The study used a mouse model that combined type 2 diabetes with fatty liver. Male C57BL/6J mice received a high-fat diet for 16 weeks, and some animals also received injections of streptozotocin to induce diabetes; control animals received a standard diet. During the final four weeks, some diseased mice underwent daily aerobic training on a motorized platform, while others received MOTS-c at 7.5 mg/kg by intraperitoneal injection. The exercise regimen consisted of 60 minutes of running six days per week. Researchers measured MOTS-c concentrations and protein expression, glucose and insulin tolerance, circulating and liver lipids, liver histology, and molecular markers associated with fat synthesis, fatty-acid oxidation and inflammation. Separate experiments used male ACE2-knockout mice, and laboratory studies used HepG2 human liver cells exposed to palmitic acid as a metabolic stressor.

Mice with MASLD had lower concentrations of MOTS-c in serum, skeletal muscle and liver than normal controls. Aerobic training reversed these reductions, increasing skeletal-muscle expression and secretion and raising local MOTS-c levels in the liver. Administering MOTS-c directly also increased its expression in skeletal muscle, consistent with an autocrine effect, although exercise was more effective at elevating the peptide. The investigators proposed that aerobic activity may promote skeletal-muscle production and secretion of MOTS-c, which could then act on the liver. However, the experiment did not isolate the peptide’s contribution to all exercise effects: the training program altered several metabolic processes at once, and the investigators did not use a MOTS-c-specific knockout or antagonist.

After four weeks, both exercise and MOTS-c treatment lowered fasting blood glucose and reduced the area under the glucose- and insulin-tolerance curves in wild-type MASLD mice. Neither intervention significantly changed body weight. Exercise appeared more effective at restoring insulin sensitivity, whereas MOTS-c produced a marked improvement in glucose tolerance. The results therefore do not support treating the peptide and exercise as interchangeable. Their measured metabolic effects differed, and exercise increased the expression of ACOX1 and CPT-1, genes associated with fatty-acid beta-oxidation, whereas MOTS-c did not significantly increase these genes. Exercise was more effective at elevating MOTS-c than the injected peptide, which the authors attributed as a possible explanation rather than a directly tested mechanism.

Liver histology showed that both interventions reduced hepatic lipid accumulation. Serum and liver triglyceride concentrations fell, and serum low-density lipoprotein levels declined, while high-density lipoprotein levels did not differ significantly. At the molecular level, MOTS-c and aerobic exercise lowered expression of fatty acid synthase and acetyl-CoA carboxylase, which are involved in fatty-acid synthesis. They also reduced the inflammatory transcripts for interleukin-1 beta and tumor necrosis factor alpha. These changes accompanied less liver steatosis on hematoxylin-and-eosin and Oil Red O staining. Sirius Red staining and alpha-smooth-muscle actin staining did not indicate significant fibrosis in the experimental groups, meaning the study chiefly demonstrated effects on steatosis and metabolic or inflammatory markers rather than reversal of advanced liver scarring.

Hepatic ACE2 emerged as a molecular link between MOTS-c treatment and the improved liver phenotype. ACE2 expression was reduced in MASLD mice but was restored by either MOTS-c or exercise. The same general pattern appeared in HepG2 cells stressed with palmitic acid: ACE2 protein declined under metabolic stress and was partially restored by MOTS-c. ACE2 is a member of the angiotensin-converting enzyme family within the renin–angiotensin system, which the authors’ earlier research had linked to hepatic lipid balance. The present findings associate increased hepatic ACE2 with reduced steatosis and inflammation in the experimental model. The knockout experiments provided more direct evidence by testing what happened when ACE2 was absent.

That dependence was tested in mice lacking ACE2. In ACE2-knockout animals with MASLD, MOTS-c no longer significantly improved glucose or insulin tolerance, and its reductions in liver fat, triglycerides and expression of fat-synthesis and inflammatory genes were diminished or absent. By contrast, aerobic exercise still reduced hepatic steatosis and triglycerides in the knockout mice, altered fatty-acid synthesis and oxidation markers, and suppressed inflammatory gene expression. The divergence suggests that MOTS-c depends heavily on ACE2 for many of its measured effects in this model, while exercise engages additional mechanisms that do not require ACE2. It does not show that exercise acts exclusively through the peptide, and the study did not determine whether skeletal-muscle MOTS-c secretion or circulating peptide levels changed in the knockout animals.

The cell experiments placed phosphorylated AMPK, an energy-sensing kinase, upstream of the ACE2 response. Both MOTS-c and exercise increased phosphorylated AMPK in the livers of wild-type MASLD mice, while MOTS-c raised ACE2 and lowered fatty acid synthase protein. In palmitate-stressed HepG2 cells, MOTS-c similarly increased AMPK phosphorylation and ACE2 expression. Adding the AMPK inhibitor Compound C attenuated the MOTS-c-dependent increase in ACE2 and its suppression of fatty acid synthase and inflammatory genes. These findings support involvement of AMPK in the MOTS-c–ACE2 pathway. Pharmacological inhibition alone does not identify the precise molecular connection between AMPK activation and ACE2 regulation, however, and the authors did not establish whether the change involved ACE2 transcription, protein stability or another mechanism. They also proposed that transcriptional regulators such as SIRT1 or PPAR-gamma might participate, but that possibility was not tested.

Several design features limit how far the findings can be generalized. The investigators studied male mice and a human hepatoma cell line rather than patients with MASLD, and there were no human trial data. The MOTS-c intervention was administered by intraperitoneal injection, while exercise was delivered through a controlled platform-training regimen, so the routes and exposures were not directly equivalent. Small experimental groups, with several assays based on three to six animals, also constrain the precision of some estimates. The authors acknowledged the absence of a MOTS-c knockout mouse and a specific antagonist, which prevented direct loss-of-function testing of the peptide itself. They also noted potential safety concerns associated with systemic MOTS-c exposure, including possible effects on tumor progression and atherosclerosis. In addition, the model did not demonstrate significant fibrosis, leaving its relevance to advanced cirrhosis unresolved.

The broader significance is that the study offers a mechanistic explanation for one component of exercise’s metabolic effects: aerobic activity increased skeletal-muscle MOTS-c in diabetic MASLD mice, and the peptide was associated with activation of hepatic AMPK, restoration of ACE2 expression and reduced lipogenesis and inflammation. The intervention resembled exercise in improving steatosis and glucose regulation, but it did not reproduce every exercise effect. Its strongest metabolic contribution in the model was improved glucose tolerance, while exercise more clearly restored insulin sensitivity and promoted fatty-acid oxidation. Future translational studies would need to test whether the AMPK–ACE2 mechanism operates in people with MASLD, determine whether MOTS-c can be delivered safely and effectively, and establish which exercise protocols reliably increase endogenous production. Until such evidence is available, the results identify a promising pathway and experimental therapeutic target rather than a clinically established therapy.

Subject of Research: Experimental evidence linking exercise-induced skeletal-muscle MOTS-c to hepatic ACE2 and reduced MASLD features in mice and liver cells.

Article Title: Aerobic exercise induced skeletal muscle MOTS-c secretion: A novel therapy for MASLD via hepatic ACE2 regulation

Article References: Li, R., Li, F., Chen, Q., Gao, Y., Wu, Z., Deng, H., & Yuan, L. (2026). Aerobic exercise induced skeletal muscle MOTS-c secretion: A novel therapy for MASLD via hepatic ACE2 regulation. Scientific Reports, 16(1), Article 33291. https://doi.org/10.1038/s41598-026-60273-8

Image Credits: AI Generated

DOI: 10.1038/s41598-026-60273-8

Keywords: MOTS-c, MASLD, aerobic exercise, skeletal muscle, hepatic ACE2, AMPK, fatty liver, myokines, mouse model, liver metabolism, Aerobic, exercise

The editorial, led by Keying Zhang of Southeast University’s Department of Physical Education, together with Chunmei Cao of Tsinghua University and Yih-Kuen Jan of the University of Illinois, frames what they see as the central challenge of modern exercise neuroscience. The field, they argue, has spent years accumulating evidence that aerobic exercise is good for the brain. The harder question — and the one this Research Topic confronts — is when those benefits emerge, for whom, at what dose, and through which specific neural processes. The five contributing studies, which include three evidence syntheses, one electroencephalography microstate investigation, and one multimodal magnetic resonance imaging study, suggest that the answer is not a single mechanism but a mosaic of context-dependent ones.

