Age-related Effects Research Articles

Age-related effects of neuromuscular fatigue and acute recovery responses on maximal and rapid torque measures of the leg extensors and flexors.

To examine the effects of neuromuscular fatigue and recovery on maximal and rapid torque characteristics in young and old men for the leg extensors and flexors. Twenty-one young (age = 24.8years) and 19 old (72.1years) men performed maximal voluntary contractions (MVCs) before and at 0, 7, 15, and 30min following an intermittent submaximal fatigue task. Outcome measures included endurance time, maximal (peak torque; PT) and rapid (absolute and normalized rate of torque development; RTD and nRTD) torque characteristics. The old men had greater endurance times than the young men. Differential recovery patterns were observed for PT, and early and late RTD phases between the leg extensor and flexor musclegroups such that the early rapid torque variables and the flexors demonstrated slower recovery compared to later rapid torque variables and the extensors. The normalized RTD variables were reduced less after the fatigue task and differential muscle and age effects were observed where the flexors were reduced more at the early phase (nRTD1/6) compared to the extensors, however, for the later phase (nRTD2/3) the young men exhibited a greater reduction compared to the old men. Dissimilar fatigue recovery patterns across different phases of RTD, lower limb muscles, and age groups may have important fatigue-related performance and injury risk implications across the adult lifespan.

Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis.

Emapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ by orders of magnitude between patients with primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS; a form of secondary HLH) in systemic juvenile idiopathic arthritis (sJIA). Therefore, this study aimed to develop a population pharmacokinetic model for emapalumab across a patient population with a wide range of total (free and emapalumab-bound) IFNγ levels using observations from patients with primary HLH or MAS in sJIA in clinical trials. Pharmacokinetic data were pooled (n = 58; 2709 observations) from studies enrolling patients administered emapalumab for primary HLH or MAS in sJIA. Patients with primary HLH were administered emapalumab 1mg/kg (potentially increasing to 3, 6, and up to 10mg/kg based on clinical response) every 3days. Patients with MAS in sJIA were administered emapalumab 6mg/kg, followed by 3mg/kg every 3days until day 15 and twice weekly until day 28. An earlier population PK model was re-parameterized using this data. The final model for emapalumab comprised a 2-compartment model with first-order elimination. Emapalumab clearance remains constant when the total IFNγ concentration (free and emapalumab-bound) is < ~ 10,000pg/ml but increases proportionally to total IFNγ concentration above this threshold. Emapalumab clearance was estimated to be 0.00218, 0.00308, 0.00623 and 0.01718 l/h at total serum IFNγ concentrations of 103, 104, 105 and 106pg/ml, respectively, with corresponding terminal half-lives of 19.2, 13.8, 7.18 and 3.12days for a 1-year-old patient weighing 10kg with primary HLH. The median terminal half-life for emapalumab in patients with MAS in sJIA was estimated to be 24.0 (range, 6.13-32.4)days, which is similar to observations in healthy volunteers. Emapalumab pharmacokinetics in patients with primary HLH and MAS in sJIA were described by a two-compartment model with fixed allometric exponents and an age-related effect. Differences in total IFNγ levels between patients with primary HLH and MAS may affect emapalumab pharmacokinetics, suggesting that each indication may require different dosing to rapidly control hyperinflammation. Clinicaltrials.gov identifiers: NCT01818492, NCT03311854 and NCT02069899.

Duration, numerosity and length processing in healthy ageing and Parkinson’s disease

People constantly process temporal, numerical, and length information in everyday activities and interactions with the environment. However, it is unclear whether quantity perception changes during ageing. Previous studies have provided heterogeneous results, sometimes showing an age-related effect on a particular quantity, and other times reporting no differences between young and elderly samples. However, three dimensions were never compared within the same study. Here, we conducted two experiments with the aim of investigating the processing of duration, numerosity and length in both healthy and pathological ageing. The experimental paradigm consisted of three bisection tasks in which participants were asked to judge whether the presented stimulus (i.e. a time interval, a group of dots, or a line) was more similar to the short/few or long/many standards. The first study recruited healthy young and elderly participants, while the second recruited healthy elderly participants and patients with Parkinson’s disease, a clinical condition commonly associated with temporal impairments. The results of both experiments showed that discrimination precision differed between domains in all groups, with higher precision in the numerosity task and lower sensitivity in judging duration. Furthermore, while discrimination abilities were affected in healthy elderly and, even more so, in Parkinson’s disease group, no domain-specific impairments emerged. According to our research, reduced discrimination precision might be explained by an alteration of a single system for all quantities or by an age-related general cognitive decline.

