bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of GrimAge DNA methylation components and 2-year mortality in the Health and Retirement Study
Authors: Meier Helen , Mitchell Colter , Crimmins Eileen , Thyagarajan Bharat , Faul Jessica 
Published: December 2021

Abstract
DNA methylation (DNAm) patterns related to age and aging phenotypes (i.e., epigenetic clocks) are of growing interest as indicators of biological age and risk of negative health outcomes. We investigated associations between the components of GrimAge, an epigenetic clock estimated from DNAm patterns for seven blood protein levels and smoking pack years, and 2-year mortality in the Health and Retirement Study (HRS) to determine if any of the DNAm subcomponents were driving observed associations. A representative subsample of individuals who participated in the HRS 2016 Venus Blood Study were included in this analysis (N=3430). DNAm was measured with the Infinium Methylation EPIC BeadChip. Deaths that occurred between 2016 and 2018 contributed to 2-year mortality estimates (N=159, 4.5% of the sample). Weighted logistic regression estimated the association first between GrimAge and 2-year mortality and second between the DNAm subcomponents and 2-year mortality. All models were adjusted for age, sex, race/ethnicity, education, current smoking status, smoking pack years and cell composition of the biological sample. The average GrimAge for participants with and without 2-year mortality was 77 years 68 years respectively. A one-year increase in GrimAge was associated with 17% higher odds of 2-year mortality (95% CI: 1.16, 1.17). Two of the seven DNAm blood protein subcomponents of GrimAge (TIMP metallopeptidase inhibitor 1, adrenomedullin) and DNAm smoking pack years were associated with 2-year mortality and DNAm smoking pack years appeared to drive the overall GrimAge association with 2-year mortality. GrimAge was a better predictor of 2-year mortality than the DNAm subcomponents individually.
Global phosphoproteomic profiling of skeletal muscle in ovarian hormone-deficient female mice
Authors: Peyton Mina , Yang Tzu-Yi , Higgins LeeAnn , Markowski Todd , Parker Laurie , Lowe Dawn 
Published: December 2021

Abstract
Dynapenia, the age-related loss of skeletal muscle strength without the loss of muscle mass, significantly impacts the activities and quality of life of the aging population. Studies have shown that dynapenia occurs earlier in females than males in both human and rodent studies. Moreover, in females, estrogen deficiency has been shown to contribute to the loss of skeletal muscle strength as well as blunted recovery of strength after injury. The maintenance of skeletal muscle contractile function is vital to the overall health of women, especially as women live 1/3 of their life in an estrogen deficient state. Reversible protein phosphorylation is an indispensable post-translational modification, playing a key role in signal transduction pathways. Phosphorylation of skeletal muscle proteins have been shown to regulate sarcomeric function, excitation-contraction coupling, energy metabolism, and fiber-type composition. To define the physiological changes in the skeletal muscle phosphoproteome associated with estrogen deficiency, we used an ovariectomy model coupled with mass spectrometry. We identified, in total, 5,424 unique phosphorylation sites and 1,177 phosphoproteins in the tibialis anterior muscle. Ingenuity Pathway Analysis show decreased phosphorylation of contractile proteins and significant predicted inhibition of the upstream kinase, CDK6 (z-score -2.0) in ovariectomized compared to control muscles. Our results suggest that estrogen deficiency remodels the skeletal muscle phosphoproteome which may alter phosphorylation signaling that might contribute to the loss of strength in females.
Nuclear Architecture Disruption During Aging Causes Misexpression of Genes Lacking CpG Islands
Authors: Lee Jun-Yeong , Davis Ian , Beck Samuel 
Published: December 2021