The most striking pattern to emerge from the collection is an asymmetry in the evidence itself. Emotional outcomes are the most consistently supported behavioral domain across the five articles, while cognitive benefits appear less uniform and sleep benefits remain only weakly connected to direct mechanistic evidence. In one of the outcome-focused reviews, Wang and colleagues synthesized 19 randomized controlled trials in healthy adults and found that acute aerobic exercise reliably increased positive mood and reduced negative mood, while longer-term exercise programs reduced negative mood. Pooled effects on cognition and sleep, however, did not reach statistical significance. That dissociation — robust mood effects alongside weaker cognitive and sleep signals — is exactly the kind of outcome-specific variation the editorial argues the field must take seriously rather than average away.

A second review, by Yang and colleagues, examined 14 randomized trials involving 982 university students and found reductions in depressive symptoms, anxiety symptoms, and perceived stress following exercise interventions. Notably, the dose-response analyses suggested that psychological benefits may vary with how exercise is prescribed — the intensity, duration, frequency, and total length of the intervention. But the authors were careful to present their proposed dose ranges as indicative rather than definitive thresholds, a caution that reflects a deeper problem in the literature. Exercise dose is not a single number. It is a composite of intensity, duration, frequency, total intervention length, modality, and adherence, and different studies weight these components differently, making it genuinely difficult to compare prescriptions across trials or to isolate which component drives which benefit.

This is where the editorial stakes its central claim: aerobic exercise should not be treated as a unitary exposure producing a unitary benefit. Some of the variation across studies certainly reflects differences in design, measurement, and intervention reporting — the methodological noise that plagues any young field. But the editors argue that reproducible differences across outcomes and populations may also carry biologically meaningful information. Distinguishing the two is now the field’s central methodological task, and it is one that matters for anyone hoping to translate exercise science into precise, individualized prescriptions.

The electrophysiological studies in the collection push the question from whether exercise changes brain activity to how those changes are actually expressed. Liu and colleagues synthesized 13 randomized controlled trials and found that exercise interventions were associated, on average, with greater EEG alpha-band power — a spectral measure often linked to relaxed wakefulness and cortical inhibition. But the heterogeneity across studies was substantial, and the prediction interval crossed the null, meaning that individual studies could plausibly show effects in either direction. The editors also note that because the review included exercise modalities beyond aerobic exercise, its findings are better interpreted as broad evidence of exercise-related electrophysiological modulation than as an aerobic-specific neural signature. Alpha power, moreover, is highly sensitive to recording state and analytic choices, which cautions against treating any single spectral measure as a context-free biomarker of exercise benefit.

Perhaps the most conceptually innovative contribution comes from Yao and colleagues, who examined a different dimension of EEG organization altogether. Rather than measuring signal magnitude, they studied EEG microstates — brief, quasi-stable patterns of scalp electrical activity that are thought to reflect the sequential activation of large-scale brain networks. Their study compared adolescents with depressive symptoms and healthy peers who completed both traditional and virtual-reality-enhanced aerobic cycling sessions. Both conditions improved mood, but the VR-enhanced exercise was accompanied by distinctive changes in microstate dynamics, including reduced occurrence of microstate C, prolonged duration of microstate D, and altered transitions between states. Selected microstate measures were also associated with post-exercise mood. These findings remain candidate neural correlates rather than established mechanisms, but they raise a testable hypothesis: the immediate psychological response to exercise may be reflected partly in the way large-scale neural states reorganize over time, not merely in how strong the underlying signals are.

The structural side of the story comes from Zhang and colleagues, who combined structural MRI, resting-state functional MRI, and graded exercise testing in 32 men spanning high-level endurance athletes, moderately trained runners, and active controls. Their analysis found that aerobic-capacity indicators were associated with gray-matter volume, fractional amplitude of low-frequency fluctuation, and degree centrality across distributed cortical and cerebellar regions — though the pattern became more selective after multiple-comparison correction. The editors are careful about what this means. The study does not provide evidence for a defined training trajectory, in which fitness progressively sculpts specific regions. Instead, it offers a broader view of aerobic fitness as a distributed brain-physiology phenotype, with descriptive differences across training levels that were less stable in sensitivity analyses and should remain hypothesis-generating rather than conclusive.

Read together, the EEG and MRI studies raise what the editors call a multiscale question: how are rapid neural responses to a single bout of exercise related, if at all, to the brain characteristics observed across different levels of fitness and training experience? A single cycling session alters microstate dynamics within minutes. Years of endurance training appear associated with distributed differences in gray matter and functional connectivity. Whether these are points on a single continuum — acute responses that, repeated over time, consolidate into structural and functional adaptation — or fundamentally separate phenomena, remains one of the field’s most important open questions. The honest answer, the editors concede, is that methodological heterogeneity, limited longitudinal evidence, modest sample sizes, and the correlational nature of several brain-behavior relationships continue to constrain mechanistic interpretation.

The path forward, they argue, is not simply to accumulate more evidence that exercise is beneficial, but to connect currently separated levels of explanation. Future studies should integrate multidimensional exercise dose, physiological responses, behavioral outcomes, and multimodal brain measures within randomized and longitudinal designs, while explicitly distinguishing acute neural responses from adaptations that emerge with repeated training. One emerging experimental opportunity is the integration of virtual reality with aerobic exercise. Beyond its obvious appeal for engagement and adherence, VR may allow contextual and sensory features to be manipulated while key exercise parameters are held constant — a design that could finally test whether similar physiological demands produce different neural and psychological responses under different experiential conditions. The working framework the editors propose treats exercise as a multiscale process in which dose and context shape physiological state, acute neural dynamics, repeated adaptation, and ultimately behavioral outcome. The key question, and the one that could transform exercise from a general recommendation into a targeted intervention, is whether transient exercise-related neural responses can be linked prospectively to durable adaptation and to individual differences in cognitive, sleep, and emotional benefit.

Subject of Research: Brain-based neural mechanisms underlying the effects of aerobic exercise on cognition, sleep, and emotional wellbeing

Article Title: Editorial: Brain-based mechanisms underlying the cognitive, sleep, and emotional benefits of aerobic exercise

Article References: Zhang, K., Cao, C., & Jan, Y.-K. (2026). Editorial: Brain-based mechanisms underlying the cognitive, sleep, and emotional benefits of aerobic exercise. Frontiers in Human Neuroscience, 20, Article 2010856. https://doi.org/10.3389/fnhum.2026.2010856

Image Credits: AI Generated

DOI: 10.3389/fnhum.2026.2010856

Keywords: aerobic exercise, EEG microstates, alpha-band power, brain plasticity, cognition, mood, sleep, virtual reality, MRI, exercise dose, depression, neuroscience

A new analysis of one of the most rigorously designed trials in this field now complicates that assumption. In a pre-specified secondary biomarker analysis of the PHYS-STROKE trial, published in Frontiers in Stroke, researchers led by Torsten Rackoll of Charité—University Medical Center Berlin examined whether four weeks of moderate-intensity treadmill training, started in the early subacute phase after stroke, could raise serum BDNF compared with an active control. The answer, measured carefully across six months of follow-up, was no.

PHYS-STROKE was a multicentre, randomized, assessor-blinded trial conducted across seven rehabilitation clinics and early-rehabilitation wards in the Berlin area between 2013 and 2017. Two hundred participants, enrolled between 5 and 45 days after an imaging-confirmed ischemic or hemorrhagic stroke, were allocated equally to two interventions. The experimental group completed up to 20 supervised sessions of body-weight-supported treadmill walking, with intensity prescribed at 55 to 65 percent of age-predicted maximal heart rate and monitored continuously through heart-rate sensors. The control group received progressive muscle relaxation based on the Jacobson method, matched in session frequency and duration but deliberately designed to avoid cardiovascular activation. Both groups continued their standard rehabilitation, which in Germany includes daily physiotherapy and, as needed, occupational, speech, and neuropsychological therapy.

