Experimental Gerontology

ObjectiveLoss of skeletal muscle mass and performance is a hallmark of ageing. Mitochondrial function has been suggested as a critical determinant of skeletal muscle performance. However, mixed results have been reported regarding mitochondrial function in older individuals. Therefore, the primary objective of this systematic review is to determine whether 31P-MRS-derived {tau}PCr, reflecting mitochondrial oxidative capacity, is reduced in ageing skeletal muscle. MethodsA preregistered systematic literature review was performed using the databases MEDLINE, EMBASE, SPORTDiscus, and Cochrane Central Register of Controlled Trials (CENTRAL). Papers were included if they reported {tau}PCr as measured by 31P-MRS; and studied individuals over 65 years of age in combination with a younger control group. Differences between young and older groups were assessed using random effects meta-analysis. ResultsWe included 20 papers in total, of which 2 measured 2 muscles, 5 focused on the tibialis anterior (TA) muscle, 11 on the calf muscles, 5 on the quadriceps, and 1 on the flexor digitorum longus. No statistically-significant differences were found in {tau}PCr between older and younger adults for all muscles combined (Hedges g=0.11 (p=0.487). Inter-study heterogeneity was high ({tau}2=0.36, I2=72.49%, H2=3.64). Sub-analyses for the individual muscles showed longer {tau}PCr in the quadriceps (g=0.65, p<0.001) in older adults, but shorter {tau}PCr in the TA muscle (g=-0.64, p<0.001). For the calf muscles, no differences were detected between older and young individuals (g=0.20, p=0.377). ConclusionNo uniform age-related decline was found for {tau}PCr when comparing all studies together. Substantial heterogeneity was observed between the individual muscles, with {tau}PCr being prolonged in the upper leg muscles in older adults, but shortened in the tibialis anterior. This suggests more work using standardised settings and well-defined cohorts is needed.

Introduction: Frailty is a dynamic condition associated with increased vulnerability to adverse health outcomes in older adults. While previous research has primarily focused on deficit-based mental health factors, such as depression and loneliness, less is known about the role of positive mental health determinants, including well-being, resilience and social connectedness, in the development and progression of frailty. Understanding both risk and protective factors is essential for informing public health strategies aimed at promoting healthy ageing. This study aims to examine the longitudinal relationship between mental health and frailty in a nationally sampled population of adults aged 50 years and older in Slovenia. Methods and analysis: This longitudinal observational study will collect data at four time points over a two-year period (January 2026-March 2028). A stratified random sample of community-dwelling adults aged 50-84 years will be drawn from the national population registry, with 5,000 individuals invited to participate in the first wave. Frailty, mental health and a set of social, psychological, and health-related factors will be assessed. Data will be analyzed using a combination of descriptive, inferential and longitudinal statistical methods to examine associations between frailty and mental health over time. Potential explanatory factors will also be explored within the longitudinal framework, and additional analyses will assess the impact of attrition. Ethics and dissemination: The study has been approved by the Ethics and Deontology Committee of the National Institute of Public Health. Participation is voluntary, and informed consent will be obtained from all participants. Data will be anonymized and handled in accordance with applicable data protection regulations. Findings will be disseminated through peer-reviewed publications, conference presentations and public health reports to inform strategies for promoting healthy ageing.

Background: Sleep problems are common in older people and have been associated with increased fall risk, but the mechanisms underlying this relationship remain unclear. Gait quality reflects balance control and neurological function and may provide insight into pathways linking sleep health and falls. Methods: Data from 758 community-dwelling older people ([&ge;]65 years; mean age 75.8 years, 69.3% women) were analysed. Sleep problems were assessed at baseline using a self-reported item (Patient Health Questionnaire-9, question 3). Daily-life gait quality and habitual walking speed were derived from one week of wearable sensor monitoring. Falls and injurious falls were prospectively recorded over 12 months. Associations between sleep problems, gait quality, and fall incidence were examined using regression models adjusted for demographic, pain and cognitive factors, and use of sleeping medication. Results: Sleep problems were reported by 43.9% of participants. Sleep problems were not associated with habitual walking speed, but were associated with lower gait quality in daily life (adjusted {beta} = -0.15, 95% CI -0.27 to -0.03). Participants reporting sleep problems had higher incidence rates of total falls (adjusted IRR = 1.42, 95% CI 1.07 to 1.90) and injurious falls (adjusted IRR = 1.50, 95% CI 1.07 to 2.10). Conclusions: Self-reported sleep problems were associated with impaired real-world gait quality and substantially higher rates of falls and injurious falls in older people. These findings suggest that sleep problems may increase fall risk by altering balance control rather than by reducing walking speed. Sleep should be considered when managing fall risk, and fall risk should be considered in older people with sleep complaints.

