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Metabolomic ageing across mental and behavioural disorders.

BACKGROUND: Individuals with mental disorders face excess morbidity and premature mortality. Accelerated ageing has been proposed as a contributing mechanism but population-scale evidence across diverse diagnoses is limited. OBJECTIVE: To examine whether metabolomic ageing differs across mental disorders and whether associations vary by sex, age group and genetic liability. METHODS: Using plasma metabolomic profiles from UK Biobank participants, we applied a metabolomic ageing clock (MileAge) to estimate disorder-specific differences between metabolite-predicted and chronological age. Mental disorders were ascertained from health records and self-reported physician diagnoses. We analysed nine diagnostic groups and 45 individual disorders and assessed sex and age group differences and associations with polygenic scores. FINDINGS: Among 225&#x2009;212 participants (54% female; mean age 56.97), 38&#x2009;524 had a diagnosis preceding baseline. Substance use, psychotic, affective and neurotic disorders were associated with a metabolite-predicted age older than chronological age, largest for psychosis (&#x3b2;=0.556, 95% CI 0.250 to 0.861, p<0.001). Obsessive-compulsive and eating disorders were associated with a metabolite-predicted age younger than chronological age. Several associations were stronger in males and in individuals aged <65 years. Higher genetic liability to depression, autism and attention-deficit/hyperactivity disorder predicted an older metabolomic age (&#x3b2; range=0.020&#x2009;to 0.047), whereas polygenic scores for psychosis and tobacco use disorder predicted a younger metabolomic age (&#x3b2; range=-0.023&#x2009;to -0.040). For obsessive-compulsive disorder and anorexia nervosa, clinical and genetic associations indicated younger metabolomic ageing. CONCLUSIONS: Metabolomic ageing in mental disorders is heterogeneous. While many disorders are associated with an older biological age, some are linked to a younger biological age. Divergence between genetic liability and clinical phenotypes suggests that non-genetic factors shape biological ageing differences. CLINICAL IMPLICATIONS: Biological age should not be assumed to uniformly exceed chronological age across mental disorders. Sex and age-specific approaches could improve understanding of biological ageing processes in psychiatry.

Humans

Adolescents' Growing Sensitivity to Psychosocial Stressors: Evidence From Two Decades of Health Behaviour in School-aged Children (HBSC) Data in the Nordic Countries.

PURPOSE: We tested a perception-based explanation for rising psychosomatic complaints among adolescents in the Nordic countries. Specifically, we examined whether adolescents have become more sensitive to psychosocial stressors, reflected in stronger associations between stressors and psychosomatic complaints in 2022 than in 2002. METHODS: Data were drawn from the 2002 to 2022 waves of the Health Behaviour in School-aged Children survey among 15-year-olds in five Nordic countries (N = 7,263 in 2002 and 6,739 in 2022). Psychosomatic complaints were examined in relation to stressors in the following three domains: interpersonal relationships, school-related strain, and body- and activity-related factors. Moderated regression analyses tested whether associations between stressors and complaints differed between survey years. Sex and perceived family finances were included as covariates. RESULTS: Four of five psychosocial stressors showed stronger associations with psychosomatic complaints in 2022 than in 2002. Perceived poor family finances, although less prevalent in 2022, were more strongly related to complaints. Girls consistently reported higher levels of psychosomatic complaints, and the association between school pressure and complaints was stronger among girls. DISCUSSION: Although several psychosocial stressors declined in prevalence, their associations with psychosomatic complaints strengthened over time. These findings suggest that rising complaints may reflect changes in how psychosocial stressors are linked to adolescents' psychosomatic symptoms, rather than increases in exposure to those stressors. This shift highlights the importance of considering how adolescents interpret and respond to everyday stress when addressing population trends in mental health.

Humans

Age-related differences in motor unit behaviours and maximal strength: A systematic review and meta-analysis.

