Experimental Gerontology

INTRODUCTION: Determining whether plasma biomarkers are preferentially associated with Alzheimer's disease (AD)-related rather than age-related brain atrophy patterns may clarify their prognostic and diagnostic clinical use. METHODS: Using data from the Baltimore Longitudinal Study of Aging (N=818), we examined cross-sectional plasma A{beta}42/A{beta}40, GFAP, NfL, p-tau181, and p-tau217 measurements obtained while participants were cognitively unimpaired (CU). During follow-up, 104 participants developed mild cognitive impairment (MCI)/dementia (74 due to AD, 24 due to non-AD, 6 unknown etiology). 2,293 longitudinal brain MRIs were used to quantify multidimensional atrophy pattern scores reflecting brain age (SPARE-BA), AD-like patterns (SPARE-AD), and five dominant dimensions of atrophy (R-indices). We investigated the associations of plasma biomarkers and atrophy pattern scores at index visit with conversion to MCI/dementia due to AD. We then examined the associations of plasma biomarkers with longitudinal change in pattern scores using linear mixed effects models. RESULTS: p-tau181, A{beta}42/A{beta}40 (Lumipulse), and p-tau217 were associated with incident MCI/dementia due to AD but not non-AD etiologies, while GFAP was associated with incident MCI/dementia due to both AD and non-AD. All four biomarkers were associated with longitudinal SPARE-AD changes. A{beta}42/A{beta}40 (Quanterix and Lumipulse), p-tau181, and p-tau217 were associated with longitudinal parieto-temporal atrophy. p-tau217 was the only biomarker associated with longitudinal medial temporal lobe atrophy. We did not find associations between plasma biomarkers and SPARE-BA or R-indices capturing subcortical, diffuse cortical, or perisylvian atrophy. DISCUSSION: Among CU individuals, plasma p-tau217 was associated with subsequent MCI/dementia due to AD and showed the most extensive associations with longitudinal AD-related brain atrophy.

The effects of older age on the oxidation of energy substrates (carbohydrates, fats) over 24 hr and during activities of daily living (ADL) may have substantial implications for metabolic health. To examine this issue, we evaluated age-related differences in substrate oxidation for 24 hr and periods of sleep, ADLs, and a 30-min treadmill walk (30MTW, 1.3m{middle dot}s^-1) in 17 young (29 {+/-} 5 yr, mean {+/-} SD, 6F) and 16 older (72 {+/-} 5, 8F) healthy active adults. Oxygen consumption (&VdotO2) and carbon dioxide production were measured using a 32,500 L room calorimeter to quantify substrate oxidation, which was normalized to body mass (kJ{middle dot}kg^-1) and total energy expenditure (%). Separately, &VdotO2peak was measured during an incremental treadmill test to exhaustion. &VdotO2peak (ml{middle dot}kg^-1{middle dot}min^-1) was lower in older adults compared with young adults. Older adults oxidized fewer carbohydrates than young over 24 hr (kJ{middle dot}kg^-1, %), sleep (kJ{middle dot}kg^-1), and ADLs (kJ{middle dot}kg^-1, %); and fat oxidation was greater in older than young over 24 hr (kJ{middle dot}kg^-1, %) and ADLs (kJ{middle dot}kg^-1, %). Carbohydrate oxidation did not differ by group during the 30MTW (kJ{middle dot}kg^-1, %), but fat oxidation was greater in older (kJ{middle dot}kg^-1) despite their walking at a greater relative intensity. These results indicate that older adults derived oxidative energy differently than young over 24 hr and during daily tasks. The lower carbohydrate and greater fat contribution to daily energy requirements may be meaningful in the development of metabolic disease in older adults.