ObjectiveTo investigate the effects of breaking up prolonged sedentary behavior (SB) on daily movement behavior and energy balance in adults with overweight/obesity. MethodsThirty participants (16F/14M; 34.2{+/-}7.3y; 29.5{+/-}3.2kg/m2) were randomized to either BREAK (nine hourly 5-min brisk walking bouts) or a duration-matched intervention, ONE (45-min brisk walking), both performed 5 days/week for 6 weeks. Pre- and post-intervention, daily SB and physical activity (PA; accelerometry), body composition (doubly labeled water [DLW]), total daily energy expenditure (TDEE; DLW), appetite, and fasting leptin were measured. Linear-mixed effects models tested time effects and time-by-group interactions. ResultsOnly BREAK reduced prolonged SB (-8%; interaction: p=0.043). Both groups shifted SB-PA composition toward greater moderate-to-vigorous PA with proportional reductions in SB and light PA (time: all p[&le;]0.011), which were associated with increases in TDEE (+0.67 MJ/d; time: p=0.040). Body and fat mass increased in ONE only (interaction: p=0.061 and p=0.055). No differences were noted in energy intake, appetite, or leptin levels. ConclusionsSpreading short PA bouts throughout the day increases MVPA and TDEE to the same extent as a traditional continuous PA bout. Future studies should investigate whether minor differences in body composition are driven by distinct behavioral/physiological compensations influenced by the daily pattern of PA/SB. STUDY IMPORTANCE QUESTIONSO_LIWhat is already known about this subject? O_LIAcutely, breaking up prolonged sedentary behavior (SB) with short bouts of physical activity (PA) increases energy expenditure and reduces food cravings compared to a single continuous PA bout. C_LIO_LISingle continuous PA bouts have been associated with compensatory reductions in non-exercise activities (daily living activities) in some studies, which may attenuate increases in total daily energy expenditure (TDEE) and limit effects on body mass and adiposity. C_LI C_LIO_LIWhat are the new findings in your manuscript? O_LIPerforming brisk walking either through frequent, short bouts spread across the day or as a single continuous bout over 6 weeks increases moderate-to-vigorous PA (MVPA) at the expense of SB and light PA and increases TDEE to a similar extent in adults with overweight or obesity. C_LIO_LIHowever, only the frequent, short active breaks reduced time spent in prolonged SB (>60 min), an independent cardiometabolic health risk factor. C_LIO_LIDespite no differences in energy intake, appetite, or plasma leptin concentration, the single continuous bouts were associated with a small, non-robust increase in body and fat mass, whereas these remained stable in the active breaks group, suggesting differential compensatory adaptations. C_LI C_LIO_LIHow might your results change the direction of research or the focus of clinical practice? O_LIPromoting frequent, short bouts of PA throughout the day can improve daily movement and help meet current PA/SB guidelines to a similar extent as traditional PA strategies, while also reducing prolonged sedentary time. C_LIO_LIThis strategy may help limit compensatory responses sometimes observed in response to continuous MVPA bouts, offering a new tool to manage body weight. C_LIO_LIHowever, differences in body composition outcomes were small and not robust, and future studies are needed to determine whether these patterns translate into meaningful long-term effects on energy balance and weight regulation. C_LI C_LI

INTRODUCTIONHealthful dietary patterns may attenuate dementia risk by preserving cerebrovascular health. Prior work has focused on systemic arterial stiffness, but cerebrovascular measures may be more sensitive to neuroprotective effects of diet. We examined associations between Mediterranean diet adherence, prefrontal cortex (PFC) arterial elasticity, and cognition in older adults. METHODSParticipants were 198 older adults (58% female; mean age 65.6 years) from the Newcastle ACTIVate cohort. Mediterranean Diet (MedDiet) scores were derived from the Australian Eating Survey food frequency questionnaire. Pulse Relaxation Function (PReFx), an index of PFC arterial elasticity, was measured using pulse Diffuse Optical Tomography. Cognition was assessed with CANTAB and a cued task-switching paradigm. RESULTSHigher MedDiet was associated with higher PFC arterial elasticity. MedDiet was not associated with cognition, and PReFx did not mediate diet-cognition associations. DISCUSSIONGreater Mediterranean diet alignment was cross-sectionally associated with PFC arterial elasticity, suggesting a pathway through which diet may influence brain health in ageing.

