bluuebunny/crossref_metadata_2025_split huggingface dataset:
IDENTIFYING PHENOTYPES OF OLDER ADULTS PLANNING FOR ALZHEIMER’S DISEASE SUPPORT
Authors: Miller-Winder Amber , Ramirez-Zohfeld Vanessa , Relerford Raven , Schierer Allison , Olvera Charlie , Murawski Alaine , Lindquist Lee 
Published: January 2025

Abstract
Older adults (OAs) with Alzheimer’s Disease (AD) often need additional support (e.g. in-home caregivers) but are unprepared. We modeled the types of plans OAs make surrounding long-term care (LTC)/ home support in the event of AD to describe different planning phenotypes. The Plan Your Lifespan (PYL) study examines OAs’ decision-making process about LTC/home support in the event of AD. Subjects are surveyed every 6 months about cognitive, social, functional, environmental factors; including living/support preferences. We employed mixed analytic methods (qualitative coding and GLMM). 293 subjects enrolled (mean age 73.5 yrs,72.7% female, 40.4% URM). Almost half (47.4%, n=139) experienced cognition decline with 10.3% identifying worsening memory loss. We identified four planning phenotypes: Deniers overlook the possibility of developing AD. Subjects with no measured cognitive impairment were 35% less likely to plan; Do-gooders plan to avoid burdening family and often complete an Advanced Directive (OR 1.75 [p &lt; 0.05, 1.20-2.54]) or Living Will (OR 1.56 [p &lt; 0.05, 1.08-2.25]; Defeaters do not plan due to external limitations; a below average Consumer Health Activation score (OR 0.65 [p &lt; 0.05, 0.43-0.98]) signaled 35% less likely to plan; and Dumpers leave planning to their family; displaying sufficient social support (OR 2.4 [p &lt; 0.05, 1.39-4.15]) and limited health literacy (OR 1.99, [p &lt; 0.05, 1.24-3.2]). Helping OAs consider their support needs through identification of different phenotypes may allow providers to intervene early. Phenotypes depend on health literacy, social support, self-efficacy, and finances. Further research will examine how planning phenotypes change over time and how plans are implemented to best care for OAs with AD.
SUBJECTIVE COGNITIVE DECLINE IN OLDER ADULTS: THE ROLE OF Α-SYNUCLEIN AND AMYLOID PATHOLOGIES
Authors: Thomas Kelsey , Bangen Katherine , Rotblatt Lindsay , Tosun Duygu , Galasko Douglas 
Published: January 2025

Abstract
Some studies show subjective cognitive decline (SCD) to be an early marker associated with Alzheimer’s pathology. However, until recently, it has been impossible to measure Lewy body pathology in vivo, so its association with SCD is unknown. Participants without dementia (451 CN; 476 MCI) from the Alzheimer’s Disease Neuroimaging initiative were classified as positive or negative for amyloid (A+ or A-) using cerebrospinal fluid (CSF) Aβ42 and for α-synuclein (α-syn+ or α-syn-) using the CSF Seed Amplification Assay (441 A-/α-syn-, 80 A-/α-syn+, 331 A+/α-syn-, and 75 A+/α-syn+). Both participant- and study partner-reported SCD were measured using the Everyday Cognition (ECog) total and domain scores. Per self-report, after adjusting for age, education, sex/gender, race/ethnicity, APOE ε4+, and cognitive group, the A+/α-syn+ group had the greatest SCD relative to the other three pathology groups. The A-/α-syn+ group did not differ from the A-/α-syn- group on any ECog scores. None of these associations were moderated by cognitive status. Per study partner report, a similar pattern of results was observed, but the A+/α-syn- and A+/α-syn+ groups only significantly differed on the planning subscale despite A+/α-syn+ consistently having higher SCD. These results were moderated by cognitive group for the ECog total, memory, language, visuospatial, and divided attention scores such that associations were largely driven by the MCI group. In older adults without dementia, α-syn+ alone did not contribute to greater SCD; however, A+/α-syn+ had the greatest SCD as rated by both participant and study partner, highlighting the importance of measuring co-pathologies to understand SCD etiologies.
ASSOCIATION BETWEEN POLYPHARMACY AND Α-KLOTHO IN US OLDER ADULTS: THE MEDIATION ROLE OF INFLAMMATORY MARKERS
Authors: Wei Kai , Chen Chun , Yang Yanping , Wang Libin , Sun Shuimei 
Published: January 2025

Abstract

Introduction
Polypharmacy may lead to adverse health outcomes in older adults, but the relationship between polypharmacy and accelerated aging is not well understood. This study aims to investigate the association between polypharmacy and α-klotho, a blood anti-aging protein, using large population-based data.

