Age-related Effects Research Articles

P1200 Increasing rate of hospitalization for inflammatory bowel disease is an age-related effect: A Canadian population-based study

Abstract Background Inflammatory bowel diseases (IBDs), including Crohn’s Disease (CD) and Ulcerative Colitis (UC), are chronic diseases that pose significant challenges to patients and healthcare systems. To understand trends in the risk of all-cause hospitalization for individuals with CD and UC we explored age, period, and cohort effects in Canada. Methods We utilized repeated cross-sectional survey data from the 2005-2014 Canadian Community Health Survey (CCHS) to identify individuals with self-reported CD or UC. These individuals were linked to their hospitalization records from the Discharge Abstract Database (DAD) and were followed for three years. Cross-classified random-effects two-level models were used to estimate fixed effects for age and its quadratic term (level 1) and random effects for time periods and birth cohorts (level 2), adjusted for sex, on the risk of hospitalization within three years. Results An estimated 84,000 CD and 113,000 UC individuals were eligible for study inclusion. From this, an estimated 30,250 and 39,890 all-cause hospitalizations occurred within three years post-entry into the study for CD and UC individuals, respectively. Broadly, the risk of hospitalization within three-years increased with age and across birth-cohorts, with older cohorts experiencing greater risks of hospitalization. A small, but statistically significant temporal effect was identified for both CD and UC groups. Within birth cohorts, the risk of hospitalization increased across ages for CD, but in individuals with UC, the risk of hospitalization decreased across ages, except for the two oldest birth cohorts. Conclusion Overall, results support the hypothesis that age effects are primarily responsible for fluctuations in the risk of hospitalizations1. Risk of all-cause hospitalization has remained relatively stable from 2005 to 2014 in Canada and differences across time periods may be a consequence of the age-distribution at each time period. As the prevalence of CD and UC continues to rise and the Canadian population continues to be comprised of growing number of older-aged individuals, increasing the allocation of healthcare resources to prevent age-related risks of hospitalizations would be beneficial to reduce hospital burdens.

Effectiveness of exercise on sarcopenia in HIV patients: a systematic review of current literature

ABSTRACT Exercise is vital in managing sarcopenia in people living with HIV (PLWH). This study explores the role of exercise in reducing sarcopenia in HIV patients. A systematic search of electronic databases including PubMed, Scopus, and Web of Science identifed relevant articles published in English up to April 2024. Inclusion criteria were: 1) humans aged 18 or older, 2) clinical trials involving exercise interventions, 3) outcomes addressing aging-related effects, and 4) English-language original articles. Study quality and risk of bias were assessed using the Newcastle-Ottawa scale (NOS). Ten studies with 2039 participants met the criteria. Exercise interventions included resistance training, cardiorespiratory training, and combined approaches at various intensities. Regular exercise can help prevent muscle wasting in PLWH and mitigate age-related sarcopenia. HIV itself is a risk factor for sarcopenia, but resistance training combined with moderate to high-intensity cardiorespiratory training, can increase muscle mass, reducing sarcopenia risk and improving life expectancy in PLWH. The findings emphasize the effectiveness of exercise, particularly combined resistance and cardiorespiratory training, in mitigating sarcopenia in PLWH. Healthcare providers are urged to promote exercise interventions as a preventive measure against sarcopenia in this clinical population.

Ecometabolomics of Loggerhead Sea Turtles (Caretta caretta): The Impact of Age on Metabolomic Profiles.

To investigate the impact of age on the metabolomic profile of loggerhead sea turtles (Caretta caretta), this study analyzed 100 plasma samples of individuals across two age groups-50 post-hatchlings and 50 juveniles-from various locations along the Mediterranean coastline. Both targeted and untargeted metabolomic analyses were performed on the samples. Our results demonstrated a significant age-related effect on the metabolomic profiles in both analyses. Specifically, post-hatchling turtles exhibited increased levels of urea (p < 0.001), triglyceride (p = 0.0003), cholesterol (p < 0.001), lysoPE (18:1/0:0) (p < 0.001), 7-HDoHE (p = 0.0121), pyrrolidinebutanoic acid (p < 0.001), formiminoglutamic acid (p < 0.001), pyroglutamic acid (p < 0.001), lysoPC (0:0/20:4) (p < 0.001), lysoPE (22:6/0:0) (p < 0.001), 1-acyl-sn-glycero-3-phosphocholine (p < 0.001), DL-homocysteine (p < 0.001) and gamma-Glutamyltyrosine (p < 0.001). Conversely, post-hatchlings showed reduced levels of total protein (p < 0.001), glucose (p = 0.0002), uric acid (p < 0.001), inorganic phosphorus (p = 0.0018) and calcium (p = 0.0410) compared with juveniles. These findings suggest significant physiological changes between the age groups, likely due to differentiated feeding patterns. Further research is needed to better understand the metabolic profiles and complex physiological and nutritional interactions of this species.

