bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXERCISE AND IMMUNE FUNCTION FROM GESTALT COHORT: THE BENEFICIAL EMERGING ROLE OF INTEGRATED STRESS RESPONSE
Authors: Donega Stefano , Banskota Nirad , Singh Amit , Kaileh Mary , Bektas Arsun , De Supriyo , Sen Ranjan , Ferrucci Luigi 
Published: January 2025

Abstract
Exercise significantly impacts immune function by influencing physiological health, which in turn reduces disease susceptibility, combats immune-senescence, and lowers infection risks. Despite these effects, there are still important unanswered questions regarding the impact of exercise on the transcriptome of immune cells, age-related responses, inflammation modulation, and anti-aging benefits. In the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) study involving 99 participants aged 22-92, RNA-sequencing was conducted in parallel on 11 immune cell types - B cells, T/CD4+, T/CD8+ (naïve and effector/central memory) cells, monocytes, granulocytes, and natural killer cells - to investigate their correlation with exercise (VO2 peak) using Differential Gene Expression (DGE) and Gene Set Enrichment Analysis (GSEA). Lymphoid B, T and NK cells, exhibited distinct clustering from myeloid cells in both young and old participants (&lt; 44 and &gt;66 years old), with 26 shared genes identified across multiple immune-cell types, reflecting enrichment for 14 energy-mitochondrial pathways associated with increased exercise. Interestingly, while mRNA splicing pathways were upregulated in the young group, older individuals displayed upregulated pathways linked to the Integrated Stress Response (ISR), a signaling pathway previously found to be activated by ER stress, hypoxia, amino acid deprivation, glucose deprivation, and viral infection etc. By utilizing a scoring system for inflammation, senescence, and mitochondria (QuickGO-EBI, SenMayo, and MitoCarta 3.0), we identified clusters of shared genes affected by physical activity. Overall, the findings suggest that stress-induced molecular responses to enhanced aerobic capacity and exercise offer potential benefits for improving the health and well-being of older individuals.
THE SIGNALING PATHWAY OF SRF-SIRTUIN-2 GENE AND MITOCHONDRIAL FUNCTION
Authors: Zhang Xiaomin , Azhar Gohar , Ameer Fathima , Wei Jeanne Y 
Published: January 2025

Abstract

Background
The sirtuin-2 (SIRT2) is one of the seven sirtuin proteins that deacetylate histones and other non-histone proteins. SIRT2 is localized mainly in the cytoplasm, but it may shuttle into the nucleus. SIRT2 regulates cellular metabolism, growth, stress response and aging. However, the transcription factors that regulate the SIRT2 gene have not been fully elucidated. Here we report the identification of two novel binding sites for the serum response factor (SRF) in the SIRT2 promoter, and the effect of SIRT2 gene expression on mitochondrial function.

Methods
The transcription factor binding sites in the SIRT2 promoter were analyzed with bioinformatic tools, including TRANSFAC, TFBIND and were verified with sequence analysis. SH-SY5Y cells were cultured in either regular serum or low serum medium to simulate an ischemia condition, respectively. The mitochondrial function was measured with a Seahorse XFe96 Analyzer.

Results
and conclusions We have identified two novel SRF binding sites in the human SIRT2 gene promoter, indicating that SRF binds to the SIRT2 promoter, and may recruit SRF cofactors to regulate the SIRT2 gene. SIRT2 plasmid transfection affects mitochondrial function. In the simulated ischemia condition, SIRT2 expression increased the mitochondrial oxygen consumption rate (OCR), while reducing the glycolysis rate (ECAR), suggesting that SIRT2 improves oxidative phosphorylation and protects cells from ischemia. In addition, the biological activators and inhibitors of the Rho/SRF signaling pathway could be used to modulate SIRT2 expression, thereby regulating mitochondrial function in aging and senescence.
XANTHURENIC ACID (XA) TREATMENT IMPROVES OVERALL HEALTH IN AGED MICE
Authors: Vyavahare Sagar , Kumar Sandeep , Gupta Sonu Kumar , Ding Kehong , Isales Carlos , Fulzele Sadanand 
Published: January 2025