Methods
The study selected 3569 participants aged 65-79 years with serum α-klotho test data and prescription information from the National Health and Nutrition Examination Survey (2007-2016). Participants taking 5 or more medications simultaneously were classified as having polypharmacy. Weighted linear regression analyses were conducted to evaluate the association between polypharmacy and α-klotho. Mediation analysis was conducted to investigate the impact of inflammatory biomarkers, including the systemic immune-inflammation index, systemic inflammation response index, and neutrophil-to-lymphocyte ratio, on the relationship between polypharmacy and α-klotho levels.

Results
The polypharmacy group consisted of 1,591 participants (weighted percentages 42.7%). The median level of α-klotho in the polypharmacy group was 733.16[594.47, 911.63] pg/mL, which was significantly lower than that in the non-polypharmacy group. After adjusting for multiple variables, polypharmacy remained significantly negatively associated with α-klotho (β-coefficient -0.0506, 95% CI -0.0855 to -0.0157), and this significant association were observed in men and women, respectively. Further mediation analyses revealed that the association between polypharmacy and α-klotho was mediated by inflammatory biomarkers, with the proportion of mediation ranging from 6.11% to 11.82% (all P &lt; 0.01).

Conclusion
These findings suggest that polypharmacy is closely linked to circulating α-klotho levels, which may be partly mediated by inflammation.
INFLAMM-AGING IS NOT A UNIVERSAL AGING MECHANISM ACROSS DIVERSE HUMAN POPULATIONS
Authors: Franck Maximilien , Tanner Kamaryn , Ferrucci Luigi , Gurven Michael , Mehrjerd Ameneh , Yeong Joe , Hertel Johannes , Cohen Alan A 
Published: January 2025

Abstract
Inflamm-aging, defined by age-associated increases in inflammatory cytokines, is thought to be a universal mammalian aging mechanism associated with higher chronic disease risk, as observed in industrialized populations like the InCHIANTI cohort (Italy). However, consensus regarding its precise nature and a measurement framework is lacking. Its relevance and measurement applicability across diverse human populations, especially in non-industrialized societies with high infection burdens, remain unclear. We aimed to characterize inflamm-aging across four populations, examining its relation to age and chronic diseases. Through principal components and factor analysis, we studied immune variation within the InCHIANTI, Singapore Longitudinal Ageing Study (SLAS), Study of Health in Pomerania (SHIP), and Tsimane Health and Life History Project (THLHP) cohorts—Amerindian forager-horticulturalists from the Bolivian Amazon. We compared immune axes’ relationships with age and chronic diseases across cohorts. We observed major differences in the structure of inflammatory and immune variation across populations. Notably, the primary immune axis in the THLHP cohort diverged significantly from those in the InCHIANTI, SLAS and SHIP cohorts, with the latter two aligning more closely with the inflamm-aging phenomenon—albeit with variations in their manifestations. Furthermore, these axes did not consistently correlate with age across cohorts and exhibited differential impacts on chronic diseases, with the primary axes identified in InCHIANTI and SLAS showing stronger associations with chronic diseases. Our findings suggest inflamm-aging is not universal. There appear to be significant environmental and lifestyle impacts on inflammatory and immune variation leading to differences in how inflammation drives disease susceptibility across populations.
INTERACTION OF SPERMIDINE AND A LOW-METHIONINE DIET ON LIFESPAN IN MTDNA-DEFICIENT SACCHAROMYCES CEREVISIAE
Authors: Su Wei-Hsuan , Cheng Evien , Cervantes Laura Hernandez , Nishitani Megan , Schriner Samuel 
Published: January 2025

