruption.

Lead author Jeffrey Kelu, a King’s College London research associate, described the experimental approach: “We monitored these genetically altered zebrafish over two years, comparing them to healthy controls. No significant differences in muscle size or function were observed in the early stages of life – at six months and one year. However, by the two-year mark, the fish with disrupted muscle clocks displayed clear signs of premature ageing. They were smaller, weighed less, swam less frequently, and moved more slowly, all hallmarks of sarcopenia and overall physical decline – a pattern also seen in human shift workers.”

The study also uncovered the underlying mechanisms contributing to this accelerated ageing. The muscle clock is critical for managing protein turnover, a process essential for muscle maintenance. It activates the breakdown of defective muscle proteins during rest, preventing the accumulation of cellular damage. When this clock is disrupted, the faulty proteins remain, gradually undermining muscle function and accelerating physical decline. This insight explains why muscle deterioration occurs more rapidly in those with irregular work schedules.

Dr Kelu emphasised the broader implications of this work: “In the UK, approximately four million shift workers are essential to keeping businesses, healthcare, and emergency services running around the clock. Our study adds to the growing understanding that the disruption of circadian rhythms can have widespread health impacts, particularly on muscle health. This knowledge is crucial for developing strategies to support the long-term well-being of shift workers.” Looking ahead, the researchers are exploring potential treatments aimed at countering these effects. Preclinical studies are underway, investigating drugs that could modulate specific clock proteins, potentially slowing or reversing muscle decline in those whose work patterns disrupt their natural biological rhythms.

More information: Jeffrey Kelu et al, Muscle peripheral circadian clock drives nocturnal protein degradation via raised Ror/Rev-erb balance and prevents premature sarcopenia, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2422446122

Journal information: Proceedings of the National Academy of Sciences Provided by King’s College London

Klotho: The Age-Defying Protein for Health and Longevity

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An international study led by the Institut de Neurociències at the Universitat Autònoma de Barcelona (INc-UAB) has provided compelling evidence that increasing levels of the Klotho protein in mice can extend lifespan and significantly improve both physical and cognitive health during ageing. Published in the journal Molecular Therapy, this research represents a crucial step towards understanding how to counteract the physical decline and neurological deterioration associated with old age. The study was spearheaded by Professor Miguel Chillón, an ICREA researcher at the INc-UAB, and focused on the secreted form of the Klotho protein (s-KL), known for its potential to promote healthy ageing.

As we age, the body naturally undergoes physical and cognitive changes. Muscle and bone mass gradually decline, leading to frailty and a heightened risk of falls and fractures, while neurons in the brain progressively degenerate, losing vital connections. This neurological decay underlies the increased prevalence of diseases like Alzheimer’s and Parkinson’s. Addressing these changes in a world where populations live longer is challenging for medical science. Researchers are therefore keen to explore therapies that can extend lifespan and preserve the quality of life in later years.

The INc-UAB team approached this challenge by treating young mice with gene therapy vectors designed to increase s-KL production. These vectors introduced copies of the gene encoding s-KL into the mice’s cells, prompting them to produce the beneficial protein. The treatment was delivered intravenously and directly into the brain, ensuring that central nervous system tissues received sufficient s-KL. By the time the mice reached 24 months of age, roughly equivalent to 70 human years, the treated animals exhibited significant improvements in muscle, bone, and cognitive health compared to their untreated peers. This indicates that enhancing s-KL levels can effectively mitigate some of the most debilitating aspects of ageing.

The physical benefits were particularly striking. Mice that received the s-KL treatment lived 15 to 20 per cent longer and demonstrated superior physical performance, with larger muscle fibres and less fibrosis, pointing to improved muscle health. Bone health also improved, especially in female mice, where the treatment preserved the internal bone structure (trabeculae), potentially reducing the risk of osteoporosis. These findings suggest that s-KL may offer broad protective effects against the musculoskeletal decline associated with ageing.

The cognitive improvements were equally promising. In the brain, s-KL treatment stimulated the growth of new neurons and enhanced immune activity in the hippocampus, a critical region for learning and memory. These findings are particularly encouraging given the high burden of neurodegenerative diseases in older populations. “We have been exploring the therapeutic potential of Klotho for some time, particularly in the context of neurodegenerative disorders,” explains Professor Chillón. “This study expands on that work, demonstrating that s-KL may promote broader aspects of healthy ageing.”

With these promising results, the research team has moved to protect their findings through three new patents covering the use of Klotho for treating muscle, bone, and cognitive deficits and increasing lifespan. The researchers hope to refine the delivery methods for s-KL, potentially enabling safe and effective human applications. “If we can develop a viable delivery system, s-KL could significantly enhance quality of life as people age, helping to build a healthier society overall,” they conclude, underscoring the transformative potential of their work.