The participants were genuinely impaired. The median National Institutes of Health Stroke Scale score was 8, and the median Barthel Index, a measure of functional independence, was 50, indicating moderate to severe disability. Mean serum BDNF at baseline was 17.2 nanograms per milliliter, and mild depressive symptoms were common. Fasting blood samples were drawn at baseline, immediately after the four-week intervention, and at three and six months after stroke. Serum mature BDNF was quantified using a Luminex-based multiplex immunoassay targeting the mature BDNF region, with samples stored at minus 80 degrees Celsius and analyzed in three calibrated batches.

The statistical approach was appropriately conservative. The primary analysis used linear mixed-effects models for repeated measures, with treatment group, time, and their interaction as fixed effects, adjusted for baseline BDNF, age, sex, stroke severity, platelet count, depressive symptoms measured with the CES-D scale, pre-stroke smoking status, and study center. Because platelets store and release BDNF during coagulation, platelet count was included as a covariate. Missing data, which were substantial—156 of 200 participants had at least one follow-up measurement, and only 118 had complete data across all time points—were handled with multiple imputation by chained equations across 1,000 imputed datasets, with complete-case and change-score analyses run as sensitivity checks.

The headline result was unambiguous. Serum BDNF rose modestly across the whole cohort, with most of the increase occurring between baseline and three months after stroke, and then remained stable. But at six months, the estimated mean concentration was virtually identical between groups: 24.6 nanograms per milliliter in the aerobic training group versus 24.3 in the relaxation group, an adjusted difference of minus 1.15 nanograms per milliliter with a p-value of 0.74. Crucially, the same null result appeared immediately after the intervention period, when a biological effect of four weeks of training would have been most detectable. The convergence of initially divergent baseline values—BDNF was higher in the training group at the start—may partly reflect regression to the mean rather than any treatment effect, a caveat the authors acknowledge openly.

Exploratory analyses probing whether depressive symptoms, intervention dose, or sex modified the treatment effect found no robust signals. The one nominally significant subgroup finding—higher six-month BDNF among women than men in the relaxation group, but not in the training group—emerged without correction for multiple testing, in small subgroups, and without a clear biological rationale. The researchers are explicit that this should be treated as hypothesis-generating at most and likely reflects chance or non-specific recovery rather than a distinct effect of relaxation therapy.

Why did the exercise fail to move BDNF when the same intervention reliably raises it in healthy people? The authors point to several plausible explanations. Stroke triggers systemic inflammation, autonomic dysregulation, altered platelet dynamics, and often involves medications and comorbidities that all shape circulating BDNF. Reduced exercise capacity in moderately to severely affected patients may also have limited the physiological stimulus. Perhaps most importantly, the intervention was deliberately pragmatic and safety-oriented: moderate-intensity continuous training was the standard, safe approach for early subacute rehabilitation when the trial was designed, not a protocol optimized to maximize neurotrophin release. Recent evidence, including a network meta-analysis in adults, suggests that acute BDNF responses are more consistent after high-intensity interval exercise than after moderate continuous exercise, and the moderate target heart rates used here may simply have been insufficient to trigger meaningful release.

The study also carries an important methodological message for the field. Serum BDNF is an imperfect proxy for brain BDNF signaling. It is heavily influenced by platelet storage and release, by clotting and centrifugation protocols, by circadian rhythms, and by metabolic and pharmacological factors, and serum and plasma measurements are not interchangeable. Recent methodological reviews have highlighted wide variability in how stroke studies handle these pre-analytical variables, complicating comparisons across trials. The trial also did not measure the BDNF Val66Met genotype, which influences activity-dependent BDNF release and could contribute to inter-individual variability. And because blood was not sampled during or immediately after individual exercise sessions, transient within-session BDNF spikes cannot be ruled out.

The authors are careful about what their findings do and do not mean. A null result on peripheral BDNF does not exclude exercise-related effects on central neuroplasticity or on functional recovery through other biological pathways, nor does it rule out acute, higher-intensity, genotype-dependent, or subgroup-specific neurotrophin responses. What it does argue against is the notion that a clinically feasible, four-week, moderate-intensity aerobic programme, delivered in the early subacute window to a heterogeneous and substantially impaired population, produces a robust and sustained elevation of circulating BDNF. For clinicians and researchers, the implication is that future studies of exercise-induced neuroplasticity after stroke should consider denser biomarker sampling around exercise sessions, individualized and potentially higher exercise intensity prescriptions, and biological stratification of patients, rather than assuming that any aerobic programme will uniformly engage the BDNF pathway. The sensitive window after stroke may indeed be real, but the molecular levers required to pull it appear more selective, and more demanding, than the field has often assumed.

Subject of Research: Effects of a four-week moderate-intensity aerobic exercise intervention on serum brain-derived neurotrophic factor in subacute stroke patients

Article Title: Serum BDNF in subacute stroke: effects of a four-week aerobic exercise intervention in the PHYS-STROKE trial

Article References: Rackoll, T., Doppelbauer, L., Neumann, K., & Nave, A. H. (2026). Serum BDNF in subacute stroke: effects of a four-week aerobic exercise intervention in the PHYS-STROKE trial. Frontiers in Stroke, 5, Article 1897859. https://doi.org/10.3389/fstro.2026.1897859

Image Credits: AI Generated

DOI: 10.3389/fstro.2026.1897859

Keywords: stroke, BDNF, aerobic exercise, neuroplasticity, stroke rehabilitation, PHYS-STROKE trial, randomized controlled trial, neurotrophins, Serum, subacute, effects, four-week

The research, led by Lakmi C. Subasinghe of the Faculty of Medicine at the University of Colombo, together with Bhawani Yasassri Alvitigala and Ahalyaa Sivashangar of the Department of Pathology, recruited 126 participants aged 20 years and older. The cohort was evenly split between 63 yoga practitioners training at the Bhudeva Yoga and Fitness Lounge center and 63 aerobic exercisers using the University of Colombo gymnasium. To ensure a meaningful comparison, the researchers imposed strict participation criteria: every participant had to have practiced their respective exercise modality for more than two months, with a minimum commitment of six hours per week during the preceding month. This threshold was designed to exclude casual dabblers and capture the physiological effects of sustained, regular training rather than short-term adaptation.

The choice of outcome measures reflects the central role these three fitness components play in everyday function. Lower limb muscle strength underpins walking, climbing stairs, rising from a chair, and virtually every locomotor task; its decline with age is a major driver of disability and loss of independence. Flexibility of the hamstrings, lower back, and hip complex determines range of motion and injury resilience. Balance, meanwhile, is the silent guardian against falls, which the World Health Organization identifies as a leading cause of injury-related death and morbidity in older adults. As noncommunicable diseases rise across South Asia and globally, public health interest in accessible exercise modalities that preserve these capacities has intensified, providing the motivation for the study.

The researchers used three simple, widely validated field tests. Lower limb strength was assessed with the wall sit test, an isometric endurance challenge in which participants hold a seated position against a wall with knees bent at right angles, loading the quadriceps, hamstrings, and gluteal muscles without movement. Flexibility was measured with the classic sit-and-reach test, which quantifies the ability to flex forward at the hips and reach toward or beyond the toes, primarily probing hamstring and lumbar extensibility. Balance was evaluated with the single-leg stance test, requiring participants to stand motionless on one leg, a task that integrates visual, vestibular, and proprioceptive inputs with the rapid corrective muscle activity known as postural control. Group differences were then analyzed using mean comparisons between the two cohorts.

The findings were striking. Yoga practitioners outperformed aerobic exercisers on the wall sit test, holding the isometric position for a mean of 0.46 plus or minus 0.41 units compared with 0.34 plus or minus 0.23 in the aerobic group, a difference that reached statistical significance at p equal to 0.047. The flexibility gap was even more dramatic: on the sit-and-reach test, yoga practitioners averaged 44.81 plus or minus 10.88 centimeters, while aerobic exercisers managed 30.97 plus or minus 8.91 centimeters, a difference of nearly 14 centimeters that was highly significant at p less than 0.001. For anyone who has watched a seasoned yogi fold effortlessly into a forward bend while a runner grimaces at the same task, the result will come as little surprise, but quantifying the gap so starkly gives the observation real scientific weight.

Balance told the opposite story. On the single-leg stance test, aerobic exercisers held their position for a mean of 2.53 plus or minus 1.53 units, roughly double the 1.40 plus or minus 0.46 achieved by the yoga group, and this difference was also highly significant at p less than 0.001. The finding is intriguing because yoga is often assumed to be the balance-building exercise par excellence, given its repertoire of one-legged postures such as tree pose and warrior III. Yet in this Sri Lankan cohort, the aerobic exercisers were the steadier group on one leg, suggesting that the dynamic, repetitive weight-shifting demands of sustained aerobic activity may train the postural control system in ways that static yoga holds do not, at least as measured by this particular test.