Abstract
Spermidine and a low-methionine diet are two strategies shown to extend lifespan in model organisms, such as yeast, worms, flies, and rodents. Mitochondrial dysfunction is one of the theories explaining how organisms age. In previous studies, we used yeast lacking mtDNA (rho0) as a model for mitochondrial dysfunction. We found that spermidine was not only unable to extend lifespan in rho0 yeast, but actually shortened lifespan. Spermidine and methionine are closely linked metabolically as S-adenosylmethionine from the methionine cycle can be used to synthesize spermidine. And in turn, 5’-methylthioadenosine from the conversion of spermidine to spermine can be used to synthesize methionine. While we found that low-methionine treatment could extend wild-type yeast (rho+) lifespan compared to high-methionine treatment, rho+ yeast were shorter lived than rho0 yeast when both were subjected to low methionine. Thus, the action of low methionine appears to be opposite that of spermidine in rho0 cells, while being similar to spermidine in rho+ cells. This suggests that mitochondrial function plays a significant role in the ability of both treatments to modulate lifespan. We also observed that spermidine could rescue low-methionine toxicity in rho0 yeast, presumably by providing methionine through the pathway mentioned. We then uncovered that deficiency of CYT1 (a subunit of mitochondrial complex III) alone replicates the effect of complete mtDNA-deficiency with respect to spermidine toxicity. Future work will continue to explore the interaction between spermidine and low-methionine modulation of lifespan with the goal of identifying the molecular targets involved.
LONGITUDINAL STUDY OF R1RHO DISPERSION IMAGING OF AGING MUSCLE IN FISCHER RATS
Authors: Adelnia Fatemeh , Wang Feng , Gore John 
Published: January 2025

Abstract
Aging is associated with impaired endothelium-dependent vasodilation, leading to impaired muscle perfusion and organ dysfunction. It has been shown that impaired muscle perfusion may result in insufficient delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationships between microvascular structure, impairment of perfusion, and muscle damage has been limited using traditional muscle perfusion measures, which are mostly invasive and risky. We developed a non-invasive 3D R1ρ dispersion MRI method at weak locking field frequencies to quantify microvasculature restructuring in skeletal muscle. This method provides a unique way of characterizing the size and density of capillaries. We successfully developed the protocol and applied it to the lower leg of F334 female rats of different ages. The whole lower leg of each rat was also imaged using conventional RARE pulse sequences to quantify the T2 values of the muscles. Our data show ΔR1ρ (=R1ρ{0Hz} - R1ρ{240Hz}) fraction values in calf muscles of 15 months F344 female rats (n=8) are significantly (p-value=0.03) higher than 6 months old rats (n=8). We interpret this measure as a possible new biomarker that characterizes changes in microvascular structure with aging. The T2 value also significantly increased in older rats (=30.25ms) compared to younger groups (=27.7ms), possibly reflecting higher inflammation in muscle in agreement with previously published results. The future direction of this ongoing study is to compare these results with data collected from male rats and validation of the ΔR1ρ fraction as a biomarker using ex-vivo histology.
METABOLOME-WIDE STUDY OF CVD IN SWEDISH TWINS
Authors: Skovgaard Asmus Cosmos , Mak Jonathan K L , Hägg Sara , Jylhävä Juulia , Soerensen Mette 
Published: January 2025

Abstract
Globally, cardiovascular diseases (CVD) are the leading cause of death, with coronary artery disease (CAD) and stroke as the most frequent diseases. The molecular basis of CVD is potentially confounded by genetic and environmental factors, an issue which is reduced by investigating intra-pair differences in twins. Here, we study 11,228 twins with nuclear magnetic resonance-based metabolome data and register based diagnoses on incident CAD and stroke collected from the Swedish Patient Register. Statistical analyses were performed both at the individual level and twin-pair level by Cox regression analysis. Biomarkers being significant (FDR&lt; 0.05) both at the individual level and twin pair level in analysis of CAD were identified and LASSO analysis was used to identify the most influential independent biomarkers. A more explorative approach was taken for stroke by applying a cut off of p value&lt; 0.05. Different biomarkers were found for CAD and stroke, which can indicate that the biological mechanisms are partly distinct in the two diseases. We found that ApoB-containing lipoproteins are more positively associated with CAD, which might be due to their pro-atherogenic effects. Contrary, ApoA1-containing lipoproteins are more negatively related to stroke possibly due to their anti-atherogenic effects and potential ability to cross the blood-brain-barrier, an ability not shared with the ApoB-containing lipoproteins. In conclusion, we present novel biomarkers for CAD and stroke by performing metabolomic analyses in twins, thereby lowering the confounding induced by shared genetic and environmental factors, a study design which is rare within the CVD field.
ORA BIOMEDICAL: ACCELERATING DRUG DISCOVERY FOR GEROSCIENCE
Authors: Muir Michael , Blue Benjamin , Kaeberlein Matt , Lee Mitchell 
Published: January 2025

