Experimental Gerontology

We examined whether a 24-week resistance training program influenced brain amyloid-{beta} (A{beta}) and Alzheimers Disease (AD)-related blood-based biomarkers. Ninety cognitively normal, physically inactive older adults aged 65-80 years were randomly allocated to a 24-week resistance training program (three [~]60-min supervised sessions/week) or a wait-list control group. Primary analyses assessed exercise-induced changes in brain A{beta} (Centiloid values) and plasma ptau217/A{beta}1-42 IPMS ratio. Secondary analyses examined ptau217/A{beta}42 SIMOA ratio, ptau217, ptau181 and A{beta}42/40, as well as potential interactions with sex, age, education, apolipoprotein {varepsilon}4 (APOE4) status, amyloid PET-positivity, and comorbidities. The intervention produced no significant differences on brain A{beta} or AD-related blood-based biomarkers (p>0.05) compared to the control group. However, the ptau217/A{beta}1-42 IPMS ratio showed a small, non-significant increase in the control group (SMD = 0.162; 95% CI: -0.159 to 0.483) while remaining stable in the exercise group (SMD = 0.01; 95% CI: -0.291 to 0.310) with a similar trend for ptau217/A{beta}42 SIMOA. Moderator analyses indicated differential responses by amyloid PET-positivity and APOE4 status on brain A{beta} (p for interaction<0.05), with increases observed in APOE4 carriers and amyloid PET-positive individuals in the control group, whereas those allocated to the exercise intervention reduced their levels. The specificity observed within our subgroups suggests that resistance exercise may serve as a targeted intervention to modulate AD pathophysiology, raising new questions regarding its broader role in the delay of the disease in vulnerable populations.

Introduction: Stair walking challenges balance and coordination in older people. Bench-stepping training improves stair climbing speed in healthy older women. This study assessed whether bench-stepping also improves dynamic balance and movement complexity during stair walking. Methods: Stair walking data were obtained from a previous study involving 45 healthy older women (69y+/-4) that assessed the effects of a 12-week bench-stepping intervention with non-training controls. Centre-of-mass acceleration was measured during stair ascent and descent. Linear dynamics included time, acceleration magnitude, and harmonic ratios (HR; indicating symmetry). Movement complexity was quantified using nonlinear dynamics including sample entropy (SE), recurrence quantification analysis (RQA), and fractal dimension (FD). Results: For stair ascent, increased speed (p =0.018, R2partial =0.093,) was accompanied by proportional increases in acceleration magnitudes (p=<0.039, R2partial =0.078-0.101). SE decreased more in the intervention group (p=<0.012, R2partial =0.049-0.101), indicating more predictable dynamics. In contrast, for stair descent, no changes in speed or acceleration magnitudes were observed. However, SE (p =0.001, R2partial =0.082) and maximum RQA line length (p= 0.008, R2partial =0.057) of vertical acceleration increased significantly compared to controls, indicating lower predictability and more persistent recurring patterns. No significant changes were found for other outcomes. Exploratory factor analysis revealed distinct differences in motor behaviour between stair ascent and descent. Conclusion: Bench-stepping training induced measurable changes in stair walking dynamics. Specifically, sample entropy shows potential as a sensitive marker of altered motor complexity, particularly of vertical accelerations. Interestingly, the direction of changes in unpredictability differed between stair ascent and descent, suggesting different underlying control strategies.

Clustering effects, such as those introduced by housing animals in shared cages, are often overlooked in preclinical lifespan studies, despite their potential to distort variance estimates and inflate Type I error rates, leading to misleading conclusions. This methodological oversight reduces statistical rigor and may undermine the reliability of findings. To address this gap, the current study examines the impact of accounting for clustering and nesting effects on lifespan analyses by comparing the results of statistical models which both account for and ignore these effects. Using 2019 data from the Interventions Testing Program (ITP), a large-scale initiative evaluating the effects of compounds on lifespan in UM-HET3 mice as a case study, we illustrate how different modeling approaches influence statistical estimates and conclusions. Clustering and nesting effects were addressed using linear mixed effects, and Cox frailty models, both of which explicitly account for cage-level dependencies and different levels of data nesting. Comparisons were made between unadjusted lifespan analyses and those incorporating clustering and nesting adjustments. The results of this case study indicate that properly adjusting for clustering and nesting effects can change the conclusions drawn from statistical significance tests as compared to unadjusted model approaches, and so it remains best practice to properly account for clustering and nesting to reduce the potential for inflated Type I error rates. These findings highlight the importance of accounting for clustering and nesting in preclinical research to ensure valid and robust statistical inference. By demonstrating the practical application of clustering adjustments, this work underscores the broader implications for improving reproducibility and rigor in lifespan studies and other experimental designs.