Abstract
Global disorganization of chromatin architecture, characterized by disrupted nuclear lamina and associated heterochromatin, is commonly observed in various aging contexts, including premature aging diseases, cellular senescence, and normative aging. Although these conserved structural changes have been reported for over two decades, their impact on transcription and contribution to age-related degenerative changes remain unclear. Here we show that genes not associated with CpG islands (CGI- genes), which form heterochromatin when transcriptionally silent, are globally misexpressed in aged nuclei with disrupted chromatin architectures. Our data also show that CGI- gene misexpression is a direct outcome of nuclear architecture disruption. Notably, CGI- gene misexpression explains the molecular basis of various defects observed during aging, including loss of cellular identity and increased noises in transcription. We also show that uncontrolled secretory phenotypes commonly observed during aging are largely attributable to CGI- gene misexpression, which drives disruption of intercellular communication and fuel chronic inflammation in aged tissues. Our large-scale meta-analysis further demonstrates that CGI- gene misexpression is a common feature of mammalian aging and age-associated diseases. Interestingly, CGI- gene misexpression can be suppressed by anti-aging interventions. Our study suggests that age-associated CGI- gene misexpression is a novel biomarker of physiological aging which offers an effective therapeutic target for delaying or ameliorating degenerative changes associated with aging.
Perceived Control and Cognitive Function Among Acute Ischemic Stroke Patients in China
Authors: Liu Zhijian , Kong Xiangjing , Wang Jing , Wang Qin , Wu Bei , Li Juan 
Published: December 2021

Abstract
This study explored an association between perceived control and cognitive function among 437 acute ischemic stroke (AIS) patients in China. We collected data from one stroke center in each of the three cities (Shanghai, Nanjing, and Linyi) from June to December, 2020. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA), and perceived control was assessed by Perceived Control in Health Care Questionnaire at acute stage. Hierarchical linear regression was used. The average of perceived control and MoCA were 81.36±0.877 and 19.66±0.304, respectively. A number of 374 (85.6%) patients were in cognitive impairment and 63(14.4%) were cognitively normal. Perceived control was positively associated with cognitive function (β=0.103, p＜0.001). After controlling for stroke severity, age, gender and education, the association was still significant (β=0.041, p=0.014). These findings suggest that perceived control may be a potential target in cognitive interventions for AIS patients.
Early Life Thymectomy Induces Glucose Intolerance in Middle-Aged Mice
Authors: Buckley David , Sharma Sunita , Trott Daniel 
Published: December 2021

Abstract
Previously we have found that T cells contribute to age-related glucose intolerance. The purpose of this study was to test the hypothesis that early life thymectomy at 3wks of age induces T cell aging and subsequent impairments in glucose homeostasis in otherwise young animals. Male C57BL6 mice underwent thymectomy (thymex; n=7) or sham surgery (control; n=7) at 3wks of age. A glucose (2g/kg) tolerance test (GTT) was performed at 6 and 9mo via intraperitoneal injection. Following euthanasia at 9mo of age, splenic T cell phenotype was assessed by flow cytometry. Group differences were assessed by independent samples t-test or repeated measures ANOVA and Bonferroni post-hoc test. Data are presented as mean±SEM. At 6mo, the thymex animals had a significantly lower fasting glucose compared to controls (156.8±7.9mg/dl,174.1±5.8mg/dl, p=0.06). During the GTT, 6mo old thymex mice had a greater area under the curve (AUC) compared to controls (31893.8±612.3mg/dl, 28020.9±1112.9mg/dl, p=0.03). At 9mo, the thymex mice had greater fasting glucose compared to controls (215.6±11.6mg/dl, 176.3±7.9mg/dl, p=0.016), as well as a greater GTT AUC (61445.4±1949.2mg/dl, 41527.5±2530.3mg/dl, p=0.0001). The thymex group also had increased fasting and glucose stimulated insulin levels compared to controls (0=1.3±0.2ng/ml 0.3±0.1ng/ml, p=0.01; 15=1.7±0.2ng/ml,0.44±0.1ng/ml, p=0.0014). Thymex mice exhibited a blunted splenic CD4:CD8 ratio (0.5±0.2, 1.1±0.2, p=0.04) compared to controls and a trend toward a memory CD8+ T cell phenotype (23.1±11.6%, 7.1±2.6, p=0.08), both consistent with aging. This data indicates that early life thymectomy may accelerate T cell aging, resulting in impairments in glucose tolerance in otherwise young and middle aged mice.
The Role of the Human Immune System in the Aging Process: a Mathematical Model of Cell and Cytokine Activation
Authors: Talaei Kian , Garan Steven , Martins Nuno , Cho Joshua , Jahansooz Julia , Bhullar Puneet , Suen Elliott , Piszker Walter 
Published: December 2021