Abstract
Small molecule interventions that directly target the molecular mechanisms of aging have the potential to revolutionize 21st century health and preventative medicine. Altering the trajectory of aging holds incredible economic value in humans, companion pets, and other animals. The longevity biotechnology sector is quickly growing to meet this opportunity, but a relatively small number of interventions and aging targets are poised for clinical development. Ora Biomedical, Inc. is a pharmaceutical company launched out of the Kaeberlein Lab at the University of Washington. We routinely test natural products, pharmaceuticals, combinatorial mixtures, and biologics to identify those that impact biological aging. Our drug screening uses the WormBot-AI platform, which leverages AI, robotics, and C. elegans to enhance the efficiency and accuracy of pre-clinical drug discovery. The WormBot-AI is the best in class for high-throughput intervention testing with lifespan, disease progression, and health measures as primary endpoints. We have also used our platform to launch the Million Molecule Challenge (MMC), a crowdfunded open science initiative. We show here the open access data crowd-funded by scientists and community members from over twenty countries. Furthermore, as a resource and tool for the broader aging science community, we have launched the MMC dashboard. This allows any member of the aging research community to access this crowd-funded data. Ora Biomedical is currently soliciting partnerships with both academic and non-academic aging researchers. We offer a wide array of screening services in multiple disease and mutant models as well as custom intervention validation experiments.
RELATIONSHIPS BETWEEN BLOOD BIOENERGETICS AND LEG COMPOSITION ACROSS THE HUMAN LIFE COURSE
Authors: Arciniega Adrian , Phang Howard , Bergstrom Jaclyn , Molina Anthony 
Published: January 2025

Abstract
The human aging process is marked by changes in body composition, such as muscle loss and bone loss, which may be related to mitochondrial dysfunction. Peripheral blood mononuclear cells (PBMCs) are being used to report on systematic mitochondrial function and have been associated with the bioenergetic capacity of various tissues. Given the ability of PBMCs to recapitulate systemic bioenergetics, we investigated the associations between PBMC bioenergetics and lower extremity composition. We hypothesized that PBMC bioenergetics are significantly associated with measures of leg composition. In this study we utilized data from the San Diego Nathan Shock Center (SD-NSC) clinical cohort which measured blood cell bioenergetics and body composition in healthy adults across the human life course. Pearson Correlation analysis (ntotal=48) revealed strong negative correlations between PBMC respiration and leg bone mineral content (basal r=-0.358, max r=-0.274), femoral area (basal r=-0.369, max r=-0.308), and femoral bone mineral content (basal r=-0.405, max r=-0.329). Partial correlation analyses indicated that significant associations persist when controlling for age and BMI. Further stratification by sex revealed that these relationships were primarily driven by female participants (n=29). These results suggest that blood bioenergetics are related to leg composition in adults regardless of age and play a role in body composition, particularly among women.
IMPACT OF ALZHEIMER’S DISEASE ON SUPRACHIASMATIC NUCLEUS CONNECTIVITY, SLEEP REGULATION, AND CIRCADIAN RHYTHM
Authors: Shen Yiyi , Calligaro Hugo , Lam Michael , Khov Brian , Kim Keunyoung , Ju Wonkyu , Ellisman Mark , Panda Satchidananda 
Published: January 2025