More information: Joan Roig-Soriano et al, Long-term effects of s-KL treatment in wild-type mice: Enhancing longevity, physical well-being, and neurological resilience, Molecular Therapy. DOI: 10.1016/j.ymthe.2025.02.030

Journal information: Molecular Therapy Provided by Universitat Autonoma de Barcelona

Immersive VR with Scent: A Novel Approach to Cognitive Health

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As the global population ages, supporting cognitive and memory functions in older adults has become critical. According to the United Nations, by 2070, the number of people aged 65 and older is projected to surpass 2.2 billion, overtaking the global population of children under 18 for the first time in human history. This demographic shift is particularly pronounced in countries like Japan, where nearly 28.7% of the population is already aged 65 or older, making it the fastest-ageing nation in the world. As life expectancy rises and birth rates fall, the need for adequate cognitive support for older adults becomes ever more pressing, driving researchers to explore innovative strategies for preserving brain function.

One promising approach involves olfactory stimulation, leveraging the powerful link between the sense of smell and the brain’s memory centres. Unlike other senses, olfactory signals bypass the brain’s traditional sensory relay systems and connect directly to regions like the hippocampus and amygdala, which are crucial for memory and emotional processing. This unique neural pathway makes smell a potent trigger for recalling past experiences and emotions. Building on this foundation, a multidisciplinary research team from the Institute of Science Tokyo (Science Tokyo), the University of the Arts London, Bunkyo Gakuin University, and Hosei University in Japan has developed the world’s first cognitive training method for older adults that combines olfactory stimulation with virtual reality (VR). Their groundbreaking study was published in Volume 15 of Scientific Reports on 28 March 2025.

The researchers designed their cognitive training system to provide an immersive, goal-oriented experience that fully engages the brain’s sensory and cognitive networks. Professor Takamichi Nakamoto from Science Tokyo, one of the lead scientists behind the project, explains the rationale: “VR offers a powerful platform for simulating sensory experiences in a controlled, immersive setting. By combining goal-oriented tasks with real-time feedback, our VR-based olfactory training approach can increase cognitive engagement and maximise its therapeutic impact.” The system uses a specialised olfactory display that emits precise scents during VR gameplay, enhancing the realism and cognitive stimulation of the experience.

The training activity is a carefully crafted sequence designed to strengthen multiple cognitive functions. It begins in a lush virtual landscape, where participants use a VR controller to interact with their environment. The exercise starts with a “smell memory” phase, where users encounter a virtual stone statue that, when touched, releases a distinct scent along with a white vapour cloud as a visual cue, reinforcing the link between the smell and the visual stimulus. This is followed by a navigation phase, where players move through the virtual environment, guided by subtle scent trails, to locate a second scent source, a stone lantern. Upon reaching the lantern, they must identify the original scent from three differently scented vapour clouds, testing their ability to match and recall olfactory information.

This innovative training method has shown promising results in early trials. In a study involving 30 older adults aged 63 to 90, just 20 minutes of gameplay led to measurable cognitive improvements. Participants performed significantly better on various cognitive assessments, including the Hiragana Rotation Task, which tests spatial reasoning and visuospatial processing. In this task, players must determine whether rotated Japanese characters match their original forms, improving accuracy scores from 19–82 to 29–85. In a separate word-based spatial memory recall task, where participants memorised word positions within a grid, scores rose from 0–15 to 3–15, demonstrating enhanced memory retention. These gains were validated through rigorous statistical analysis, confirming the effectiveness of the olfactory-enhanced VR approach in boosting cognitive function.

Looking to the future, the research team is optimistic about the broader potential of their approach. They envision a time when olfactory-based VR could become a widely accessible tool for supporting cognitive health, particularly as scent delivery technologies become more affordable and practical for everyday use. This approach could not only aid in maintaining memory and cognitive function in older adults but also potentially slow the progression of neurodegenerative conditions like dementia. Professor Nakamoto notes, “With continued research and technological advancements, we hope to make this form of cognitive training a regular part of mental fitness for older adults, improving quality of life and mental resilience as populations continue to age.”

More information: Takamichi Nakamoto et al, Exploring the effects of olfactory VR on visuospatial memory and cognitive processing in older adults, Scientific Reports. DOI: 10.1038/s41598-025-94693-9

Journal information: Scientific Reports Provided by Institute of Science Tokyo

Cycling as a Path to Longevity and Vitality in Older Adults, Especially for Nondrivers

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In Japan, a considerable proportion of older adults rely on bicycles as a primary means of transportation. This trend is notably more prevalent than in Europe or the United States. Prior studies have highlighted the health benefits of cycling, linking it to increased physical activity and more robust social interactions. These benefits are particularly critical for older adults, as regular physical exercise can reduce the likelihood of requiring long-term care and lower overall mortality risk. However, long-term studies examining these effects within the Japanese context have been lacking despite the recognised advantages of cycling.

The present study sought to address this gap by exploring the long-term health impacts of cycling among older adults, focusing on two key research objectives. Firstly, it investigated the relationship between the frequency of bicycle use in 2013 and the subsequent need for long-term care and mortality over a decade-long follow-up period, extending to 2023. Secondly, it examined how changes in cycling habits, including nonuse, initiation, interruption, and continuation, affected the onset of long-term care needs or death at two critical points: 2013 and 2017. To provide a more nuanced understanding, the analysis focused on older adults who do not drive, recognising that nondrivers may particularly benefit from cycling to maintain independence and mobility.