Age-related Electrophysical Correlates of Cross-modal Attention Switching.

The human experience demands seamless attentional switches between sensory modalities. Aging raises questions about how declines in auditory and visual processing affect cross-modal attention switching. This study used a cued cross-modal attention-switching paradigm where visual and auditory stimuli were simultaneously presented on either spatially congruent or incongruent sides. A modality cue indicated the target modality, requiring a spatially left versus right key-press response. EEG recordings were collected during task performance. We investigated whether the mixing costs (decreased performance for repetition trials in a mixed task compared with a single task) and switch costs (decreased performance for a switch of target modality compared with a repetition) in cross-modal attention-switching paradigms would exhibit similarities in terms of behavioral performance and the ERP components to those observed in the traditional unimodal attention-switching paradigms. Specifically, we focused on the ERP components: cue-locked P3 (mixing/switch-related increased positivity), target-locked P3 (mixing/switch-related decreased positivity), and target-locked lateralized readiness potential (mixing/switch-related longer latency). In addition, we assessed how aging impacts cross-modal attention-switching performance. Results revealed that older adults exhibited more pronounced mixing and switch costs than younger adults, especially when visual and auditory stimuli were presented on incongruent sides. ERP findings showed increased cue-locked P3 amplitude, prolonged cue-locked P3 latency, decreased target-locked P3 amplitude, prolonged target-locked P3 latency in association with switch costs, and prolonged onset latency of the target-locked lateralized readiness potential in association with the mixing costs. Age-related effects were significant only for cue-locked P3 amplitude, cue-locked P3 latency (switch-related), and target-locked P3 latency (switch-related). These findings suggest that the larger mixing costs and switch costs in older adults were due to the inefficient use of modality cues to update a representation of the relevant task sets, requiring more processing time for evaluating and categorizing the target.

Static and dynamic connectivity structure of white-matter functional networks across the adult lifespan.

Aging of the human brain involves intricate biological processes, resulting in complex changes in structure and function. While the effects of aging on gray matter (GM) connectivity are extensively studied, white matter (WM) functional changes have received comparatively less attention. This study examines age-related WM functional dynamics using resting-state fMRI across the adult lifespan. We identified GM and WM functional networks (FNs) using k-means clustering. Static and dynamic analyses of WM functional network connectivity (FNC) were performed to explore age effects on WM-FNs and recurrent patterns of dynamic FNC. We identified 9 WM and 12 GM FNs. Age-related effects on WM FNC strength and WM-GM FNC dynamics included linear positive and U-shaped age trajectories in static FNC strength, and linear negative and inverted U-shaped trajectories in FNC temporal variability. Three distinct brain states with significant age-related differences were identified and validated. These findings were largely replicated in the validation analysis. High integration and low temporal variability in WM-GM FNC may indicate reduced adaptability of the network system in older adults, offering insights into brain aging processes.

Influence of age, baseline severity and follow‐up time on visual field progression in primary open angle glaucoma