The study also probed how training dose related to performance. Lower limb strength was positively correlated with the number of hours of daily practice in both the yoga and aerobic groups, indicating that more time under training translated into greater isometric leg strength regardless of modality. In the aerobic group specifically, balance and flexibility showed a strong correlation with each other, a relationship the authors report at a significance level of p less than 0.05. This coupling hints that in aerobic exercisers, the same underlying factor, perhaps overall training volume or general neuromuscular conditioning, drives both capacities, whereas in yoga practitioners the components appear to develop along more independent trajectories shaped by the specific demands of asana practice.

The authors conclude that both yoga and aerobic exercise offer distinct and complementary benefits for physical fitness. Yoga, in their analysis, appears more effective for improving lower limb strength and flexibility, while aerobic exercise may be the better choice for improving balance. For the general public, the practical implication is that the optimal exercise prescription may not be a choice between the two but a combination of both. A weekly routine that blends yoga sessions with aerobic activity could, in principle, capture the strength and flexibility gains of the former alongside the balance advantages of the latter, addressing a broader spectrum of the fitness components that sustain functional ability and quality of life across the lifespan.

Several caveats are worth keeping in mind when interpreting the results. As a cross-sectional study, the design captures a snapshot in time and cannot establish that yoga causes superior strength and flexibility or that aerobic training causes better balance; it is possible that people with certain physical attributes gravitate toward one modality over the other, a classic self-selection problem in exercise research. The participants were drawn from a single yoga center and a single university gymnasium in Colombo, which may limit how far the findings generalize to other populations, training styles, and intensity levels. The reported standard deviations, particularly the wide spread in the wall sit results, indicate considerable individual variability within each group. Nonetheless, the study, which received ethical approval from the Ethical Review Committee of the Faculty of Medicine, University of Colombo, and was conducted in accordance with the Declaration of Helsinki, adds valuable evidence from a South Asian context where such comparative fitness data remain scarce. As interest in yoga and aerobic exercise continues to grow as tools against the global tide of noncommunicable disease, studies like this one help move the conversation beyond enthusiasm and toward evidence-based exercise prescription.

Subject of Research: Comparative physical fitness outcomes of yoga versus aerobic exercise in Sri Lankan adults

Article Title: A comparative study of lower limb muscle strength, flexibility, and balance in yoga practitioners and aerobic exercise participants in Sri Lanka

Article References: Subasinghe, L. C., Alvitigala, B. Y., & Sivashangar, A. (2026). A comparative study of lower limb muscle strength, flexibility, and balance in yoga practitioners and aerobic exercise participants in Sri Lanka. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05644-4

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05644-4

Keywords: yoga, aerobic exercise, physical fitness, lower limb strength, flexibility, balance, Sri Lanka, cross-sectional study, wall sit test, sit-and-reach test, single-leg stance, noncommunicable diseases

Menopause marks the point at which a woman’s periods stop due to declining hormone levels, typically occurring between the ages of 45 and 55. The years surrounding this transition, known as perimenopause, are characterised by fluctuating oestrogen levels that can destabilise mood long before periods cease entirely. It is estimated that around 13 million women in the UK are currently perimenopausal or menopausal. Beyond the well-known physical symptoms such as hot flushes, many women experience depression, low mood, anxiety, stress, and difficulties with thinking and memory. These psychological symptoms can have a significant impact on daily functioning, relationships and careers, yet the pharmacological and therapeutic options available to address them remain constrained.

The UCL-led team set out to determine whether exercise, one of the most accessible and low-cost interventions available, could move the needle on these psychological outcomes. The researchers divided the physical activity examined across the twelve trials into two distinct categories. The first, aerobic-based interventions, included walking, Zumba, aerobic exercise, dance and Taekwondo. The second, mind-body activities, comprised yoga, tai chi, Pilates and stretching. This distinction proved important, because the two categories appeared to deliver somewhat different benefits, with aerobic exercise showing the strongest effects on depressive symptoms and overall quality of life, while mind-body practices stood out for improving psychological quality of life specifically.

The mechanisms proposed for the aerobic benefits are rooted in well-established exercise physiology. The researchers point to increased endorphin release linked to mood enhancement, a neurochemical effect that may be particularly relevant during perimenopause, when oestrogen fluctuations increase vulnerability to mood instability. Oestrogen is known to interact with neurotransmitter systems involved in mood regulation, so hormonal turbulence during this stage may leave the brain more sensitive to stress and low mood. Interventions that reliably trigger endorphin release could therefore provide a buffer against this heightened vulnerability, offering a non-pharmacological counterweight to the hormonal shifts underway.

Practical considerations also favoured the aerobic programmes. The researchers noted that aerobic-based interventions tended to involve fewer sessions, suggesting they may be easier to fit into the lives of midlife women facing time and energy constraints. In one trial, women were instructed to walk three times per week for 30 minutes, while in another participants attended three one-hour Zumba classes per week. Across the twelve randomised trials, participants were generally required to attend multiple sessions per week, depending on the type of exercise prescribed. The relative simplicity of lacing up walking shoes or joining a dance class, compared with more demanding regimens, may be a decisive factor for women juggling work, family and the fatigue that often accompanies the menopausal transition.

Mind-body activities, by contrast, delivered their strongest improvements in psychological quality of life. These practices incorporate mindfulness, breathwork and body awareness, elements that may enhance emotional regulation. The dosing in these trials was often more intensive: in one study, women attended two weekly 75-minute yoga sessions, while in another participants attended daily one-hour yoga classes. The emphasis on slow, deliberate movement combined with attention to breathing and bodily sensation may help women develop greater equanimity in the face of symptoms that can otherwise feel unpredictable and distressing, though the review’s authors frame this as a plausible explanation rather than a settled mechanism.

The timing of benefits also varied across the menopausal stages. Improvements in depression, mood and quality of life were particularly evident among women in early post menopause, the stage of life that begins twelve consecutive months after a woman’s final menstrual period. Physical activity was also associated with improvements in depressive symptoms during perimenopause. This pattern suggests that exercise may offer benefits throughout the transition, but that women who have completed the hormonal shift may experience the most pronounced gains in overall wellbeing. For clinicians, this raises the possibility of tailoring exercise recommendations to a patient’s specific stage rather than treating menopause as a single homogeneous phase.

The researchers hope their findings will highlight physical activity as a low-cost and widely available intervention option for women experiencing psychological symptoms during menopause, particularly in comparison with other approaches such as hormone therapy and cognitive behavioural therapy. Lead author Simone Saidel, an NHS Clinical Psychologist who was a researcher at UCL when the review was conducted, noted that treatment options for menopause are limited, with many women unable to or choosing not to take hormone therapy. She also pointed to significant health inequalities in terms of HRT access, and ethnic variations in attitudes towards it. In this context, she said, the study plays an important role in expanding the options available for symptom management, whereby clinicians may recommend exercise as an early intervention or an adjunct to medical or psychological treatments.

Senior author Professor Aimee Spector, Director of the UCL Menopause Mind Lab in the UCL Division of Psychology and Language Sciences, described physical activity as an effective, accessible, non-pharmacological strategy to support psychological wellbeing and quality of life during midlife menopause. She observed that the majority of the interventions used group-based formats, which are likely to foster social connection and peer support, both factors associated with improved quality of life during menopause. The team believes this social dimension may have contributed to the improved mood and quality of life observed, adding a further layer to the case for group fitness classes, walking groups and communal yoga sessions as vehicles for menopause support beyond the physiological effects of the exercise itself.

The evidence base underpinning these conclusions is drawn from seven countries: Brazil, China, Tunisia, India, Iran, Korea and the United States, giving the review a broad international scope. However, the researchers are candid about its limitations. The evidence base remains limited, with substantial variation between studies, and many of the studies were judged to be at high risk of bias, underscoring the need for further high-quality trials. The team also emphasises that more research is needed to establish which forms of physical activity are most beneficial and how they can best be incorporated into support and care for women experiencing menopause. Even so, for the millions of women navigating this transition with limited treatment options, the message from this review is a pragmatic one: movement, whether a brisk walk or a yoga class, may be one of the simplest tools available for protecting mood and quality of life during menopause.