Abstract
The role of the human immune system as a factor in the aging process has led to extensive research in the field of infection biology and bioinformatics. Cell-based mathematical models have previously been used to simulate the immune system in response to pathogens. A variety of cells, such as activated and resting macrophages, plasma cells, antibodies, helper T cells, T-lymphocytes, and B-lymphocytes, have already been simulated by mathematical models. This work aims to incorporate cytokines in these mathematical models to create a more comprehensive simulation that can predict cytokine levels in response to a Gram-positive bacterium, S. aureus. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) were studied to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus ex vivo. The results of the simulation were compared to ex vivo human whole blood data to test its accuracy. The future expansion of this model may provide a clearer image of the various interactions within the immune system and this improved model of the immune system may also facilitate a better understanding of the mechanisms that lead to the degradation of the immune system during the aging process.
The Impact of Social Isolation on Cognition and Quality of Life Among Stroke Patients in China
Authors: Kong Xiangjing , Li Juan , Liu Zhijian , Wang Jing , Wu Bei 
Published: December 2021

Abstract
This study examined the impactof social isolation on cognitive function and Quality of Life (QoL) among acute ischemic stroke (AIS) patients in China. We conducted in-person interviews among 206 AIS patients during the acute stage and at 3-month after onset in three cities between May 2020 and February 2021. The data was collected during and post-COVID-19 period in China. We conducted bivariate and multipleregression analyses.Results show that over time, average level of social isolation decreased, and cognitive function and QoL increased.After controllingfor covariates, social isolation was negatively associated with cognitive function (β=-0.438, p&lt;0.01) and QoL (β=-2.521, p&lt;0.01). These findings suggest that addressing the issue of social isolation could potentially impact patients’ cognitive function and QoL.Future studies are needed to further examine the linkages between long-term social isolation and changes in cognitive function and QoL among AIS patients.
Mechanisms of Cell Non-Autonomous Longevity Regulation
Authors: Leiser Scott , Choi Hyo , Miller Hillary , Bhat Ajay , Howington Marshall , Dean Elizabeth , Huang Shijiao 
Published: December 2021

Abstract
An organism’s ability to respond to stress is crucial for long-term survival. These stress responses are coordinated by distinct but overlapping pathways, many of which also regulate longevity across taxa. Our previous work identified a cell non-autonomous signaling pathway led by the hypoxia-inducible factor and resulting in induction of flavin-containing monooxygenase-2 (fmo-2) to promote health and longevity. Our current work identifies a distinct cell non-autonomous pathway downstream of dietary restriction (DR) that also relies on fmo-2 induction to promote health and longevity. We now find that these cell non-autonomous pathways can be mimicked by small molecule interventions that increase longevity by inducing fmo-2. Based on the commonalities of these pathways, we hypothesized that fmo-2, a classically annotated xenobiotic enzyme, might play a key endogenous role in responding to metabolic stress. Our resulting data, using metabolic profiling and further epistatic analysis, both support this hypothesis and link fmo-2’s mechanism to modifications in one-carbon metabolism (OCM), a key intermediate pathway consisting of the folate and methionine cycles. Using mathematical modeling and a labeled metabolomics approach, we were able to further identify the likely mechanism of fmo-2-mediated metabolic effects and connect them to both OCM and downstream components. We propose that fmo-2 is induced cell non-autonomously to modify systemic metabolism and longevity, and that fmo-2 is a key member of a conserved metabolic stress response.
Total Transcriptome Responses to Low and Higher Intensity Aerobic Exercise Interventions in Older Adults
Authors: Smith Meghan , McWilliams Gabriella , Bryan Angela , Seals Douglas , LaRocca Thomas 
Published: December 2021