Aims/Purpose: Challenges in modeling rates of visual field (VF) progression relate to flooring effects and sensitivity to inclusion criteria like follow‐up (FU) duration. We explored the relationship between VF progression and age, disease severity, and FU duration in primary open angle glaucoma (POAG).Methods: Mean Deviation (MD) of 655 POAG eyes of 424 patients from the UZ Leuven Glaucoma Clinic with at least 5 VFs and 2 years of follow‐up were used. Baseline severity was defined as Above 0 (≥0dB), mild ( &lt; 0 and ≥‐6dB), moderate ( &lt; ‐6 and ≥‐12dB), advanced ( &lt; ‐12 and ≥‐15dB), and severe ( &lt; ‐15dB) disease. Linear mixed models and changepoint detection were used. Sensitivity analysis of modeled progression rates within each severity group was done by varying maximally included duration of FU.Results: MD progression rates per year were ‐0.34dB (p &lt; 0.001) for Above 0, ‐0.49dB (p &lt; 0.001) for mild, ‐0.49dB (p &lt; 0.001) for moderate, ‐0.26dB (p = 0.009) for advanced, and +0.1dB (p = 0.317) for severe POAG. Random effects correlation between baseline MD and progression rates was 0.36. The fixed effects for age and test related learning effect were non‐significant (p = 0.65) and ‐0.21 (p = 0.004) respectively. The correlation between the implied slope and baseline age was ‐0.26. Changepoint analysis showed that group level progression estimates stabilized when minimum FU times were at least 2.17, 1.99, 2.18, and 4.56 years for mild, moderate, advanced and severe POAG respectively.Conclusions: Older patients progress faster across severity levels and a significant learning effect is present when excluding patients with severe POAG. Excluding patients with a baseline MD above 0dB, the modeled average MD change is similar between mild and moderate POAG. Less progression is observed in advanced and no progression in severe POAG, consistent with the flooring effect. In mild and moderate POAG patients progression estimates converged after a minimum FU of at least 2 years.

Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis.

Multiple sclerosis (MS) can start as relapsing or progressive. While their clinical features and treatment responses are distinct, it has remained uncertain whether their pathomechanisms differ. A notable age-related effect on MS phenotype and response to immunotherapies is well acknowledged, but the underlying pathophysiologic reasons are yet to be fully elucidated. We aimed to identify disease-specific and age-related proteomic signatures using a comprehensive targeted proteomic analysis. In our retrospective cohort study, we analyzed the CSF and serum proteome of age-matched individuals with treatment-naïve relapsing-remitting and primary progressive MS, neurologic controls (NC), and individuals with neuroborreliosis using targeted proteomics and validated findings in an independent cohort. Proteomic results were integrated with clinical and laboratory covariates. Among 2,500 proteins, 47 CSF proteins were distinct between individuals with MS (n = 60) and NC (n = 20), with a subset also differing from those with neuroborreliosis (n = 8). We identified MS-associated proteins, including novel candidate biomarkers such as LY9 and JCHAIN, and putative treatment targets, such as SLAMF7, BCMA, and IL5RA, for which drugs are already licensed in other indications. The CSF proteome differences between relapsing and progressive MS were minimal, but major changes were noted in individuals older than 50 years, indicating a shift from MS-associated inflammatory to age-related protein signature. NEFL was the only serum protein that differed between individuals with MS and controls. This study unveils a unique CSF proteomic signature in MS, providing new pathophysiologic insights and identifying novel biomarker candidates and potential therapeutic targets. Our findings highlight similar immunologic mechanisms in relapsing and progressive MS and underscore aging's profound effect on the intrathecal immune response. This aligns with the observed lower efficacy of immunotherapies in the elderly, thus emphasizing the necessity for alternative therapeutic approaches in treating individuals with MS beyond the age of 50.

Association of critically short telomeres with brain and blood markers of ageing and Alzheimer’s disease in older adults