Human life expectancy has increased dramatically over the past two centuries, marking a significant public health achievement. While some projections predict a future where median lifespans reach 100 years, others contend that further longevity will depend on breakthroughs targeting the biological processes of aging. Recent studies in mice have demonstrated that telomerase activation, achieved via gene therapy and transgenic approaches, can extend both median and maximum lifespans substantially without an accompanying increase in cancer risk. We analysed survival data from three such studies using the Gompertz mortality model and show that these interventions reduce the slope parameter, indicative of a slower aging rate, rather than merely lowering baseline mortality. This observation challenges traditional models that assume independent, additive damage accumulation, suggesting instead that aging is driven by a limited number of interdependent processes with significant cross-talk. Mathematical modelling indicates that only three to five processes with substantial cross-talk may account for the observed deceleration. Extrapolation using Swedish survivorship data further implies that a reduction in the aging rate, similar to that seen in mice, could elevate the median human lifespan from 85 to over 100 years. These findings provide a compelling framework for developing targeted anti-aging interventions and a new perspective on the modifiability of the aging process.

BACKGROUNDFall injuries in older adults are devastating and often caused by impaired reactive balance to unexpected trips and slips, which conventional exercise programs do not target. This study examined whether a low-dose perturbation balance training (PBT) program among older adults can improve balance recovery following trips and slips and reduce falls and fall injuries. METHODS111 older adults (65+ years) were randomised into an intervention or control group. The intervention group undertook one weekly PBT session for three weeks on the Trip and Slip Walkway, followed by three-monthly PBT booster sessions over one year, for a total of six sessions. The control group received an educational booklet. Blinded staff assessed laboratory-falls induced by a trip and slip with a safety harness at baseline and one year. Number of falls and fall injuries in daily life were collected weekly for one year. RESULTSCompared to the control group, the intervention group experienced a 26% reduction in laboratory falls at 12 months (RR = 0.74; 95% CI: 0.54, 0.99; P = .040) but not different in number of falls, trip-and slip-encounters in daily life. However, fall-related injuries were reduced by 57% (rate ratio = 0.43; 95% CI: 0.19, 0.94, P = .024) over one year. A reduction in falls occurred within the first three months, with greater benefit among participants who completed at least three training sessions. CONCLUSIONSA low-dose PBT program can improve reactive balance over 12 months and reduced injurious falls by 57%, with benefits likely due to enhanced reactive balance rather than proactive gait strategies. Older adults may require at least three sessions to achieve meaningful fall reduction, with periodic booster sessions to sustain benefits. Incorporating PBT into exercise programs may enhance their efficacy in preventing falls and fall injuries in daily life. Key PointsA low-dose perturbation-based training program (six sessions over 12 months) improved reactive balance at 12 months and reduced injurious falls by 57%. Benefits are likely due to task-specific improvements in reactive balance against trips and slips rather than proactive gait strategies or other risk factors. Incorporating PBT into exercise programs may improve their efficacy in preventing falls and fall injuries in daily life. Why does this paper matter?Falls are the leading cause of injury-related hospitalization and loss of independence in older adults. By targeting reactive balance--an ability neglected by conventional exercise programs--it offers a novel, evidence-based approach to enhance fall prevention and reduce injuries.