0978 A Spectrum of Altered Non-rapid Eye Movement Sleep in Schizophrenia

Abstract Introduction Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations (SO), are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses which treat all patients as a unitary set, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, illness duration and ageing, cognitive profiles and medication regimens. Methods Using newly collected high-density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported (Kozhemiako et. al, eLife, 2022) group-level mean differences between patients and controls (original N=130). Then in the combined sample (N=301 including 175 patients), we characterized patient-to-patient variability in NREM neurophysiology. Sleep EEG preprocessing was conducted using an open-source package called Luna (http://zzz.bwh.harvard.edu/luna/). Results We replicated all group-level mean differences and confirmed the high accuracy of our predictive model (Area Under the ROC Curve, AUC = 0.93 for diagnosis). Compared to controls, patients showed significantly increased between-individual variability across many (26%) sleep metrics, with patterns only partially recapitulating those for group-level mean differences. Although multiple clinical and cognitive factors were associated with NREM metrics including spindle density, collectively they did not account for much of the general increase in patient-to-patient variability. Medication regime was a greater (albeit still partial) generator of variability, although original group mean differences persisted after controlling for medications. Some sleep metrics including fast spindle density showed exaggerated and accelerated age-related effects in SCZ, and patients exhibited older predicted biological ages based on an independent model of ageing and the sleep EEG. Conclusion We demonstrated robust and replicable alterations in sleep neurophysiology in individuals with SCZ and highlighted distinct patterns of effects contrasting between-group means versus within-group variances. That increased NREM heterogeneity was not explained by traditional clinical or cognitive patient assessments suggests the sleep EEG provides novel, nonredundant information to support the goals of personalized medicine. Collectively, our results point to a spectrum of NREM sleep deficits among SCZ Support (if any)

No difference in postprandial mesenteric blood flow between healthy younger and elderly individuals

We recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged < 30 years and 17 elderly subjects aged > 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal). Postprandial blood flow dynamics in SMA did not differ between young and elderly subjects. A noticeable inter-individual variation in postprandial intestinal blood flow increase was found, and approximately 30% of the variation could be explained by the preprandial blood flow. Regardless of age, some subjects showed a remarkable transient SMA blood flow increase immediately after meal intake. This study provides tentative evidence that postprandial blood flow dynamics in SMA in healthy young and elderly subjects do not substantially differ, indicating that age is without impact on vascular response in SMA as an indicator for regulation of mesenteric perfusion in response to food intake.

Morphological processing across the adult lifespan: a tale of gains and losses

Despite increasing research on language in aging, age effects on morphological processing have received comparatively little attention. Some previous evidence suggests that while regular morphology (e.g., walk-walked) may remain relatively stable in older age, irregular morphology (e.g., bring-brought) shows signs of age-related decreases in processing efficiency. However, the underlying reasons for these declines are unclear. The current study sought to investigate the cognitive underpinnings of age-related effects on German noun plurals: default plurals (posited to follow a default rule [e.g., Zebra-Zebras 'zebra(s)']) and predictable and unpredictable non-default plurals (closed class plurals, in which the plural is either phonologically predictable from the singular [e.g., Flasche-Flaschen 'bottle(s)'] or unpredictable [e.g., Nest-Nester 'nest(s)']). In a cross-modal priming experiment, 283 healthy German native speakers (aged 18–91 years) performed lexical decisions on singular nouns which take different types of plural affixes, and which were primed by either their plural form ("morphological condition") or an unrelated noun ("unrelated condition"). Additionally, several cognitive abilities (declarative, procedural, and working memory, interference control, processing speed) were tested to assess their mediating role for morphological processing. The results revealed distinct developmental trajectories for default versus non-default plurals: priming effects (unrelated-morphological condition) for predictable and unpredictable non-default plurals decreased with increasing age, with age-related declines in declarative memory mediating these declines. In contrast, priming effects for default plurals increased with increasing age. Although the reasons for this increase remain to be clarified, we suggest lifelong experience with the computation of these forms as a possible mechanism.

