bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONTRIBUTION OF CHRONIC CONDITIONS TO MORTALITY: DIFFERENCES BY RACE AND ETHNICITY
Authors: Quiñones Ana , Elman Miriam , McAvay Gail , Wyk Brent Vander , Nagel Corey , Allore Heather 
Published: December 2023

Abstract
Health disparities exist in the timing, order, and accumulation of chronic somatic and neurodegenerative conditions, which are associated with increased health care utilization, expenditure, and mortality. We assessed the contribution of coexisting conditions to mortality among Hispanic, non-Hispanic (NH) White, and NH Black older adults in the United States to measure their burden. We used nationally-representative data from the Health and Retirement Study (HRS) from 1998-2016 (n=11,532). This analysis estimates the absolute additive contributions of seven somatic and two mental/neurodegenerative conditions using a longitudinal average attributable fraction derived from a survey-weighted multivariable discrete survival model adjusted for sociodemographic characteristics (sex, education, net worth, body-mass index, coupled, insured, and any of six ADLs lasting three or more months “because of physical, mental, emotional, or memory problems”). Conditions accounted for over 60% of mortality in each racial/ethnic group (64.0%, 62.2%, and 70.5% in Hispanic, NH White, and NH Black adults, respectively). Although we found that cardiovascular diseases (heart disease and hypertension) were the greatest contributor to morality in each racial/ethnic group, the impact of other conditions varied by race/ethnicity. Leading contributors to mortality were diabetes (12.0%) and dementia (7.2%) for Hispanic participants; cancer (13.0%) and lung disease (10.7%) for NH White participants; and diabetes (11.5%), lung disease (7.4%), and dementia (7.3%) in NH Black participants. This study provides insights into racial and ethnic differences in the contribution of chronic somatic and neurodegenerative conditions to mortality and may help target efforts for specific preventative care services to populations most impacted by them.
SOCIAL CHARACTERISTICS OF RACIAL MINORITY STROKE SURVIVORS AND PERCEIVED DISCRIMINATION: A SECONDARY ANALYSIS
Authors: Williams Lilcelia , Antoan Jordann , Harris Tina , Hammel Joy , Leland Natalie , Skidmore Elizabeth 
Published: December 2023

Abstract
African American and Black persons experience significant disability after stroke. They also experience high external stressors, including discrimination, which may attenuate stroke recovery. Further understanding of the associations among external stressors, disability severity, and attenuated recovery are important to reduce healthcare disparities and improve patient outcomes. However, persons of the same race may not have the same lived experiences due to variations in social characteristics such as age or education. Associations between these social characteristics and perceived discrimination may offer insights into the recovery of older adult African American and Black stroke survivors. We conducted a secondary analysis of 11 poststroke patients who were recruited to participate in the Black Lived Experiences of Stroke Study (female=10, age=67±11, ≥2 years post-secondary education=63%) to assess the frequency of perceived discrimination. Perceived discrimination was measured with the Everyday Discrimination Scale survey. We examined correlations between age and education and perceived discrimination using Cramer’s V tests. Semi-structured participant interviews were also examined for examples of perceived discrimination during poststroke healthcare. Nine participants reported perceived discrimination post-stroke. Analyses revealed a clinically meaningful but not statistically significant relationship between chronological age and perceived discrimination (Cramer’s V=0.62, p=0.12). There was no meaningful relationship between educational level and perceived discrimination. All participants reported challenges with communication, missed diagnoses and poor delivery of care poststroke. Findings support the need for additional research to examine the relationships between participants’ social characteristics and perceived discrimination among Black and African American stroke survivors, and the impact on stroke recovery.
THE GRAYING RAINBOW: TRACING LGBTQI AGING IN SCANDINAVIAN LITERATURE
Authors: Christiansen Mats , Handelsman-Nielsen Mika , Mehdiyar Manijeh 
Published: December 2023