The aim of the study was to explore the role of tennis in the promotion of health and prevention of disease. The focus was on risk factors and diseases related to a sedentary lifestyle. He registered in PROSPERO (CRD420251016042) a comprehensive literature search was performed across eight databases (PubMed, Scopus, Web of Science, EBSCO, Apunts Medicina de lEsport, SciELO, MedlinePlus, and Google Scholar) to identify relevant studies published between 2010 and 2025. 17922 articles were found; 18 in relation to the topic we develop in this article, to be studies of either cross sectional or longitudinal design, case- control studies, or experimental studies. ObjectivesTo evaluate the impact of tennis on life expectancy and its association with the reduction of mortality in different population groups. To investigate the effects of tennis on neuroplasticity and its influence on improving cognitive function, especially in older people. To explore the potential of tennis as a cognitive stimulus for the prevention and rehabilitation of neurological and mental health disorders. To propose practical implications for the incorporation of tennis in public health, active ageing and cognitive rehabilitation programmes. ResultsThe practice of tennis is associated with cognitive benefits, improvements in physical and bone health. It is also beneficial for people who have suffered from problems with their heart. The methods used to assess these effects vary between the studies reviewed. From the research it can be concluded that there are very few studies that relate the parameters of physical activities and executive functions, and that there is no heterogeneity between them. In the present study, we aim to explore the association between tennis training experience and executive functions from 4 to 94 years of age, tennis the sport for life. ConclusionTennis has a positive impact on overall fitness. Some injuries related to this sport can evolve to chronic in the lower limbs, muscles and tendons, with significant gender differences. Therefore, it is necessary to implement injury prevention strategies.

Ageing is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females demonstrate a distinct pattern of muscle ageing compared to males, potentially due to menopause where endogenous sex hormone production declines. This systematic review aims to investigate the current knowledge about the role of oestrogen in female skeletal muscle ageing. A systematic search of MEDLINE complete, Global Health, Embase, PubMed, SPORTDiscus, and CINHAL was conducted. Studies were considered eligible if they compared a state of oestrogen deficiency (e.g. postmenopausal females) or supplementation (e.g. oestrogen replacement therapy) to normal oestrogen conditions (e.g. premenopausal females or no supplementation). Outcome variables of interest included measures of skeletal muscle mass, function, damage/repair, and energy metabolism. Quality assessment was completed with the relevant Johanna Briggs critical appraisal tool, and data were synthesised in a narrative manner. Thirty-two studies were included in the review. Compared to premenopausal females, postmenopausal females display reduced muscle mass and strength, but the effect of menopause on markers of muscle damage and expression of the genes involved in metabolic signalling pathways remains unclear. Some studies suggest a beneficial effect of oestrogen replacement therapy on muscle size and strength, but evidence is largely conflicting and inconclusive, potentially due to large variations in the reporting and status of exposure and outcomes. The findings from this review points toward a potential negative effect of oestrogen deficiency in ageing skeletal muscle, but further mechanistic evidence is needed to clarify its role. Graphical abstract figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/23290199v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@97b4ecorg.highwire.dtl.DTLVardef@1e71a43org.highwire.dtl.DTLVardef@16d4a9corg.highwire.dtl.DTLVardef@3d7ac3_HPS_FORMAT_FIGEXP M_FIG C_FIG The role of oestrogen in female skeletal muscle ageing. {uparrow} = significant increase, {downarrow} = significant decrease, = = significantly different, ? = mixed evidence, p<0.05. ALM: appendicular lean mass; AMPK: adenosine monophosphate kinase; CSA: cross-sectional area; PGC-1: peroxisome proliferator-activated receptor gamma coactivator 1-alpha. Created with BioRender.com.