The dose-response of six months of controlled exercise was studied in 72 subjects aged 50 to 70 years, with 1-4 training sessions per week, focusing on DNA methylation-based aging. Epigenetic age reduction increased with exercise dose, with about 255 MET-hours aligning with a one-year decrease in Robust PhenoAge acceleration- a volume consistent with WHO physical activity guidelines. The finding that relative ventricular posterior wall thickness and muscular quotient change in tandem with Robust PhenoAge acceleration suggests that epigenetic clocks reflect genuine organ-level rejuvenation. The DNA methylation-based protein prediction identified TGF-aplha, TIMP1, and adrenomedullin as showing a dose-response relationship with exercise volume. The exercise intervention yielded systemic health benefits, improved some cardiac parameters measured by echocardiogram, increased HDL levels, lowered blood pressure, reduced android fat mass, and notably, enhanced physiological functions, including cognitive performance. The program increased the relative abundance of microbes supporting intestinal barrier integrity and decreased pro-inflammatory bacterial populations. Serum N-lactoyl-phenylalanine levels showed a downward trend after six months of exercise, while trimethylamine N-oxide levels rose in male participants. This single-arm exercise study identified a dose-response relationship between cumulative exercise dose and Robust PhenoAge or GrimAge acceleration, strengthening the evidence that the observed associations are attributable to exercise exposure rather than background factors or confounders. The results further support the idea that regular physical activity can influence biological age by improving cardiac structure and function, and indicate that PhenoAge and GrimAge effectively reflect age-related cardiac changes.

Recent epidemiological studies suggest poor hydration is a modifiable risk factor for aging-related chronic disease. We tested whether serum sodium was associated with accelerated biological aging. We analyzed data from 363,286 adults (18-80 years) from 20 years of electronic medical records from a large healthcare system, as well as 24,611 adults (18-80 years) from National Health and Nutrition Examination Survey (NHANES) continuous (1999-2018). Seven key biomarkers were used to calculate biological age (BA) using the Klemera and Doubal method. We then reran the calculation using only the four variables with highest correlation with age as a robustness check. In both models, there was a significant linear association between age adjusted serum sodium and advanced biological aging, especially in the young cohorts. In the 7-variable model, in the Leumit dataset, the males in the highest sodium level versus the lowest, had a biological age that was 0.88 (95% CI 0.68-1.08) years accelerated and for females 2.32 (2.14-2.51) years. In NHANES dataset biological age of males at the highest sodium level was 1.92 (0.98-2.87) years accelerated as compared to those in the lowest sodium group. For females, the largest difference was for those 41-50 (1 year, .30-1.79). Increased serum sodium in the normal range is associated with accelerated biological aging in the general population, especially among people aged 18-50. Intervention studies are needed to confirm the link between hydration and biological aging.

The metabolic cost of walking is widely used to evaluate human performance and effectiveness of clinical interventions. Decades of laboratory research, largely based on treadmill experiments, have established a canonical relationship between walking speed and metabolic cost, and suggested that ageing shifts this relationship upward, implying reduced efficiency in older adults. However, this relationship has not been well tested during overground walking across matched speeds. We compared healthy younger (n=16; 26{+/-}2yr) and older (n=11; 74{+/-}3yr) adults across eight outdoor overground walking trials at different speeds: preferred walking speed (PWS), three fixed speeds (0.8, 1.2, 1.6 m{middle dot}s-{superscript 1}), and four speeds at {+/-}5% and {+/-}10% of PWS. Contrary to our hypothesis, older adults did not show higher gross or net metabolic cost of walking (GCOW and NCOW) than younger adults at any speed; rather, both trended consistently lower in older adults, reaching significance for GCOW at 0.8 m{middle dot}s-{superscript 1} only. Comparisons of resting metabolic rate and respiratory exchange ratio to prior reference groups did not indicate that our older cohort was unusually fit. Independent of age, GCOW was significantly higher at 0.8 m{middle dot}s-{superscript 1} than at the remaining speeds (1.2-1.6 m{middle dot}s-{superscript 1}), confirming that walking at slower speeds increases GCOW. These findings challenge the view that ageing intrinsically increases the energetic cost of walking, suggesting instead that previously reported upward shifts in cost may reflect treadmill-specific constraints or speed effects. Future work is needed to explore direct comparisons of outdoor, overground walking with treadmill walking at fixed speeds in both younger and older adults.