Ageing is associated with a decline in strength; however, the neural mechanisms underpinning these changes remain poorly understood. Motor unit discharge rate (MUDR) and recruitment threshold (MURT) regulate the magnitude of motoneuron output through rate coding and orderly recruitment, while discharge rate variability (MUDRV) reflects the steadiness of motoneuron output. Yet, age-related differences in these properties remain inconsistent across the literature. Therefore, this systematic review and meta-analysis quantified age-related differences in motor unit behaviours and their contribution to maximal isometric strength. Electronic databases (Medline, Embase, Scopus, PsycINFO, Ovid Emcare, CENTRAL, and Web of Science) were searched up to May 2025, yielding 1493 records; of these, 48 studies met the inclusion criteria. Standardised mean differences (SMDs) were calculated using random-effects models to compare older and younger adults, and methodological quality was assessed using the AXIS tool. Older adults exhibited markedly lower maximal strength than younger adults (SMD = -1.01; 95% CI -1.22, -0.79). MUDR was lower in older adults across all contraction intensities, with greater reductions at high forces (> 60% maximal voluntary contraction (MVC): SMD =&#x202f;-0.65; 95% CI -0.96, -0.34) compared to low forces (< 30% MVC: SMD = -0.34; 95% CI -0.50, -0.18). Discharge rate variability was greater (SMD = 0.44; 95% CI 0.15, 0.72), whereas recruitment thresholds relative to MVC were lower (SMD = -0.42; 95% CI -0.80, -0.03) in older adults. Collectively, these findings suggest that age-related alterations in motor unit discharge behaviour may contribute, at least in part, to reduced maximal strength in older adults.

Aging

Sex differences in social dominance emerge late in life in a gregarious bird.

Social dominance shapes group structure and the collective behaviour of gregarious animals. Senescence, the progressive physiological deterioration associated with ageing, may influence behaviour, including social dominance, while reproductive roles may lead to different onset times or rates of senescence between the sexes. However, how ageing shapes sex differences in sociality remains poorly understood, largely due to the scarcity of long-term studies comparing male and female social behaviour. To address this gap of knowledge, we monitored dominance hierarchies during foraging in an ageing, semi-natural population of adult common waxbills (Estrilda astrild). Our study lasted 5&#x2009;years, which is more than most adult waxbills would live in the wild, to facilitate detecting effects of senescence. At the onset of the study, sex differences in dominance were negligible but became pronounced with ageing during breeding seasons. In contrast, sex differences remained weak during non-breeding seasons. Females showed stronger longitudinal and seasonal changes in dominance than males, whose dominance patterns remained more consistent across breeding and non-breeding periods. Nonetheless, social dominance also increased, on average, as the number of years until death decreased. Although sex differences in animal sociality are often thought of as largely fixed, our findings reveal a dynamic pattern in which sex differences in dominance emerge with ageing and are context-dependent, varying across breeding seasons. Overall, our results suggest that senescence and seasonal context shape sociality later in life.

behavioural ageing

Association of Social Support With Oral Health in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Social support is an important determinant of health in later life, yet no study has synthesised the relevant evidence. This systematic review and meta-analysis aimed to synthesise evidence on the association between social support (functional, structural, and perceived dimensions) and oral health among older adults aged 75&#x2009;years and over. METHODS: The review process, using a systematic approach and random-effects meta-analysis, was conducted in accordance with PRISMA guidelines. Searches were carried out in Medline, Embase, and CENTRAL up to November 2025. Eligible studies examined associations between social support and oral health, including dentition status, oral conditions, oral function, oral health behaviours, and oral health-related quality of life. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Forty studies were included. Meta-analyses showed that low functional support-defined as having fewer people to rely on-was associated with edentulism (OR 1.21, 95% CI: 1.15, 1.27) and non-regular dental service use (OR 1.20, 95% CI: 1.17, 1.23). Low structural support, in terms of living conditions, was associated with edentulism and lacking functional dentition (OR 1.34, 95% CI: 1.02, 1.75; and OR 1.41, 95% CI: 1.20, 1.67, respectively). The evidence on the associations between low social support and other oral health measures was sparse and heterogeneous. CONCLUSION: Poor social support was associated with poor dentition status and oral health behaviours among older adults aged 75&#x2009;years and over. These findings underscore the importance of incorporating psychosocial factors into oral health assessment and care planning for this population. TRIAL REGISTRATION: PROSPERO; registration number: CRD420251231319.