Subject of Research: The effects of physical activity interventions on psychological symptoms and quality of life during menopause

Article Title: Physical activity may improve mood and quality of life during menopause

Article References: Physical activity may improve mood and quality of life during menopause. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: menopause, perimenopause, physical activity, depression, quality of life, aerobic exercise, yoga, mind-body interventions, systematic review, meta-analysis, UCL, women's health

The study, conducted by Yixuan Wu and Yin Wu of Soochow University, is the first to simultaneously compare the cognitive effects of specific exercise modalities in older adults with mild cognitive impairment, a transitional state between normal aging and dementia that affects a surging share of the world’s aging population. Because no disease-modifying drugs currently exist for dementia, identifying interventions that work during this early window has become a global public health priority, and physical exercise has emerged as the cornerstone of prevention efforts.

To build their treatment hierarchy, the researchers sifted through 6,737 records from PubMed, Embase, Web of Science, and the Cochrane Library, ultimately including 16 randomized controlled trials involving 1,208 participants with a mean age over 65. The trials, conducted across China, South Korea, Pakistan, Brazil, Turkey, Poland, and Japan, lasted 12 to 24 weeks with two to three sessions per week. Global cognition was measured with standardized instruments, the Montreal Cognitive Assessment or the Mini-Mental State Examination, allowing effects to be pooled across studies using standardized mean differences.

Network meta-analysis is a statistical technique that goes beyond traditional pairwise comparisons. Rather than asking only whether exercise A beats a control group, it synthesizes both direct head-to-head evidence and indirect evidence across an entire network of interventions, even when two treatments have never been tested against each other in the same trial. The researchers used a frequentist framework in Stata, checked for consistency between direct and indirect evidence with the design-by-treatment interaction model, and ranked interventions using SUCRA values, which express the probability that a treatment is the best option.

The results were striking. Compared with an active control group, combined exercise, which integrates physical exertion with concurrent cognitive tasks, produced the largest improvement in cognitive scores, with a standardized mean difference of 3.78 and a 68.0 percent probability of being the single most effective intervention. Multicomponent exercise, which blends aerobic and resistance elements, showed a significant effect of 1.71, and plain aerobic exercise a significant effect of 1.47. Tai Chi and coordination training showed positive trends but their confidence intervals crossed the line of no effect, likely because those arms contained fewer participants.

The ranking probabilities tell the story in sharper relief. Tai Chi came second with a 15.9 percent probability of being the best treatment, followed by coordination training at 13.3 percent, while passive and active controls consistently ranked at the bottom. The pattern points to a unifying principle: interventions demanding high cognitive and neural engagement, whether through dual-task loads or complex motor sequencing, confer superior benefits over those requiring purely physical exertion.

The mechanism, the authors argue, is neuroplasticity operating on two fronts at once. Physical exertion alone increases cerebral blood flow and upregulates brain-derived neurotrophic factor, a protein that supports the survival and growth of neurons. Adding a simultaneous cognitive load forces the brain to allocate attention and executive resources efficiently, and this synergistic stimulus appears to drive deeper structural and functional adaptations in the prefrontal cortex and hippocampus, the very regions most affected in mild cognitive impairment. In effect, synapses generated by physical activity are immediately pressed into service by cognitive demand, maximizing cognitive reserve.

Tai Chi’s strong showing provides quantitative backing for traditional mind-body practices. Unlike the repetitive, automated motor patterns of treadmill walking, Tai Chi demands sustained focused attention, sequential memorization of intricate movement routines, and deep mindful breathing, effectively embedding a physical-cognitive dual task within a single activity. The authors also highlight a second pathway: mind-body exercises modulate the autonomic nervous system, downregulating sympathetic hyperactivity and reducing cortisol, a stress hormone known to accelerate hippocampal atrophy. Tai Chi may thus stimulate neural networks while simultaneously shielding the brain from stress-induced damage.

The analysis is not without caveats. Many included trials failed to report precise exercise intensity data, such as target heart rate zones or perceived exertion ratings, preventing a definitive dose-response analysis. Some network nodes, notably coordination training, contained few direct comparisons, producing wider confidence intervals, and the studies varied in how faithfully interventions were delivered and how strictly participants adhered to them. The authors call for larger multi-arm trials directly comparing combined training with Tai Chi and aerobic exercise, and for stricter adherence to reporting standards such as the CERT consensus.

Still, the consistency checks were reassuring: no significant global inconsistency emerged between direct and indirect evidence, and a comparison-adjusted funnel plot showed no evidence of publication bias. For clinicians, physical therapists, and the growing population of older adults worried about memory, the practical message is clear. A brisk walk is good, but a workout that also makes you think, whether a dual-task class, a coordination drill, or a Tai Chi session, may be the most powerful prescription available for slowing cognitive decline before it becomes dementia.

Subject of Research: Comparative efficacy of exercise modalities for global cognition in older adults with mild cognitive impairment

Article Title: Comparative efficacy of exercise modalities for mild cognitive impairment in older adults: A network meta-analysis

Article References: Wu, Y., & Wu, Y. (2026). Comparative efficacy of exercise modalities for mild cognitive impairment in older adults: A network meta-analysis. iScience, 29(11), Article 117561. https://doi.org/10.1016/j.isci.2026.117561

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117561

Keywords: mild cognitive impairment, network meta-analysis, combined exercise, Tai Chi, aerobic exercise, coordination training, neuroplasticity, BDNF, dual-task training, dementia prevention, cognitive reserve, older adults

The endothelium, the delicate single layer of cells lining the interior of every blood vessel, is far more than passive plumbing. It actively regulates vascular tone by releasing vasodilating and vasoconstricting compounds, controls oxidative processes, modulates cell adhesion, and influences arterial stiffness. When the endothelium falters, vessels stiffen, their dilatory responses weaken, and the earliest silent stages of cardiovascular disease take hold. Flow-mediated dilation of the brachial artery, measured with high-resolution ultrasound after a temporary ischemic stimulus, captures this dysfunction early and tracks closely with coronary artery function, which is why the research team led by Simon Iskra and Armin Paravlić of the University of Ljubljana centered their analysis on it.

To assemble the evidence, the researchers searched six major databases from inception through multiple updated searches in 2023, 2025 and 2026, screening nearly 1,900 records against strict PICOS criteria. Only randomized controlled trials in adults that reported brachial artery flow-mediated dilation alongside at least one secondary outcome made the cut. The final pool spanned healthy volunteers and patients with cardiovascular disease, metabolic syndrome, diabetes, kidney disease, cancer, and even mental and neurological disorders. Participants ranged from about 20 to 78 years old, 43 percent were women, and interventions lasted from four to 26 weeks, with roughly two-thirds of study arms using continuous training and one-third using interval formats.

The headline result survived every robustness check the team threw at it. A random-effects model yielded a mean difference of 2.35 percent in flow-mediated dilation, a fixed-effects model produced 1.90 percent, and a trim-and-fill adjustment for publication bias still left a significant adjusted estimate of 1.74 percent. Sensitivity analysis removing the single largest study did not change the conclusion. Heterogeneity was high, as expected when pooling trials across such diverse populations and protocols, but the direction and clinical relevance of the effect were consistent. By the classification scheme the authors applied, the pooled gain qualifies as small but clinically meaningful, sitting above the 1 percent threshold considered the minimal clinically important difference.

The most novel contribution, however, lies in the meta-regression, which asked which physiological changes actually drive the vascular improvements. Four clusters emerged as significant moderators. Greater reductions in body weight and body fat were associated with larger gains in endothelial function, with regression coefficients of -4.021 and -1.721 respectively. Drops in systolic and diastolic blood pressure also tracked with better flow-mediated dilation, at coefficients of -0.525 and -0.484. On the positive side, improvements in maximal oxygen uptake, the classic index of cardiorespiratory fitness, showed a strong association with endothelial gains at a coefficient of 0.656, and changes in insulin levels moderated the effect as well. Notably, blood lipids, fasting glucose, HbA1c, and insulin resistance measured by HOMA-IR did not significantly moderate the vascular response, suggesting lipid and glucose improvements run on partly independent tracks.