The first strand of this research revealed that older adults who cycled in 2013 faced a significantly lower risk of requiring long-term care and a reduced likelihood of death over the following decade compared with those who did not cycle. This protective effect was especially pronounced among nondrivers, underscoring the critical role of cycling in supporting healthy ageing for those without access to cars.

The second aspect of the study provided further insights, demonstrating that older adults who continued cycling for at least four years, from 2013 to 2017, experienced notably lower risks of requiring long-term care and reduced mortality rates over the subsequent six years, compared with those who remained non-cyclists. This trend was even more striking among nondrivers, who sustained their cycling habits, and those who took up cycling during this period exhibited a significantly lower likelihood of needing long-term care.

These findings collectively suggest that cycling is a potent “lifestyle companion” for older adults, promoting both physical and mental well-being while potentially extending life expectancy. This is particularly relevant in Japan, where many older individuals voluntarily surrender their driving licences, making alternative forms of mobility increasingly crucial for maintaining independence. Given this demographic shift, there is a clear need for supportive policies and community initiatives that encourage and facilitate cycling among older adults, particularly those without the option to drive.

In conclusion, promoting cycling among older adults enhances their physical health. It contributes to broader social and psychological well-being, reducing the strain on long-term care systems and fostering a higher quality of life. As the ageing population in Japan continues to expand, recognising and nurturing this connection between mobility and health could have profound implications for public health strategies, helping to create a more active and resilient older generation.

More information: Kenji Tsunoda et al, Changes in cycling and incidences of functional disability and mortality among older Japanese adults, Transportation Research Part F: Traffic Psychology and Behaviour. DOI: 10.1016/j.trf.2025.03.006

Journal information: Transportation Research Part F: Traffic Psychology and Behaviour Provided by University of Tsukuba

Unlocking the Age-Defying Benefits of Black Tea and Berries

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A recent study has revealed that a diet rich in black tea, berries, citrus fruits, and apples could significantly promote healthier ageing. The research, conducted collaboratively by Edith Cowan University (ECU), Queen’s University Belfast, and the Harvard T.H. Chan School of Public Health, highlights the potential benefits of flavonoid-rich foods in reducing the risk of key aspects of unhealthy ageing, such as frailty, impaired physical function, and poor mental health. Flavonoids, naturally occurring compounds in various fruits and vegetables, are known for their powerful antioxidant and anti-inflammatory properties, making them an essential dietary component for those seeking to maintain their physical and mental well-being as they age.

Dr Nicola Bondonno, an adjunct lecturer at ECU, emphasised that the ultimate goal of medical research extends beyond simply prolonging life. Instead, the focus is on ensuring individuals remain healthy and active throughout their lifespan. “We know from previous studies that people who consume more flavonoids tend to live longer and are less likely to develop major chronic diseases like dementia, diabetes, or heart disease,” she explained. “Our latest findings reinforce this, demonstrating that those with higher flavonoid intake also tend to experience healthier ageing.”

The study, which analysed health data from a substantial cohort of 62,743 women and 23,687 men over 24 years, found that women with the highest flavonoid intakes had a 15% lower risk of frailty, a 12% lower risk of impaired physical function, and a 12% lower risk of poor mental health compared to those with the lowest flavonoid consumption. While the impact appeared to be more pronounced among women, men with higher flavonoid intakes still benefited, showing a notably lower risk of poor mental health. These findings suggest that the protective effects of flavonoids against the physical and cognitive declines often associated with ageing vary across genders, possibly influenced by differences in study follow-up times rather than inherent biological disparities.

A senior author, Professor Aedin Cassidy from Queen’s University Belfast, elaborated on how flavonoids might support healthy ageing. “Flavonoids are well known for their ability to reduce oxidative stress and inflammation, support blood vessel health, and help maintain skeletal muscle mass – all of which are critical for preventing frailty and maintaining physical function as we grow older,” she noted. Cassidy also pointed out that flavonoid-rich foods, such as berries, apples, red wine, oranges, and tea, have long been associated with these health benefits, reinforcing the value of these everyday foods in a balanced diet.

The study also found that even moderate increases in flavonoid consumption could yield significant benefits. For instance, participants who boosted their intake of flavonoid-rich foods by just three servings a day experienced a 6% to 11% lower risk across all three ageing outcomes in females, and a 15% lower risk of poor mental health in males. This suggests that relatively simple dietary adjustments could have a meaningful impact on long-term health outcomes, potentially delaying or preventing the onset of age-related decline.

Professor Eric Rimm from the Harvard T.H. Chan School of Public Health highlighted the broader implications of these findings, noting that they underscore the potential for straightforward dietary modifications to enhance the quality of life as people age significantly. “Overall, our results point to the power of nutrition in optimising healthy ageing, reinforcing the idea that what we eat truly matters as we strive to live longer and healthier lives,” he said.

More information: Nicola Bondonno et al, Associations between flavonoid-rich food and flavonoid intakes and incident unhealthy aging outcomes in older United States males and females, American Journal of Clinical Nutrition. DOI: 10.1016/j.ajcnut.2025.02.010

Journal information: American Journal of Clinical Nutrition Provided by Edith Cowan University

Is Your Heart Ageing Ahead of Schedule?