Abstract
Our published studies demonstrated disturbance in the Tryptophan-kynurenine pathway with age, notably marked by increased kynurenine levels. This study aimed to examine the levels of serum xanthurenic acid (XA) in aged mice and investigate the potential impacts of XA treatment on their overall health, specifically musculoskeletal health. Our findings revealed that XA serum levels decrease with age. The XA treatment decreased pro-inflammatory cytokines (TNF-α, IL-1, IFN-γ, IL-6) in serum. Moreover, XA treated aged mice showed improved various health parameters compared to controls. They displayed improved grip strength, locomotor activity, and increased endurance. Musculoskeletal analyses unveiled improved bone microarchitecture and increased muscle fiber size in XA-treated mice group. Molecular studies elucidated that XA treatment prevented oxidative stress (SOD2), reduced senescence markers (p16, p21), and mitigated inflammation (IL1-β) in the muscles of aged mice. Interestingly, XA treatment also correlated with decreased apoptosis (Caspase-3, Caspase-7) in muscle tissues, indicative of improved cellular survival. The molecular analysis showed a fostering environment for myogenesis (increased MyoD and Myogenin expressions) in XA-treated mice muscles. These comprehensive results suggest a promising therapeutic role for XA, emphasizing its potential as a critical metabolite in age-related pathogenesis.
ADVANCE CARE PLANNING AND END-OF-LIFE EXPERIENCES OF HIGH HEALTH CARE UTILIZERS IN THE LAST YEAR OF LIFE
Authors: Marin Omar , Bandi Sriya , Duty Charlotte , Tate Alex 
Published: January 2025

Abstract
As the U.S. population continues to get older, Americans are projected to consume more healthcare than ever before. Advance care planning (ACP), which documents future goals of care in the context of limited decision-making capacity, is essential to delivering patient-centered care aligned with wishes and values and correlates with less utilization at the end-of-life (EOL). ACP is critical for high healthcare utilizers, who have multiple comorbid conditions and often unmet social needs. This pilot study used proxy postmortem interviews (n=20) to identify and explicate the most common factors shaping the EOL care experiences of high healthcare utilizers dwelling in vulnerable Chicago neighborhoods, and ACP’s role in these experiences. Modified open coding of data revealed five central themes in shaping decedents’ EOL experiences and ACP: (1) decedent support from immediate network ties, (2) patient acceptance of declining health, (3) proxy confidence in EOL decision making, (4) individual values motivating pursuing certain types of care, and (5) an orientation towards the treatment imperative, defined by Shim et al. (2008) as an inexorable momentum towards treatment at any cost. Within the last 12 months of life, even if patients had a formal or informal ACP in place, proxies reported a default to more medical intervention by patients. Just five proxies reported care transitions to palliative/hospice care. This pilot study presents a novel approach to better understanding EOL care and experiences of vulnerable high healthcare utilizers and underscores a need for further investigation into the relationship between ACP and EOL experiences among this group.
VIRTUAL REALITY FOR TREATMENT OF DEPRESSION IN AN OLDER ADULT WITH PARKINSON’S DISEASE
Authors: Lohmar Sabine , Fiske Amy 
Published: January 2025

Abstract
Research on the effectiveness of virtual reality, an interactive computer-generated environment, as a form of behavioral activation for older adults with depression, has been minimal but promising (Yen & Chui, 2021). A case study of an older male nursing home resident with Parkinson’s Disease who uses a wheelchair is presented to provide clinical evidence for the value of using virtual reality in treating depression in older adults with physical limitations. Virtual reality sessions consisting of immersive and interactive outdoor experiences (e.g., fishing, hunting, hiking, kayaking) were conducted for an average of 20 minutes once every two weeks for six months. The Geriatric Depression Scale Shortened Form (GDS-S) was administered before, during, and after the use of virtual reality to assess depressive symptoms. The patient’s depressive symptoms improved from intake (GDS-S = 11) to termination (GDS-S = 4). Moreover, subjective reports from the patient indicated an overall elevation in mood, perceived enjoyment, increased motivation, and reduced pain. This case study demonstrates the potential benefits of virtual reality for physically limited older adults with depression who may face barriers, for example, due to a movement disorder, to engaging in previously enjoyed activities.
BUSYNESS MAY NOT MATTER: ASSOCIATIONS BETWEEN BUSYNESS, ACTIVITY ENGAGEMENT, AND COGNITION
Authors: Bielak Allison 
Published: January 2025