Who Will Be More Egocentric? Age Differences in the Impact of Retrospective Self-Experience on Interpersonal Emotion Intensity Judgment.

This study investigates whether the retrospective self-experience of older adults affects and biases interpersonal emotion judgment more than that of younger adults by adopting the paradigm of the self-generated anchoring effect. Participants (older adults: n = 63; younger adults: n = 65) were required to retrospectively consider their self-experiences and judge their possible emotion intensity in anchor-generating scenarios (high- or low-anchor scenarios). Subsequently, participants estimated the protagonist's emotion intensity in target scenarios. The age-related interaction effect showed that older adults exhibited a significant self-generated anchoring effect in more emotion categories (four emotions) compared with younger adults (two emotions). After controlling for inhibition or working memory as a covariant, this interaction effect was no longer significant. The results from multilevel regression analysis also indicated the significant effect of self-emotion across all models on participants' judgment of others' emotions. The results indicated that older adults were more affected by retrospective self-experiences, leading to more egocentric judgment, than younger adults. This different influence from the retrospective self-experiences might partially have been caused by the age-related difference in cognitive abilities.

Apigenin and Rutaecarpine reduce the burden of cellular senescence in bone marrow stromal stem cells.

Osteoporosis is a systemic age-related disease characterized by reduced bone mass and microstructure deterioration, leading to increased risk of bone fragility fractures. Osteoporosis is a worldwide major health care problem and there is a need for preventive approaches. Apigenin and Rutaecarpine are plant-derived antioxidants identified through functional screen of a natural product library (143 compounds) as enhancers of osteoblastic differentiation of human bone marrow stromal stem cells (hBMSCs). Global gene expression profiling and Western blot analysis revealed activation of several intra-cellular signaling pathways including focal adhesion kinase (FAK) and TGFβ. Pharmacological inhibition of FAK using PF-573228 (5 μM) and TGFβ using SB505124 (1μM), diminished Apigenin- and Rutaecarpine-induced osteoblast differentiation. In vitro treatment with Apigenin and Rutaecarpine, of primary hBMSCs obtained from elderly female patients enhanced osteoblast differentiation compared with primary hBMSCs obtained from young female donors. Ex-vivo treatment with Apigenin and Rutaecarpine of organotypic embryonic chick-femur culture significantly increased bone volume and cortical thickness compared to control as estimated by μCT-scanning. Our data revealed that Apigenin and Rutaecarpine enhance osteoblastic differentiation, bone formation, and reduce the age-related effects of hBMSCs. Therefore, Apigenin and Rutaecarpine cellular treatment represent a potential strategy for maintaining hBMSCs health during aging and osteoporosis.

A Comprehensive Examination of Prediction-Based Error as a Mechanism for Syntactic Development: Evidence From Syntactic Priming.

Prediction-based accounts of language acquisition have the potential to explain several different effects in child language acquisition and adult language processing. However, evidence regarding the developmental predictions of such accounts is mixed. Here, we consider several predictions of these accounts in two large-scale developmental studies of syntactic priming of the English dative alternation. Study 1 was a cross-sectional study (N = 140) of children aged 3-9 years, in which we found strong evidence of abstract priming and the lexical boost, but little evidence that either effect was moderated by age. We found weak evidence for a prime surprisal effect; however, exploratory analyses revealed a protracted developmental trajectory for verb-structure biases, providing an explanation as for why prime surprisal effects are more elusive in developmental populations. In a longitudinal study (N = 102) of children in tightly controlled age bands at 42, 48, and 54 months, we found priming effects emerged on trials with verb overlap early but did not observe clear evidence of priming on trials without verb overlap until 54 months. There was no evidence of a prime surprisal effect at any time point and none of the effects were moderated by age. The results relating to the emergence of the abstract priming and lexical boost effects are consistent with prediction-based models, while the absence of age-related effects appears to reflect the structure-specific challenges the dative presents to English-acquiring children. Overall, our complex pattern of findings demonstrates the value of developmental data sets in testing psycholinguistic theory.