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Researchers at the University of East Anglia (UEA) have developed a pioneering method to measure the ‘true age’ of the heart using MRI technology. Detailed in a published study, this breakthrough could transform how heart disease is diagnosed and managed. Rather than simply reflecting a person’s chronological age, this innovative approach calculates the heart’s ‘functional age’ – a measure of how well it performs relative to its biological age. The hope is that this technique will allow doctors to detect heart problems much earlier, providing a critical window for intervention before severe symptoms or life-threatening events occur.

Dr Pankaj Garg, the lead researcher from UEA’s Norwich Medical School and a consultant cardiologist at the Norfolk and Norwich University Hospital, emphasises the potential impact of this work. “Imagine discovering that your heart is actually ‘older’ than you are,” he says. “For people living with conditions like high blood pressure, diabetes, or obesity, this is often the case. Our new MRI approach doesn’t just count birthdays – it measures how well your heart is holding up, providing a more accurate picture of cardiovascular health.” This new perspective on heart health could be particularly valuable for those with chronic conditions, as it offers a more precise assessment of the long-term strain on the heart.

The research involved collaboration with hospitals in the UK, Spain, and Singapore, where the team studied MRI scans from 557 people – 191 healthy individuals and 366 with conditions such as high blood pressure, diabetes, or obesity. Using advanced imaging techniques, they measured key indicators of heart function, including the size and strength of the heart’s chambers. These measurements were then used to create a mathematical model calculating the heart’s functional age. This model was tested against the data from healthy hearts to ensure accuracy, providing a reliable method for assessing heart age.

The results were striking. In healthy individuals, the heart’s functional age typically matched their chronological age. However, for those with chronic health issues, the gap was often significant. Dr Garg notes, “For example, a 50-year-old with high blood pressure might have a heart that functions like it’s 55 or older. In some cases, the difference was even more pronounced, highlighting the accelerated aging that can occur with conditions like diabetes, obesity, or atrial fibrillation.” This finding underscores the critical importance of early detection and proactive management in preventing heart disease.

Dr Garg believes this approach could be a game changer for cardiovascular care. By providing a clearer, more accurate picture of heart health, this MRI method can potentially catch problems before they become severe, offering doctors a powerful tool to intervene early. “This is more than just a diagnostic breakthrough,” he says. “It’s a way to potentially add years to a person’s life by slowing down the heart’s ageing through lifestyle changes or medical treatments.”

Ultimately, this research could have far-reaching implications for public health. Encouraging individuals to take control of their heart health earlier may reduce the global burden of heart disease, one of the leading causes of death worldwide. As Dr Garg puts it, “Knowing your heart’s true age could be the wake-up call people need to take better care of themselves, whether eating healthier, exercising more, or following their doctor’s advice. It’s about giving people a fighting chance against heart disease and helping them live longer, healthier lives.”

More information: Pankaj Garg et al, Cardiovascular magnetic resonance imaging markers of ageing: a multi-centre, cross-sectional cohort study, European Heart Journal Open. DOI: 10.1093/ehjopen/oeaf032

Journal information: European Heart Journal Open Provided by University of East Anglia

Understanding the Cognitive Risks of Early Menopause

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A team of researchers from the Tohoku University Graduate School of Medicine and the Tokyo Metropolitan Institute of Medical Science has found that women who experience menopause before the age of 40 tend to have worse cognitive outcomes than those who reach menopause after the age of 50. This significant finding, published on 15 April 2025 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, provides valuable insights for clinicians assessing dementia risk in female patients. Given the global prevalence of dementia among women, this research adds an essential piece to the puzzle of understanding how biological factors influence cognitive health.

The researchers chose to explore this connection because dementia disproportionately affects women, suggesting the presence of sex-specific risk factors. Early menopause has long been linked to a higher risk of late-life depression, a known contributor to dementia. However, direct evidence of the impact of early menopause on cognitive decline has been scarce. By focusing on this relationship, the study aims to clarify whether early menopause itself is a direct risk factor, independent of other contributing conditions like depression.

For the study, the team analysed data from the English Longitudinal Study of Ageing, which included 4,726 women and 4,286 men. Participants were classified into three menopausal age groups: early menopause, mid-range menopause, and late menopause. Cognitive function was assessed through tests measuring orientation, immediate and delayed recall, and verbal fluency, providing a comprehensive overview of mental performance. To ensure accurate results, the researchers adjusted for baseline modifiable dementia risk factors, such as cardiovascular health and lifestyle factors, which are known to influence cognitive decline.

Lead author Miharu Nakanishi from the Tohoku University Graduate School of Medicine emphasised the importance of isolating the impact of early menopause from other risk factors. “Since early menopause is associated with a higher risk of depression, which itself increases the risk of dementia, it was crucial to control for this factor to determine if early menopause directly contributes to cognitive decline,” Nakanishi explained. After these adjustments, the study found that women who reached menopause before 40 had significantly poorer cognitive outcomes at two-year follow-up assessments, including worse orientation and immediate and delayed recall. In contrast, women who reached menopause at or after 50 outperformed a comparison group of men, suggesting a potential protective effect associated with later menopause.