BackgroundAccumulation of critically short telomeres (CST) is implicated in decreased tissular regenerative capacity and increased susceptibility to degenerative diseases such as Alzheimer’s disease (AD). Telomere shortening has also been associated with age-related brain changes. However, it remains unclear whether CST accumulation is directly associated with AD markers or instead amplifies age-related effects, potentially increasing susceptibility of developing AD in cognitively healthy older adults.MethodsThis cross-sectional study used baseline data of 129 community-dwelling cognitively healthy older adults from the Age-Well trial (NCT02977819), aged 65 years and older enrolled between 2016 and 2018, in France. Using linear regressions, we analyzed the relationship between an innovative marker of telomere shortening, the percentage of CST (%CST), structural, functional and molecular neuroimaging outcomes, and multiple blood-based biomarkers related to AD pathophysiology. The effect of apolipoprotein E ε4 genotype (APOE4) was assessed on these relationships using interaction analysis.ResultsA higher %CST was associated with lower global kurtosis fractional anisotropy (β = -.230; P = .010), particularly in frontal and temporal regions. A higher %CST was also related to higher plasma levels of Neurofilament light chain (β = .195; P = .020) and a lower subiculum volume (β = -.206; P = .020), although these associations did not meet the threshold for multiple comparisons. %CST was not associated with AD-related neuroimaging markers, including the AD-sensitive gray matter pattern (β = -.060; P = .441), glucose metabolism pattern (β = -.099; P = .372), brain perfusion pattern (β = -.106; P = .694) or hippocampus volume (β = -.106; P = .194). In APOE4 carriers, higher %CST was associated with lower subiculum (β = -.423; P = 0.003), DG (β = -.410; P = 0.018) and CA1 volumes (β = -.373; P = 0.024), even though associations with DG and CA1 volumes did not survive multiple comparison.ConclusionsAlthough an increase in %CST does not appear to be directly linked to the pathophysiology of AD in cognitively healthy older adults, it could heighten the susceptibility of APOE4 carriers to develop AD plausibly due to greater vulnerability to age-related effects. However, longitudinal studies would be necessary to determine whether %CST influences the development and progression of AD later in life.

Feasibility and Repeatability of an Abbreviated Auditory Perceptual and Cognitive Test Battery.

Auditory perceptual and cognitive tasks can be useful as a long-term goal in guiding rehabilitation and intervention strategies in audiology clinics that mostly operate at a faster pace and on strict timelines. The rationale of this study was to assess test-retest reliability of an abbreviated test battery and evaluate age-related auditory perceptual and cognitive effects on these measures. Experiment 1 evaluated the test-retest repeatability of an abbreviated test battery and its use in an adverse listening environment. Ten participants performed two visits, each including four conditions: quiet, background noise, external noise, and background mixed with external noise. In Experiment 2, both auditory perceptual and cognitive assessments were collected from younger adults with normal hearing and older adults with and without hearing loss. The full test battery included measures of frequency selectivity, temporal fine structure and envelope processing, spectrotemporal and spatial processing and cognition, and an external measure of tolerance to background noise. Results from Experiment 1 showed good test-retest repeatability and nonsignificant effects from background or external noise. In Experiment 2, effects of age and hearing loss were shown across auditory perceptual and cognitive measures, except in measures of temporal envelope perception and tolerance to background noise. These data support the use of an abbreviated test battery in relatively uncontrolled listening environments such as clinic waiting rooms. With an efficient test battery, perceptual and cognitive deficits can be assessed with minimal resources and little clinician involvement due to the automated nature of the test and the use of consumer-grade technology. https://doi.org/10.23641/asha.28021070.

Small Extracellular Vesicles Isolated from Cardiac Tissue Matrix or Plasma Display Distinct Aging-Related Changes in Cargo Contributing to Chronic Cardiovascular Disease.

Aging is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and numerous other diseases, but the mechanisms of these aging-related effects remain elusive. Chronic changes in the microenvironment and paracrine signaling behaviors have been implicated, but remain understudied. Here, for the first time, we directly compare extracellular vesicles obtained from young and aged patients to identify therapeutic or disease-associated agents, and directly compare vesicles isolated from heart tissue matrix (TEVs) or plasma (PEVs). While young EVs showed notable overlap of miRNA cargo, aged EVs differed substantially, indicating differential age-related changes between TEVs and PEVs. TEVs overall were uniquely enriched in miRNAs which directly or indirectly demonstrate cardioprotective effects, with 45 potential therapeutic agents implicated in our analysis. Both populations also showed increased predisposition to disease with aging, though through different mechanisms. PEVs were largely correlated with chronic systemic inflammation, while TEVs were more related to cardiac homeostasis and local inflammation. From this, 17 protein targets unique to TEVs were implicated as aging-related changes which likely contribute to the development of cardiovascular disease.

Changes in Hippocampal Volume after Traumatic Brain Injury (TBI).