Abstract
Background: There have been several international reviews about aging LGBTQI health and living conditions, but where policy, social insurance, and services differ. The Public Health Agency of Sweden was given a government assignment to review the literature on LGBTI, emphasizing Scandinavian literature. Method: This scoping review includes peer-reviewed literature published in English or Scandinavian languages from January 1, 2012, to May 2022. Literature was searched in PsycINFO, PubMed, Web of Science, CINAHL, International Bibliography of the Social Sciences (IBSS), Social Science Database, Applied Social Sciences Index & Abstracts (ASSIA), and Sociological Abstracts, Sociology Database. Initially, 11,428 articles were found. After removing duplicates using Rayyan and reviewing titles and abstracts, 54 articles were read in full. After the final review, 16 articles remained. Thematic analysis was used to produce themes from the reviewed literature. Findings: The following two themes were identified: Aspects of health and Living conditions. Studies were primarily interpretive. There is a lack of studies about some subgroups of older LGBTQ people in this context; for instance, there are insufficient studies on older lesbian women and gay men. Furthermore, there is a lack of studies on somatic health for older LGBTQ people, generally. Comparatively, albeit in small samples, we better understand trans descriptions of aging than lesbian women and gay men. There were no studies found on intersex individuals. Implications: There remains a paucity of literature regarding the life and living conditions for LGBTQI older adults in Nordic countries.
THE INFLUENCE OF RURALITY AND FRAILTY ON HEALTH OUTCOMES IN OLDER ADULTS
Authors: Spangler Hillary , Mitchell Emma , Lynch David , Haaland Perry , Batsis John 
Published: December 2023

Abstract

Background
Frailty is a syndrome representing a decline in physical function and an increased vulnerability to stressors. Older adults in rural areas may be at increased risk for frailty and adverse outcomes due to worse overall health. Our aim was to identify how rural/urban residence can influence frailty status.

Methods
We used National Health and Aging Trend Study (2011-2020) data, a cohort of Medicare beneficiaries. Participants were categorized as robust, pre-frail, and frail (Fried’s frailty phenotype). Rural residence included counties outside of a metropolitan statistical area (Office of Management and Budget). Participants were excluded if frailty components or geographical status were incomplete. We used logistic regression analyses for the relationship between adverse outcomes (death, nursing home placement over 2011-2020), rural/urban, and frailty status.

Results
Of 7,393 participants (57.2% female), median age range was 75-80 years and 19.4% were rural residents. Rates of robust, pre-frailty, and frailty were 41.4%, 48.4%, and 10.2%, respectively. There was no difference of frailty status by rural status nor was there a frailty x rural interaction. Older adults with pre-frailty (OR=1.18; 1.05-1.34) and frailty (OR=1.01; 0.82-1.24) had higher risk of residing in rural than urban areas. Rural residence (OR=1.75;1.33-2.24), pre-frailty (OR=1.87;1.54-2.28) and frailty (OR=3.62; 2.79-4.71) had higher risk of adverse outcomes.

Conclusion
Participants with pre-frailty had higher odds of living in a rural area. Similarly, participants in rural areas had higher odds of adverse outcomes. These findings may highlight health care disparities in rural areas and opportunities for system- and individual-level interventions to prevent frailty development.
A GENETICALLY INFORMED STUDY ON THE ETIOLOGICAL ASSOCIATIONS AMONG EPIGENETIC CLOCKS
Authors: Penichet Eric , Beam Christopher , Bakulski Kelly , Turkheimer Eric , Higdon Kristin , Ryan Lesa , Sikes Kendra , Davis Deborah 
Published: December 2023

Abstract
Epigenetic clocks are believed to capture the molecular footprints of biological programs that subserve innate aging processes. Although epigenetic clocks can predict disease phenotypes and mortality with a high degree of accuracy, little is known about the extent to which they capture the same (or different) developmental and maintenance mechanisms. Quantitative genetic studies may provide useful information on the etiological links between epigenetic clocks, particularly pertaining to the question of whether they are influenced by a common set of genetic and environmental factors. Using preliminary data from the Louisville Twin Study, this study used a multivariate independent pathway model to examine the shared and unique genetic and environmental influences of three epigenetic clocks (GrimAge, HannumAge, PhenoAge). Participants consisted of 43 monozygotic pairs and 30 (18 same-sex) dizygotic twin pairs with a mean age of 54.5 years (sd = 5.27). Phenotypic analyses revealed significant correlations among the clocks (r = 0.63 - 0.78). Subsequent multivariate biometric analyses showed that there were common genetic and nonshared environmental influences across all three clocks (p &lt; 0.001), with unique genetic and nonshared environmental influences specific to GrimAge and HannumAge (p &lt; 0.001). To examine the sources of covariation between these variables, biometric regression models were used to decompose the covariance between each of the clocks (GrimAge and Hannum, Hannum and PhenoAge, PhenoAge and GrimAge) into genetic and environmental components. These analyses revealed large, significant genetic correlations (rg = 0.80-0.86) and medium to large, significant nonshared environmental correlations (re = 0.37-0.73) among the clocks.
ALTERED GENE EXPRESSION PROFILE OF AGING BONE MARROW MESENCHYMAL STEM CELLS
Authors: Su Yun , Chen Jie , Isales Carlos , Shi Xingming 
Published: December 2023