BackgroundTraining studies typically investigate the cumulative rather than the analytically challenging immediate effect of exercise on cognitive outcomes. MethodsWe investigated the dynamic interplay between single-session exercise intensity and time-locked cognition in older adults with suspected Alzheimers dementia (N = 17) undergoing a 24-week dual-task regime. We specified a state of the art hierarchical Bayesian continuous- time dynamic model with fully connected state variables to analyze the bidirectional effects between physical and cognitive performance over time. ResultsHigher physical performance was dynamically linked to improved memory recognition (-1.335, SD = 0.201, 95 BCI [-1.725, -0.954]). The effect was short-term, lasting up to five days (-0.368, SD = 0.05, 95 BCI [-0.479, -0.266]). Clinical scores supported the validity of the model and observed temporal dynamics. ConclusionHigher physical performance predicted improved memory recognition in a day- by-day manner, providing a proof-of-concept for the feasibility of linking exercise training and cognition in patients with Alzheimers dementia. HighlightsO_LIHierarchical Bayesian continuous-time dynamic modelling approach C_LIO_LI72 repeated physical exercise (PP) and cognitive (COG) performance measurements C_LIO_LIPP is dynamically linked to session-to-session variability of COG C_LIO_LIHigher PP improved COG in subsequent sessions in subjects with Alzheimers dementia C_LIO_LIShort-term effect: lasting up to four days after training session C_LI Research in ContextO_LISystematic review: Training-induced effects on cognitive outcomes in Alzheimers dementia and/or associated dynamic Bayesian modelling approaches were reviewed. Although studies showed exercise-induced cognitive improvements or maintenance, most of these studies fail to capture the dynamic nature of the change and interplay of physical (PP) and cognitive (COG) performance. C_LIO_LIInterpretation: Using a sophisticated hierarchical Bayesian continuous-time dynamic modelling approach, a fully connected state variable model was specified. PP is dynamically linked to COG, i.e. higher PP predicted improved COG in subsequent sessions. This effect was rather short term, lasting for up to five days. C_LIO_LIFuture direction: Our results support exercise-induced effects on cognition. The cognitive system was still able to fluctuate and change favourably even in a sample with Alzheimers dementia. Further studies using dynamic modelling are necessary to replicate findings and examine other contributors to cognitive volatility in dementia. C_LI

Background: Coronary artery disease (CAD) increases the risk of cognitive impairment, dementia, and brain structural alterations. This heart-brain connection suggests that exercise-induced cardiovascular responses may influence brain regions vulnerable to Alzheimer's disease (AD), the most common cause of dementia. This study aimed to examine the effects of 12-weeks of either high-intensity interval training (HIIT) plus resistance training (RT) or HIIT alone on AD brain signatures in individuals with CAD, to explore moderating factors, and to assess associations between changes in AD brain signatures and cognition and physical fitness. Methods: This secondary analysis of a single-site, three-arm, single-blinded randomized controlled trial included 105 individuals with CAD (50-75 years; 21% female) randomly allocated to HIIT+RT, HIIT, or usual care (UC) groups. T1- and diffusion-weighted magnetic resonance imaging were acquired before and after the 12-week intervention. Primary outcomes were thickness/volume and gray matter mean diffusivity (GMMD) signatures, derived from seven cortical regions and the hippocampus. Moderators included age, sex, education, and baseline AD brain signatures. Results: For the thickness/volume signature, no between-group differences in changes were observed between HIIT+RT and UC (+0.13 standardized mean difference [SMD]; 95% CI, -0.07 to 0.33) or between HIIT and UC (-0.1 SMD; 95% CI, -0.3 to 0.1); however, a small but significant between-group difference in change was found between HIIT+RT and HIIT, in favor of HIIT+RT (+0.23 SMD; 95% CI, 0.03 to 0.42). For the GMMD signature, no significant between-group differences in changes were found between HIIT+RT and UC (+0.08 SMD; 95% CI, -0.18 to 0.34), HIIT and UC (+0.1 SMD; 95% CI, -0.16 to 0.36), or HIIT+RT and HIIT (-0.02 SMD; 95% CI, -0.28 to 0.23). No moderation effects were identified, and no associations were observed between changes in AD brain signatures and cognition or physical fitness. Conclusion: A 12-week HIIT+RT intervention was more effective than HIIT alone in increasing the thickness/volume signature in individuals with CAD, yet no differences were observed compared to UC and the interventions did not affect the GMMD signature. These findings suggest that the intra-session inclusion of RT with HIIT may enhance AD-related brain macrostructure in individuals with CAD more than just HIIT training.

BackgroundThe distinction between healthy and pathological ageing has led to the concept of vitality capacity (VC), which can be understood as the bodys physiological reserve. An individuals VC can be estimated using 12 biomarkers spread across 3 domains: immune and stress response, energy and metabolism and neuromuscular function. Vitality capacity may be preserved by lifelong physical activity. This cross-sectional study aimed to examine the relationship between lifelong aerobic physical activity and VC. MethodsVC of 20 lifelong active and 19 inactive healthy adults aged >55 years was assessed using 12 biomarkers across the three VC domains. Domain-specific z-scores were calculated and averaged to derive a global VC score. Principal component analysis was performed and loadings extracted to estimate domains weight, and multiple correlations were conducted to identify associations among biomarkers, domains and VC scores. ResultsVC was higher in lifelong active participants (+0.2 z-score units, p = 0.006) and correlated with age (r = -0.53, p < 0.001). Neuromuscular domain contributed most to VC variability, and the immune and stress response domain was higher in the active group (+0.4 z-score units, p = 0.001) as energy/metabolism among female participants (+0.5 z-score units, p.adj = 0.006). ConclusionLifelong aerobic physical activity is associated with higher VC in older adults, particularly within the immune and stress response domain. These findings highlight the role of physical activity in preserving the physiological reserve and reinforce the relevance of lifelong aerobic physical activity as a driver of healthy ageing.