Physical activity (PA) is effective to counteract age-related declines. However, inter-individual variability in training adaptations may limit prediction of individual responses and intervention optimization. Daily PA behavior may contribute to this variability. The objective was to examine daily PA behavior through a 12-week supervised power training (PT) and its associations with clinical adaptations in 36 older men. Time of PA, step count, total (TEE) and active (AEE) energy expenditure, metabolic equivalents of task (METs), and sedentary time were assessed using a 3D accelerometer for three days surrounding PT sessions (Day-PT-1, Day-PT and Day-PT+1) at pre-(T0) and mid-intervention (6-week; T6). Physical performance, body composition and muscle function were assessed pre-(T0) and post-(T12) intervention. PA behavior outcomes did not change between T0 and T6, except for METs which decreased by 0.2 METS (T0:1.44{+/-}0.34 vs. T6:1.25{+/-} 0.18; p=0.003 [13%]). At T6, day-to-day fluctuations were observed for PA behavior on Day-PT-1 and Day-PT+1 compared with Day-PT (all ps<0.05). Following the intervention, body composition and muscle characteristics improved significantly. Between T6-Day-PT-1 and T6-Day-PT, greater increases in time of PA were associated with lower Fast Timed Up and Go speed adaptation (p=0.02), and greater reductions in step count were associated with greater reductions in muscle power (p=0.02). Finally, increases in step count and time of PA were associated with greater upper limb strength (p=0.04) and muscle pennation angle (p=0.02). PA behavior appears modulated during a 12-week PT intervention in healthy older men. Thus, PA behavior surrounding training sessions could be an important compensatory factor contributing to adaptations variability.

Background: Associations of sleep duration and insomnia symptoms with cognitive decline are inconsistent, and whether they represent modifiable risk factors or early manifestations of neurodegeneration may depend on life stage. We examined how sleep-cognition associations vary with age (44 to >90 years). Methods: We studied 16,884 participants from three cohorts with harmonised measures. In the English Longitudinal Study of Ageing (ELSA: n=9,473, median age 64, range 50 to >=90), linear mixed-effects models examined age-specific differences in cognitive change (recall and fluency) associated with sleep duration, difficulty falling asleep, nocturnal awakenings, incorporating sleep-by-age-by-time interactions, with initial adjustment for sociodemographic factors and further adjustment for health and lifestyle factors. Sleep characteristics showing consistent age-dependent associations in ELSA were further evaluated in Whitehall II (n=5,580, median age 55, range 44 to 68) and the Rush Memory and Aging Project (MAP: n=1,831, median age 80, range 53 to 102). Findings: In ELSA, difficulty falling asleep >=1 time/week (vs <1 time/week) was associated with less favourable 5-year change in recall at age 50 (difference -0.12 SD, 95% CI -0.20 to -0.04), with the association attenuating and reversing towards more favourable change at older ages (p-interaction=0.009 [linear], 0.016 [quadratic]). These persisted after further adjustment for health and lifestyle factors. Short sleep (<=6 h) showed similar patterns that attenuated after further adjustment. Similar age gradients were observed for difficulty falling asleep in Whitehall II and MAP. There was no evidence of age modification on long sleep and nocturnal awakenings. Interpretation: The cognitive implications of sleep disturbances vary by life stage. In midlife, difficulty falling asleep was associated with faster cognitive decline, supporting its role as a modifiable risk factor. In advanced age, the reversal is consistent with diminished arousal capacity accompanying prodromal dementia. Funding: US National Institute on Aging

Importance: Long-term exposure to higher average air pollutant concentrations is associated with poorer cognitive health, but annual averages can obscure substantial differences in day-to-day exposure. Whether recurrent high pollution days are associated with long-term cognitive aging trajectories among people with similar overall air pollution exposure is unclear. Objective: To determine whether the annual number of days exceeding World Health Organization daily guideline values for nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) is associated with subsequent cognitive decline after accounting for annual mean air pollutant exposure. Design: Prospective cohort study using data from waves 1-10 (2002-03 to 2021-23) of the English Longitudinal Study of Ageing. Setting: Population-based cohort of community-dwelling adults in England. Participants: 12,235 adults aged 50+ years at analytic baseline. Exposures: Number of days exceeding World Health Organization daily guideline values ('exceedance days') for NO2, PM2.5, and PM10, derived from residence-linked environmental estimates during the calendar year preceding the analytic baseline. Main Outcomes and Measures: Baseline cognitive performance and model-estimated 14-year cognitive decline (corresponding to the 75th percentile of follow-up duration) in episodic memory and verbal fluency. Results: Exceedance days were not associated with baseline memory or verbal fluency after adjustment for annual mean air pollutant exposure. More NO2 exceedance days were associated with faster cognitive decline: comparing the 75th percentile with the median of NO2 exceedance days, the difference in 14-year decline was -0.09 SD (95% CI, -0.17 to -0.01; p = 0.02) for memory and -0.10 SD (95% CI, -0.19 to 0.00; p = 0.04) for fluency. PM2.5 and PM10 exceedance days were not associated with cognitive decline. Conclusions and Relevance: In this cohort study of older adults, a higher number of NO2 exceedance days was associated with faster subsequent cognitive decline after adjustment for annual mean air pollutant exposure. This suggests that daily exposure to high NO2 concentrations may be related to accelerated cognitive aging even when offset by lower exposure on other days, potentially providing a new rationale for identifying and prioritizing areas with recurrent high NO2 exposure and the local emission sources contributing to it.