Humans

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals

Polygenic and developmental profiles of autism differ by age at diagnosis.

Although autism has been historically conceptualised as a condition that emerges in early childhood, many autistic people are diagnosed later in life. It is unknown whether earlier and later diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, comparable to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be decomposed into two modestly genetically correlated (rg = 0.38, SE = 0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis, and lower social and communication abilities in early childhood but is only modestly genetically correlated with ADHD and mental health conditions. Conversely, the second factor is associated with later autism diagnosis, increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder and mental health conditions. These findings indicate that earlier and later diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.

Journal Article

Polygenic and developmental profiles of autism differ by age at diagnosis.

Although autism has historically been conceptualized as a condition that emerges in early childhood1,2, many autistic people are diagnosed later in life3-5. It is unknown whether earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, similar to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be broken down into two modestly genetically correlated (rg&#x2009;=&#x2009;0.38, s.e.&#x2009;=&#x2009;0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis and lower social and communication abilities in early childhood, but is only moderately genetically correlated with attention deficit-hyperactivity disorder (ADHD) and mental-health conditions. Conversely, the second factor is associated with later autism diagnosis and increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with ADHD and mental-health conditions. These findings indicate that earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualize autism and provide a model to explain some of the diversity found in autism.

Humans

Factors associated with better emotional, behavioural and educational outcomes in children with mild intellectual difficulties.

BACKGROUND: Children with mild intellectual difficulties (MID) are at increased risk of poor mental health and functional outcomes compared to typically developing children. Previous research has primarily focused on deficit-based comparisons. However, substantial heterogeneity exists in this population, ranging from significant impairment to positive adaptation. Our aim was to test predictors of better emotional, behavioural and educational outcomes in children with MID, with a particular interest in potentially modifiable protective factors. METHODS: Two UK cohorts, the Avon Longitudinal Study of Parents and Children (ALSPAC; N&#xa0;=&#xa0;6926) and the Millennium Cohort Study (MCS; N&#xa0;=&#xa0;8814) were used to examine the associations between independent and cumulative individual, family and social factors in childhood and adolescence and emotional, behavioural and educational outcomes at age 16/17 for children with or without MID. We additionally considered a composite measure of positive developmental outcomes capturing good outcomes across these three domains. RESULTS: Children with MID (ALSPAC, N&#xa0;=&#xa0;312 [4.5%] and MCS, N&#xa0;=&#xa0;364 [4.1%]) as a group experienced fewer protective predictors compared to children without MID. Physical activity, family social advantage, school enjoyment and good peer relations were each associated with better outcomes in both groups. Cumulative counts of childhood and adolescent factors were strongly associated with better adolescent outcomes, with a ten-fold difference in the probability of positive outcomes among those with the most and least protective predictors amongst children with MID. CONCLUSION: This study underscores the importance of a multi-faceted approach to supporting children with MID. Further research is required to establish the causal nature of the observed associations, but the findings hold promise for preventative approaches that harness child strengths and build support across family, school and social domains.