Gaze data of 4243 participants shows link between leftward and superior attention biases and age.

Healthy individuals typically show more attention to the left than to the right (known as pseudoneglect), and to the upper than to the lower visual field (known as altitudinal pseudoneglect). These biases are thought to reflect asymmetries in neural processes. Attention biases have been used to investigate how these neural asymmetries change with age. However, inconsistent results have been reported regarding the presence and direction of age-related effects on horizontal and vertical attention biases. The observed inconsistencies may be due to insensitive measures and small sample sizes, that usually only feature extreme age groups. We investigated whether spatial attention biases, as indexed by gaze position during free viewing of a single image, are influenced by age. We analysed free-viewing data from 4,243 participants aged 5-65 years and found that attention biases shifted to the right and superior directions with increasing age. These findings are consistent with the idea of developing cerebral asymmetries with age and support the hypothesis of the origin of the leftward bias. Age modulations were found only for the first seven fixations, corresponding to the time window in which an absolute leftward bias in free viewing was previously observed. We interpret this as evidence that the horizontal and vertical attention biases are primarily present when orienting attention to a novel stimulus - and that age modulations of attention orienting are not global modulations of spatial attention. Taken together, our results suggest that attention orienting may be modulated by age and that cortical asymmetries may change with age.

Comparing spatial navigation in a virtual environment vs. an identical real environment across the adult lifespan

Virtual environments (VEs) are increasingly being used as a research platform for investigating human responses to environmental variables. While VEs provide tremendous advantages in terms of variable isolation and manipulation, and ease of data-collection, some researchers have expressed concerns about the ecological validity of VE-based findings; that is, their transferability to real-world contexts. In the current study we created a virtual replica of a real-world, multi-level educational facility, and compared data collected in the VE vs. the real-world environment as participants completed identical navigational tasks. We found significant differences in all of the measures used, including distance covered, number of mistakes made, time for task completion, spatial memory, extent of backtracking, observation of directional signs, perceived uncertainty levels, perceived cognitive workload, and perceived task difficulty. We also analyzed potential age-related effects to look for heightened VE/real-world response discrepancies among older adult participants (age 55 or over) compared to younger adults (18–30 years of age). This analysis yielded no significant age-by-condition interaction effects. Finally, we examined the spatial distribution of self-reported wayfinding uncertainty across the building floorplan, finding that areas in which uncertainty was most pronounced were similar between the real-world and VE settings. Overall, these findings indicate that while virtual reality can be a useful design research tool, caution is needed when interpreting and generalizing its results.

Age-related effects on a hierarchical structure of canine cognition

The current study investigates whether there are statistically independent age-related influences on the canine cognitive structure and how individual factors moderate cognitive aging on both cross-sectional and longitudinal samples. A battery of seven tasks was administered to 129 pet dogs, on which exploratory and confirmatory factor analyses were employed to unveil the correlational structure underlying individual differences in cognitive performance. The best-fitting model featured a hierarchical structure with two first-order cognitive domains (individual problem solving, learning) and a second-order common factor. These higher order factors exhibited consistency over a period of at least 2.5 years. External validation linked the common factor positively to discrimination and reversal learning performance, exploration, neophilia, activity/excitability, and training level while negatively to cognitive dysfunction symptoms, suggesting that it is a good candidate for a general cognitive factor (canine g). Structural equation models identified three distinct age-related influences, operating on associative learning, on memory, and on canine g. Health status moderated the negative age-canine g relationship, with a stronger association observed in dogs with poorer health status, and no relationship for dogs in good health. On a longitudinal sample (N = 99), we showed that the direction and magnitude of change in canine g over up to 3 years is affected by various interactions between the dogs’ age, communication score, baseline performance, and time elapsed since the baseline measurement. These findings underscore the presence of a general cognitive factor in dogs and reveal intriguing parallels between human and canine aging, affirming the translational value of dogs in cognition and aging research.

Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression.