Background: The determinants of immunoglobulin E (IgE) remain poorly understood in older adults, a population with an increasing burden of chronic diseases. Identifying IgE's determinants may improve its clinical interpretation in the evaluation of allergic and IgE-related conditions. Objective: To investigate age, sex, smoking, alcohol, body mass index (BMI), corticosteroid use, and season as potential determinants of total IgE (tIgE) and inhaled allergen-specific IgE (sIgE). Methods: Using Rotterdam Study data, we investigated the determinants of tIgE and sIgE using multivariable linear regression. Longitudinal changes and the effects of corticosteroids were assessed with linear mixed models. Results: We included 8769 participants, of which 478 had repeated IgE measurements. Age showed a U-shaped relationship with tIgE and L-shaped relationship with sIgE (both p<0.001). Women had lower tIgE (OR [95%CI]: 0.69 [0.65-0.74]), whereas current smokers (1.34 [1.23-1.46]), higher BMI (1.01 [1.01-1.02]), topical corticosteroid users (1.27 [1.07-1.50]) and inhaled corticosteroid users (1.93 [1.64-2.26]) showed higher tIgE. Women (0.96 [0.92-1.00]), former smokers (0.87 [0.83-0.91]) and current smokers (0.72 [0.68-0.76]) had lower sIgE, whereas topical corticosteroid users (1.20 [1.07-1.35]) and inhaled corticosteroid users (1.20 [1.07-1.35]) showed higher sIgE. Over time, tIgE and sIgE decreased (p<0.001) but did not significantly change after corticosteroid use. Conclusion: We identified age, sex, smoking, BMI, season and topical and inhaled corticosteroids as determinants of tIgE and sIgE. Incorporating these determinants may improve IgE's clinical interpretation for the diagnosis and management of allergic and IgE-related conditions. Future research should investigate how these determinants shape IgE's relationship with chronic diseases in aging populations.

BackgroundActivities of Daily Living (ADL) assessments are essential outcome measures in rehabilitation and long-term care, but primarily focus on task completion and provide limited insight into the postural control structures underlying movement failure. This paper proposes the Four Movement Screen Structure (4MS), a theoretical framework that reconceptualizes human movement control through four postural control phases: supine, sitting, standing, and single-leg standing. The framework proposes that functional decline may present with non-continuity, asymmetry, and compensatory preservation, rather than a simple reversal of motor development. MethodsAn exploratory, hypothesis-generating cross-sectional study was conducted with 297 certified care recipients (mean age 80.5 years) across multiple day-service facilities in Japan. Each participant was assessed using both the Barthel Index (BI) and the 4MS evaluation. Descriptive statistics, Pearson correlations, chi-square tests, and Fishers exact tests were used to explore the structural properties of the framework. ResultsThe mean BI total was 89.0 (SD = 13.8); the mean 4MS total score was 7.75 (SD = 2.02). A moderate positive correlation was found between BI total and 4MS total score (r = 0.471, p < 0.001, 95% CI [0.378, 0.555]). Of the five defined decline types, four were observed: mixed (57.6%), supine-dominant (21.2%), standing-dominant (5.7%), and single-leg-dominant (15.5%); sitting-dominant was not observed. The supine phase was the primary intervention target in 74.4% of cases--a finding we term the "supine paradox." In a subsample of 274 participants, 90.0% of those in the low supine score group (0-1.0, n = 170) performed rising from supine independently, suggesting that this paradox reflects qualitative deficits in foundational motor control masked by compensatory strategies. ConclusionsThese exploratory findings are broadly consistent with the non-reversal hypothesis and suggest that 4MS may capture structural dimensions of postural control not fully represented by conventional ADL assessment. As a hypothesis-generating study, these findings should be interpreted as generating testable hypotheses for future longitudinal and interventional research. Keywords: Postural control; Activities of daily living; Motor development; Functional decline; Barthel Index; Long-term care; Supine paradox; Non-reversal hypothesis; Geriatric assessment; Exploratory study

Abstract/SummaryO_ST_ABSBackground/ObjectiveC_ST_ABSCommon measures of physical activity (PA) based on duration and intensity do not fully capture its complexity. Adding additional PA components of muscle strength, mechanical strain, and turning actions, can provide a more complete view of activity behavior. Furthermore, PA behaviors differ between men and women. Therefore, the goal of this study is to identify and cluster similar long-term PA patterns over time for each PA component, examined separately for men and women. MethodsWe used data from 4963 participants (52% women; mean age 66 years, SD = 8.6) of the Longitudinal Aging Study Amsterdam (1992-2019). PA component scores were assigned to self-reported activities, and Sequence Analysis with Optimal Matching was used to identify and cluster similar activity patterns over a period of 10 years, separately for each component and stratified by sex. ResultsPA components varied by sex and displayed a unique mix of trajectories, including predominately low, medium, or high activity, increasing or decreasing patterns, and trajectories characterized by early or late mortality. Importantly, trajectories remained independent, indicating that changes in one PA component were not linked to changes in others. ConclusionOlder men and women follow distinct and independent long-term PA trajectories across components, underscoring that PA behavior cannot be described by a single dimension. Significance/ImplicationsThe observed independence and heterogeneity of trajectories suggest that muscle strength, mechanical strain, and turning actions capture meaningful and distinct aspects of PA that are not reflected by traditional measures alone. Future PA-strategies could incorporate these dimensions and acknowledge sex-specific patterns to better reflect natural movement. The independence of components suggests that future interventions should target multiple dimensions, as changes in one component may not translate to others. Such an approach may support more tailored and sustainable PA interventions in later life.