Study objectives: Aging is associated with increased sleep complaints and changes in sleep architecture, microstructure and rest-activity rhythms. Meditation-based interventions have shown benefits on subjective sleep quality, but their effects on objective sleep parameters remain largely underexplored. This study investigated the effects of an 18-month meditation intervention on sleep combining subjective (questionnaires) and objective (polysomnography and actigraphy) measures in older adults. Methods: A total of 120 cognitively unimpaired older adults ([&ge;]65 y) with minimal sleep complaint completed questionnaires, one week of actigraphy and in-home polysomnography at baseline, and again 18 months later. Following the baseline visit, participants were randomly assigned to one of 3 groups: meditation training, non-native language training (active control), or passive control. Group-by-visit interactions were examined using mixed-effects models for sleep questionnaires, actigraphy-derived metrics, sleep architecture and microstructure, including slow waves, spindles, and spectral power. Results: Compared to the passive control group only, meditation training was associated with greater ease of morning awakening (p=0.04). No significant intervention effects were observed for any other sleep parameter, including actigraphy- and polysomnography-derived measures. These findings remained unchanged after adjustment for depressive symptoms and trait anxiety. Conclusion: In cognitively unimpaired older adults, this 18-month meditation intervention yielded only limited improvements in subjective sleep assessment. Meditation may therefore have subtle effects on self-reported sleep quality in this healthy older population, although no effects on objective sleep measures were detected. Future studies should examine whether adapting the content, intensity, or timing of meditation practice and enrolling populations with clinically meaningful sleep disturbances or psychoaffective symptoms may yield greater benefits.

Purpose: Treadmills (TM) are widely used for gait assessment in older adults (OA), yet their ecological validity across inclined terrain remains underexplored. This study compared spatiotemporal, physiological, and kinetic gait outcomes between TM and overground (OG) walking across flat, uphill, and downhill terrain in OA and younger adults (YA), and examined sensorimotor predictors of speed discrepancies. Methods: Twenty-six OA (70{+/-}6 years; 22 women) and 24 YA (26{+/-}5 years; 7 women), none with prior TM experience, completed matched TM and OG trials across three terrain conditions. Self-selected TM speed was determined using a bidirectional protocol. The modified Clinical Test of Sensory Interaction in Balance quantified sensorimotor profiles. Mixed-design ANCOVAs and multiple regression examined condition, inclination, and group effects with sex as a covariate. Results: TM speeds were consistently slower than OG across all conditions in both groups ({Delta} = -0.35 m/s, d = -1.67), with shorter stride length, lower cadence, and altered support phase timing; YA showed larger reductions and a greater shift toward double support than OA. Foot clearance at midswing was largely preserved across modalities. TM walking elicited higher heart rate and RPE despite slower speeds, most pronounced in OA uphill. Ground reaction forces and loading rates were substantially reduced on the TM. Sensorimotor profiles predicted the downhill speed discrepancy (R2 = 0.49), with vestibular and somatosensory contributions as independent predictors alongside age group. Conclusion: TM-derived speed, spatiotemporal, and physiological measures are not interchangeable with real-world ambulation data in OA across inclined terrain.