These findings suggest that women who experience early menopause may constitute a unique, sex-specific high-risk group for cognitive decline. While hormone replacement therapy (HRT), a standard treatment for menopausal symptoms, did not appear to influence cognitive outcomes in this study significantly, the results underscore the need for further research to explore the biological mechanisms linking female hormone levels to mental health. Understanding this connection could pave the way for targeted treatments aimed at delaying or preventing dementia in at-risk women.

More information: Miharu Nakanishi et al, Associations among age at menopause, depressive symptoms, and cognitive function, Alzheimers & Dementia. DOI: 10.1002/alz.70063

Journal information: Alzheimers & Dementia Provided by Tohoku University

How Shifts in Gut Bacteria with Age Might Elevate Leukemia Risk

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In collaboration with an international team, researchers at Cincinnati Children’s have made a groundbreaking discovery linking gut health to blood cancer risk. This connection, detailed in a study published on 23 April 2025 in the journal Nature, sheds light on how changes in the gut as we age might significantly influence the development of leukaemia and potentially other age-related diseases. The findings offer fresh insights into the complex interactions between our digestive system, immune function, and cancer risk, opening new avenues for early intervention and preventive care.

As people grow older, or when their gut health is compromised by illness, the intestinal lining can become more permeable, allowing bacteria and their metabolic byproducts to enter the bloodstream. One such molecule, a bacterial sugar known as ADP-heptose, has emerged as a critical signal that can drive the expansion of dormant, pre-leukaemic blood cells. This process is a crucial step in the progression from early, symptomless cell changes to full-blown blood cancer. By establishing this previously hidden link, the study marks a significant advance in understanding how age-related changes in the gut microbiome can trigger blood cell transformations.

Dr Daniel Starczynowski, PhD, director of the Advanced Leukaemia Therapies and Research Centre at Cincinnati Children’s and the study’s corresponding author, highlighted the importance of this discovery. “Our research shows that age-associated changes in the gut are a non-traditional but significant risk factor for blood cancers. This insight could transform our approach to preventing these diseases, potentially allowing us to intervene before pre-leukaemic cells evolve into aggressive malignancies,” he said. Co-author Dr Puneet Agarwal, PhD, an associate staff scientist in the Division of Experimental Hematology and Cancer Biology, added, “This study underscores the importance of maintaining gut health as we age, as it could significantly impact the risk of developing blood cancers.”

Leukaemia remains a significant health burden, particularly for older adults. According to the US National Cancer Institute, more than 470,000 Americans are currently living with leukaemia, and over 62,000 new cases are diagnosed each year, with nearly 24,000 deaths projected in 2024 alone. Despite improved survival rates, leukaemia remains a life-threatening condition, with individuals over the age of 65 facing a disproportionately high risk. While scientists have long recognised that the ageing immune system and genetic mutations play key roles in this elevated risk, the findings from Starczynowski’s team suggest that microbial shifts within the gut might also be a critical but underappreciated factor.

The team’s experiments revealed that as the gut lining becomes more permeable with age, common gut bacteria, including gram-negative strains, can release increasing amounts of ADP-heptose. This sugar, typically confined to the gut, can leak into the bloodstream and act as a potent activator of pre-leukaemic cells. Once in the blood, ADP-heptose triggers the formation of tiny cellular structures called TIFAsomes, which serve as internal signals promoting the growth of pre-cancerous cells. To track this process, the researchers developed a new diagnostic tool, the TIFAsome Assay, which detects ADP-heptose activity in blood samples, potentially offering an early warning system for individuals at increased leukaemia risk.

The study also sheds light on a little-known condition called clonal haematopoiesis of indeterminate potential (CHIP), which affects an estimated 10-20% of adults over 70. CHIP is characterised by the gradual accumulation of genetic mutations in blood cells, creating clones that can progress to cancer. Using genetically modified mice designed to mimic human CHIP, the researchers demonstrated that exposure to ADP-heptose significantly accelerates the expansion of these pre-leukaemic cells, providing a direct link between gut microbial activity and blood cancer risk. This finding suggests that older adults with CHIP may be particularly vulnerable to the effects of gut-derived bacterial byproducts.

Critically, the researchers identified a potential target for therapeutic intervention. They discovered that ADP-heptose’s ability to trigger pre-leukaemic cell growth depends on a receptor protein known as ALPK1, found on the surface of mutant blood cells. Although no drug exists to inhibit ALPK1, the team pinpointed a promising lead: an enzyme produced by the gene UBE2N. Blocking this enzyme significantly reduced pre-leukaemic cell expansion in their mouse models, even in ADP-heptose presence, suggesting a possible pathway for future drug development. The team hopes that further research will develop a targeted ALPK1 inhibitor suitable for human use.

The findings underscore the importance of maintaining gut health as a potential strategy to reduce cancer risk, especially in older adults. While a targeted drug remains a longer-term goal, practical steps like dietary adjustments, prebiotics, and probiotics might offer more immediate, albeit less specific, benefits for reducing the impact of gut-derived cancer triggers. “More than 10 million older adults might have CHIP without knowing it,” Starczynowski emphasised. “Our study highlights the critical role of gut health in potentially preventing blood disorders and other age-related diseases, providing a promising direction for future research.”