Abstract
Aerobic exercise is a universally recommended strategy for increasing healthspan, and recent advances in next-generation sequencing and bioinformatics (e.g., RNA-seq/transcriptomics) have made it possible to broadly profile the molecular transducers of exercise. However, most transcriptome studies of exercise have focused on coding genes only, and the transcriptomic response to different exercise interventions has not been characterized by RNA-seq in older adults. Therefore, we performed total RNA-seq (to capture both coding and non-coding gene expression) on peripheral blood mononuclear cells collected from healthy, previously sedentary older adults (males and females, aged 70 ± 1 years). Samples were collected before and after 16 weeks of either low-intensity continuous training (LICT, 50% maximum heart rate, 3 x 30 min/week) or moderate-intensity continuous training plus interval training (MICT+IT, 60-80% maximum heart rate, progressively increased to include IT, 3 x 30 min/week). We found that both interventions modified biological processes (transcriptome modules) related to oxygen transport and reduced inflammatory signaling/immune activation processes (more pronounced with LICT). Interestingly, transcriptome changes unique to LICT subjects included increased expression of genes linked with vascularization and endothelial cell migration, whereas MICT+IT was uniquely associated with a robust increase in antioxidant response gene expression. We also observed numerous changes in long non-coding RNAs and microRNAs that could be linked with these exercise-associated gene expression changes with both interventions. These data provide a first comprehensive look into transcriptomic changes associated with moderate vs. low intensity aerobic exercise in older adults, and they suggest distinct benefits of each exercise strategy.
Valsartan and Sacubitril Combination Treatment Enhances Collagen Production in Older Adult Human Skin Cells
Authors: Marin Sela , godet Ines , Nidadavolu Lolita S , Walston Jeremy , Gilkes Daniele , Abadir Peter M 
Published: December 2021

Abstract
Collagen is a major component of the skin’s support system, allowing for firmness, elasticity, and mechanical strength. In older adults, skin collagen production decreases significantly, and is associated with increased sagging, wrinkling, and thinning. The Renin Angiotensin System (RAS) is a key hormonal system that changes with age and affects multiple organ systems. While primary health benefits of Angiotensin (Ang) receptor type1 (AT1 R) blockers (ARBs) are believed to arise from systemic effects on blood pressure. There exists a skin-specific Renin Angiotensin System (RAS), but the impact of ARBs on older skin is unknown. Human skin fibroblasts from individuals aged 2 (young individual) and 57 (older individual) were treated with drugs that alter RAS: Valsartan (an ARB) and neprilysin inhibitor Sacubitril. Fibroblast proliferation and collagen production was quantified in response to the drug treatment using fluorescence microscopy. Fibroblasts from 57-year-old individuals were slower to proliferate and had less collagen content as compared to fibroblasts from young individual. Valsartan alone treatment had no effect on collagen production from young or old fibroblasts. In contrast, Sacubitril treatment increased collagen production by approximately three-fold in young (2.87 ± 0.27 RFU, P&lt;.0001), and older (2.93 ± 0.53 RFU, P&lt;.0001) fibroblasts. Concomitant treatment with Valsartan and Sacubitril increased collagen production by five-fold increase (5.36 ± 1.08 RFU, P&lt;.0001) in young fibroblasts, and four-fold (4.18 ± 0.96 RFU, P=.003) in older cells. This study demonstrates a novel use for the widely prescribed drug combination, Sacubitril and Valsartan, which significantly improves collagen production in older adult fibroblasts.
A Study of C2C12 Myoblast Bioenergetics in Response to the CCG-1423 Rho A Inhibitor
Authors: Nguyen Bachkhoa , Ameer Fathima , Crane Jasmine , Azhar Gohar , Zhang Xiaomin , Wei Jeanne 
Published: December 2021

