bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXPLORING THE IMPACT OF INTERMITTENT HYPOXIA THROUGH A COMPREHENSIVE MULTI-OMICS APPROACH IN AGED MOUSE MODELS
Authors: Donega Stefano , McDevitt Ross , Hernandez Rolando , Chisolm Cindy , FIshbein Kenneth , McCart Elizabeth , Wilgenburg Brian , Ferrucci Luigi 
Published: January 2025

Abstract
Comprehending aging’s molecular mechanisms, like RNA splicing and AMPK signaling, is vital for tackling age-related issues and boosting resilience. Oxygen fluctuations from obstructive sleep apnea (OSA) cause Intermittent Hypoxia (IH), affecting respiratory functions and health, prompting adaptive responses to counter reduced energy production. Mice as models allow simulating disorders and studying muscle cell protection under low oxygen levels. Over the past two years, we have collected more than 1500 samples from 15 different tissues of adult (9-11 months) and old (20-23 months) mice exposed to IH at 21% to 5% oxygen concentration in 2:30 minutes cycles, for 8 hours a day over 4-8 weeks, aiming to construct a comprehensive murine IH atlas by employing cutting-edge technologies across diverse tissues. Analyses include conducting detailed transcriptomic analyses of muscle tissues using hybrid RNA-seq to identify changes in splicing isoforms during IH experiments, exploring transitions between fast-to-slow fiber types, studying mitochondrial morphology using C57/BL6 and mtKeima mouse strains (both wild-type and Alzheimer’s disease models), investigating brain spatial transcriptomics to understand the neurological effects of IH, analyzing cardiorespiratory disruptions by examining the epigenetic clock of the heart and spleen, and delving into the role of liver extracellular vesicles (EVs), particularly exosomes, in our sensitive mouse IH model. The overarching goal of this project is to integrate omics data comprehensively to elucidate the impact of alternate hypoxia on health and aging and develop innovative therapeutic strategies that minimize damage in patients affected by this highly prevalent conditions in older persons.
MAPPING LONGEVITY PATHWAYS THROUGH MITOCHONDRIAL DYSFUNCTION: ROLES OF THE MICROBIOME AND METABOLISM IN AGING
Authors: Bitto Alessandro 
Published: January 2025

Abstract
Biological aging is characterized by a progressive deterioration of fundamental biological functions in living organisms, often codified as hallmarks or pillars. Longevity interventions impact these hallmarks, slowing down or even reversing their deterioration. Thus, we hypothesize that longevity interventions may be applied to chronic diseases characterized by failure of one or more of these fundamental biological processes, regardless of biological age. Herein, we describe how geroscience can be leveraged to gather new insight into etiology, progression, management, and treatment of chronic mitochondrial disease. With the aid of a mitochondrial dysfunction model, we investigate the effects on intermediate metabolism and the intestinal flora of two longevity interventions, the antidiabetic drug acarbose and the mTOR inhibitor rapamycin. Furthermore, we propose that models of chronic disease can be leveraged to study the mechanisms of action of known longevity pathways and develop new interventions. We describe the critical role of fatty acid metabolism in the treatment of mitochondrial disease and hypothesize that similar mechanisms may contribute to the longevity effects of mTOR inhibition in aging models.
MICROBIOME ROLE IN COGNITIVE IMPAIRMENT: MIAGB COHORT INSIGHTS
Authors: Mishra Sidharth , Buddendorff Lauren , Hoover Julia , Shukla Rohit , Kumar Vivek , Jain Shalini , Yadav Hariom 
Published: January 2025