Beneath these statistical associations lies a coherent mechanistic story. During aerobic exercise, blood flow to working muscles surges, subjecting the vessel walls to elevated shear stress. This mechanical signal activates endothelial nitric oxide synthase, boosting production of nitric oxide, the principal vasodilator of healthy arteries. The meta-analysis confirmed this biochemistry in blood: nitric oxide and its metabolites rose substantially, with standardized mean differences of 1.23 for both, while endothelin-1, the vessels’ chief constricting agent, fell moderately. Enhanced nitric oxide bioavailability combined with reduced endothelin-1 shifts vascular tone toward dilation, plausibly explaining much of the measured improvement in flow-mediated dilation, even though the biomarkers themselves did not reach statistical significance as moderators, likely because relatively few studies measured them.

The hemodynamic findings add another layer. Aerobic training produced small but significant reductions in systolic pressure, diastolic pressure, and mean arterial pressure, and the meta-regression tied these blood pressure drops directly to endothelial gains. The authors interpret this as evidence of a feedback loop: healthier endothelia dilate more readily, lowering vascular resistance and pressure, which in turn protects the vessel wall. Arterial stiffness told a subtler tale. Peripheral stiffness, measured at the brachial-ankle segment, decreased significantly, but central stiffness, measured at the carotid-femoral segment, and the augmentation index did not change. The researchers attribute this to the time course of vascular remodeling, since peripheral arteries adapt faster than the stiffer central vessels, and to the small number of trials that measured central outcomes alongside flow-mediated dilation.

Cardiorespiratory fitness emerged as perhaps the most intriguing partner in the adaptation. Maximal oxygen uptake rose moderately across trials, and the stronger the fitness gains, the stronger the endothelial improvements. The relationship is likely bidirectional. Repeated shear stress from training enhances nitric oxide signaling and vascular homeostasis, while preserved endothelial function optimizes skeletal muscle perfusion and oxygen delivery, supporting further fitness gains. The authors caution that because the meta-regression works at the study level, causality cannot be established; the pattern reflects interconnected adaptations rather than a simple cause-and-effect chain. Still, the convergence of fitness, body composition, blood pressure, and insulin changes as moderators paints exercise as a multi-front intervention rather than a single-target drug.

Body composition results carried their own surprise. Even though the analysis excluded trials that combined exercise with dieting, aerobic training alone significantly reduced body weight, body mass index, and body fat percentage, with no change in skeletal muscle mass. The regression confirmed that fat loss amplified the vascular benefit, and the authors suggest that shrinking adipose tissue dampens chronic low-grade inflammation, a process tightly linked to endothelial health. Inflammation markers moved in the expected direction, with a small significant fall in C-reactive protein and a moderate, near-significant decrease in TNF-alpha. Lipid changes were real but modest, with small rises in HDL cholesterol and small falls in LDL and triglycerides, while glucose metabolism improved through fasting glucose, HbA1c, and insulin resistance, even without significant changes in insulin itself.

The authors are candid about limitations. The restriction to trials reporting brachial artery flow-mediated dilation means conclusions may not generalize to other endothelial assessments. Flow-mediated dilation tends to normalize over longer interventions as structural remodeling proceeds, so pooled changes may understate peak functional adaptation. Pooling healthy and clinical populations yields general tendencies rather than disease-specific prescriptions, and the use of standardized mean differences for secondary outcomes, while necessary given heterogeneous measurement methods, obscures absolute changes. Publication bias was detected for the primary outcome and several secondary markers, though corrections preserved the core finding. Even so, the message is hard to dismiss: aerobic exercise acts simultaneously on fat mass, fitness, blood pressure, insulin regulation, nitric oxide signaling, and inflammation, and these converging pathways collectively rebuild endothelial function. For clinicians and the public alike, the analysis reinforces aerobic training as one of the most powerful non-pharmacological tools available for protecting the vascular system, with benefits that compound across nearly every measurable dimension of cardiovascular health.

Subject of Research: Effects of aerobic exercise on endothelial function and cardiovascular disease markers

Article Title: Impact of Aerobic Exercise on Endothelial Function and Other Cardiovascular Disease Markers in Health and Disease: A Systematic Review and Meta-analysis with Meta-regression of Randomized Controlled Trials

Article References: Iskra, S., Turnšek, G., Drole, K., & Paravlić, A. (2026). Impact of Aerobic Exercise on Endothelial Function and Other Cardiovascular Disease Markers in Health and Disease: A Systematic Review and Meta-analysis with Meta-regression of Randomized Controlled Trials. Sports Medicine – Open, 12(1), Article 150. https://doi.org/10.1186/s40798-026-01110-0

Image Credits: AI Generated

DOI: 10.1186/s40798-026-01110-0

Keywords: aerobic exercise, endothelial function, flow-mediated dilation, cardiovascular disease, meta-analysis, nitric oxide, blood pressure, cardiorespiratory fitness, body composition, insulin, arterial stiffness, vascular health

Cellular senescence is a state in which cells permanently stop dividing but refuse to die. First described in 1961 by Leonard Hayflick and Paul Moorhead, senescence was once viewed as a simple safeguard against cancer. Scientists now understand it as a far more complex condition: senescent cells suffer mitochondrial dysfunction, oxidative stress, and DNA damage, and they secrete a potent cocktail of inflammatory and fibrotic molecules known as the senescence-associated secretory phenotype, or SASP. Factors such as interleukin-6, tumor necrosis factor alpha, and transforming growth factor beta can spread inflammation and even push neighboring cells into senescence themselves, creating a self-amplifying cycle of tissue deterioration.

In the heart, this matters enormously. Senescent cardiomyocytes—the contractile muscle cells—show impaired shortening, defective calcium handling, and resistance to apoptosis through pro-survival pathways. Senescent fibroblasts and endothelial cells contribute to fibrosis and maladaptive remodeling. Together, these changes stiffen the left ventricle, impair its relaxation, and set the stage for heart failure, particularly the diastolic form in which the heart fills poorly despite pumping adequately. Prior work had shown that senolytic drugs such as dasatinib plus quercetin, or the BCL-family inhibitor navitoclax, could clear senescent cardiac cells when given to already-aged mice, but the chronic, preventive effects of these drugs on the heart remained largely unexplored.

The research team, based at McMaster University, set out to close that gap with an unusually long experiment. They began treating twelve-month-old mice—roughly early middle age in mouse terms—with one of four regimens for nine months: a vehicle control, biweekly oral doses of dasatinib plus quercetin, twice-weekly treadmill exercise sessions, or both interventions combined. By the end of the study, the animals had reached twenty-one months of age, the threshold of old age. A separate cohort of four-month-old young mice served as a healthy benchmark. Crucially, both male and female mice were included, and the investigators reported no significant sex differences in any outcome.

The functional results were striking. Using high-frequency ultrasound, the researchers measured how quickly the left ventricle relaxed between beats—the isovolumetric relaxation time—and combined contraction and relaxation measures into the myocardial performance index, a sensitive gauge of overall cardiac health. Naturally aged control mice showed relaxation times roughly 40 percent longer and performance indices about 44 percent higher than the best-performing treatment groups, indicating substantially worse myocardial function. Exercise-treated mice also displayed a markedly better E/A ratio, a frontline marker of diastolic filling, suggesting that aerobic training preserved the ventricle’s ability to relax and fill with blood. Notably, systolic measures such as ejection fraction were largely preserved across all aged groups, reinforcing the growing view that diastolic decline, not systolic failure, is the dominant functional signature of the aging heart.

Beneath those functional improvements lay a cellular story. Using immunofluorescence to detect the canonical senescence markers p16, p21, and gamma-H2AX—a marker of DNA damage—the team counted labeled cardiomyocytes and interstitial cells across four regions of each heart. Exercise reduced p16-positive cardiomyocytes by 29 percent, senolytics by 21 percent, and the combination by 27 percent compared with aged controls. Similar reductions appeared for p21, with exercise cutting positive cardiomyocytes by nearly half, and for gamma-H2AX, where the combined intervention lowered DNA-damage-positive cells by 36 percent. Interstitial cells followed the same pattern. The researchers also found that p21 expression was highest in the central left ventricle and lower at its anterior and posterior edges, revealing a spatial heterogeneity in cardiac senescence that whole-tissue analyses can easily miss.