Abstract
Participating in a greater variety and frequency of activities is associated with higher cognitive performance across adulthood. A potentially related metric is perceived busyness (Martin & Park, 2003), defined as scheduled activity patterns. Few studies have investigated this metric, with one finding that those who rated themselves as busier performed higher on a range of cognitive tests (Festini et al., 2016). The present study aimed to answer several questions: 1) Does the link between busyness and cognition replicate?; 2) Does stress interact with busyness in predicting cognition?; 3) How similar is busyness to frequency and variety of activity engagement?; 4) Does busyness predict cognition better than activity variety or frequency? Adults aged 60–92 years (M=70.5, n=206) completed questions related to busyness (in a typical week, how busy is your schedule), stress towards busyness, activity based on past 2-year participation, and cognitive tests. Hierarchical linear regressions controlling for age and education showed busyness was not a significant predictor of processing speed, episodic memory, vocabulary, executive functioning, or reasoning, but did significantly predict working memory (Std B=-.16). Stress about busyness did not interact with busyness for any cognitive domain. Busyness was weakly correlated with activity variety and frequency (rs=.20) and did not significantly predict cognition beyond the activity variables. Although a simple measure of busyness was used, greater busyness was not related to higher cognition. Busyness was only weakly related to the activity indices, and findings suggest that activity variety and frequency might be more valuable measures in evaluating cognition.
DOMAIN-SPECIFIC SUBJECTIVE COMPLAINTS AND OBJECTIVE COGNITIVE SCORES IN OLDER ADULT CANNABIS USE
Authors: Anquillare Elizabeth , Coromac-Medrano Juliamaria , Neiderman Adrianna , Thayer Rachel 
Published: January 2025

Abstract
Research on the cognitive effects of cannabis among older adults remains sparse and equivocal. Subjective cognitive complaints are predictive of future objective cognitive decline; however, few studies have explored this relationship in older adults with cannabis use (OACU) and domain-specific relationships have yet to be investigated. This study aimed to identify relationships between subjective and objective cognition across attention, memory, and executive functioning in a pilot sample of OACU. Participants included OACU between 60 and 79 years (N=17, Mage=68.29, SD=5.61), of which 94% were White and 59% were women. An average 15.94 years of education (SD=2.38) was reported. Participants completed online questionnaires regarding subjective cognition and participated virtually in a brief cognitive assessment battery. Items from the subjective cognition questionnaires were separated by domain and correlations were run between domain-specific subscales and standardized scores on the objective cognitive tests. Worse performance on a switching task was negatively associated with subjective attention (r=-.59, p&lt;.05), memory (r=-.63, p&lt;.05), and executive function (r=-.62, p&lt;.05). Additionally, worse performance on an inhibition task was negatively associated with better subjective attention (r=-.50, p&lt;.05), memory (r=-.51, p&lt;.05), and executive function (r=-.52, p&lt;.05). Similar negative correlations between measures of subjective cognition and objective memory and attention performance demonstrated a medium effect size without achieving statistical significance. Overall, subjective cognition was associated with executive functioning performance more than memory or attention performance. This pattern suggests OACU tend to describe their cognitive function broadly. Providers may wish to ask more nuanced questions to ensure comprehensive understanding of subjective cognitive functioning.
THE EFFECTS OF LISTENING WHILE DRIVING IN OLDER AND YOUNGER ADULTS
Authors: Bak Katherine , Russo Frank , Pichora-Fuller M Kathleen , Campos Jennifer 
Published: January 2025