Objectives: Cardiovascular disease (CVD) is a leading cause of mortality and disability in older populations. This study aimed to identify CVD risk factors in community-dwelling older adults and to examine whether frailty-related factors (sarcopenia and nutritional status) interact with chronic kidney disease (CKD). Methods: This cross-sectional study included 307 community-dwelling Japanese adults aged [&ge;]65 years between September 2024 and March 2025. CVD history was assessed based on self-reported physician diagnoses obtained through a structured questionnaire. Lifestyle-related factors included hypertension, diabetes, dyslipidemia, and body mass index (BMI). Frailty-related factors included sarcopenia (Asian Working Group for Sarcopenia 2019 criteria), nutritional status (Mini Nutritional Assessment-Short Form), and physical activity (International Physical Activity Questionnaire-Short Form). CKD was defined using the estimated glomerular filtration rate (eGFR): non-CKD ([&ge;]60 mL/min/1.73 m2) and CKD (<60 mL/min/1.73 m2). Multivariable logistic regression identified independent correlates of CVD, and interactions between CKD and frailty-related factors were tested. Results: The prevalence of CVD was 17.9%. Independent correlates included CKD (aOR 5.0), hypertension (aOR 4.0), male sex (aOR 3.1), undernutrition (aOR 2.7), sarcopenia (aOR 2.7), and low physical activity (aOR 2.5). No significant interactions were observed between CKD and sarcopenia (p = 0.70) or nutritional status (p = 0.40). Conclusions: CKD, sarcopenia, undernutrition, and low physical activity were independently associated with CVD, with no interaction between CKD and frailty factors. These findings suggest that integrated management addressing both renal function and frailty-related factors may be important for CVD prevention in older adults.

Abstract Background: Resilience is acknowledged to be an important component for successful aging in older adults, but there is scant evidence with which to inform public health interventions for this age group. The aim of this study is to determine whether the public health intervention, mindfulness for later life is both feasible and acceptable to older adults. Methods: Participants were recruited from September 2021 to June 2022 through older adult organisations and charities, such as the University of the Third Age, Age UK, and Age Concern, and by adverts distributed through village newsletters and support organisations. Participants were offered six weekly sessions of mindfulness therapy, the program was based on the mindfulness-based stress reduction program, each session was two hours long with 10-15 participants per program. The following two pre-defined indicators of success needed to be met for the program to be deemed feasible: successful uptake (recruitment of 30 participants over nine months) and initial engagement. Results: Thirty-three potential participants were screened for eligibility over nine months, 31 of whom were recruited to the study (103% of the target sample). Of these, 28 participants (90%) completed four or more online sessions. Thus, predefined indicators of feasibility were met. Conclusions: This study supports the feasibility of delivering the mindfulness for later life program as a public health intervention, including recruitment and treatment completion. A full-scale trial to assess the clinical- and cost-effectiveness of the intervention including its long-term effects is warranted.

BackgroundNepal is experiencing a rapid demographic shift toward an aging population, with concurrent increase in morbidity and medication-related problems. Despite this, the multidimensional experience of medication-related burden (MRB) and refill adherence remain under-studied, particularly through the lens of socio-demographic, clinical and medication-related predictive features. This study aimed to assess MRB and medication adherence, and utilize machine learning (ML) architectures to identify complex factors influencing both. MethodsA cross-sectional study conducted among 390 ambulatory older patients (aged[&ge;]65 years) at Bharatpur Hospital, Nepal. MRB and medication adherence was assessed using Living with Medications Questionnaire (LMQ-3) and Adherence to Refills and Medication Scale (ARMS). Six ML architectures (Ordinary Least Square, LightGBM, Random Forest, XGBoost, SVM, and Penalized linear regression) were employed to predict ARMS and LMQ scores using various socio-demographic, clinical and medication-related predictive features. Model explainability was provided through SHAP (Shapley Additive exPlanations). All the analysis were performed using R. ResultsThe median LMQ-3 score was 110.0 (IQR 14.0), reflecting a moderate medication-related burden, while the median ARMS score of 21.0 (IQR 6.0) indicated moderate non-adherence. Random forest was the superior predictive model for both MRB and adherence. SHAP analysis revealed requiring assistance for medication and polypharmacy as the most significant drivers of both increased burden and poor adherence. Interaction analysis revealed that while polypharmacy typically worsens adherence, the risk is partially mitigated when patients receive physical or cognitive assistance. Additional, financial factors and employment status emerged as significant predictors. ConclusionOlder patients in Nepal face a significant medication-related burden and non-adherence, driven largely by regimen complexity and the need for support. The high predictive accuracy of ML models suggests that clinical interventions should prioritize simplified regimens and patient-centered counseling for those with high dependency. These findings provide a data-driven rational for policy-level medication optimization strategies in Nepals evolving healthcare system. Author SummaryAs ageing occurs, there is high chance of presence of the chronic conditions. For management of these conditions, older people are often prescribed with multiple medications and often are vulnerable to those medications whose risk outweighs benefits. As a result there is high chance of occurrence of adverse effects; these effects have caused substantial degradation of the health related quality of life. Although pharmacotherapy is the mainstay of the chronic disease management, older people often feel medication burden. Medication burden is practical experience arising from the practical and psychological challenge while managing medications. Research shows high burden causes the non-adherence, a significant problem among older adults, causing significant problem in pharmacotherapy. Hence, we used validated Questionnaire for assessing the medication burden and medication adherence among older ambulatory adults attending the central hospital of Nepal. We used machine learning approach for the high prediction of the predictors influencing the medication related burden and mediation adherence. Moderate burden was observed among older adults and moderate non-adherence was also observed. We found needing assistance for medication management and multiple medications were the strongest predictors for both Medication burden and non-adherence. Our Study provides new insights and area for the implementation of clinical intervention for the medication optimization.