Abstract
Circadian disruption, notably sleep disturbances, serves as an early indicator of Alzheimer’s disease (AD), preceding cognitive symptoms such as memory impairment. Despite this, the underlying anatomical and functional mechanisms driving circadian disruption in AD remain elusive. The suprachiasmatic nucleus (SCN) serves as the central pacemaker regulating circadian rhythm and as the principal hub for entraining circadian rhythm. Here, we explore the relationships between SCN connectome evolution, sleep regulation, and circadian rhythm disruption in the APP/PS1 mouse model. In 3 to 8-month-old APP/PS1 mice, we obtained SCN image volumes via serial block-face scanning electron microscopy. We noted serval modifications in SCN connectomics, including a dendro-dendritic chemical synapse network reduction, crucial for synchronicity between SCN neurons, and a reduction of axonal boutons volume. In addition, we recorded electroencephalograms, electromyograms, temperature, and locomotor activity of 8-month-old WT and APP/PS1 mice to assess their sleep patterns. APP/PS1 mice displayed significantly reduced rapid-eye-movement sleep, associated with a reduced daily temperature amplitude and locomotor hyperactivity. Lastly, in 10 to 15-month-old APP/PS1 mice, we measure locomotor and metabolic activity change in response to acute light stimulation and light-dark cycle shift. APP/PS1 mice showed a decreased circadian fluctuation in metabolic activity and an impaired response to acute light pulse stimulation or phase shift. These preliminary results suggest considerable changes in the SCN connectivity may be responsible for circadian disruption in those with AD. Further investigation will evaluate the use of non-pharmacological approaches to mitigate the observed circadian disruption.
DEPRESCRIBING AMONG OLDER ADULTS WITH CANCER
Authors: Coates Martha , Hajjar Emily , DiMaria-Ghalili Rose Ann 
Published: January 2025

Abstract
Older adults with cancer experience high rates of polypharmacy (&gt;5 medications daily) and potentially inappropriate medication use which are associated with adverse health outcomes and negatively impact quality of life. Deprescribing, the process of lowering drug exposure or removing medications that could cause harm or no longer provide benefit, can reduce the risk of negative outcomes. There is limited research examining the acceptance toward deprescribing in older adults with cancer, therefore the purpose of this study was to examine deprescribing acceptance among Medicare beneficiaries with cancer. We utilized the National Health and Aging Trends Study Round 6 (2016) dataset and included individuals who answered the Medication Attitudes Module (n=1975). Among the participants, 6.1% (n=121) reported having a history of cancer and over half were experiencing polypharmacy. Older adults with cancer strongly agreed or agreed that they took a large number of medications (63%), would like to reduce their medications (74.4%) and if their doctor suggested it they would stop one or more of their medications (95.8%). Despite these high levels of agreement, participants were also found to disagree they took medications they didn’t need (77%) and highly agreed all of their medications were necessary (93.3%). Older adults with cancer are willing to stop medications they may no longer need if suggested by their healthcare provider, but strongly disagree they are taking medications they do not need. Further research is needed to examine patient perceived facilitators and barriers to deprescribing medications that may no longer be needed in individuals with cancer.
ASSOCIATION BETWEEN COUNTY TEMPERATURE AND LIMITATIONS IN ADLS IN A REPRESENTATIVE SAMPLE OF 1.7 MILLION OLDER ADULTS
Authors: Fuller-Thomson Esme , Brooks Holly , Fuller-Thomson Elysia , MacNeil Andie 
Published: January 2025

Abstract
Few studies have explored whether there is an association between area temperature and limitations in Activities of Daily Living (ADLs) such as serious difficulty with bathing and dressing. The objectives of this study were: (1) To examine the relationship between average county temperature during the coldest month of the year (i.e., January or February) (&lt; 27°F, 27-31.9°F; 32-36.9°F; 37-41.9°F; ≥42°F) and the prevalence and adjusted odds of limitations in ADLs; and (2) To examine the relationship between the area’s hottest month’s average temperature (&lt; 70°F, 70-74.9°F, 75-79.9°F, ≥80°F) and the prevalence and adjusted odds of limitations in ADLs. The sample included 1.7 million adults aged 65+ who responded to the nationally representative American Community Survey (2012-2017). After adjustments for age, sex, education, household income, race and time zone, there was a robust dose-response relationship indicating those living in areas with a higher average temperature during the coldest month had higher odds of limitations in ADLs. For example, in comparison to older adults living in regions where the coldest month’s average temperature was &lt; 27°F, those living in areas where the temperature was slightly above freezing (32-36.9°F) had 22% higher adjusted odds of ADL limitations (OR=1.22; 95%CI=1.19, 1.25) and those living in regions where the temperature averaged ≥42°F had 33% higher odds (OR=1.33: 95%CI-1.30, 1.36). There was no significant relationship between the regional hottest month’s average temperature and ADL limitations. Future research is needed to explore why the absence of sub-freezing temperatures is associated with elevated odds of ADLs.