Mesenchymal stem cells (MSCs) are known to promote tissue regeneration and suppress excessive inflammation caused by infection or trauma. Reported evidence indicates that various factors influence the expression of MSCs' endogenous immunomodulatory properties. However, the detailed interactions of MSCs with macrophages, which are key cells involved in tissue repair, and their regulatory mechanisms are not completely understood. We herein investigated how age-related immunomodulatory impairment of MSCs alters the interaction of MSCs with macrophages during bone healing using young (5-week old) and aged (50-week old) mice. To clarify the relationship between inflammatory macrophages (M1) and MSCs, their spatiotemporal localization at the bone healing site was investigated by immunostaining, and possible regulatory mechanisms were analyzed in vitro co-cultures. Histomorphometric analysis revealed an accumulation of M1 and a decrease in MSC number at the healing site in aged mice, which showed a delayed bone healing. In in vitro co-cultures, MSCs induced M1 apoptosis through cell-to-cell contact but suppressed the gene expression of pro-inflammatory cytokines by soluble factors secreted in the culture supernatant. Interestingly, interleukin 38 (Il-38) expression was up-regulated in M1 after co-culture with MSCs. IL-38 suppressed the gene expression of inflammatory cytokines in M1 and promoted the expression of genes associated with M1 polarization to anti-inflammatory macrophages (M2). IL-38 also had an inhibitory effect on M1 apoptosis. These results suggest that MSCs may induce M1 apoptosis, suppress inflammatory cytokine production by M1, and induce their polarization toward M2. Nevertheless, in aged conditions, the decreased number and immunomodulatory function of MSCs could be associated with a delayed M1 clearance (i.e., apoptosis and/or polarization) and consequent delayed resolution of the inflammatory phase. Furthermore, M1-derived IL-38 may be associated with immunoregulation in the tissue regeneration site.

Gap in Noise Auditory Brainstem Responses: A Systematic Review

Background and Objectives: The gap in noise auditory brainstem responses (GIN-ABR) is a valuable assessment tool for auditory temporal processing, offering non-invasive and objective measurements encompassing the entire auditory system from the cochlea to the brainstem. This method has been utilized in investigating various factors, including age-related effects, hearing loss, and tinnitus. This systematic review was conducted to present a thorough examination of (GIN-ABR), encompassing its methodology, applications, and inherent limitations. Methods: This study was conducted based on preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Cochrane, PubMed, and Ovid databases were used to extract English articles from 1990 to June 2023. The search terms used were “gap in noise auditory brainstem response”, “ABR gap detection”, “ABR gap duration”, “ABR gap threshold”, and “ABR temporal processing”. Articles were included if gap-evoked ABR was used, investigating the effect of any factor on the responses, and using any gapped stimulus type. Articles whose evoked potentials did not include ABR waves were excluded. The outcome of interest was gap-evoked ABR in different participant groups. Results: A total of 10 studies were deemed suitable for inclusion in the review. The articles were reviewed that including the study population, the methods, and the results. Despite the variability in the results of the studies, in the aged group, longer latency shifts and decreased peak amplitude were reported compared to the young group. Correspondence of behavioral thresholds with GIN-ABR has also been mentioned in studies. Conclusion: The GIN-ABR method has been extensively utilized in investigating various factors, including age-related effects, hearing loss, and tinnitus. Notably, GIN-ABR has several clinical advantages, such as cost-effectiveness, shorter test duration, independence from alertness levels, attention, sleep depth fluctuations, or medication. Additionally, it has shown its compatibility with psychophysical tests. Further research is warranted to explore the impact of various factors on different components of GIN-ABR. Consequently, with its promising findings and growing body of research, the gap in noise test has the potential to be gradually integrated into the set of audiological clinical evaluations.

High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats.

We investigated the age-related effects of the lipid-lowering drug fenofibrate on renal stress-associated effectors. Young and old rats were fed standard chow with 0.1% or 0.5% fenofibrate. The kidney cortex tissue structure showed typical aging-related changes. In old rats, 0.1% fenofibrate reduced the thickening of basement membranes, but 0.5% fenofibrate exacerbated interstitial fibrosis. The PCR array for stress and toxicity-related targets showed that 0.1% fenofibrate mildly downregulated, whereas 0.5% upregulated multiple genes. In young rats, 0.1% fenofibrate increased some antioxidant genes' expression and decreased the immunoreactivity of oxidative stress marker 4-HNE. However, the activation of cellular antioxidant defenses was impaired in old rats. Fenofibrate modulated the expression of factors involved in hypoxia and osmotic stress signaling similarly in both age groups. Inflammatory response genes were variably modulated in the young rats, whereas old animals presented elevated expression of proinflammatory genes and TNFα immunoreactivity after 0.5% fenofibrate. In old rats, 0.1% fenofibrate more prominently than in young animals induced phospho-AMPK and PGC1α levels, and upregulated fatty acid oxidation genes. Our results show divergent effects of fenofibrate in young and old rat kidneys. The activation of multiple stress-associated effectors by high-dose fenofibrate in the aged kidney warrants caution when applying fenofibrate therapy to the elderly.