More information: Daniel Starczynowski et al, Microbial metabolite drives ageing-related clonal haematopoiesis via ALPK1, Nature. DOI: 10.1038/s41586-025-08938-8

Journal information: Nature Provided by Cincinnati Children’s Hospital Medical Center

Innovative Model Predicts Early Signs of Alzheimer’s Disease

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In a groundbreaking study, researchers in the laboratory of Prof. Lucía Chávez Gutiérrez at VIB-KU Leuven have made significant strides in understanding the genetic factors that contribute to familial Alzheimer’s disease (fAD). Their findings, recently published in Molecular Neurodegeneration, reveal that specific genetic mutations act as molecular clocks, precisely influencing the age at which the disease manifests. This discovery could transform early diagnostic practices and pave the way for more personalised treatment strategies for those at risk, offering hope for improved outcomes in a condition that has long defied precise prediction.

Alzheimer’s disease remains one of the most prevalent and challenging neurodegenerative disorders globally, affecting approximately 50 million people. Despite decades of intensive research, the exact mechanisms driving this devastating disease remain only partially understood. A defining feature of Alzheimer’s pathology is the formation of amyloid plaques within the brain – dense, insoluble clusters of misfolded amyloid-β (Aβ) peptide fragments. These toxic aggregates are produced through a complex molecular cascade, regulated primarily by the γ-secretase enzyme and a network of key proteins. They are believed to be critical in destroying neurons, leading to cognitive decline.

Familial Alzheimer’s disease is a rare, early-onset form of the condition that accounts for a small fraction of total Alzheimer’s cases. It is caused by inherited mutations in three critical genes: amyloid precursor protein (APP), Presenilin 1 (PSEN1), and Presenilin 2 (PSEN2). These genetic variants significantly increase the likelihood of developing Alzheimer’s at a much younger age, often decades before the more common sporadic form of the disease. However, the precise role these mutations play in driving disease onset has been a topic of intense scientific debate for decades. Understanding this link is essential for improving the accuracy of clinical diagnoses and developing targeted therapies.

“Patients with familial Alzheimer’s disease often inherit spontaneous genetic mutations, but until now, clinicians have struggled to provide precise, mutation-specific predictions regarding disease onset,” explains Prof. Lucía Chávez Gutiérrez. “Our team has developed a method to experimentally assess the likelihood of specific mutations causing the disease, along with a means to estimate the likely age of onset.” This innovative approach represents a significant breakthrough, offering a clearer understanding of how each mutation can influence the disease progression timeline.

Building on their earlier work focusing on PSEN1, the VIB-KU Leuven team has expanded their analysis to include all three significant familial Alzheimer’s genes – PSEN1, PSEN2, and APP. Their comprehensive genetic studies reveal that each of these genes contributes uniquely to the timing of disease onset, effectively functioning like ticking biological clocks. They discovered robust, gene-specific correlations between particular mutations and the age at which symptoms first appear, offering a much clearer picture of the genetic underpinnings of familial Alzheimer’s disease.

Their findings also highlight a critical link between the ratio of long-to-short Aβ peptides and the timing of disease onset. For many years, researchers have recognised that longer Aβ peptides are particularly toxic, potentially triggering the molecular pathways that lead to Alzheimer’s. This study demonstrated that even a modest, 12% shift in the Aβ peptide profile could delay the onset of familial Alzheimer’s by as much as five years, suggesting a promising therapeutic target. “This finding highlights the potential of targeting γ-secretase to alter the balance of Aβ peptides, offering a potential pathway to delay or even prevent disease onset,” notes Prof. Chávez Gutiérrez.

Beyond simply mapping genetic contributions, the research team has also developed a versatile analytical framework with dual functions. It can assess the pathogenic potential of individual genetic variants and identify patients who may carry genetic modifiers or have experienced environmental exposures that alter their expected disease onset. This approach provides a critical tool for genetic counselling and risk assessment, moving the field closer to truly personalised medicine for Alzheimer’s patients.

The researchers are optimistic that their predictive model for disease onset could transform patient care. “Our model represents a critical step toward personalised treatment strategies,” adds Sara Gutiérrez Fernández, the study’s first author. “With continued research, we aim to refine this model further, ultimately providing clinicians with more precise tools for early diagnosis and patient management.” As this line of research advances, it promises to reshape our understanding of familial Alzheimer’s disease, offering new hope to those at risk of this devastating condition.

More information: Sara Gutiérrez Fernández et al, Spectrum of γ-Secretase dysfunction as a unifying predictor of ADAD age at onset across PSEN1, PSEN2 and APP causal genes, Molecular Neurodegeneration. DOI: 10.1186/s13024-025-00832-1

Journal information: Molecular Neurodegeneration Provided by Vlaams Instituut voor Biotechnologie

Keeping Your Brain Sharp: The Role of Exercise

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When Ulrik Wisløff and Atefe R. Tari from the Norwegian University of Science and Technology (NTNU) released their book “Microtraining – 7 Weeks to Boost Fitness and Strength” earlier this year, it captured significant attention in Norway. The book highlighted a simple yet powerful message – even small amounts of physical activity can yield substantial health benefits. Building on this idea, the researchers have shifted their focus to how physical fitness impacts brain health, collaborating with colleagues from the Queensland Brain Institute in Australia. Their latest findings, published in the British medical journal The Lancet, underscore exercise’s vital role in supporting cognitive function as we age.