Abstract
Driving collisions are a top cause of accidental death globally and adults aged 65+ are overrepresented. Driving is a highly complex task, requiring sensory processing, motor control, and divided attention. Driving is especially challenging when simultaneously listening to a passenger. Age-related declines in sensory (e.g., hearing) and cognitive abilities (e.g., working memory) may result in increased effort while listening. High listening effort may reduce spare cognitive capacity, thereby limiting the cognitive resources available to support driving. However, there are very few realistic and controlled experiments examining how the demands of listening while driving are managed in older adults. Therefore, the main objective of this study was to examine performance during a driving-while-listening task in older (aged 61-80 years, 15 female) and younger (aged 20-36 years, 12 female) adults with normal hearing/vision, and cognition, using a high-fidelity driving simulator. Participants completed a driving task at two different driving loads (e.g., straight in rural (low) vs. left turn in city (high)), a listening task (Connected Speech Test [CST]) at two different listening loads (+4 signal-to-noise ratio [SNR], 0 SNR), and both tasks together, to examine dual-task costs. Results demonstrated that only older adults showed significantly lower CST accuracy scores in the dual- compared to single-task conditions across both SNRs. Both older and younger adults showed significantly greater SD of lane position in the dual- compared to the single-task conditions, only under high driving load. Findings may inform educational practices, policies, and technological solutions to maintain and support safe driving among older adults.
VULNERABILITY PROFILES: CHALLENGES FOR METACOGNITIVE INTERVENTIONS WITH OLDER ADULT
Authors: Pearman Ann , Hertzog Christopher , Hughes MacKenzie , Giannotto Emily 
Published: January 2025

Abstract
The metacognitive intervention approach has great promise for improving older adults’ everyday functioning. Results from our studies (Hertzog et al., 2021; Pearman et al., 2020; Pearman et al., 2023) and many others point to potential issues with intervention compliance and realization of intervention benefits in some older adults. Based on the first author’s clinical geropsychology work with older populations and observing our study participants, we argue that there are individual differences in who benefits from interventions and why they do so. This presentation will focus on our everyday memory training approach to evaluate variables that influence training benefit, including rates of attrition/drop-out, compliance with instructed task training, and improvements on outcome variables. Individual difference variables of interest include global cognition as measured by the Telephone Interview for Cognitive Status (TICS) and personality traits as measured by the AB5C with a particular focus on neuroticism and conscientiousness. The TICS was related to objective performance improvement on an associated learning task for both the intervention as well as the control group. Higher TICS scores were related to less improvement from T1 to T2 (r = -.39, p &lt;.05). Personality variables correlated with post-test subjective memory but only in the intervention group, where people high in neuroticism scored lower on memory self-efficacy and higher on memory complaint [r = -.45 & r =.41 (respectively), p &lt;.05]. These findings suggest that specific personal characteristics present barriers to adoption and maintenance of trained metacognitive strategies.
NEIGHBORHOOD STREET CONNECTIVITY, FOOD ACCESS, AND MORTALITY AMONG OLDER ADULTS: EDUCATION AND GENDER DIFFERENCES
Authors: Cheung Pui Yin , Curtis David , Wen Ming 
Published: January 2025

Abstract
Disadvantages in multiple dimensions have garnered increasing attention with strong empirical support. This study examines whether the intersection between education and gender reveals novel neighborhood effects. Two particular areas of neighborhood built and service environments are examined: pedestrian-oriented street connectivity and residing in a low-food-access tract. They are important for health among older adults, given their limited functioning and health challenges. We examined the second and third waves of the MIDUS study, restricted to those aged 65 or above in the second wave. We estimated a series of discrete-time hazard models with 12,141 person-years across 15 years and included individual-level sociodemographic control variables. We also controlled for tract-level characteristics: urban/rural categories, median household income, percentages with college or above education, and racial/ethnic percentages. Interaction between any single dimension of disadvantage and pedestrian-oriented street connectivity didn’t reveal significant differential relationships with mortality. However, better street connectivity was associated with less hazard of mortality among less-educated men once three-way interactions between education, gender, and street connectivity were introduced. In contrast, well-educated older adults residing in a low-food-access tract had a significantly higher hazard of mortality than those not residing in such a tract. The model with three-way interactions revealed more adverse effects of residing in a low-food-access tract among well-educated men only. The findings reveal mortality differences by education and health and their interactions with neighborhood characteristics despite no apparent differences based on a single dimension of disadvantage, supporting the usefulness of the perspective of disadvantages in multiple dimensions.
DOES DEPRESSION EXPLAIN COGNITIVE CHANGES IN PSYCHOTHERAPY? A MEDIATION ANALYSIS
Authors: Post Emily , Walker Teresa , Schurr Matthew , Renn Brenna 
Published: January 2025