BackgroundEarly recognition of dementia-related changes is critical for timely intervention. The AD8 Dementia Screening Interview (AD8) detects subtle cognitive and functional changes, yet its broader associations with health and wellbeing among Chinese-speaking older adults remain underexplored. MethodsA cross-sectional study was conducted with 144 community-dwelling Chinese older adults (mean age 73.1 years; 81.3% female). Participants completed sociodemographic, health, functional, and psychosocial measures, including the AD8 and the Geriatric Depression Scale (GDS-15). Exploratory Factor Analysis (EFA) assessed the dimensionality of the AD8, and binary logistic regression examined associations between AD8 items and demographic, health, functional, and psychosocial outcomes. ResultsChronic disease was prevalent (68.1 percent), and 13.2 percent reported a mental health disorder. EFA identified three domains: memory impairment, executive and interest decline, and functional recall difficulties, explaining 61.7 percent of the variance. Logistic regression showed predictive roles for judgment problems (AD8_1), repetition (AD8_3), financial difficulties (AD8_6), tool-use difficulties (AD8_4), and daily memory problems (AD8_8). Financial and executive difficulties were associated with age and mobility challenges, while repetition predicted psychological disorders and hopelessness. Judgment problems were linked to lower life satisfaction and happiness but greater helplessness. Worthlessness was predicted by financial, tool-use, and memory difficulties, whereas intact temporal recall (AD8_5) was protective. Several outcomes including boredom, low energy, and staying home were not significant. ConclusionDistinct AD8 items predicted vulnerabilities across physical, psychological, and social domains. Findings highlight the multidimensional value of the AD8 as a culturally relevant screening and risk stratification tool for community-based assessments of Chinese older adults. Summary Statement Implications for PracticeO_ST_ABSWhat does this research add to existing knowledge in gerontology?C_ST_ABSThis study shows that specific AD8 items identify early multidimensional vulnerability among community-dwelling Chinese-speaking older adults. Difficulties with judgment, repetition, financial management, tool use, and daily memory were associated with functional limitations and psychosocial distress, extending the AD8 beyond dementia screening alone. The identification of three AD8 domains supports a broader understanding of early cognitive change as involving cognitive, functional, and emotional processes. The findings contribute culturally specific evidence from an under-researched population in gerontological research. What are the implications of this new knowledge for nursing care with older people?For nursing practice, the AD8 provides a brief, feasible tool to support holistic assessment in community and aged care settings. Key AD8 indicators can guide nurses in identifying older people at risk of functional decline and emotional vulnerability, enabling earlier, person-centred interventions. The findings highlight the importance of culturally and linguistically appropriate assessment when caring for diverse ageing populations. How could the findings be used to influence policy or practice or research or education?The results support integrating brief cognitive screening into routine nursing assessments and community-based aged care services to promote early identification and ageing in place. Nursing education should emphasise interpreting cognitive screening within psychosocial and cultural contexts. Longitudinal research is needed to assess intervention effectiveness. Key Points[tpltrtarr] Early cognitive changes matter for older Chinese-speaking adults, because difficulties with judgment, repetition, financial management, and tool use (AD8 domains) were consistently linked to poorer functional and psychosocial outcomes. [tpltrtarr]Beyond dementia screening, the AD8 proved useful for detecting vulnerabilities in wellbeing and daily functioning, extending its role beyond diagnostic sensitivity. [tpltrtarr]A cultural focus is vital, as this study is among the first to examine AD8 associations in older Chinese-speaking adults, underscoring the need for culturally tailored screening. [tpltrtarr]The psychosocial impact of cognitive changes was evident, with strong associations to helplessness, worthlessness, and reduced life satisfaction, reinforcing the overlap between cognitive and emotional health. [tpltrtarr]In practice, integrating AD8 screening into community and primary care could help identify at-risk individuals early and support targeted interventions in culturally and linguistically diverse populations.