ALSPAC

Effects of short-bout accumulated exercise on postprandial metabolism in adults: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the acute effects of short-bout accumulated exercise (SBAE) interrupting prolonged sedentary behaviour on postprandial glucose, insulin, and triglycerides in adults. METHODS: Systematic searches in PubMed, Web of Science, Embase, Cochrane Library, CINAHL, SPORTDiscus, and CNKI (inception to 10 December 2025) identified randomised crossover trials comparing SBAE (&#x2264;10&#x202f;min/bout, inter-bout interval &#x2265;30&#x202f;min or adequate recovery) with continuous sedentary behaviour. Outcomes included postprandial glucose, insulin, and triglyceride AUCs. Standardised mean differences (SMD) were pooled using random-effects models. RESULTS: Thirty-one publications reporting data from 29 independent cohorts involving 573 unique participants (mean age 47.8&#x202f;&#xb1;&#x202f;20.3 years; 47.5% female; mean BMI 29.0&#x202f;&#xb1;&#x202f;5.1&#x202f;kg/m&#xb2;) were included. Compared with continuous sedentary behaviour, SBAE significantly reduced glucose AUC (SMD = -0.53, 95% CI: -0.71 to -0.34, P&#x202f;<&#x202f;0.001) and insulin AUC (SMD = -0.58, 95% CI: -0.85 to -0.31, P&#x202f;<&#x202f;0.001), but not triglyceride AUC (SMD = -0.17, 95% CI: -0.48 to 0.15, P = 0.306).Exploratory subgroup analyses showed statistically significant reductions in glucose and insulin for walking and for inter-bout intervals <&#x202f;60&#x202f;min, but not for standing alone or intervals &#x2265;&#x202f;60&#x202f;min. A statistically significant insulin-lowering effect was observed in obese individuals. CONCLUSION: SBAE acutely improves postprandial glucose and insulin control. Exploratory subgroup analyses showed statistically significant effects for walking and for inter-bout intervals <&#x202f;60&#x202f;min, but these comparisons are observational and no formal interaction test was conducted. These findings provide preliminary evidence for acute SBAE in sedentary populations, though long-term health effects and real-world generalisability require further investigation.

Adult

Men's experiences of multiple long-term conditions and/or disability in the UK Game of Stones weight management trial: a mixed-methods evaluation.

OBJECTIVES: To explore experiences, health outcomes and retention of men with multiple long-term conditions (MLTCs) and/or disability within the Game of Stones weight management randomised controlled trial (RCT). DESIGN: Mixed-methods process evaluation within an RCT where secondary outcomes included the Weight Self-Stigma Questionnaire, EuroQol 5-Dimension 5-Level (EQ-5D-5L), EQ-5D-5L anxiety and depression subscale, Patient Health Questionnaire-4 and retention. Semistructured interviews were conducted at 12 months and analysed using the framework method. SETTING: Conducted across three UK trial centres: Belfast, Bristol and Glasgow. PARTICIPANTS: 585 men with obesity (mean (SD) age, 50.7 (13.3) years) were randomised to one of three groups: behavioural text messages with financial incentives, texts alone or waiting-list control. Interviews were conducted with 54 participants from the two intervention groups. RESULTS: 235 (40%) participants lived with MLTCs, 181 (31%) had a single condition, 167 (29%) had no conditions and 165 (29%) had a disability. Of those with MLTCs, 99 were disabled and 93 were living in deprived areas. Participants with MLTCs and/or disability were older, fewer had a degree-level qualification and fewer were in full-time work. Retention at 12 months was higher for men with disability (76%) or no long-term conditions (75%) and lower for men with diabetes (65%). Self-reported weight stigma, well-being and quality-of-life scores improved or stayed the same for men living with MLTCs in the intervention groups; however, results for anxiety and depression screening scores were inconsistent. Participant experiences indicated complex dynamic health, social and life situations which could provide motivation to lose weight for some but not others. Hospitalisation and poor mobility, with inability to exercise, were demotivating for making changes to reach weight loss targets. CONCLUSIONS: Men living with MLTCs and/or disability varied from very successful weight loss and improved health to not prioritising or feeling helped by the programme or disengagement due to immobility or diabetes. TRIAL REGISTRATION NUMBER: isrctn.org Identifier: ISRCTN91974895.

Humans

Chaperone-mediated autophagy regulates neuronal activity by sex-specific remodelling of the synaptic proteome.