IntroductionFalls are a major cause of injury-related morbidity, mortality, and healthcare utilisation among older adults, with the greatest burden occurring in those aged [&ge;]80 years. Multicomponent exercise programmes that include balance and resistance exercises reduce falls, whereas the effect of resistance training delivered as a standalone fall-prevention intervention remains uncertain. Existing resistance-training trials have generally been small, underpowered for fall outcomes, and have produced inconsistent findings, despite reduced muscle strength being an important modifiable risk factor in the oldest old. The resistance training prescription used in these studies has not always aligned with recommendations for optimal strength adaptations in terms of intensity or progressive overload, which may explain this uncertain efficacy. Therefore, this study aims to determine whether 12 months of high-intensity progressive resistance training reduces fall rates in community-dwelling adults aged [&ge;]80 years with reduced muscle strength. Methods and analysisThis single-centre, randomised controlled trial conducted in Trondheim, Norway, includes 241 community-dwelling adults aged [&ge;]80 years with reduced muscle strength. Participants are randomly assigned (1:1) to either standard care with written physical activity guidance or a twice-weekly high-intensity progressive resistance training intervention for 12 months. The primary outcome is the rate of falls over 12 months. Secondary outcomes include time to first fall, fall-related injuries, muscular function, physical performance, balance, body composition, cardiometabolic health, cognition, and participant-reported outcomes. Cost-effectiveness is assessed from a healthcare perspective over the 12-month intervention period using costs and quality-adjusted life years. Analyses follow the intention-to-treat principle, using negative binomial regression for the primary outcome. The first participant was included on 30 March 2023, and the last participant was included on 29 September 2025. The 12-month intervention period is expected to be completed by September 2026. Ethics and disseminationThe study has received approval from the Regional Committee for Medical and Health Research Ethics in Norway (REK; reference number 462261). All participants provided written informed consent before participating. Findings will be shared via peer-reviewed publications, conference presentations, and communication with stakeholders and the public. Trial registration numberClinicalTrials.gov (NCT05691166), registered 11 January 2023. Available at: https://clinicaltrials.gov/study/NCT05691166

This study aimed to quantify the longitudinal tracking and cross-sectional construct validity of a single-item questionnaire measuring recreational physical activity frequency (RPAF) in the Womens Healthy Ageing Project. At baseline, 474 participants aged 45-55 reported RPAF from 1993 to 2014. Longitudinal tracking of the RPAF item was assessed as a consecutive-wave and baseline-referenced measure using linear weighted kappa (LWK), Spearman correlations, exact agreement and within-one-category agreement. Construct validity in the form of convergent and known-group validity was assessed using the International Physical Activity Questionnaire (IPAQ) leisure activity domains, Short Form 36 physical function (SF-36-PF) subscale, Timed Up and Go (TUG), hand grip strength (HGS) and waist-to-height ratio (WHtR). 474 participants provided baseline RPAF data. Pairwise longitudinal samples ranged from 176 to 459 across the study. Consecutive-wave LWK ranged from 0.38 to 0.49, and Spearman correlations ranged from 0.44 to 0.57. Exact and within-category agreement ranged from 41.4%-50.8% and 72.0%-79.0%. Baseline-referenced LWK ranged from 0.22 to 0.47, with Spearman correlations of 0.29 to 0.56. RPAF correlated with total IPAQ leisure score (rs = 0.60), IPAQ walking score (rs = 0.58), SF-36-PF (rs = 0.33) and TUG score (rs = -0.25). No significant correlation was identified between RPAF, HGS or WhTR. RPAF discriminated known groups for WHO guideline-sufficient activity, SF-36-PF, and TUG fall risk. The RPAF item demonstrated fair-to-moderate agreement in consecutive waves, with weaker baseline-referenced tracking. Cross-sectional validity was highest with total IPAQ leisure activity. The item may provide a pragmatic measure for RPAF in womens cohort studies.