To investigate hippocampal volume changes in moderate to severe traumatic brain injury (TBI) patients compared to healthy controls and assess their association with post-traumatic epilepsy (PTE), focusing on age-related effects. Imaging and demographic data for TBI patients were obtained from the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) database; healthy controls matched by age and sex were sourced from Alzheimer's Disease Neuroimaging Initiative (ADNI), the National Institute of Mental Health (NIMH) Intramural Healthy Volunteer Dataset, the Parkinson's Progression Markers Initiative (PPMI), and the Autism Brain Imaging Data Exchange (ABIDE). MRI images for TBI subjects were obtained within 14-32 days post-injury. MRI data were preprocessed and segmented using FreeSurfer's recon-all pipeline and the hippocampal subfield segmentation module. TBI patients showed significantly smaller average hippocampal volumes than controls (β = -191.0, p = 8.33e-04, FDR p = 1.47e-03, Cohen's d = -0.36), notably in the right and left CA1 head regions. No significant hippocampal volume differences were found between TBI+ and TBI- patients overall. In patients aged 60+, TBI+ patients had significantly larger volumes in the right CA1 head than TBI- patients (β = 57.43, p = 0.0300, FDR p = 0.040; Cohen's d = 1.06). Hippocampal atrophy is evident in TBI patients but not directly linked to PTE development in most age groups. In patients over 60, hypertrophy in the right CA1 head may be associated with PTE, suggesting age and regional hippocampal changes influence epilepsy risk post-TBI. These findings highlight the complexity of hippocampal involvement in PTE and suggest potential shared mechanisms with neurodegenerative disorders such as Alzheimer's disease.

Effector-dependent decline in strength and subcortical motor excitability with aging.

A decline in upper limb strength is common with normal aging. However, whether age-related strength decline is paralleled by reduced excitability of descending motor pathways is unclear. The reticulospinal tract is a key subcortical pathway involved in gross motor output and exhibits increased excitability following resistance training. Here, we sought to determine age-related effects on strength and reticulospinal excitability in flexors and extensors of the upper limb in humans. In 15 younger and 14 older adults, we quantified upper limb strength using dynamometry, and reticulospinal excitability by using transcranial magnetic stimulation to elicit ipsilateral motor evoked potentials. We observed a decline in flexion, but not extension strength, in older compared with younger adults. This behavioral pattern was paralleled by an age-related reduction in ipsilateral motor evoked potential presence specific to flexor muscles. Our findings indicate that reduced excitability of the reticulospinal tract, which exhibits strong innervation of flexor muscles, may be a key contributor to upper limb strength decline commonly observed in older adults.

Seasonal Changes and Age-Related Effects on the Intestinal Microbiota of Captive Chinese Monals (Lophophorus lhuysii).

The Chinese monal (Lophophorus lhuysii) is a large-sized and vulnerable (VU in IUCN) bird from southwestern China. This study applied 16S rRNA high-throughput sequencing to comprehensively examine the gut microbiota of captive Chinese monals (located in Baoxing, Sichuan, China) across varying seasons and life stages. Dominant bacterial phyla identified included Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. Significant seasonal and age-associated shifts were observed within specific bacterial groups, particularly marked by seasonal fluctuations in beta diversity. Moreover, linear discriminant analysis effect size (LEfSe) and functional predictions highlighted distinct winter signatures, indicating possible functional shifts in energy metabolism and disease resistance. In mid-aged adults, an expansion of Gamma-Proteobacteria suggested an elevated susceptibility of the gut microbiota of Chinese monals to chronic disorders and microbial imbalance. Putative pathogenic bacteria exhibited increased abundance in spring and summer, likely driven by temperature, host physiological cycles, interspecies interactions, and competition. These findings imply that the diversity, and structure of the gut microbiota in captive Chinese monals are strongly influenced by seasonal and age-related factors. The insights provided here are essential for improving breeding strategies and preventing gastrointestinal diseases in captivity.

Age-related changes in pupil dynamics and task modulation across the healthy lifespan.

The pupil is modulated by luminance, arousal, bottom-up sensory, and top-down cognitive signals, and has increasingly been used to assess these aspects of brain functioning in health and disease. However, changes in pupil dynamics across the lifespan have not been extensively examined, hindering our ability to fully utilize the pupil in probing these underlying neural processes in development and aging in healthy and clinical cohorts. Here, we examined pupil responses during the interleaved pro-/anti-saccade task (IPAST) in healthy participants across the lifespan (n = 567, 5-93 years of age). Based on the extracted measurements of pupil dynamics, we demonstrated age-related changes in pupil measures and task modulation. Moreover, we characterized the underlying factors and age-related effects in components of pupil responses that may be attributed to developmental and aging changes in the associated brain regions. Finally, correlations between factors of pupil dynamics and saccade behaviors revealed evidence of shared neural processes in the pupil and saccade control circuitries. Together, these results demonstrate changes in pupil dynamics as a result of development and aging, providing a baseline with which altered pupil responses due to neurological deficits at different ages can be studied.