Abstract
Aging population is increasing, leading to a rise in aging-related conditions, specifically diseases like Alzheimer’s disease and its related dementia (ADRD), which have poor prognosis and lack prevention and treatment strategies. Although we do not fully understand the complex pathology of ADRD, emerging evidence indicates that abnormalities in the gut microbiome contribute to ADRD pathology, but how this occurs remains largely unknown. Utilizing samples and datasets from a multi-site and comprehensive clinical study called the Microbiome in aging Gut and Brain (MiaGB) consortium, of comprising 30 older adults with mild cognitive impairment (MCI) and 43 age- and sex-matched cognitively healthy controls, we found that older adults with MCI have higher levels of circulating gut permeability markers (lipopolysaccharide [LPS] binding protein [LBP] and sCD14) and systemic inflammation markers (IL-6, CRP, and IL-1β). Increased gut permeability (leaky gut) is an understudied source of systemic inflammation as it allows pro-inflammatory ingredients including LPS and microbes from the gut lumen to enter the bloodstream, instigating systemic inflammation. Interestingly, increased LPS and TLR4 activation were found in the circulation of MCI participants compared to controls. Furthermore, we discovered that gut microbial metabolite- ethanolamine utilization pathways were decreased in MCI compared to controls. These abnormalities are significantly associated with reduced cognitive function (MoCA scores) in older adults. These findings provide mechanistic insight into how abnormalities in the gut microbiota, with reduced ethanolamine utilization, result in ethanolamine accumulation in the gut, inducing leaky gut, which in turn activates systemic inflammation, ultimately accelerating cognitive decline in older adults.
MULTIMODEL APPROACHES IDENTIFY CONSERVED ROLE OF TRP CATABOLIC PATHWAY IN THE REGULATION OF LIFE- AND HEALTHSPAN
Authors: Oz Naci , Kaya Alaattin 
Published: January 2025

Abstract
The activity of the conserved Kynurenine (KYN) pathway, a major catabolic pathway of Tryptophan (trp), is controlled mainly by the indoleamine 2,3-dioxygenases IDO1, and IDO2, which catalyze the first rate-limiting step of trp catabolism by converting trp into kynurenic acid. The KYN pathway is the sole de novo NAD+ biosynthetic pathway, generating NAD+ from ingested trp. In addition, increased Ido1/2 activity, and intermediate metabolites such as quinolinic acid, as a result of normal aging, are mechanistically linked to inflammaging and neurodegenerative disorders such as Alzheimer’s diseases. Therefore, circulating kynurenines were suggested as a potential biomarker of frailty in humans. In contrast, decreased trp degradation has been beneficially implicated as a potent regulator of age-related diseases and lifespan. Although the KYN pathway is a viable therapeutic target against aging and age-related diseases, there have been no comprehensive studies in mice to understand the role of the KYN pathway in regulating life- and healthspan. To understand the conserved effect of the KYN pathway in modulating life- and healthspan, we developed individual and combined whole-body knockout transgenic mouse strains lacking genes IDO1, IDO2 or IDO1/IDO2. Using multi-omics approaches, we comprehensively characterized the tissue and sex-specific biological age and molecular and metabolic alterations mediated by KYN pathway deficiency. Along with the healthspan measurements, we showed a potentially conserved role that decreased trp catabolism might be a conserved modulator of life- and healthspan.
MUSCLE PRESERVATION AND PHYSICAL ACTIVITY: HYBRID TRANSCRIPTOMIC ANALYSIS IN A MONKEY MODEL
Authors: Donega Stefano , Banskota Nirad , De Supriyo , Ferrucci Luigi 
Published: January 2025

Abstract
Muscle strength declines with age, leading to decreased mobility. Old sedentary people have been reported with imbalance in energetic metabolism, a pro-inflammatory profile, and proteolysis. Engaging in exercise, beyond just strength training, has been shown to mitigate this decline, although the underlying biological mechanisms remain unclear. Rhesus monkeys, trained to run on treadmills, present a valuable model for investigating the mechanisms involved in the preservation of muscle function induced by physical activity. We trained 27 males and females monkeys aged 9-15 years for 2 month to run on a ramp up to 1h for 3-5 days/week for 3 months. Continuous monitoring of heart rate, temperature, and physical activity levels was conducted using implantable data loggers, along with daily tracking of body weight and food intake. Vastus lateralis muscle punches were collected at baseline, after 3-months treadmill and ensuing 3-week sedentary state to perform deep hybrid RNA-seq combining deep short-reads (800M, Illumina) and long-reads (PacBio). Treadmill intervention revealed an enrichment in MAPK activity, keratinocyte proliferation, extracellular transport and microtubule formation alongside reductions in ribosomal compartments, ncRNA processing and lysosome. Upon transitioning to a sedentary state, the same subjects increased in extracellular matrix, immune cells migration and chemotaxis (leukocytes, granulocytes, neutrophils and monocytes) and reduced mitochondrial component and function, spliceosome, U2 complex, and ribosome. On-going analyses are focusing on differential splicing and proteomics interaction. These preliminary data suggest at RNA level, exercise enriches muscle function and metabolism while sedentary leads to decreased mitochondrial function and immune cell dynamics in monkeys.
NICOTINAMIDE RIBOSIDE SUPPLEMENTATION PROTECTS AGAINST VIRAL-INDUCED NEURODEGENERATION IN AGED MICE
Authors: Enterria-Morales Daniel , Gonzalez Anais Claire , Jallorina Bianca , Martinez Adrian , Doan Andrew , Karve Aadit , Joya Mikaela , Shtrahman Matthew 
Published: January 2025