Abstract
Aging is a complex process that affects many physiological systems, including bone metabolism. To gain insight into the molecular mechanisms underlying age-related bone loss, we conducted RNA-seq analysis of mesenchymal stem cells (MSCs) isolated from the bone marrow of 6-month and 24-month-old C57Bl/6 mice. We identified 5857 differentially expressed genes, out of 19,324 genes, with an absolute fold change greater than 1.4 and FDR q-value less than 0.05. These genes are involved in a variety of biological processes, including metabolism, immune response, and signal transduction. KEGG pathway enrichment analysis revealed 28 significantly enriched pathways, suggesting that multiple pathways contribute to age-related bone loss. Our findings provide a foundation for future studies aimed at elucidating the molecular mechanisms underlying age-related bone loss and identifying potential therapeutic targets for the prevention and treatment of osteoporosis.
ANALYSIS OF CIRCADIAN TRANSCRIPTION ACTIVATOR BMAL1 AND CLOCK BINDING TARGETS IN YOUNG AND OLD MOUSE SKELETAL MUSCLE
Authors: Zhang Xiping , Viggars Mark , Esser Karyn 
Published: December 2023

Abstract
Circadian rhythms play important roles in many physiological processes and circadian rhythm disturbances are often observed in older people. Circadian rhythms are regulated by a molecular clock mechanism that is found in virtually all cells of the body. The core clock mechanism consists of transcriptional activators (BMAL1 and CLOCK) and the feedback negative regulators (PER and CRY). Beyond keeping daily time, the core clock factors regulate a daily gene expression program and this daily program is diminished with age. Skeletal muscle is critical in supporting systemic metabolism and mobility. Loss of muscle strength in older people are related to increased morbidity and mortality. Our previous studies have shown a significant decline of circadian genes with age in skeletal muscle and there are very few circadian genes in common between young and old mouse muscle. To understand the mechanism of the diminished circadian gene expression with age, we performed ChIPseq to determine BMAL1 and CLOCK binding and ATACseq to determine chromatin accessibility with muscle from young (6 months) and old (27 months) mouse. The ChIPseq result showed that BMAL1 and CLOCK shared more than 8,000 binding peaks in young muscle and less than 200 binding peaks in old muscle. The ATACseq identified that chromatin accessibility altered in more than 7000 sites with age and BMAL1:CLOCK binding sites were less accessible with age. In conclusion, our research has demonstrated that muscle chromatin accessibility changes with age and the core clock factors are important regulators of gene expression in skeletal muscle.
CAN ACUTE MUSCLE DAMAGE LEAD TO OSTEOARTHRITIS?
Authors: Awad Kamal , Moore Logan , Huang Jian , Brotto Leticia , Brotto Marco 
Published: December 2023

Abstract
Skeletal muscles are crucial for maintaining musculoskeletal homeostasis, as they provide mechanical support, joint stability, and biochemical functions via myokine secretion. We investigated whether acute muscle damage or weakness could contribute to the development of osteoarthritis (OA). Using a chemical damage model, we induced muscle damage by injecting 1.2% barium chloride into the tibialis anterior muscle, resulting in an immune response characterized by a significant increase in the concentration of Prostaglandin E2 (PGE2) and other lipid mediators derived from the EPA and DHA signaling pathways, as quantified using our innovative lipidomics methods. The muscle damage was confirmed and visualized by muscle histomorphometry. The damage resulted in muscle weakness, detected by a significant decrease in grip strength at 4-days post-injury, but without changes in mice activity measured with force-plate actimeter. After 1-month post-injury, grip strength and muscle histology returned to normal, but histological changes were observed in the articulating cartilage, indicating surface erosion and cartilage matrix loss (OARSI grade 4). We used Raman Spectroscopy and micro-CT to confirm the joint alterations observed in the changes in subchondral bone and increased bone volume fraction in the cortical shell of the subchondral bone, respectively, features characteristic of OA in rodents and humans. These findings suggest that muscle weakness or imbalance due to injury can contribute to joint degeneration. This study highlights the significance of muscles in preventing OA and provides a novel approach for exploring the relationship between muscle damage and OA development. This new model could prove valuable for aging research.
EPIGENETIC AGE DYNAMICS AND EMBRYONIC MORTALITY POINT TO GASTRULATION AS AGING GROUND ZERO IN XENOPUS LAEVIS
Authors: Zhang Bohan , Gladyshev Vadim 
Published: December 2023