Chaperone-mediated autophagy (CMA) declines in ageing and neurodegenerative diseases. Loss of CMA in neurons leads to neurodegeneration and behavioural changes in mice but the role of CMA in neuronal physiology is largely unknown. Here we show that CMA deficiency causes neuronal hyperactivity, increased seizure susceptibility and disrupted calcium homeostasis. Pre-synaptic neurotransmitter release and NMDA receptor-mediated transmission were enhanced in CMA-deficient females, whereas males exhibited elevated post-synaptic AMPA-receptor activity. Comparative quantitative proteomics revealed sexual dimorphism in the synaptic proteins degraded by CMA, with preferential remodelling of the pre-synaptic proteome in females and the post-synaptic proteome in males. We demonstrate that genetic or pharmacological CMA activation in old mice and an Alzheimer's disease mouse model restores synaptic protein levels, reduces neuronal hyperexcitability and seizure susceptibility, and normalizes neurotransmission. Our findings unveil a role for CMA in regulating neuronal excitability and highlight this pathway as a potential target for mitigating age-related neuronal decline.

Animals

Self-reported physical activity in a randomized study from Norwegian Healthy Life Centres.

AIM: This study examines firstly if participation in a three-month intervention at Norwegian Healthy Life Centres (HLCs) improved self-reported physical activity (SR-PA), and secondly to what extent physical activity (PA) status at six months and changes from baseline were associated with demographic and motivational predictors. BACKGROUND: Regular PA is promoted as a central component of public health initiatives aimed at preventing noncommunicable diseases. METHODS: This randomized controlled trial included 118 participants (57 in the intervention group) recruited from HLCs in South-western Norway. The intervention effect was assessed by comparing the intervention group with the waiting-list control group after six months. We examined sociodemographic and motivational predictors of change combining both groups into a single cohort. This trial was registered at ClinicalTrials.gov (ID: NCT02247219). FINDINGS: At six-month follow-up, participants in the intervention group reported higher levels of SR-PA compared with the control group. The estimated effect was modest (B = 0.26, 95% CI -0.01 to 0.53), equivalent to &#x2248;0.37 SD. Although the confidence interval included zero, the estimate remained compatible with a modest positive effect. Autonomous motivation and social support were positively associated with SR-PA after 6 months, while psychological defiance showed a negative association. Autonomous motivation and psychological defiance impacted PA change during the 6-month period in opposite directions.

Humans

Factors Associated With Menopause Symptoms: A Systematic Review and Meta-Analysis.

BACKGROUND: Menopause, marked by hormonal decline and menstrual cessation, is associated with various symptoms. Socio-demographic and behavioural factors may influence symptom type and severity. Understanding these associations can inform better symptom management. OBJECTIVES: To identify factors associated with the presence and severity of menopausal symptoms through systematic review and meta-analysis. SEARCH STRATEGY: We searched Medline, Embase, CINAHL and Cochrane for studies on demographic, behavioural, or health factors linked to vasomotor, vaginal dryness and joint symptoms in women aged 40-60. SELECTION CRITERIA: Studies reporting odds ratios or raw numbers for symptom presence or severity were included. DATA COLLECTION AND ANALYSIS: Studies were combined for meta-analysis, reporting odds ratios and 95% confidence intervals. Quality assessment was performed to quantify the risk of bias. RESULTS: Of 9228 screened articles, 61 were meta-analysed. Compared with White women, Black women had higher odds of vasomotor symptom presence (OR 1.65, 1.41-1.94) and severity (OR 1.91, 1.10-3.29), and vaginal dryness presence (OR 1.27, 1.10-1.47), while Asian had lower vasomotor symptom presence and severity (OR 0.40, 0.22-0.72; OR 0.55, 0.53-0.56). Higher education (OR 1.31, 1.09-1.56), high income (OR 1.41, 1.01-1.97) and depression (OR 2.36, 1.51-3.70) were associated with increased presence of vasomotor symptoms. Smoking and obesity were associated with both presence (OR 1.63, 1.30-2.04 and 1.35, 1.02-1.78) and severity (OR 1.56, 1.07-2.27 and 1.42, 1.11-1.83) of vasomotor symptoms. CONCLUSION: Socio-demographic and behavioural factors, including ethnicity, education, income, smoking, obesity and depression, influence menopausal symptoms, highlighting the need for personalised care. TRIAL REGISTRATION: PROSPERO number: CRD42023459154.

Humans

Profile of the BREATHE cohort for risk-based breast screening in Singapore.