. Abstract Objectives. Prior research has identified associations between sleep health and cognitive function. Our aim was to investigate multiple domains of sleep health and their associations with cognitive function in a diverse sample of older adults. Methods. These data are from an observational study in Chicago, USA, that enrolled adults aged 55 years and older without cognitive impairment at baseline and followed a subset for up to 2 years. Sleep was measured with 7 days of wrist actigraphy and we examined sleep duration (amount), sleep fragmentation (an index of restlessness and sleep quality), sleep start time and sleep regularity (based on the within-subject standard deviation of sleep start time). . Participants also completed tasks from the NIH Toolbox to estimate fluid cognition and the Trail Making Test (Trails B) to assess attention and processing speed. A subset of participants was examined at a follow-up visit that included only the NIH Toolbox assessment. Results. Our sample included 324 participants (63.6% women, 37.3% African American/Black, 13.6% Hispanic/Latino). Greater sleep fragmentation and less sleep regularity were associated with worse fluid cognition and Trails B scores (all p<.01). Longer sleep duration and earlier sleep start times were associated with better performance on Trails B. No sleep measures were associated with change in the fluid cognition score over an average of 1.9 years (n=133). Discussion. These findings support a cross-sectional association between cognitive function and multiple domains of sleep health, including duration, quality, timing and regularity, in a diverse sample of older adults.

Background: Emerging evidence suggests that alterations in the gut microbiome may contribute to mental health outcomes through the gut-brain axis. However, older adults with post-traumatic stress disorder (PTSD) remain underrepresented in microbiome research. This pilot study investigated associations between PTSD symptoms, dietary fibre intake, cognitive function, and gut microbiome functional capacity in adults aged 50 years and older. Methods: Participants with PTSD symptoms and trauma-exposed controls (TEC) completed validated assessments of mental health, trauma exposure, and dietary fibre intake. A subset of participants provided stool samples for microbiome analysis and undertook cognitive function assessment. Quantitative PCR was used to assess phylum-level taxonomy and butyrate-producing bacterial pathways (terminal butyrate generating enzyme), with abundances normalised to the 16S rRNA gene. Results: Participants with PTSD demonstrated significantly greater mental health symptom burden and poorer performance on cognitive tasks related to executive function, working memory, and learning. Dietary fibre intake did not differ significantly between PTSD and TEC groups and no significant differences in overall microbial composition were identified at the phylum level. In contrast, differences were more apparent when assessing functional microbiome pathways, with butyrate kinase abundance significantly lower in PTSD participants than TEC participants. When stratified by fibre intake, a greater butyrogenic capacity was observed in the High fibre TEC participants compared to the Low fibre TEC participants, while little difference was observed in the PTSD fibre-stratified groups. Substantial inter-individual variation was also evident across both taxonomic and functional measures. Conclusions: These findings suggest that functional characteristics of the gut microbiome may provide greater insight into PTSD-related biological processes than broad taxonomic measures alone. Dietary fibre intake may be associated with greater butyrate-producing capacity in trauma-exposed older adults without PTSD symptoms, although this relationship appeared less evident among older adults living with PTSD symptoms. These findings support further investigation of microbiome function, diet, and cognition within the gut-brain axis. Larger studies incorporating metagenomic and metabolomic approaches are warranted.

Aging is associated with proteome remodelling and progressive accumulation of insoluble proteins. Identifying age-enriched proteins that undergo aggregation and evaluating compounds capable of modulating their behaviour may provide insights into interventions that promote healthy aging. Here, we report a proteome-guided strategy to identify age-associated aggregation-prone proteins and evaluate phytochemicals targeting conserved proteins in Caenorhabditis elegans. We identified proteins whose abundance increased more than four-fold in aged worms compared with young worms, many of which also accumulated in the age-associated insoluble proteome, and subsequently identified their human orthologs for comparative analysis. Based on biological relevance, structural conservation, and availability of high-confidence structural models, glutamine-fructose-6-phosphate aminotransferase-2 (GFAT-2) was selected for molecular docking. Screening of fifteen phytochemicals against C. elegans GFAT-2 and its human ortholog GFPT1 identified quercetin as the strongest predicted binder, exhibiting conserved interactions with both proteins. However, treatment of worms with quercetin did not significantly alter global protein insolubility during aging. This may reflect its ability to modulate inappropriate protein-protein interactions without substantially affecting the overall aggregation burden. These findings underscore the need for experimental validation of favourable in silico docking predictions. More broadly, this study provides a proteome-guided framework for prioritizing age-associated aggregation-prone proteins as candidate therapeutic targets for preserving proteostasis during aging.