Perhaps the most compelling finding was correlational: across all animals, the abundance of p16- and p21-positive cells tracked closely with worse cardiac function. Higher marker levels were associated with longer relaxation times, higher myocardial performance indices, and lower cardiac output and stroke volume, with correlation coefficients reaching 0.53. Marker expression was also coordinated across cell types—p21-positive cardiomyocytes and interstitial cells correlated with a striking r of 0.91—suggesting that senescence in the aging myocardium behaves as a tissue-wide phenomenon rather than a collection of isolated bad cells. This statistical link between senescent burden and functional decline strengthens the causal plausibility of the interventions, even though correlation alone cannot prove mechanism.

The study was not without surprises. At the whole-heart level, neither exercise nor senolytics significantly reduced p16 or p21 protein expression, and mRNA results were inconsistent, with the combined group paradoxically showing elevated p53 gene expression. Canonical SASP factors measured in heart tissue and serum—using western blotting, quantitative PCR, and the sensitive Olink proteomics panel—showed no differences between young, aged, and treated animals. The authors suggest several explanations: whole-heart lysates dilute cell-specific signals, twenty-one months may be too early for a pronounced SASP surge, and cardiac cells may secrete atypical SASP profiles dominated by fibrotic and hypertrophic factors rather than classic inflammatory cytokines. The disconnect between cellular and whole-tissue measurements is itself informative, indicating that senolytic and exercise effects are most visible at the single-cell level during early old age.

Equally notable was what did not happen: combining the interventions produced no additive benefit. Exercise and senolytics each worked about as well alone as together, contradicting the researchers’ initial hypothesis. One possibility is that both interventions converge on the same downstream targets—the p16, p21, and p53 pathways and inflammatory signaling—so that once senescent cell clearance reaches a ceiling, adding a second tool yields diminishing returns. Another is that at twenty-one months, the pool of senescent cells is still moderate; exercise during the off-weeks of the intermittent senolytic schedule may have already depleted the cells that dasatinib and quercetin would otherwise have cleared. The timing of treatment relative to senescence accumulation may therefore be decisive, and the authors caution that early senolytic use could theoretically remove cardiomyocytes from a tissue with minimal regenerative capacity.

The broader implications are tantalizing. This is the first demonstration that aerobic exercise can act as a natural senolytic in the aging heart, extending earlier findings in skeletal muscle and in young animals. It is also the longest senolytic intervention yet tested in cardiac tissue, showing that preventive, rather than rescue, administration of dasatinib plus quercetin can limit senescent cell accumulation over most of a mouse’s adult life. For a rapidly aging human population facing rising rates of heart failure with preserved ejection fraction, the message is doubly appealing: one intervention is already available in every gym, while the other is advancing through the emerging field of geroscience. The authors emphasize that long-term efficacy, optimal dosing, and systemic effects must be validated before clinical translation, but the vision of preserving cardiac function by targeting the cellular biology of aging itself has moved a meaningful step closer to reality.

Subject of Research: Effects of chronic senolytic treatment and aerobic exercise on cellular senescence and myocardial function in the aging mouse heart

Article Title: Chronic Senolytic Treatment and/or Aerobic Exercise Reduce Senescence and Improve Myocardial Function During Aging in the Heart

Article References: Bevington, R. T., Johnson, A. L., Hockey, B. L., Fajardo, V. A., & Parise, G. (2026). Chronic Senolytic Treatment and/or Aerobic Exercise Reduce Senescence and Improve Myocardial Function During Aging in the Heart. Aging Cell, 25(10), Article e70759. https://doi.org/10.1111/acel.70759

Image Credits: AI Generated

DOI: 10.1111/acel.70759

Keywords: cellular senescence, senolytics, dasatinib, quercetin, aerobic exercise, aging heart, myocardial function, cardiomyocytes, SASP, diastolic function, p16, p21

The trial, known as FASTEX, was conducted by researchers at the Exercise Medicine Research Institute at Edith Cowan University in Perth, Australia, working with clinicians at Sir Charles Gairdner Hospital, Fiona Stanley Hospital and Joondalup Health Campus. Women with histologically confirmed breast cancer who were scheduled to receive neoadjuvant or adjuvant chemotherapy, with or without immunotherapy, were invited to take part. Rather than being randomly assigned, participants chose their own intervention: thirteen women opted for the supervised exercise programme, five chose a fasting-mimicking diet arm reported separately, and because no eligible participants volunteered for usual care, a convenience control group of six women was recruited to provide blood samples for biomarker comparison.

The exercise prescription was deliberately pragmatic. Sessions lasted roughly sixty minutes and combined a warm-up, fifteen to twenty minutes of aerobic work on a treadmill or stationary bike, twenty to twenty-five minutes of resistance training targeting the major upper- and lower-body muscle groups, and a cool-down. Participants were asked to attend two supervised sessions during chemotherapy weeks and three during non-treatment weeks, with intensity individually tailored to maintain a target rating of perceived exertion between twelve and sixteen on the Borg six-to-twenty scale. Loads and volumes were progressively increased, and by the end of the twelve weeks the average resistance training load had risen by ten to sixty per cent, with total training volume approximately doubling.

Feasibility was the study’s primary outcome, and the results were encouraging. Retention reached 84.6 per cent, with eleven of thirteen participants completing the programme; the two withdrawals were both related to travel rather than to the exercise itself. Attendance averaged 83.6 per cent and adherence to the prescribed sessions 77.9 per cent, both exceeding the pre-defined thresholds of 75 per cent. Most missed sessions were attributable to treatment-related side effects such as fatigue, gastrointestinal symptoms and pain, while session modifications were typically driven by medical considerations such as the presence of a PICC line or by comorbidities. Only one adverse event, a transient episode of mild hypotension in a participant with pre-existing hypertension, was recorded across the entire intervention.

The immunological findings formed the scientific core of the study. Using spectral flow cytometry on cryopreserved peripheral blood mononuclear cells, the researchers characterised T cell and natural killer cell subsets in fine detail, tracking differentiation, activation, senescence and exhaustion markers. Compared with controls, the exercising women showed a significantly greater increase in CD8-positive effector memory cells re-expressing CD45RA, known as EMRA cells, with a large effect size, alongside a significant reduction in CD8-positive naïve T cells. Signals toward significance were also observed for central memory CD8 cells, for CD8 cells expressing CD57, and for CD8 cells expressing PD-1, each of which shifted more in the exercise group than in the controls.

Interpreting these shifts requires care, and the authors were explicit about the alternatives. An expansion of EMRA and CD57-positive CD8 T cells could, in principle, indicate immunosenescence, the accumulation of terminally differentiated cells with limited proliferative capacity. However, EMRA cells commonly express high levels of cytotoxic machinery and can execute immediate effector functions, and PD-1, although classically an exhaustion marker, is also transiently upregulated during T cell activation. Because no changes were seen in other exhaustion markers such as CTLA-4 and TIM-3, the researchers suggest the pattern may instead reflect a functional shift toward a low-proliferative but highly cytotoxic effector state, consistent with preclinical work showing that muscle-derived metabolites such as lactate can promote cytotoxic differentiation of CD8 T cells.

Metabolic data added a second layer of interest. The control group showed a significant rise in fasting insulin over the study period while the exercise group did not, a between-group difference that reached statistical significance. Because glucose levels did not change in parallel, the authors interpret the insulin rise in controls as consistent with compensatory hyperinsulinaemia driven by emerging peripheral insulin resistance, a well-recognised consequence of chemotherapy that is linked to adiposity, inflammation, hormonal alteration and loss of muscle. Exercise, by enhancing skeletal muscle insulin sensitivity and GLUT4-mediated glucose uptake, may have blunted this trajectory, although the authors caution that the control group’s samples were not collected in a fasting state, a logistical constraint that limits firm conclusions.

Body composition and patient-reported outcomes rounded out the picture. Despite ongoing chemotherapy, the exercising women maintained stable body weight, fat mass and lean mass, with signals toward modest gains in lean mass of roughly 0.8 kilograms. This stability matters clinically, because chemotherapy typically drives fat gain and lean tissue loss, and higher adiposity after diagnosis predicts poorer breast cancer-specific and overall survival. On the questionnaire side, global quality of life measured by the EORTC QLQ-C30 improved significantly, rising by 16.7 points, with smaller improvements across physical, emotional and social functioning domains, and fatigue showed a signal toward improvement on the FACIT-F Trial Outcome Index. Participants rated the burden of the programme as very low and reported perceived benefits for well-being and treatment tolerance.