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.

BackgroundDespite cardiovascular disease being a leading cause of death globally, secondary prevention strategies following myocardial infarction are under-researched compared to primary prevention. ObjectivesTo explore relationships between indicators of sleep quality, inflammation, and myocardial infarction recurrence and the conditional role of psychological stress in these pathways to assess evidence for reducing MI recurrence by improving sleep quality and implementing stress management techniques. MethodsA secondary analysis (N = 156) of cross-sectional study data was conducted. Participants mean age was 65 years and all had experienced one or more myocardial infarctions within the previous 3-7 years. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Inflammatory markers were collected via blood assay and included C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. Psychological stress was evaluated using a self-reported Likert-scale question. Correlational analysis and conditional path analyses examined relationships between variables of interest. ResultsSignificant associations between sleep quality, inflammation, psychological stress, and MI recurrence were observed. Sleep quality predicted elevated inflammation markers. Psychological stress moderated the relationship between sleep quality and MI recurrence, with higher stress amplifying the risk. Sleep quality did not directly predict MI recurrence. ConclusionFindings suggest that improving sleep quality may be an effective secondary prevention strategy for reducing MI recurrence. The effect may be increased when combined with targeted stress management interventions. Further research is warranted to explore biobehavioral mechanisms underlying these associations to develop targeted interventions for aging individuals at risk.

Physical activity has been suggested to project again brain atrophy, but also to be a determinant of physical activity in older adults. However, research is needed to confirm this bidirectional relationship. Therefore, this research aimed to study the bidirectional relationship between physical activity and brain structure in older adults from the UK Biobank. A total of 3,027 (62.45 {+/-} 7.27 years old, 51.3% females) had physical activity and MRI data at baseline and follow-up. Physical activity was assessed through a self-reported questionnaire. T1-weighted MRI and diffusion tensor imaging were used to quantify brain volumes and white matter microstructure, respectively. Cross-lagged panel models were performed to estimate bidirectional associations, and linear mixed-effects models (LMM) to investigate the consistency of findings. Overall, our main findings suggest that higher hippocampal volume (Standardized Beta Coefficient ({beta})=0.075, pFDR<0.001), frontal volume ({beta}=0.043, pFDR=0.037), and global fractional anisotropy ({beta}=0.042, pFDR=0.028) were associated with more do-it-yourself (DIY) activities (e.g., watering the lawn or digging) levels at follow-up. In addition, strenuous sports at baseline were positively associated with hippocampal volume over time ({beta}=0.011, pFDR=0.108). Although this association did not survive/was not significant after adjustment for multiple comparisons, was confirmed by the LMM. In contrast, higher levels of walking for pleasure were negatively associated with white matter volume at follow-up ({beta}= -0.026, pFDR=0.008). In conclusion, there is a bidirectional association between physical activity and brain structure in healthy middle-aged and older adults. However, further research is needed to understand why physical activity subdomains are associated differently with brain structures and features during aging.

BackgroundA subset of older adults, known as SuperAgers (SAs), exhibit exceptional resilience to these effects, displaying cognitive abilities at the same level or exceeding those 20-30 years younger. To date however, there is little understanding as to which factors may be responsible for SA enhanced cognitive abilities in old age. This systematic review aimed to identify and evaluate the evidence for an association between lifestyle factors and SA status. MethodsA systematic literature search in accordance with the PRISMA guidelines was conducted across MedLine, Embase, Ovid, Global Health, APA PsychArticles, and PsycINFO from inception to 06/11/23 of studies investigating the link between SA status and one or more lifestyle factors. ResultsA systematic search identified 13 studies which met the inclusion criteria. Eleven investigated the relationship between two or more lifestyle factors with the most common lifestyle factor examined being mental health followed by physical activity, social engagement and smoking. Mixed results were observed across the included studies while social engagement and mental health emerged as the most likely lifestyle factors to be positively associated with SA status, there was considerable heterogeneity in the measures used to assess different lifestyle factors. ConclusionNo clear conclusions could be drawn as to which lifestyle factors are associated with SA status due to scarcity of studies and heterogeneity in the measurement of different lifestyle factors.