Autophagy is a hallmark of aging, but autophagy-related proteins have not been exclusively targeted to attenuate the progressive decline in physical function associated with aging. Here, we combined Tat-Beclin1, an autophagy agonist, and endurance training to determine whether Tat-Beclin1 enhances exercise adaptation in old male mice. Tat-Beclin1 was administered intraperitoneally (TB group, 15 mg/kg, 2x/week) as a standalone therapy, or in combination with endurance training (TB+Exe group, 70% of maximal running speed 3x/week) for 1 month in 23-month-old male C57BL/6J mice. Control groups were age-matched cage controls and exercise-only groups. Animals were assessed for grip strength, endurance capacity on a treadmill, and balance and coordination on a rotarod. Gastrocnemius/plantaris (G/P) and tibialis anterior muscles were harvested for western blotting, myofiber typing, and proteomic profiling (G/P only). TB+Exe led to significant increases in grip strength, endurance capacity, and balance and coordination performance beyond those observed in the TB and Exe groups alone. Autophagy markers, including Beclin1, the LC3B-II/I ratio, and p62, did not differ among groups. A proteomic analysis of the G/P muscle revealed that TB upregulated biological processes involved in muscle contraction and adaptation, whereas TB+Exe increased mitochondrial bioenergetic processes and, surprisingly, upregulated acute inflammatory responses, including proteins such as haptoglobin and orosomucoid-1. We conclude that combining Tat-Beclin1 and endurance training may represent a new approach to attenuate aging-related decline in physical function. New & NoteworthyWe show evidence that combining Tat-Beclin1 and endurance training (TB+Exe) resulted in greater improvements in physical function in 24-month-old male mice than either standalone therapy. We also show that TB+Exe upregulates traditional exercise-like biological processes and unexpectedly upregulates acute-inflammatory proteins (e.g., orosomucoid-1), which are thought to improve physical function in preclinical studies. Our study suggests that TB may be a new drug enhancing physical function, especially when combined with endurance training in old male mice.

Sarcopenia is a geriatric condition characterized by the loss of muscle strength, muscle mass, and physical performance, yet its neural mechanisms remain insufficiently understood. This study aimed to identify cortical indicators of motor and cognitive functioning in individuals with sarcopenia using functional near-infrared spectroscopy (fNIRS), along with electromyography (EMG) and hand dynamometer measurements. 30 sarcopenia patients (age 67.33 {+/-} 7.48, F/M: 22/8) and 38 healthy controls (age 65.37 {+/-} 4.18, F/M: 29/9) participated in three experimental sessions designed to probe different neural systems: a Hand Grip task to assess motor function, an N-Back task to evaluate working memory, and an Oddball task to measure attention and inhibitory control. fNIRS measurements were carried out during all experimental sessions, while EMG and force output were extracted from the Hand Grip task. Group differences and neural-behavioral relationships were examined using t-tests, correlations, and repeated measures analyses. Participants with sarcopenia demonstrated significantly reduced EMG activity and force production. Although motor cortex responses during the Hand Grip task were similar between groups, the N-Back task revealed lower activation in the precentral, middle frontal, and superior frontal regions in the sarcopenia group. In contrast, the Oddball task showed increased right-hemisphere activation in sarcopenic individuals, suggesting compensatory recruitment. Significant correlations between cortical activity, grip strength, and Chair Stand Test performance indicated shared neural pathways linking motor and cognitive function. These findings highlight altered neural processing in sarcopenia and emphasize the importance of integrating neuroimaging with clinical measures to advance early detection and targeted intervention strategies. HighlightsO_LIfNIRS assessed motor and cognitive cortical activity in sarcopenia. C_LIO_LISarcopenia showed lower EMG amplitude and grip force output. C_LIO_LINo group difference in motor cortex activation during hand grip. C_LIO_LIN-back revealed lower frontal and precentral activation in sarcopenia. C_LIO_LIOddball showed higher right-hemisphere activation in sarcopenia. C_LI