Seven participants received neoadjuvant chemotherapy, allowing a preliminary look at pathological complete response, the disappearance of invasive cancer in the resected specimen. Three of four exercising patients and all three controls achieved a complete response, a uniformly high rate that precludes any conclusion about whether exercise influenced treatment efficacy, particularly since the one non-responder had inflammatory breast cancer, a subtype associated with lower response rates. The authors stress that future studies should directly test whether exercise-induced immune modulation translates into improved therapeutic response.

The limitations of the pilot are substantial and the authors acknowledge them candidly. Participants self-selected into the exercise arm, raising the possibility that the programme appealed mainly to motivated women with the transport, time and physical capacity to attend supervised sessions, so feasibility in the broader population may be lower. The sample was small, the control group was a convenience sample of unequal size, menopausal status differed between groups at baseline, and chemotherapy regimens and blood sampling intervals varied. No functional immune assays or tumour infiltration analyses were performed, so it remains unknown whether the observed phenotypic changes alter immune cell behaviour in practice. Even so, the study’s comprehensive immune phenotyping, combined with concurrent metabolic, body composition and quality of life assessments, marks it as one of the most detailed portraits to date of what exercise does inside the bodies of women fighting breast cancer, and it lays the groundwork for the larger randomised trials that will determine whether training through chemotherapy can genuinely sharpen the immune system’s anti-tumour arsenal.

Subject of Research: Exercise training during chemotherapy for early-stage breast cancer and its effects on immune and metabolic outcomes

Article Title: Exploring the feasibility of exercise training during (neo)adjuvant chemotherapy in women with early-stage breast cancer: a pilot study examining immune and metabolic outcomes

Article References: Crespo-García, C., Bettariga, F., Taaffe, D. R., Campbell, J. P., Peddle-McIntyre, C. J., Jeffery, E., Redfern, A. D., Rinaldi, C. A., Galvao, D. A., & Newton, R. U. (2026). Exploring the feasibility of exercise training during (neo)adjuvant chemotherapy in women with early-stage breast cancer: a pilot study examining immune and metabolic outcomes. Supportive Care in Cancer, 34(10), Article 1013. https://doi.org/10.1007/s00520-026-11179-8

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11179-8

Keywords: breast cancer, chemotherapy, exercise oncology, CD8 T cells, immune modulation, insulin resistance, body composition, quality of life, cancer fatigue, pilot study, resistance training, aerobic exercise

The study, led by Jingyi Xie and Zhide Liang with corresponding author Bin Wang, pooled data from 7,760 participants with coronary heart disease across 129 randomised controlled trials. That scale matters. Individual trials of exercise in cardiac patients are often small, brief, and heterogeneous, making it difficult to compare one training modality against another with any statistical confidence. By using a network meta-analysis — a technique that simultaneously compares multiple interventions, both through direct head-to-head trials and indirect comparisons across the network of studies — the team could rank exercise modalities that had rarely, if ever, been tested against each other in the same experiment.

The outcome the researchers focused on was peak oxygen uptake, or VO₂peak, the maximum rate at which the body can consume oxygen during incremental exercise. Cardiologists prize this measurement because it integrates the performance of the entire oxygen transport chain: the lungs, the heart’s pumping capacity, the vasculature, and the oxidative machinery of skeletal muscle. In patients with coronary heart disease, higher VO₂peak consistently tracks with lower mortality, fewer hospitalisations, and better quality of life, which is why guidelines from bodies such as the American College of Sports Medicine place cardiorespiratory fitness at the centre of exercise prescription.

The headline finding is that most exercise modalities outperformed control conditions, but two stood out. Interval aerobic exercise training — sessions built around alternating periods of higher and lower intensity — produced a mean improvement of 3.43 millilitres per kilogram per minute in VO₂peak compared with control, with a 95 percent credible interval of 2.87 to 3.99. Combined aerobic and resistance exercise training came next, with a mean difference of 2.49 (95 percent credible interval: 1.81 to 3.17). For context, even modest gains in peak oxygen uptake on the order of one metabolic equivalent are associated with clinically meaningful reductions in cardiovascular risk, so differences of this magnitude across an entire rehabilitation population are far from trivial.

Why might interval training hold an edge? The physiological rationale is that repeated bouts near a patient’s tolerance impose a potent stimulus on both central cardiovascular function and peripheral muscle oxidative capacity, while the recovery intervals allow total work to accumulate without excessive fatigue. The combined-training result is similarly intuitive: resistance work complements aerobic conditioning by improving skeletal muscle strength and mass, which can raise the ceiling on whole-body oxygen consumption. But the authors are careful to temper these rankings. They report substantial heterogeneity across trials and describe the certainty of the modality-specific comparisons as low, meaning the ordering of interventions should be read as exploratory rather than definitive.

What sets this analysis apart from earlier meta-analyses is its second analytical engine. The team deployed a meta-analytic random forest, or MARF, a machine learning model trained on study-level characteristics to predict how large an exercise effect would be, and then interpreted the model using Shapley Additive Explanations, or SHAP. SHAP values, a technique rooted in cooperative game theory, quantify how much each feature — such as participant age, intervention length, or training intensity — contributes to each prediction. This approach lets researchers probe heterogeneity in a way traditional subgroup analyses cannot, revealing which variables genuinely drive differences between trials rather than merely appearing to.

The machine learning exploration converged on a clear signal: intervention length emerged as an influential study-level moderator of effect. In plain terms, longer programmes were associated with bigger improvements in fitness. This aligns with the biology of training adaptation, where structural and enzymatic remodelling of heart and muscle tissue accrues over weeks and months, not days. It also carries a practical warning for health systems that fund short courses of cardiac rehabilitation and then discharge patients, potentially cutting the adaptation curve short at its steepest point.

The dose-response analyses added further nuance. Using meta-regression models, the researchers found that greater weekly exercise dose was generally associated with larger improvements in VO₂peak — more volume, more benefit, at least across the range studied. Per-session dose, however, told a different story: the relationship was inverted-U-shaped, rising to a peak and then declining. That shape suggests there is an optimal amount of work per session beyond which additional load yields diminishing, or even counterproductive, returns — a pattern consistent with the idea that overly demanding single sessions may compromise quality, adherence, or safety in a cardiac population.

The authors frame their conclusions with deliberate caution. Exercise-based cardiac rehabilitation does improve VO₂peak in adults with coronary heart disease, they conclude, but the substantial heterogeneity and low-certainty evidence limit confidence in the precise ranking of modalities. They recommend that exercise dose and programme duration be considered alongside patient characteristics, comorbidity burden, and safety when designing rehabilitation programmes, and they stress that these exploratory, aggregate-level findings require prospective validation before they can guide individualised exercise prescriptions. Notably, the research received no specific external funding, and the authors declare no competing interests.

Even with those caveats, the study marks a methodological milestone. Pairing network meta-analysis with interpretable machine learning offers a template for how exercise science — a field drowning in small, heterogeneous trials — might extract more reliable guidance from the evidence it already has. For clinicians, the actionable takeaways are refreshingly concrete: favour interval-based aerobic work or combined aerobic-resistance programmes where feasible, extend programme duration where possible, and think in terms of weekly dose rather than pushing any single session to its limit. For patients, the message is simpler and older than any algorithm: the exercise you do consistently, at an appropriate dose, over a long enough period, is what reshapes the heart’s capacity — and with it, the odds of a longer life.

Subject of Research: Comparative effects of exercise modalities on peak oxygen uptake in coronary heart disease rehabilitation

Article Title: Exercise-based management of patients with coronary heart disease: an integrated network meta-analysis and machine learning exploration

Article References: Xie, J., Liang, Z., Wang, B., Cai, X., & Gan, Z. (2026). Exercise-based management of patients with coronary heart disease: an integrated network meta-analysis and machine learning exploration. BMC Medicine. https://doi.org/10.1186/s12916-026-05229-5

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05229-5

Keywords: coronary heart disease, cardiac rehabilitation, peak oxygen uptake, interval training, network meta-analysis, machine learning, random forest, SHAP, exercise dose-response, aerobic exercise, resistance training, VO2peak