Abstract
Recent studies on embryonic development revealed a natural rejuvenation event followed by epigenetic aging. Here, we developed a frog aging clock based on the DNA methylation profile in the African clawed frog Xenopus laevis. Application of this clock to Xenopus laevis early embryonic development identified a decrease in epigenetic age during early embryogenesis, with the minimal epigenetic age reached around gastrulation. We further examined the individual developmental trajectories of 6,457 embryos and found that this minimum age is also accompanied by a higher incidence of disrupted development. Taken together, our data point to gastrulation as a critical stage for aging and natural rejuvenation, characterized by the lowest epigenetic age and increased mortality, defining aging ground zero as the basepoint where rejuvenation ends and the aging process begins.
EPIGENETIC AGING AND RHEUMATOID ARTHRITIS
Authors: Mukherjee Nandini , Harrison Tracie 
Published: December 2023

Abstract
Indicators of biological aging with rheumatoid arthritis (RA), a chronic autoimmune disease, are not yet fully known. In this cross-sectional study, we tested associations between plasma indicators of epigenetic aging using online data (GSE42861) regarding RA and DNA methylation from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Peripheral blood DNA methylation of participants 18-70 years old was assessed using Illumina HumanMethylation450 arrays. Horvath’s online DNA Methylation Age Calculator determined DNAm estimate of Telomere length (DNAmTL), Hannum’s, Horvath’s 2013 and 2018 epigenetic ages, PhenoAge and GrimAge and the respective age accelerations. Association of RA prevalence with epigenetic age were determined using linear regression, correcting for false discovery rate. We identified significant associations of RA with age acceleration measures of Horvath 2013 (Estimate:-1.34 ; FDR p-value: 1.0 × 10-2) and Horvath 2018 (Estimate:-1.32; FDR p-value: 4.0 × 10-5), extrinsic age acceleration (Estimate: 1.34 ; FDR p-value: 1.0 × 10-2), PhenoAge acceleration (Estimate: 2.31; FDR p-value: 1.1 × 10-5), GrimAge (Estimate: 2.54; FDR p-value: 1.0 × 10-2) and GrimAge acceleration (Estimate: 3.15 ; FDR p-value: 1.7 × 10-17), adjusting for sex and smoking (FDR p-value&lt;=0.05). In sex stratified analyses, first-generation clocks were associated only in women, but no sex specific effects for PhenoAge or GrimAge accelerations were identified. The second generation ‘biological’ clocks PhenoAge, GrimAge and its components showed higher epigenetic age acceleration in RA cases compared to healthy controls. We conclude that second generation indicators of epigenetic aging provide promise as markers of biological aging in people with RA.
EVIDENCE THAT CONSERVED ESSENTIAL GENES ARE ENRICHED FOR PRO-LONGEVITY FACTORS
Authors: Kaya Alaattin 
Published: December 2023