BackgroundThe maintenance of skeletal muscle health plays a pivotal role in prolonging both the lifespan and healthspan. However, muscle mass and strength exhibit significant declines with age. Ageing is associated with a reduced muscle protein synthesis response to key anabolic stimuli, including the androgen hormone testosterone, termed anabolic resistance. Testosterone enacts its anabolic effects in muscle through androgen receptor (AR) mediated pathways. Emerging evidence suggests that AR availability may represent a rate-limiting factor in androgen signalling, with AR saturation occurring below physiological testosterone levels in some tissues. Prior research in rodents has reported age-related reductions in AR expression, suggesting changes in AR protein content may constitute a key component of anabolic resistance. However, reports of the effects of age on the human skeletal muscle AR are inconclusive and limited by small sample sizes. Therefore, this study aimed to characterise age-related changes in expression of the AR, its regulators and downstream target genes in human skeletal muscle. MethodsWe developed and used a novel R-based pipeline, MetAR, to perform reproducible meta-analyses of publicly available bulk RNA-Seq datasets from NCBI GEO and investigate associations between target gene expression and variables of interest without the need for high-performance computing. Eligible datasets included skeletal muscle samples from healthy adult males aged [&ge;]18 years, with an age range of [&ge;] 10 years and sample size [&ge;] 6. Raw counts data were downloaded, appraised and TMM normalised. Dataset-level associations between age and target gene expression were assessed using linear and generalised additive models (GAMs). Random-effects meta-analyses were performed, and heterogeneity, publication bias and leave-one-out sensitivity assessed. ResultsSixteen skeletal muscle bulk RNA-seq datasets (n = 364; age 18-92 years) were eligible for inclusion in the meta-analyses. AR expression was negatively associated with age ({beta} = -0.006 log2 TMM-CPM per year, p < 0.001) corresponding to a 4.4% decrease in expression per decade. Age was also associated with a significant reduction in expression of various regulators of AR stability, transcriptional activity and nuclear transport. Additionally, steroidogenic enzymes and key downstream targets of the AR, including genes encoding for key structural proteins and mitochondrial function were negatively associated with age. ConclusionsCollectively, these findings suggest a multi-faceted age-associated remodelling of AR expression, signalling and nuclear transport that may contribute to the development of anabolic resistance and consequent age-associated muscle loss.

Abstract Background: Insufficient physical activity, excessive sedentary time, and suboptimal sleep are linked to premature mortality and chronic disease and may contribute to social inequalities in health, but most evidence is self-reported. Device-measured, nationally representative data capturing the full 24-hour movement spectrum remain scarce, particularly among older adults. This study examined social, economic, and environmental disparities in 24-hour movement behaviours in the 2021-23 English Longitudinal Study of Ageing (ELSA) accelerometry sub-study. Methods: A subset of 5,382 ELSA participants (71.9%) was invited to wear an Axivity AX3 wrist accelerometer for eight days, with 4,354 (80.9%) agreeing. Raw data were processed using machine learning to derive step count, sleep duration, moderate-to-vigorous and light physical activity, sedentary time, and time in bed. Cross-sectional associations with sex, age, education, marital status, wealth, and urbanicity were examined using linear regression. Findings: Data from 3,648 participants (mean age 68.5 {+/-} 9.3 years; 44.3% men) were included in wear time analyses (median 6.6 days, IQR 6.0-6.9), with 3,161 (86.7%) having sufficient wear time for movement behaviour analyses. Older, unmarried, or lower education/wealth participants were less active, more sedentary, and slept less. Rural participants were more active than urban participants. Women accumulated fewer steps and less moderate-to-vigorous physical activity and sedentary time, but more light activity and longer sleep than men. Interpretation: Social, economic, and environmental disparities exist across the full 24-hour movement spectrum, highlighting population groups for targeted interventions. Follow-up data will clarify how 24-hour movement behaviours influence healthy ageing and contribute to social inequalities in health.

BackgroundEmerging research indicates that light exposure may influence sleep quality. Identifying key light-exposure behaviours associated with poor sleep quality in athletes may allow practitioners to efficiently screen for sleep difficulties and prioritise athletes for further assessment. Translating these findings into a practical screening tool could enhance willingness of high-performance professionals to monitor sleep and light exposure in athletes. HypothesisKey predictor variables identified by feature reduction techniques will lead to higher predictive accuracy in determining which light behaviours are associated with poor sleep quality in athletes. Study DesignCross-sectional study. Level of EvidenceLevel 3. Methods121 athletes from varying competitive levels completed questionnaires, including the Light Exposure Behaviour Assessment (LEBA) and Pittsburgh Sleep Quality Index (PSQI). Poor sleep quality was defined using the PSQI cut-off >5. Least absolute shrinkage and selection operator (LASSO) regression identified light exposure variables from the LEBA questionnaire most strongly associated with good and poor sleep quality in athletes. Three models were compared: a full-variable model (23 items), a factor-specific model (Factor 3: screen/device use), and a feature-reduced model (LASSO-selected items). ResultsPhone use before bed, checking phone/watch during the night, were identified as variables of greatest association with poor sleep quality and used for reduced feature set modelling. On an independent test set, the feature-reduced model achieved area under the curve (AUC) 0.83, sensitivity 0.70, and specificity 0.92. ConclusionsOur findings report that phone-related behaviours before and in bed are associated with a higher likelihood of poor sleep quality. These behaviours, combined with the developed nomogram, provide a preliminary, low-burden screening tool to identify athletes who may be experiencing sleep difficulties. The high specificity indicates that athletes flagged by the tool are likely to have genuine poor sleep quality, warranting further assessment to identify underlying causes and appropriate interventions. Clinical RelevanceEducation and interventions focused on light exposure factors were identified as most influencing sleep quality in a multifaceted athletic population and could be prioritised to optimise sleep quality. The developed sleep quality nomogram may be useful as a decision-making tool to improve sleep monitoring practice among practitioners.