DNA methylation-based age estimators (DNAm aging clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between objectively measured physical fitness, including cardiorespiratory fitness, and DNAm aging clocks are largely unknown. We investigated the relationships between physical fitness and the age-adjusted value from the residuals of the regression of DNAm aging clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of physical fitness variables to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65-72 years were used to calculate first- (i.e., DNAmHorvath and DNAmHannum) and second- (i.e., DNAmPhenoAge, DNAmGrimAge and DNAmFitAge) generation DNAm aging clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrients intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. The peak oxygen uptake (VO2peak) per kg body weight had a significant negative correlation with GrimAgeAccel (r = -0.222, p = 0.008). A comparison of the tertile groups showed that the GrimAgeAccel of the highest VO2peak group was decelerated by 1.6 years compared to the lowest group (p = 0.035). Multiple regression analysis suggested that rather than physical fitness, serum triglycerides, carbohydrate intake, and smoking status, were significantly associated with DNAmAgeAccel. In conclusion, the contribution of cardiorespiratory fitness to DNAmAgeAccel was relatively low compared to lifestyle factors such as smoking. However, this study reveals a negative relationship between cardiorespiratory fitness and DNAmAgeAccel in older men.

The brain age gap (BAG) -- the difference between chronological and neuroimaging-based predicted brain age -- has emerged as a sensitive biomarker of brain health. A higher BAG, reflecting an older-appearing brain, has been linked to cognitive decline, neurodegenerative disease, and mental disorders. Whether such apparent aging can be mitigated by targeted interventions remains unclear. Oestradiol (E2), a sex hormone fluctuating across the menstrual cycle and known for its neuromodulatory and cognitive effects, may represent one such target intervention. To test this, we conducted a double-blind, randomized, placebo-controlled crossover study in 28 premenopausal females. Each participant was assessed twice during the follicular phase, with at least two cycles between sessions, and received either 12 mg E2-valerate or a placebo before undergoing a T1-weighted MRI scan. BAG was estimated using a pre-trained Simple Fully Convolutional Network model. Predicted brain age was significantly younger following E2 administration compared to placebo. Exploratory analyses indicated that this effect may be moderated by resilience factors for mental health: Higher self-esteem and use of greater social support seeking was nominally associated with lower BAG, whereas females applying more expressive suppression showed more apparent brain aging. These findings suggest that even short-term increases in E2, together with resilience factors, can influence brain age estimates. Thus, E2 interventions may provide a targeted approach to support both brain and mental health. These findings underscore the urgent need for further research into the impact of E2 on mental health across the female lifespan.

ObjectivesThis systematic review aimed to synthesise the evidence on potential differences in financial, social, health and safety-related decision-making between younger and older adults. MethodsTrial, experimental, and prospective studies including older (60+) and younger adults that reported on quantitative decision-making outcome measures (i.e., performance in relation to achieving a specific prespecified goal) were included. ResultsDecision-making was significantly poorer (i.e., further from prespecified goals) in older compared to younger adults (k = 57, drandom = -0.17, 95% CI -0.29, -0.04, I2 = 92.92%), with high heterogeneity between studies. Age differences were observed for financial and social but not health decision-making domains. DiscussionOlder adults performed more poorly on financial and social decision-making than younger adults. Reasons for observed differences may vary (e.g., different motivation and values) and require exploration in future research. This has implications for how people of different ages are supported, especially at times of important decision-making.