The BREAst screening Tailored for HEr (BREATHE) study was established to pilot a personalised, risk-based breast cancer screening programme for a multi-ethnic Asian population. Between October 2021 and December 2023, 4592 women aged 35-59 were enrolled (73% response rate). Follow-up from February 2022 to June 2024 included 4112 participants (8.6% loss to follow-up). Data collected encompassed demographics, lifestyle factors, reproductive risks, breast cancer awareness, screening behaviours, programme satisfaction, mammography outcomes (density and recall status), and genotype data. Above-average breast cancer risk increased with age: 2% in women aged 35-39, 31% in 40-49, and 42% in 50-59. Findings suggests that women valued the knowledge of their breast cancer risk and were motivated to attend mammography. The BREATHE study confirms the feasibility and acceptability of a personalised risk-based screening programme in a multi-ethnic Asian population, highlighting the value of tailored protocols to improve early detection and outcomes. Further details are available in the study protocol and online at https://blog.nus.edu.sg/breathe/ .

Humans

Polygenic Associations between Motor Behaviour, Neuromotor Traits, and Active Music Engagement in Four Cohorts.

Phenotypic investigations have shown that actively engaging with music, i.e., playing a musical instrument or singing may be protective of motor decline in aging. For example, music training associated with enhanced sensorimotor skills accompanied by changes in brain structure and function. Although it is possible that the benefits of active music engagement "transfer" to benefits in the motor domain, it is also possible that the genetic architecture of motor behaviour and the motor system structure may influence active music engagement. This study investigated whether polygenic scores (PGS) for five behavioural motor traits, 12 neuromotor structural brain traits, and seven rates of change in brain structure traits trained from existing discovery genome-wide association studies (GWAS) predict active music engagement outcomes in four independent cohorts of unrelated individuals of European ancestry: the Canadian Longitudinal Study on Aging (CLSA; N=22,198), Wisconsin Longitudinal Study (WLS; N=4,605), Vanderbilt's BioVU Repository (BioVU; N=6,150), and Vanderbilt's Online Musicality study (OM; N=1,559). Results were meta-analyzed for each PGS main effect across outcomes and cohorts, revealing that PGS for a faster walking pace was associated with higher amounts of active music engagement. Within CLSA, a higher PGS for walking pace was associated with greater odds of engaging with music. Findings suggest a shared genetic architecture between motor function and active music engagement. Future intervention-based research should consider the genetic underpinnings of motor behavior when evaluating the effects of music engagement on motor function across the lifespan.

BioVU

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration &#xd7; intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans

Timing of adverse childhood experiences shapes epigenetic ageing and life-history outcomes.

Early-life adversity is widely linked to accelerated biological ageing, yet it remains unclear whether such associations reflect exposure during sensitive developmental periods, the cumulative burden of exposures, or temporal proximity to later outcomes. Here, we leverage life-history theory and a life course framework to nuance how the timing of adverse childhood experiences (ACEs) becomes biologically embedded through epigenetic ageing. Using longitudinal data from the Future of Families and Child Wellbeing Study (N=1,974), we apply statistical learning and structured life course modelling to test sensitive period, cumulative risk, and recency hypotheses across multiple domains of adversity (poverty, instability, deprivation, and maltreatment). We find that adversity exposure during specific developmental periods, rather than cumulative burden or recent exposure, are most strongly associated with epigenetic age acceleration in late childhood ([Formula: see text]=0.003). Moreover, the timing and direction of these effects vary by adversity type. Epigenetic ageing is in turn associated with later health-related risks ([Formula: see text]=0.29, SE=0.06; [Formula: see text]=1.62, SE=0.27) and demographic behaviour ([Formula: see text]=0.21, SE=0.08; [Formula: see text]=0.22, SE=0.11), and further mediates the association between ACEs and outcomes in young adulthood, particularly for BMI ([Formula: see text]=0.003, SE=0.002, [Formula: see text]=11%). These findings demonstrate that childhood adversity may be linked to biological ageing in developmentally specific and domain-dependent ways, with certain developmental periods appearing more sensitive to adversity exposure than others.

Humans