Background: Despite the growing global burden of multimorbidity, the patterns of disease combinations, have not been extensively categorized. We aimed to explore the predictors, health consequences, and patterns of discordant and concordant multimorbidity. Methods: We used the 2018 China Health and Retirement Longitudinal Study (CHARLS), a representative database of adults aged >45 years from China. We conducted logistic regression analyses to assess the likelihood of having discordant (conditions from different disease systems) versus concordant (only cardiometabolic, or only respiratory diseases) multimorbidity, and to compare the health status and healthcare utilization between patients with discordant and concordant multimorbidity. Latent class analysis (LCA) was applied to both the entire sample and to patients with discordant multimorbidity to identify clusters of disease combinations. Results: The sample included 1668 patients with concordant (mainly cardiometabolic), and 7306 patients with discordant, multimorbidity. Female patients, patients living in rural settings, former and current smokers, and patients engaging in high-intensity physical activity, were more likely to have discordant instead of concordant multimorbidity. Depression, limitations in daily activities, poor self-reported health, and frequent healthcare use were more common in patients with discordant than concordant multimorbidity. The LCA identified five clusters when all multimorbid patients were included (cardiometabolic, arthritis-digestive, respiratory, multisystem, and arthritis-hypertension classes), and four clusters when restricted to discordant multimorbidity (digestive, arthritis-cardiometabolic, respiratory, and multisystem classes). Conclusion: Discordant multimorbidity is associated with poorer health and increased use of healthcare. Cardiometabolic diseases, arthritis, and digestive diseases have a central role in defining disease patterns.

Intrinsic capacity (IC) summarizes functional health across multiple domains in healthy aging research, yet evidence on whether IC can be measured and tracked before older age remains limited. Using data from the 1958 British birth cohort at ages 50 and 62 (N = 7,804), we examined whether IC could be measured as a coherent, valid and longitudinally comparable construct from midlife to early old age. A second-order model applied to 30 indicators across sensory, cognitive, physical, psychological and vitality domains supported a five-domain IC construct, with scalar invariance across sweeps enabling comparison of scores over time. IC scores showed graded associations with self-rated health and chronic disease burden in the expected directions. Mean IC declined by 6.3 points on a 0-100 scale from age 50 to 62. These findings establish a basis for studying IC trajectories from midlife, before functional decline is usually clinically apparent.

Background: Individuals with coronary artery disease (CAD) are at higher risk of cognitive decline and dementia, in which gray matter cerebral blood flow (CBF) plays a critical role. This study investigated the effects of High Intensity Interval Training (HIIT) and HIIT plus resistance training (RT) on CBF and other health outcomes in individuals with CAD. Methods: This trial included 105 participants with CAD (age 62.1 (SD 6.6) years, 21% women) randomly assigned to HIIT+RT (n=37), HIIT (n=35) or usual care (n=33). The primary outcome was the change in global CBF from baseline to 12-week follow-up. Secondary outcomes included: region-specific CBF (hippocampus, precuneus, and anterior/posterior cingulate cortex), cognitive function (general cognition, episodic memory, processing speed, working memory and executive function/attentional control), peak oxygen uptake (VO2peak), muscular fitness (30s sit-to-stand) and body composition [weight, body mass index (BMI), and fat and muscle mass). Data were analyzed using available-case intention-to-treat constrained (baseline-adjusted) linear mixed models. Predefined subgroup analyses were conducted for age, sex, education, and baseline level of the outcome studied. Results: No significant between-group differences were observed in CBF changes in the whole sample. However, participants with lower CBF at baseline showed greater CBF increases in the HIIT group compared to both usual care (+7.1 ml/100g/min, P=0.02) and HIIT+RT (+5.53 ml/100g/min, P=0.04). No effects were observed on regional CBF or cognition. Both exercise groups improved VO2peak compared to usual care (HIIT+RT: +2.6; HIIT: +2.5 mL/kg/min, both P<0.001). Only HIIT+RT increased muscular fitness (vs usual care: +3.3; vs HIIT: +3.1 repetitions, both P<0.001), and only HIIT decreased BMI (vs usual care: -0.47; vs HIIT+RT: -0.44 kg/m2, both P<0.03). No life-threatening events or deaths occurred during 1995 training sessions in the exercise groups, nor in the usual care group. Conclusion: Twelve weeks of HIIT+RT or HIIT did not increase CBF in the whole sample with CAD, but HIIT effectively increased CBF in those who had poorer CBF at baseline. While no cognitive benefits were observed, we found exercise-specific improvements in other clinically relevant outcomes, such as VO2peak, muscular fitness, and BMI.