Abstract
Depression commonly affects older adults and is associated with detrimental outcomes, including cognitive impairment such as executive dysfunction. Psychotherapy effectively improves depression outcomes and may improve some aspects of cognition, but this relationship is not widely understood. This study examined the potential mediating role that depression severity might have between psychotherapy treatment and a change in cognitive test scores. Data for this secondary analysis were drawn from older adult participants (N=249, mean age = 70.2 [7.4] years) with major depressive disorder who participated in a RCT comparing two 9-week structured psychotherapies for depression. Our prior work found improvement in depression (noninferiority between treatment groups) and some improvement on measures of cognition during the RCT. Measures included pre- and post-treatment cognitive tests: Iowa Gambling Money Task, Digit Span Backwards, and Stroop test. The Hamilton Depression Rating Scale (HAM-D) assessed change in depression symptoms. Hayes PROCESS macro for SPSS analyzed separate mediation models testing depression as a mediator of treatment and each cognitive outcome. Change in depression did not mediate relationships between treatment and change in cognitive outcomes across the nine weeks of psychotherapy. While our investigation did not establish depression as a mediator of change in cognitive test performance in patients receiving psychotherapy, these findings may indicate that improvement in depression is somewhat independent of any observed changes in cognitive test performance. Future research involving a more cognitively impaired sample could strengthen these findings.
EARLY-LIFE INVOLUNTARY JOB LOSS AND LATER-LIFE DEPRESSIVE SYMPTOMS IN CHINA: A TRAJECTORY ANALYSIS
Authors: Song Qian , Dong Wuyi 
Published: January 2025

Abstract
While it is relatively well-understood that involuntary job loss (job loss thereafter) has short-term negative impacts on health of individuals, we do not know much about how early-life job loss is associated with long-term depressive symptoms, especially in the developing country contexts. In this study, we take advantage of a nationally representative sample for those aged 45 and older in the 2011-2018 China Health and Retirement Longitudinal Study as well as the Life History data collected in 2014. We investigate how early life job loss experience, much of which occurred more than two decades ago, is associated with depressive symptoms, as measured by CESD-10 (range: 0-30), in mid- and later-life. Among our sample (N=3,653), 32% of Chinese have experienced job loss at least once in their life-time. After controlling for gender, age, education, marital status, household expenditure, self-rated health and activities of daily living, we found that those who have experienced job loss showed an increased (β=.53, p&lt;.001) number of depressive symptoms at the age of 60, and with one year of increase in age, they experienced an additional.02 (p&lt;.05) growth compared to those who never experienced job loss. The timing of job loss matters. Job loss occurred during mid-career (30-45 years old) was most detrimental to later-life psychological well-being, with.98 (p&lt;.001) more depressive symptoms at age 60 and an additional.06 growth (p&lt;.05) with each year. The results highlight the long arm of early-life employment experience on the depressive symptoms of individuals even decades after.
EXPLORING THE IMPACT OF CHILDHOOD TRAUMA, SOCIAL NETWORK, AND GENDER MODERATION ON DEPRESSION AMONG OLDER ADULTS
Authors: Xu Ying , Fu Xiaoyu , Silverstein Merril 
Published: January 2025

Abstract
China’s aging population faces significant challenges, including a high prevalence of depression among older adults in rural areas (Li et al., 2021). This study investigates the impacts of childhood trauma and social network on depression among older adults and whether their impacts vary by gender in rural China. Using data from the 2021 wave of the Longitudinal Study of Older Adults in Anhui Province, our sample comprises 1558 participants, including 812 males and 746 females. Hierarchical moderated regression models were employed, controlling for age, marital status, living conditions, and education. Results revealed that childhood trauma significantly associated with older adults’ depression level; however, its impact was notably stronger for females than males, as indicated by the significant trauma x gender interaction (β = 0.048, p &lt;.05). Negative main effect of social network on depression was found (β = -0.148, p &lt;.05), suggesting that older adults with larger social network tend to have lower level of depression regardless of their gender. The findings underscore the need for gender-specific approaches to addressing trauma-related depression among older adults. Tailored interventions and supports, particularly for females who have experienced trauma, are warranted. Moreover, programs aimed at enhancing the quality of older adults’ social networks may help reduce depression in both genders.