The study presents compelling evidence that the brain, like the heart, significantly benefits from physical activity. High-intensity exercise, even in short bursts, can positively affect the brain, improving blood flow, reducing inflammation, enhancing brain plasticity, and increasing the release of protective molecules in the bloodstream. These processes are crucial because they tend to decline with age, contributing to cognitive impairment and neurodegenerative diseases. Tari and her team emphasise that these mechanisms are deeply involved in the development of conditions like dementia, making exercise a critical tool for prevention.

One of the study’s most striking conclusions is that even modest amounts of high-intensity activity can profoundly impact brain health. This is an important finding, given that many people struggle to meet current physical activity guidelines, which recommend at least 150 minutes of moderate or 75 minutes of vigorous exercise per week. “Fully 50 to 70 per cent of the population does not manage today’s activity recommendations,” Wisløff noted. The researchers argue that a shift in public health messaging, focusing on small but intense bursts of exercise, could significantly increase participation rates and improve public brain health.

Tari and Wisløff’s research highlights that this approach, which they call “microtraining”, could be particularly impactful for older adults. Small doses of high-intensity exercise, such as brisk walking or short, intense intervals, can reduce the risk of dementia by up to 40 per cent. This is a powerful message for a population increasingly concerned about cognitive decline. “It’s never too late to start,” Tari emphasised, pointing out that even those who have been largely inactive throughout their lives can still see meaningful benefits.

The researchers also stress the importance of more explicit public health guidance. While current recommendations focus on overall activity levels, the emerging evidence suggests that intensity is just as crucial, if not more so, for maintaining brain function. As Tari noted, “Today’s recommendations emphasise total activity, but we show that even small amounts of high-intensity exercise have an effect on the brain. This should be communicated more clearly – it may be what motivates people to get started.” This approach aligns with a broader trend in scientific thinking that prioritises quality over quantity regarding physical fitness.

As global life expectancy rises, the need for effective strategies to combat cognitive decline has never been more urgent. With no known cure for many neurodegenerative conditions, prevention through lifestyle changes like regular physical activity becomes essential. “Exercise is cheap, accessible, and free of side effects. It should be considered a first-line measure to preserve brain health,” Tari said. In an era where medical breakthroughs are often costly and complex, moving more, even in brief, intense bursts, may offer one of the most accessible and impactful paths to preserving mental sharpness and quality of life in later years.

More information: Atefe R. Tari et al, Neuroprotective mechanisms of exercise and the importance of fitness for healthy brain ageing, The Lancet. DOI: 10.1007/s00394-023-03123-x

Journal information: The Lancet Provided by Norwegian University of Science and Technology

Natural Spaces Can Help Reduce Urban Well-being Gaps

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The relationship between a person’s connection to nature and their overall well-being is closely influenced by the socioeconomic status of the area in which they live. This is the key finding from a recent analysis by researchers at Kobe University, who examined the impact of district-level socioeconomic conditions on nature-related well-being. The study, led by human environmental scientist Uchiyama Yuta, surveyed 3,500 residents across two major metropolitan regions in Japan—Tokyo-Yokohama and Osaka-Kobe. The aim was to explore how the proximity to and personal perception of nature influence well-being, considering the often overlooked but critical role of economic disparities.

Many city dwellers have fond memories of outdoor activities like hiking, camping, or simply walking through a local park—activities that nurture a sense of connection to the natural world. Yet, in modern urban environments, access to nature can vary dramatically depending on socioeconomic conditions. Wealthier neighbourhoods often have more green spaces and better infrastructure for outdoor activities. At the same time, economically disadvantaged areas tend to lack these amenities, compounding the stress and health challenges their residents face. Despite these apparent disparities, few studies have comprehensively examined the links between socioeconomic status, nature exposure, and well-being at a district level.

To fill this gap, Uchiyama and his team adopted a multifaceted approach. They measured both objective and subjective nature-relatedness among the participants. Objective measures included physical proximity to parks and natural areas, while subjective assessments captured personal feelings of connection to nature. These responses were then analysed alongside district-level socioeconomic data, adding a third, critical layer to understanding how these factors interact to shape well-being.

The findings, published in the journal Landscape and Urban Planning, reveal a clear trend: individuals who feel more connected to nature report higher levels of well-being. This effect is particularly strong in economically disadvantaged, densely urbanised districts. In these areas, access to green spaces serves as a crucial buffer against the stresses of urban life, offering a rare but vital source of mental and physical relief.

But why is this relationship so pronounced in less affluent areas? Previous studies have suggested that people living under significant financial and social stress derive greater benefit from natural environments, as these spaces offer respite from the daily pressures that wealthier residents can often offset through other means, such as private gardens, fitness facilities, or wellness services. In contrast, those in higher-income districts, while still benefiting from nature, have a broader range of resources available to support their health and happiness, potentially diluting the relative impact of nature exposure.