Abstract
At the cellular level, many aspects of aging are conserved across species. This has been demonstrated by numerous studies in simple model organisms like Saccharomyces cerevisiae, Caenorhabdits elegans, and Drosophila melanogaster. Functional genomic studies in these models have contributed enormously to our understanding of conserved genetic pathways influencing aging in evolutionarily divergent organisms. From this perspective, essential genes that are evolutionarily constrained and functionally conserved should be more relevant to the regulation and evolution of aging. However, because most genetic screens examine loss of function mutations or decreased expression of genes through reverse genetics, essential genes have often been overlooked as potential modulators of the aging process. By taking the approach of increasing the expression level of conserved essential genes, we found that 23% of these genes resulted in increased replicative lifespan in S. cerevisiae. This is greater than the ~3.5% of genes found to affect lifespan upon deletion, suggesting that activation of essential genes may have a relatively disproportionate effect on increasing lifespan. These essential prolongevity genes function in a variety of pathways and complexes highlighting both known and previously unknown longevity pathways and their previously unknown essential components. The results of our experiments demonstrate that essential gene overexpression is a rich, relatively unexplored means of increasing eukaryotic lifespan.
EXPRESSION OF THE TARDIGRADE DAMAGE SUPPRESSOR PROTEIN IN THE YEAST SACCHAROMYCES CEREVISIAE
Authors: Su Wei-Hsuan , Smith Jessica , Cheng Evien , Schriner Samuel 
Published: December 2023

Abstract
Tardigrades are resilient organisms that can tolerate extremes in temperature, pH, pressure, and salinity. They are also exceptionally resistant to starvation, dehydration, and irradiation. The damage suppressor (Dsup) protein is thought to be unique to tardigrades and may act by coating and protecting nuclear DNA, particularly the nucleosomes. Nuclear DNA damage and mutation may be one of the driving forces of the aging process. In addition, there has been demonstrated a clear relationship between stress tolerance and aging. In this study, we are asking whether Dsup, when expressed in the yeast Saccharomyces cerevisiae, can afford yeast with an enhanced tolerance to environmental stresses, lowered spontaneous and induced mutation rates, and extended chronological lifespan. Yeast were constructed expressing Dsup with the strong promoter TEF on a high copy plasmid containing the 2 micron origin of replication. Preliminary results show that Dsup is able to enhance yeast survival against hydrogen peroxide, but surprisingly appeared to compromise survival to the DNA damaging agent ethyl methanesulfonate (EMS). Excessive expression of Dsup may explain the unexpected toxicity to EMS. We are therefore planning to test the expression of Dsup with a lower copy plasmid. We then plan to challenge the Dsup-expressing yeast to a variety of stresses, including extremes in temperature, high salt, and heavy metals. Induced mutant frequencies and spontaneous mutations rates at the CAN1 locus will be evaluated. Ultimately, we intend to determine whether Dsup can extend yeast chronological lifespan as a direct test of nuclear DNA damage in the regulation of lifespan.
PLACENTAL MUTATIONAL BURDEN NEGATIVELY CORRELATES WITH GESTATIONAL AGE IN EARLY-ONSET PREECLAMPSIA
Authors: Chavez Hector , Guo Nicholas , Huang Molly , Meads Morgan , Aisagbonhi Omonigho , Parast Mana , Horii Mariko , Fisch Kathleen 
Published: December 2023

Abstract
The placenta exists in a hypoxic environment during early pregnancy, making it susceptible to somatic genetic mutations caused by oxidative stress and rapid cell proliferation. Oxidative stress is one of the leading factors involved in cellular aging causing genetic mutations, cellular senescence, and mitochondria dysfunction over time. While it has been demonstrated that healthy placentas accumulate somatic mutations as they develop, we hypothesize that diseased placentas display an accelerated aging phenotype through the accumulation of somatic mutations. To address this, we analyzed RNA-seq data from 84 human placentas throughout gestation from healthy (N=33) and preeclamptic pregnancies (N=51). We identified rare single nucleotide variants, insertions and deletions using GATK Best practices Workflow for RNA-seq short variant discovery using bcbio-nextgen and annotated with VEP and LOFTEE. Mutational burden, defined as the total number of rare mutations per megabase, was calculated after strict quality control and filtering for rare (gnomADg&lt; 0.05) variants using maftools in R. Linear regression models were employed to determine the association between mutational burden and gestational age. Differences in mean values were computed with a pairwise t-test . This study revealed that mutational burden in early-onset preeclampsia placentas is negatively correlated to gestational age (R^2=0.256; p-value=0.032). The early-onset preeclampsia group had a higher mutational burden relative to the other groups (p-value&lt; 0.05). This study revealed a significant correlation of mutational burden with gestational age in early-onset preeclampsia, paving the way for additional investigation of accelerated aging in placentas and its contribution to the development of preeclampsia.