Introduction: Daytime sleepiness (DS) can compromise athletic performance; however, its influence on Brazilian Jiu-Jitsu (BJJ) athletes remains poorly understood. Daytime naps have been suggested as a strategy to alleviate the effects of DS; however, their impact on physical and specific performance remains inconsistent. Thus, this study investigated the influence of different levels of daytime sleepiness on the physical and specific performance of BJJ athletes and verified the effects of daytime napping on these outcomes. Methods: This investigation employed a randomized, controlled, crossover clinical trial design involving 19 amateur Brazilian Jiu-Jitsu (BJJ) athletes who exhibited excessive daytime sleepiness. Participants performed two experimental conditions, with a 30-minute nap (N30) and without a nap (NN), in a randomized order. Vertical jump (CMJ and SJ), anaerobic power (Wingate ), kimono grip strength (KGST), and specific performance were evaluated using the Jiu-Jitsu Anaerobic Performance Test (JJAPT). Data were analyzed using mixed linear models. Results: Daytime sleepiness significantly influenced all parameters of specific performance (JJAPT), with worse performance observed in athletes classified as having abnormal sleepiness. The opportunity to nap increased the total number of repetitions in the JJAPT of four sets ({approx}20 repetitions; p < 0.001), without consistent changes in physical performance tests. An interaction between napping and sleepiness was observed in relation to isometric endurance strength, indicating that napping may provide greater benefits to athletes experiencing abnormal sleepiness. Conclusion: High levels of daytime sleepiness are associated with reduced specific performance in BJJ athletes. Daytime naps are a simple and potentially effective strategy to mitigate these effects and improve specific performance, reinforcing the importance of monitoring sleepiness and individualizing recovery strategies.

Background Attentional control declines with normal aging, yet the role of modifiable lifestyle factors in accelerating this decline remains incompletely characterised in large, diverse populations. We examined associations between four modifiable risk factors (smoking intensity, alcohol binge drinking, social satisfaction and blood pressure) and sustained attention performance in 13,866 adults drawn from the All of Us Research Program. Methods Cognitive performance was assessed using the Gradual-Onset Continuous Performance Task (GradCPT). A composite cognitive efficiency score was derived via principal component analysis of four GradCPT metrics: d' (perceptual sensitivity), response criterion, median reaction time and reaction time variability. Associations between cognitive efficiency and each risk factor were examined using multiple linear regression adjusted for age, sex and race/ethnicity. Effect sizes were expressed as age-equivalent years of cognitive aging (age-equivalent years = regression coefficient for the risk factor divided by the regression coefficient for age) to aid clinical interpretation. Results GradCPT performance declined progressively with age (p < 0.001). Social satisfaction emerged as the strongest lifestyle predictor: low social satisfaction was associated with approximately 5.8 additional age-equivalent years of cognitive aging relative to high social satisfaction. Smoking showed a dose-response pattern, with heavy smokers (> 20 cigarettes/day) exhibiting an approximately 5-year age-equivalent deficit versus never-smokers. Stage 2 hypertension showed a modest, non-significant negative association. Binge drinking showed limited significant associations, likely complicated by survivor and abstainer biases. Bootstrapped analyses of combined exposures showed that combinations of risk factors, particularly those involving low social satisfaction, produced larger cognitive deficits than expected under an additive model. Conclusions These findings support an interactive rather than a purely additive model of lifestyle-related cognitive vulnerability and highlight the GradCPT as a subclinical measure of attention-based cognitive risk in non-clinical populations. Keywords Cognitive aging, Sustained attention, GradCPT, Modifiable risk factors, Social isolation, Smoking, Hypertension, All of Us Research Program