Age-related differences in macromolecular resonances observed in ultra-short-TE STEAM MR spectra at 7T.

To understand how macromolecular content varies in the human brain with age in a large cohort of healthy subjects. In-vivo 1H-MR spectra were acquired using ultra-short TE STEAM at 7T in the posterior cingulate cortex. Macromolecular content was studied in 147 datasets from a cohort ranging in age from 19 to 89 y. Three fitting approaches were used to evaluate the macromolecular content: (1) a macromolecular resonances model developed for this study; (2) LCModel-simulated macromolecules; and (3) a combination of measured and LCModel-simulated macromolecules. The effect of age on the macromolecular content was investigated by considering age both as a continuous variable (i.e., linear regressions) and as a categorical variable (i.e., multiple comparisons among sub-groups obtained by stratifying data according to age by decade). While weak age-related effects were observed for macromolecular peaks at ˜0.9 (MM09), ˜1.2 (MM12), and ˜1.4 (MM14) ppm, moderate to strong effects were observed for peaks at ˜1.7 (MM17), and ˜2.0 (MM20) ppm. Significantly higher MM17 and MM20 content started from 30 to 40 y of age, while for MM09, MM12, and MM14, significantly higher content started from 60 to 70 y of age. Our findings provide insights into age-related differences in macromolecular contents and strengthen the necessity of using age-matched measured macromolecules during quantification.

See no evil: Attentional bias toward threat is diminished in aged monkeys.

Prior evidence demonstrates that relative to younger adults, older human adults exhibit attentional biases toward positive and/or away from negative socioaffective stimuli (i.e., the age-related positivity effect). Whether or not the effect is phylogenetically conserved is currently unknown and its biopsychosocial origins are debated. To address this gap, we evaluated how visual processing of socioaffective stimuli differs in aged, compared to middle-aged, rhesus monkeys (Macaca mulatta) using eye tracking in two experimental designs that are directly comparable to those historically used for evaluating attentional biases in humans. Results of our study demonstrate that while younger rhesus possesses robust attentional biases toward threatening pictures of conspecifics' faces, aged animals evidence no such bias. Critically, these biases emerged only when threatening faces were paired with neutral and not ostensibly "positive" faces, suggesting social context modifies the effect. Results of our study suggest that the evolutionarily shared mechanisms drive age-related decline in visual biases toward negative stimuli in aging across primate species. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using resonant ultrasound spectroscopy to characterize thermally conditioned high explosive materials

The ability to nondestructively quantify changes in mechanical properties of granular high explosive materials due to thermal conditioning is of importance for a myriad of civil and defense applications and could lead to better understanding of environmental aging-related effects for explosive material performance and safety. In this study, we report the first demonstration of using resonant ultrasound spectroscopy (RUS) to quantify the bulk elastic properties of granular high explosive materials at different bulk pressing densities and degree of thermal conditioning. Monitoring elastic property changes in granular explosive pressings has not yet been demonstrated using RUS, which is an appealing nondestructive characterization tool since it requires only dry point contact with the explosive material and can be applied to explosives with small form factors. Here, explosive material was studied in the form of binderized plastic bonded explosive pressings and unbinderized neat pressings, both of which are used commercially. Elastic stiffness coefficients calculated from the RUS measurements on the binderized and neat pressings show a significant increase for the post-conditioned samples compared to the pre-conditioned samples. This trend of increasing elastic properties with thermal conditioning was consistent for different density pressings and different thermal exposure conditions. [This work was performed by LLNL under Contract No. DE-AC52-07NA27344 and document release number LLNL-ABS-858868.]