Reflecting on the implications for urban planning and public health, Uchiyama remarked, “We anticipate that conserving and enhancing existing natural spaces, as well as organising community-focused outdoor activities, could significantly boost well-being in economically disadvantaged areas. Interestingly, our findings also highlight that childhood experiences with nature strongly predict adult well-being.” This suggests that policies ensuring equitable early-life exposure to natural environments could have lasting, positive impacts on public health.

Looking ahead, the research team plans to expand their work to explore how factors such as residential mobility and changes in socioeconomic status over time influence nature-related well-being. Uchiyama noted, “Our findings align with similar studies conducted in other regions, indicating that interventions targeting both subjective and objective connections to nature could be widely applicable, including in other rapidly urbanising regions such as Monsoon Asia.” As part of an ongoing international collaborative project, the team is now examining the links between environmental awareness, resilience, and well-being in cities like Bangkok and Manila, hoping to generate insights that can guide urban policy worldwide.

More information: Yuta Uchiyama et al, Association between objective and subjective relatedness to nature and human well-being: Key factors for residents and possible measures for inequality in Japan’s megacities, Landscape and Urban Planning. DOI: 10.1016/j.landurbplan.2025.105377

Journal information: Landscape and Urban Planning Provided by Kobe University

The Science Behind Middle-Age Weight Gain

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As we move into middle age, we commonly notice a gradual thickening around the waistline. While this change might seem merely cosmetic, it carries significant health implications. Excess abdominal fat not only accelerates the ageing process but also increases the risk of chronic conditions such as heart disease, diabetes, and metabolic disorders. Despite this, the precise biological mechanisms behind midlife weight gain have remained mysterious. However, new research from City of Hope, one of the most significant cancer research and treatment organisations in the United States and a leading centre for diabetes research, has uncovered a critical cellular trigger that might explain why our midsections tend to expand as we age. Published in Science, this breakthrough provides fresh insights into the underlying biology of age-related fat accumulation. It opens the door to potential new therapies to reduce belly fat and extend healthy lifespans.

The study, led by Dr. Qiong (Annabel) Wang, an associate professor at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute, reveals that ageing activates a unique class of adult stem cells, leading to a surge in the creation of new fat cells, particularly around the abdomen. “People often lose muscle and gain fat as they age, even if their overall body weight remains stable,” Wang explained. “We discovered that ageing triggers the arrival of a new type of adult stem cell and enhances the body’s massive production of new fat cells, especially around the belly.” This discovery is significant because it shifts the focus from simply managing calorie intake and physical activity to understanding the cellular processes that drive midlife weight gain.

To explore this phenomenon, Wang and her colleagues at City of Hope, in collaboration with researchers at the University of California, Los Angeles (UCLA), focused their attention on white adipose tissue (WAT), the primary form of body fat responsible for age-related weight gain. While it is well-known that fat cells can grow larger as we age, researchers suspect that WAT also expands by producing entirely new fat cells, effectively providing them unlimited potential to grow. To test this hypothesis, they studied a group of stem cells within WAT known as adipocyte progenitor cells (APCs). These APCs are the precursors to fat cells and can transform into fully mature fat cells under the right conditions.

The team conducted a series of experiments involving both young and older mice. They transplanted APCs from young and older mice into a separate group of young mice. The results were striking: APCs from older animals rapidly generated a colossal amount of new fat cells, while APCs from young animals did not show the same behaviour. This confirmed that older APCs are inherently programmed to produce new fat cells at a much higher rate, regardless of the age of their host. This discovery points to a fundamental difference in the biology of these stem cells as animals age, offering a new perspective on why belly fat tends to accumulate in middle age.

Delving deeper into the genetic programming of these cells, the researchers used single-cell RNA sequencing to compare APC activity in young and middle-aged mice. They found that APCs, which remain largely dormant in youth, become highly active in middle age, transforming into a new type of stem cell known as committed preadipocytes, age-specific (CP-As). These CP-As are particularly efficient at generating new fat cells, providing a cellular explanation for the notorious “middle-age spread.” Crucially, the scientists identified a key signalling pathway – the leukaemia inhibitory factor receptor (LIFR) – that drives this process. Unlike young mice, which can produce fat cells without this signal, older mice rely heavily on LIFR to sustain CP-A growth. This finding suggests that targeting the LIFR pathway could be a promising approach for preventing age-related belly fat accumulation.

Finally, the researchers extended their findings to humans by examining APCs from people of various ages. They found that CP-A cells were also present in human tissue, where they increased in number with age, confirming that this phenomenon is not just a peculiarity of mice but a fundamental aspect of human biology. “Our findings highlight the importance of controlling new fat-cell formation to combat age-related obesity,” Wang emphasised. “By understanding the role of CP-As in metabolic disorders, we could develop new therapies that prevent the buildup of belly fat and extend healthy lifespans.” Future research will focus on tracking CP-A cells in animal models, exploring their behaviour in human tissue, and developing potential drugs to block their growth, potentially offering a new path to healthier ageing.

More information: Qiong Wang et al, Distinct adipose progenitor cells emerging with age drive active adipogenesis, Science. DOI: 10.1126/science.adj0430

Journal information: Science Provided by City of Hope