Abstract
Several lines of research support the hypothesis that boosting cellular nicotinamide adenine dinucleotide (NAD+) may induce metabolic adaptation that helps neurons maintain healthy function as they age and slow neurodegeneration, making this approach a promising therapy for neuroregeneration. To prove this strategy, we tested the ability of Nicotinamide Riboside (NR), a pyridine-nucleoside precursor to NAD+, to prevent neuronal cell loss in a model of viral induced neurodegeneration using recombinant adeno-associated virus (rAAV). C57BL/6J wild-type mice (18 months old) were obtained from the National Institute of Aging (NIA). NR was administered into the animals’ drinking water (12mM) for three consecutive weeks before the injection of a recombinant rAAV expressing the LacZ gene under the control of the CMV promoter (rAAV-CMV-LacZ) at a dose of 1x1013 gc/mL into the unilateral hippocampus. For the control groups, the mice were injected either with a saline solution or with the rAAV-CMV-LacZ, but no NR supplementation was provided. For the experimental group, NR treatment was maintained for 12 weeks until the date of sacrifice. We found that NR supplementation partially rescued the rAAV-induced neurodegeneration in the CA3 of the hippocampus. NR supplementation reduced the activation of microglia and astrocytes in the CA3, partially rescuing the inflammatory response to the rAAV infection. Our findings support the idea of boosting NAD+ levels as a neuroprotective approach to metabolically help neurons of the hippocampus to respond to chronic damage in the form of aging. Further mechanistic studies are required to better understand the cellular pathways that underlie these findings.
PATIENT PRIORITIES CARE (PPC) IN HISPANIC PATIENTS WITH DEMENTIA
Authors: Mera Alejandra , Peel Emily , Naik Aanand , Samper-Ternent Rafael 
Published: January 2025

Abstract
Hispanics are the fastest growing underrepresented population in the U.S and have a higher risk of dementia compared to non-Hispanic whites. Lack of trust, limited health care access, and lack of culturally adapted interventions contribute to health disparities in this population group. Patient Priorities Care (PPC) is an evidenced-based approach that improves health outcomes in patients with multimorbidity. PPC guides patients, caregivers, and their providers to set realistic health care goals based on the patient’s values. Little is known about the benefits of PPC for Hispanics with multimorbidity and dementia. We designed and implemented a pilot feasibility study to adapt the PPC approach for Hispanics with multimorbidity and dementia (PPC-HD study). The PPC approach consists of a Priorities Setting Session with the patient, and caregiver, followed by a Care Alignment session with the patient’s clinician. In our sample of 20 Hispanics with dementia and multimorbidity, 85% of the participant care plans include patients’ preferences indicating the willingness of clinicians to use the PPC approach. Eighty-three percent of participants find PPC a rewarding experience with 67% reporting satisfaction in the availability of Spanish-speaking research staff, 61% reporting satisfaction in discussing healthcare preferences, and 56% reporting satisfaction with knowing patients’ preferences for future healthcare decisions. PPC is a feasible approach in this population group. Most clinicians used the patients’ preferences and included them in their care plans. Access to bilingual staff and delivery of the intervention in Spanish was highly valued by participants and caregivers. Participation in PPC was deemed very valuable.
SOCIAL WORKERS’ ROLE IN CULTIVATING ILLNESS UNDERSTANDING AND PROGNOSTIC AWARENESS: PERSPECTIVES FROM THE FIELD
Authors: ODonnell Arden , Gonyea Judith 
Published: January 2025