The usability and reliability of a smartphone application for monitoring future dementia risk in ageing UK adults.

The rising number of dementia diagnoses and imminent adoption of disease-modifying treatments necessitate innovative approaches to identify individuals at risk, monitor disease course and intervene non-pharmacologically earlier in the disease course. Digital assessments of dementia risk and cognitive function have the potential to outperform traditional in-person assessments in terms of their affordability, accuracy and longitudinal tracking abilities. However, their accessibility and reliability in older adults is unclear. To evaluate the usability and reliability of a smartphone assessment of lifestyle and cognitive factors relevant to dementia risk in a group of UK-based older adults. Cognitively healthy adults (n = 756) recruited through the Dementias Platform UK Great Minds volunteer register completed three assessments of cognitive function and dementia risk over a 3-month period and provided usability feedback on the Five Lives smartphone application (app). We evaluated cognitive test scores for age, gender and higher education effects, normality distributions, test-retest reliability and their relationship with participants' lifestyle dementia risk factors. Participants found the app 'easy to use', 'quick to complete' and 'enjoyable'. The cognitive tests showed normal or near-to-normal distributions, variable test-retest reliabilities and age-related effects. Only tests of verbal ability showed gender and education effects. The cognitive tests did not correlate with lifestyle dementia risk scores. The Five Lives assessment demonstrates high usability and reliability among older adults. These findings highlight the potential of digital assessments in dementia research and clinical practice, enabling improved accessibility and better monitoring of cognitive health on a larger scale than traditional in-person assessments.

Abstract B027: Exploring how aging-associated changes in autophagy dictate the development of leukemic disease

Abstract Old age leads to cellular maintenance decline, disrupting homeostasis and increasing disease risks, including cancer. Aging-related autophagy impairments contribute to harmful protein accumulation, reduced hematopoietic cell self-renewal, and impaired mitochondrial function. Autophagy plays a central role in maintaining cellular homeostasis and key cellular functions, such as cell death, cell cycle control, and differentiation. This research aims to investigate how aging-related microenvironmental changes influence Tet2 clonal hematopoiesis (CH) development, with a focus on understanding the roles of aging-associated autophagy changes. We hypothesize that the decline in cellular and tissue maintenance during aging, characterized by reduced autophagy function, contributes to changes in the bone marrow microenvironment. These changes, in turn, create a milieu conducive to the selection of oncogenic mutations. To test this hypothesis, we aimed to boost autophagy in older mice to investigate if it can mitigate oncogenesis, given that CH and cancers are less common in young individuals but prevalent in the elderly. 15-month-old mice were treated with a spermidine supplemented diet for 3 months, then LSK were transplanted with fluorescently tagged, CRISPR induced Tet2 mutations such that a small percent of HSPC bear mutations. We then monitored the competitive expansion of cells with Tet2. We found that old mice supplemented with spermidine show decreased Tet2 selection within the HSPC compartment similar to young (2mo) mice and compared to old mice on a control diet. We plan to test Tet2 competitive expansion in aged transgenic mice with high autophagy as well as the opposite experiment using transgenic young mice with decreased autophagy to further support our hypothesis. Our research emphasizes the role of autophagy in shaping the bone marrow microenvironment and influencing the development of CH. By examining how aging-associated changes in autophagy impact the selection of oncogenic mutations, our work contributes to a deeper understanding of the complex interplay between aging and cancer development. Our research has the potential to impact cancer treatment and the understanding of cancer evolution by shedding light on the mechanisms that drive oncogenic adaptation in the context of aging. Specifically, our findings suggest that enhancing autophagy in older individuals may mitigate the selection of oncogenic mutations, potentially reducing cancer risk. This insight could inform future therapeutic strategies for cancer prevention and treatment, especially in the elderly population. In summary, our research unveils the role of autophagy in modulating the aging bone marrow microenvironment's impact on CH development. By boosting autophagy in aged mice and observing reduced Tet2 selection, we provide evidence that autophagy plays a crucial role in shaping the oncogenic landscape. This underscores the potential of autophagy-enhancing interventions in countering age-related oncogenic effects. Citation Format: Amy N. Briggs. Exploring how aging-associated changes in autophagy dictate the development of leukemic disease [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B027.