BackgroundIntrinsic capacity (IC) is a composite measure, computed from five domains: cognition, psychological well-being, locomotion, vitality, and sensory. IC reflects the overall physiological reserve and functional capacity of an individual, making it a key indicator of healthy ageing. The substantial interindividual variability in IC is likely influenced by genetic (polygenic) as well as socioeconomic status and lifestyle factors. However, the interaction effect of these factors is yet to be explored. ObjectiveThis study examined (1) associations of IC with socio-economic and lifestyle factors and the polygenic scores for IC (PGS-IC) when stratified by age, and (3) the interaction effects of the PGS-IC and socio-economic or lifestyle factors on IC. MethodsOur study included 13,112 participants from the Canadian Longitudinal Study on Aging (CLSA) comprehensive cohort with complete IC variables and genetic data. Composite lifestyle scores, including the Physical Activity Scale for the Elderly (PASE), Prospective Urban Rural Epidemiological study (PURE) diet, and Mediterranean diet scores, were generated following established guidelines. Associations of IC with the socioeconomic and lifestyle factors were assessed using linear regression models adjusted for age and sex. The IC scores and the PGS-IC were developed in CLSA in our previous work, and this study tested age-stratified associations of PGS-IC with IC, and interaction effects of the PGS-IC and socioeconomic or lifestyle factors on IC using linear regression models adjusted for age, sex, and the top five genetic principal components. Statistical significance was defined as a false discovery rate (FDR) adjusted P < 0.05. ResultsThe mean age was 61 (standard deviation 9.6) years, and 50.8% were females. Higher IC was associated with higher education (B = 0.255, 95% CI: 0.180, 0.329), higher income (B = 0.392, CI: 0.322, 0.461), physical activity (PASE score: B = 0.001, CI: 0.0004, 0.001), and healthier diets (PURE diet score: B = 0.024, CI: 0.021, 0.027; Mediterranean diet score: B = 0.018, CI: 0.016, 0.021). IC was lower in previous (B = -0.093, CI: -0.121, -0.064) and current smokers (B = -0.407, CI: -0.459, -0.355) compared to never smokers. Likewise, short (<7h: B = -0.133, CI: -0.161, -0.105) and long (>9h: B = -0.258, CI: -0.392, -0.124) sleep durations were negatively associated with IC compared to those who had optimal sleep. The PGS-IC was positively associated with IC, particularly in younger adults. Significant interaction effects were observed with Mediterranean diet (B = -0.003, CI:-0.006 -, -0.0002) in whole sample, education in younger adults (B = -0.109, CI: -0.211 -, -0.007), and sleep (younger adults: long sleep, B = 0.198, CI:0.023, 0.373; older adults: short sleep, B = -0.095, CI: -0.153 -, -0.036). ConclusionNovel findings confirming the interaction effects of PGS-IC with socioeconomic and lifestyle factors suggest that there is a complex interplay between genetics and the environment in shaping IC and healthy ageing.

BackgroundMyokines, released from the contracting muscle, enable communication between the working muscles and other tissue. Their release during physical exercise is assumed to depend on mode, duration, and intensity. ObjectiveThe aim of this meta-analysis is to examine the acute changes in circulating levels of the myokines IL-6, IL-10, and IL-1ra induced by a bout of resistance exercise and to consider potential moderators of the results. MethodsSystematic literature search was conducted for resistance exercise intervention studies measuring IL-6, IL-10, or IL-1ra before and immediately after resistance exercise in healthy individuals. Random effects meta-analysis was performed for each myokine. ResultsA small to moderate positive effect of resistance exercise for IL-6 and a moderate to large positive effect for IL-1ra were detected. For IL-10 no significant effect was observed. No moderators (training status, type of exercise, risk of bias, age, exercise volume, exercise intensity, exercise dose) of the results were detected. ConclusionThis systematic review and meta-analysis clearly showed the immediate positive effects of an acute resistance exercise session on IL-6 and IL-1ra levels.

BackgroundVarious studies have shown that social adversity, such as loneliness or low SES, are linked with worse cognitive outcomes, though underlying biological mechanisms remain unclear. This scoping review aims to summarize existing evidence on biological processes that may underline this association. MethodsFollowing PRISMA-ScR guidelines, studies measuring social adversity, cognition, and at least one biological mechanism were included. Results were summarized narratively and in tabular formats. ResultsThirteen studies examined links between social adversity, cognition, and biological mechanisms. Inflammation, allostatic load, genetics and genetic aging markers were identified as potential mediators. ConclusionSeveral studies suggest that these biological mechanisms may mediate the link between social adversity and cognitive decline. However, further research is needed to clarify these complex relationships, which are crucial for developing targeted interventions, especially for socially disadvantaged populations.