Age Differences in Mental State Inference of Sarcasm: Contributions of Facial Emotion Recognition and Cognitive Performance.

Older age is associated with poorer ability to accurately infer mental states, but some mental states are more complex than others. Sarcasm is a complex mental state because the literal and intended meaning of a speaker's words are in opposition. Individuals must rely on additional cues (e.g., facial expressions, intonation) for accurate inference. We hypothesized that understanding of sarcastic versus sincere exchanges would be more sensitive to age-related difficulty in mental state understanding. We examined accuracy at identifying sarcasm among 263 adults (ages 18-90 years) using videos of social interactions in The Awareness of Social Inference Test. Hypotheses were tested using a logistic linear mixed effects model predicting correct/incorrect trial-level responses. To characterize why sarcasm differed with age, we measured 2 abilities commonly implicated in mental state understanding: facial emotion recognition and cognitive performance. Sarcasm understanding declined with age, whereas understanding of sincere exchanges did not. Both better emotion recognition and cognitive performance related to better understanding of sarcastic but not sincere exchanges. Only cognitive performance showed an age-related effect such that the cognitive performance among the oldest participants facilitated their understanding of both sarcastic and sincere exchanges. We showed that individual variation related to age and social and cognitive performance is more pronounced when the use of multiple mental state cues is more (sarcasm) or less (sincerity) necessary for accurate understanding of social interactions. Naturalistic paradigms involving multiple mental state cues can address important questions about how older adults make decisions in the real world.

The ecology of ageing in wild societies: linking age structure and social behaviour.

The age of individuals has consequences not only for their fitness and behaviour but also for the functioning of the groups they form. Because social behaviour often changes with age, population age structure is expected to shape the social organization, the social environments individuals experience and the operation of social processes within populations. Although research has explored changes in individual social behaviour with age, particularly in controlled settings, there is limited understanding of how age structure governs sociality in wild populations. Here, we synthesize previous research into age-related effects on social processes in natural populations, and discuss the links between age structure, sociality and ecology, specifically focusing on how population age structure might influence social structure and functioning. We highlight the potential for using empirical data from natural populations in combination with social network approaches to uncover pathways linking individual social ageing, population age structure and societal functioning. We discuss the broader implications of these insights for understanding the social impacts of anthropogenic effects on animal population demography and for building a deeper understanding of societal ageing in general.This article is part of the discussion meeting issue 'Understanding age and society using natural populations'.

Electronic health record biobank cohort recapitulates an association between the MUC5B promoter polymorphism and ARDS in critically ill adults.

Large population-based DNA biobanks linked to electronic health records (EHRs) may provide novel opportunities to identify genetic drivers of ARDS. Can we develop an EHR-based algorithm to identify ARDS in a biobank database, and can this validate a previously reported ARDS genetic risk factor? We analyzed two parallel genotyped cohorts: a prospective biomarker cohort of critically ill adults (VALID), and a retrospective cohort of hospitalized participants enrolled in a de-identified EHR biobank (BioVU). ARDS was identified by clinician-investigator review in VALID and an EHR algorithm in BioVU (EHR-ARDS). We tested the association between the MUC5B promoter polymorphism rs35705950 with development of ARDS, and assessed if age modified this genetic association in each cohort. In VALID, 2,795 patients were included, age was 55 [43, 66] (median [IQR]) years, and 718 (25.7%) developed ARDS. In BioVU, 9,025 hospitalized participants were included, age was 60 [48, 70] years, and 1,056 (11.7%) developed EHR-ARDS. We observed a significant age-related interaction effect on ARDS in VALID: among older patients, rs35705950 was associated with increased ARDS risk (OR: 1.44; 95%CI 1.08-1.92; p=0.012) whereas among younger patients this effect was absent (OR: 0.84; 95%CI: 0.62-1.14; p=0.26). In BioVU, rs35705950 was associated with increased risk for EHR-ARDS among all participants (OR: 1.20; 95%CI: 1.00-1.43, p=0.043) and this did not vary by age. The polymorphism was also associated worse oxygenation in mechanically ventilated BioVU participants, but had no association with oxygenation in VALID. The MUC5B promoter polymorphism was associated with ARDS in two cohorts of at-risk adults. Although age-related effect modification was observed only in VALID, BioVU identified a consistent association between MUC5B and ARDS risk regardless of age, and a novel association with oxygenation impairment. Our study highlights the potential for EHR biobanks to enable precision-medicine ARDS studies.