Abstract
For patients experiencing serious or life-limiting illnesses, informed decision-making depends on understanding prognosis and illness trajectory. Although physicians are viewed as the most appropriate group to share medical information, there is growing recognition that: a) cultivation of prognostic awareness occurs over time through a series of conversations in which patients continue to redefine medical treatments and broader life goals and b) other clinicians can contribute to these discussions. Using role theory, this qualitative study’s explores how the growing shift to a team approach is experienced by hospital-based physicians (MDs) and palliative social workers (PSWs),. Through semi-structured Zoom interviews with 17 matched MDs and PSWs across the U.S., we explored the degree of alignment or convergence of MDs’ and PSWs’ views on PSWs’ professional roles in prognostic conversations, including perceptions of role definitions, role sharing, role boundaries, and role conflicts. Interpretive description methodology, coupled with thematic analysis, revealed key insights into PSWs’ comfort levels in assuming roles and interventions in this prognostic awareness cultivation as well interprofessional convergence affirming PSWs’ role in a) assessing patients’ readiness for prognostic discussions, b) identifying gaps in patient understanding c) translating medical conditions into lived reality, and d) supporting emotional processing of patients and their families. Concerns about potential role conflicts emerged when PSWs were expected to either engage in or overstep into medically complex discussions. This study underscores the important role of social workers role in enhancing prognostic understanding and emphasizes the significance of role clarity, trust, and communication for effective interpersonal teams.
UNHOUSED OLDER ADULTS’ PREFERENCES FOR PROGNOSTIC COMMUNICATION AND ILLNESS-RELATED CARE
Authors: Latimer Abigail , Light Michael , Sasdi Olivia , Hossain Mohammad , Moser Debra , Pope Natalie 
Published: January 2025

Abstract
The number of older adults experiencing homelessness (OAEH) is growing. This vulnerable population is exposed to harsh conditions and fragmented healthcare, making even the most treatable health conditions life-threatening. Understanding seriously ill OAEH preferences for prognostic communication and illness-related care are needed research areas. This qualitative study was part of a larger project adapting Ariadne Labs’s Serious Illness Conversation Guide (SICG) for use with OAEH. We interviewed 11 unhoused older adults (≥ 50 years) with a serious illness - mostly men (n = 9) between age 53 and 72 (M = 61). Interview questions were developed corresponding to the model of prognostic communication (i.e., the SICG) with a particular interest in understanding older adults’ 1) communication preferences regarding their illness and prognosis and, 2) goals and values related to their illness and prognosis. We utilized reflexive thematic analysis which included coding and creating transcript summaries and data matrices to help the research team familiarize, condense, and observe patterns within the data. Findings reflect how 1) clinicians should deliver prognosis, 2) OAEH receive prognosis, and 3) OAEH treatment goals and values. Trust and authenticity emerged as essential components of prognostic delivery, both in what and how information is shared. Participants described past communication with healthcare professionals and the impact of these conversations. Illness-related priorities for OAEH included making practical plans for dying and death, leaving a legacy for their children, and maintaining independence. Study findings can inform clinical practice and intervention research to improve how this population receives serious illness communication.
CHRONIC PAIN, PAIN INTERFERENCES, AND COGNITION AMONG MIDDLE- AND OLD-AGED AMERICANS: A FIXED-EFFECTS ANALYSIS
Authors: Yu Chang , Barr Ashley , Yang Yulin , Grol-Prokopczyk Hanna 
Published: January 2025

Abstract

Objectives
The current study examines the relationship between chronic pain, chronic pain interference, and cognitive function in middle-aged and older Americans, focusing on how these associations may vary by educational background. Method: Data were obtained from the 2004-2006 and 2013-2017 waves of the Midlife in the United States Study (MIDUS 2 and MIDUS 3, N=6266 observations nested with 3965 individuals). We employed fixed-effects linear models to examine within-individual changes, specifically, the relationship between changes in chronic pain, pain interferences (with activity, mood, relations, sleep, and enjoyment) and their impact on cognitive function (specifically episodic memory and executive function). In addition, group differences in these fixed effects by education were examined via interaction terms.

Results
The results indicated that changes in pain negatively correlated with episodic memory, but this association was observed only for individuals without any college. Additionally, changes in pain interferences showed a negative correlation with both episodic memory and executive functioning across all levels of educational attainment.