Purpose: The neural retina and retinal pigment epithelium/choroid (RPE/Cho) are metabolically coupled. Metabolic dysfunction of the RPE/Cho contributes to photoreceptor death in age-related macular degeneration (AMD). This study aimed to determine how aging, a major risk factor for AMD, alters the proteome and metabolic pathways in the retina and RPE/Cho. Methods: We performed quantitative proteomics on neural retina and RPE/Cho from young (8-week) and old (73-week) C57BL/6J mice. The differentially expressed proteins between old and young, as well as between the retina and RPE/Cho, were visualized using volcano plots and heatmaps, and functional analyses were assessed by Gene Ontology enrichment tools. Results: Aging altered the expression of 85 retinal proteins and 272 RPE/Cho, with 16 shared between tissues. In the aged retina, proteins associated with NADP(H) metabolism, neurodegeneration, and immunity were mostly upregulated, while proteins in lipid metabolism, transcription, and epigenetic regulation decreased. In the aged RPE/Cho, all 21 significantly altered lysosomal enzymes and transport proteins increased, together with complement components, and photoreceptor outer segment proteins. These changes accompanied increases in proteins associated with lipid metabolism and protection against lipid peroxidation, while several glutathione metabolism enzymes decreased. Seven shared proteins involved in lipid and NADP(H) metabolism, changed in opposite directions between retina and RPE/Cho. Comparison of the retinal and RPE/Cho proteomes identified 3073 differentially abundant proteins, of which 2452 maintained tissue-specific differences across both age groups, while approximately 17% showed age-dependent shifts in tissue enrichment. These shifts involved proteins associated with metabolism, extracellular matrix, visual function, lysosomal pathways, and innate immunity. Within the metabolic proteome, several glycolytic and fatty acid oxidation proteins showed greater relative enrichment in RPE/Cho with age, whereas glucose transporters and mitochondrial complexes shifted toward the retina. Conclusions: Overall, these findings show that aging differentially remodels the retina and RPE/Cho proteome, accompanied by altered metabolic specialization between the two tissues.

Introduction The population of older adults in India is projected to exceed 230 million within the next decade. With increasing life expectancy, maintaining cognitive and neurobiological health becomes essential for ensuring a good quality of life. This study is a comprehensive multimodal investigation of aging and cognition in a healthy Indian cohort. The aim is to characterize cognitive, neurobiological, physiological, psychological, and molecular trajectories and their associations across the adult lifespan in India. Methods and Analysis Data will be collected cross-sectionally from healthy young (19 to 35 years, n = 100), middle-aged (40 to 55 years, n = 100), and older adults (60 to 75 years, n = 100) with regional nativity and residence in Telangana or Andhra Pradesh. Individuals with cognitive impairment or any chronic health condition will be excluded. Assessments will include standardized cognitive tests, mental health questionnaires, brain imaging, heart rate variability, and serum samples for standard blood tests and epigenetic analyses. Hair cortisol and serum inflammatory markers will also be collected to profile stress and systemic inflammation, respectively. Data from this study will help to profile healthy aging in an Indian cohort, thereby addressing critical gaps in clinical research and health policy. Ethics and Dissemination This study was approved by the Institutional Review Board at IIIT Hyderabad (IIITH-IRB-PRO-2023-11). All participants will give written consent. Results from this study will be presented at conferences and published in peer-reviewed journals. Data will also be curated for an interactive web-portal to enable researchers, clinicians, and policy makers to understand the data in meaningful ways.

Aging is accompanied by progressive neuromuscular junction (NMJ) degeneration. The C-terminal agrin fragment (CAF), a circulating product of agrin cleavage, has been proposed as a minimally invasive biomarker of NMJ degradation, but its relationships with neuromuscular and functional characteristics, and the influence of physical activity, remain underexplored. We studied 136 community-dwelling men aged 20-92 years (active, n=87; inactive, n=49). Serum CAF was measured by ELISA. The proportion of NCAM-positive fibers, a marker of myofiber denervation, was assessed in vastus lateralis biopsies (n=127). Neuromuscular outcomes included maximal voluntary isometric contraction (MVIC), lower-limb power, electromechanical delay (EMD), nerve conduction velocities, H/M ratio, central activation ratio, co-activation, and twitch characteristics. Functional capacity was assessed using the 6-minute walk test, alternating step test, Timed Up and Go, sit-to-stand tests, and fast gait speed. Serum CAF increased with age and was positively associated with NCAM-positive fiber proportion. Higher CAF was associated with lower MVIC, lower-limb power and poorer performance on all functional tests. CAF was associated with longer EMD in the overall cohort and in inactive men only, and with a lower H/M ratio in inactive men. No associations were found with nerve conduction velocities, central activation ratio, co-activation, or twitch amplitude. Active men had lower CAF levels than inactive men, particularly after age 70. Serum CAF is associated with age-related declines in neuromuscular and functional capacity and with NCAM-positive fiber prevalence, supporting its utility as an accessible biomarker of NMJ remodeling. Physical activity was associated with a more favorable CAF profile in older men.