The influence of age on gambling problems worldwide: A systematic review and meta-analysis of risk among younger, middle-aged, and older adults.

Problem gambling (PG) represents a significant public health concern with widespread effects in various cultures and regions globally, with younger individuals and males at a particularly higher risk. This disparity is attributed to a mix of cultural, developmental, and biological influences. To date, there has not been a comprehensive examination to determine whether this risk pattern holds consistently across different jurisdictions. We performed a systematic review and meta-analysis using the PRISMA framework, identifying 21 eligible studies from 18 countries, encompassing 156,249 participants (47.6% male and 52.4% female). The studies varied considerably by region (Asia: 19%, Europe: 52%, Oceania: 19%, North America: 10%), the diagnostic criteria for PG, and participation rates in gambling (ranging from 12% to 92%). Data on PG prevalence was categorised by gender and three age groups (young: 18-35, middle: 30-55, and older: 45-65). Using a random-effects meta-analysis, we found a global PG prevalence of 1.9%. Europe reported a significantly lower prevalence (1.3%) compared to North America (5.3%). Men were found to be 3.4 times more likely than women to engage in problem gambling, although the gap narrows in North America. The young demographic showed a 1.51 times higher likelihood of reporting PG compared to themiddle-aged group, whereas older adults were 0.80 times less likely to report PG. Notably, age-related effects varied significantly across regions. Our findings confirm that age and gender significantly influence PG risk across cultures, with significant heterogeneity observed across jurisdictions.

Six-year follow-up of a world record-breaking master marathon runner.

Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance [maximal oxygen consumption (V̇o2max), lactate threshold, and running economy (RE)], V̇o2max appears to be most affected by age. Although endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-yr-old distance runner who broke the marathon world record for men over 70 yr of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (∼90%) of his V̇o2max. However, V̇o2max declined by 15.1%. HRmax declined by 3.2% and maximal O2 pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O2 difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇o2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O2 difference. We speculate that these changes reflect primarily age-related processes.NEW & NOTEWORTHY We performed 6-yr follow-up testing on a world record-breaking master marathon runner. We determined that his performance declined since his record-breaking marathon in 2018 primarily due to a reduction in V̇o2max. His max heart rate (HR) changed minimally, but his peak O2 pulse decreased, suggesting that his maximal stroke volume and/or arteriovenous O2 difference decreased. These changes likely reflect primarily age-related effects in the absence of an overt pathological disease process.

Age-related effects on emotional reactions to sounds in individuals with misophonia

Misophonia, characterized by intolerance to specific sounds, triggers emotional reactions like disgust, anger, and distress. While misophonia typically begins in childhood/adolescence, its nature across the lifespan is understudied. Our study assesses audiological correlates and emotional reactions to sounds in misophonia across age groups. We recruited three groups: young misophonia (YM: 18–29 years, N = 14), mid-to-old misophonia (OM: 30–67 years, N = 17), and young controls (YC: 18–25 years, N = 26). All underwent hearing assessments (0.25–16kHz). Participants classified typical trigger and other affective sounds based on eliciting any misophonic reactions and rated their valence on a neutral to extremely unpleasant scale. Results show age-related effects in OM, with poorer hearing (&amp;gt;4 kHz) compared to YM and YC. Both groups had slower response times to trigger sounds compared to non-trigger sounds, suggesting a greater cognitive and emotional load. We found group differences on valence rating and reaction times. OM perceived sounds to be more unpleasant and responded slower to sounds relative to YM, possibly due to age or hearing loss effects. These findings suggest that misophonia may interact with auditory processing of emotions that are influenced by age and hearing acuity. Note that these results are preliminary and data collection is ongoing.