Discussion
Findings highlight the importance of not only considering the role of persistent pain but also the effects of pain interferences on cognitive decline among aging population.
FUNCTIONAL LIMITATIONS, DEPRESSIVE SYMPTOMS, AND COGNITION ACROSS MID- AND LATE-LIFE: EVIDENCE FROM CHINA
Authors: Yu Chang , Barr Ashley , Grol-Prokopczyk Hanna 
Published: January 2025

Abstract

Objectives
This study examines the time-varying effects of functional limitations (IADLs and ADLs) and depressive symptoms on various cognitive functions, including mental status and memory among middle-aged and older Chinese individuals. It also assesses whether functional limitations and depression during middle age contribute to worse cognitive function in the later years independent of yearly shifts in depression and functional limitations. Method: Using longitudinal data from the China Health and Retirement Longitudinal Study (2011-2018), we conducted mixed-effects linear models to determine the intra- and inter- individual variation on the relationship between functional limitations, depression, and cognitive functioning (N = 22,039 observations nested within 10,054 individuals).

Results
Within-individual change in functional limitations and depression negatively predict cognitive functioning, with more functional limitations and depressive symptoms predicting a lower score in cognition, memory, and mental health, independent of age. Further, disabilities and depression in mid-life continue to predict worse cognitive functioning across the course of the study independent of any later changes in functional limitations and depressive symptoms and childhood conditions.

Discussion
From a life course perspective, adverse functionalities and mental health in midlife predicts worse cognitive function in later life independent of early life experiences.
MEMORY IN LATER LIFE: HOW NONAGENARIANS AVOID FORGETTING WHAT THEY WANT TO REMEMBER
Authors: Cherry Katie , Willis Matthew , Faucheux Gavin , Bernard Dominique , Barnes Mary , Reese-Melancon Celinda , Kim Sangkyu , Jazwinski S Michal 
Published: January 2025

Abstract
Subjective perceptions of memory play an important role in cognitive adaptability in later life. While self-reported memory is typically assessed using objective surveys, few studies have examined what older people have to say about their own experiences using memory in everyday life. The purpose of this study was to examine older adults’ memory management strategies and techniques that they use in everyday life to improve recall of information they do not want to forget. Participants consisted of 50 nonagenarians (90+ years of age) and two younger reference groups (60-74 and 75-89 years) who were enrolled in the Louisiana Healthy Aging Study (LHAS). All answered two open-ended questions regarding their preferred memory management strategies used in everyday life. Narrative responses were recorded, transcribed verbatim, and content analyzed for recurring concepts. Results yielded new evidence of environmental strategies, including object placement and non-electronic external memory aids (e.g., planners, calendars), and internal mnemonic techniques (e.g., rehearsal, association). When comparing internal mnemonic techniques specifically, nonagenarians were more likely to use association, whereas their younger counterparts were more likely to use imagery. These findings suggest that memory management techniques change very little in late adulthood. This research was supported grants from by the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001-06)-02] and the National Institute on Aging (P01 AG022064).
NEIGHBORHOOD SOCIAL CAPITAL IS ASSOCIATED WITH VARIABILITY IN AMBULATORY COGNITIVE PERFORMANCE
Authors: Hyun Jinshil , Cerino Eric , Katz Mindy , Lipton Richard , Sliwinski Martin 
Published: January 2025

Abstract
Prior studies suggested that within-person variability in cognitive task performance may be an early indicator of normative and pathologic cognitive aging. However, the influence of upstream social determinants of health (e.g. neighborhood) on cognitive variability is not well characterized. The aim of this study is to examine whether neighborhood social capital is associated with within-person variability in various cognitive domains and whether these associations are mediated by individual-level behavioral factors (i.e., physical activity, social interaction). The analysis sample included 316 individuals in Bronx, NY, enrolled in the Einstein Aging Study (mean age=77). Participants performed brief tests of processing speed, memory binding, and working memory on a smartphone up to six times daily over a two-week period. Neighborhood social capital was operationalized as a composite variable comprising economic connectedness, clustering, and volunteering rates, linked to participants’ address through zip code tabulation area. Results from heterogeneous variance multilevel models suggested that living in areas with lower levels of social capital was significantly associated with greater variability in processing speed and memory binding (ps&lt;.001). Controlling for individual-level physical activity reduced the magnitude of the effects of neighborhood social capital, suggesting potential (and partial) mediating role of physical activity. In conclusion, living in areas with better community social capital may reduce the risks of cognitive impairment. It would be crucial to support upstream neighborhood-level interventions to prevent cognitive impairment among older adults. Future research should examine more precise behavioral mechanisms linked to neighborhood environments to better suggest effective intervention strategies to promote cognitive health.