Abstract
CCG-1423 is a Rho A pathway inhibitor which has been reported to inhibit Rho/SRF-mediated transcriptional regulation. SRF and SRF cofactors, which include ternary complex factors (TCFs) and myocardin-related transcription factor (MRTF), regulate various cellular functions. The Rho/SRF signaling pathway also regulates the sirtuin 2 (SIRT2) gene that contains a classic serum response element (SRE) sequence. Current research on CCG-1423 focuses on gene expression levels of SRF in response to CCG-1423 and how SRF levels affect the cells; the studies are focused on cell morphology, migration, viability/reproduction, and overall function. The pathways of this inhibitor have yet to be fully elucidated, but several have been suggested with good evidence. Our goal is to study the effect of CCG-1423 on mitochondrial function and gene expression of cells. In this work C2C12 myoblast cells have been used as an in-vitro model to study cellular bioenergetics and variations in gene expressions induced by CCG-1423. The effect of CCG-1423 on mitochondrial function was determined by measuring the mitochondrial oxygen consumption rate and glycolysis rate after treating C2C12 cells with varying concentrations of CCG-1423 overnight. In C2C12 myoblast cells, CCG-1423 treatment significantly reduced mitochondrial oxygen consumption rate (OCR) in a dose-dependent manner. However, treatment of C2C12 cells with CCG-1423 overnight increased the extracellular acidification rate (ECAR) in a dose-dependent manner. By indicating that CCG-1423 represses mitochondrial respiration via the Rho-SRF signaling pathway, the results of this study may enable a better understanding of the bioenergetics of the cell in the aging body.
The Evaluation of Smart Speaker Skills for Chronic Disease Management of Older Adults
Authors: Pighin Melissa , Choi Yong Kyung 
Published: December 2021

Abstract
A voice-activated smart speaker is an emerging technology that presents unique opportunities to support the chronic disease management of older adults. We identified the available health-related smart speaker skills in Amazon Alexa platform that support chronic disease management and assessed their functionalities to inform the development of a home-based lifestyle intervention program for older adults with cardiovascular disease and type 2 diabetes. From January to March 2021, we searched Alexa Skills using keywords related to diabetes, medication, blood pressure and nutrition management. Our search produced total 156 potentially relevant skills (63 diabetes, 57 medication, 11 blood pressure and 25 nutrition related), of which 22 skills met inclusion criteria. Apps were excluded if it was only informational, not relevant to the topic, had zero user rating, available in language other than English, and required an external device or a subscription to a specific health plan or service. 22 skills (4 diabetes, 8 medication, 3 blood pressure and 7 nutrition) were evaluated with Echo Show 8 device. The skills were evaluated using the modified version of IMS Institute for Healthcare Informatics app functionality scores and the score (0 to 11) was calculated accordingly. The median number of functionalities was 3.5 and 68% of skills (15/22) had 4 or fewer functions. The highest rated skill was a medication management app named myNurseBot having 6 out of 11 functionalities. The poor functionality score highlights a need for a more robust and comprehensive smart speaker skill to support the health management of older adults.
Civic Engagement in Retirement and the Socioemotional Experience of Pandemic Time
Authors: Bo Boroka 
Published: December 2021

Abstract
This research integrates literature from the sociology of the life course, sociology of emotions and the sociology of time to examine how Socioeconomic Status (SES) influenced retiree civic engagement during the COVID-19 pandemic. I find that SES framed both the social experience of time and the prevalent emotions experienced by retirees while physically distancing during the early days of the pandemic. These individual-level experiences translated to markedly different blueprints for civic engagement. High-SES retirees were more likely to ‘go global’, organizing to advocate for their interests. Conversely, low-SES retirees were more likely to ‘turn in’, minimizing their civic engagement. My findings reveal how existing sociopolitical inequalities may become further entrenched in public health crises. Policies aimed at combating inequalities in later life also need to consider socioemotional and sociotemporal factors.
Daily Cognitive Difficulties and Social Experiences Among Older Adults
Authors: Zhaoyang Ruixue , Mogle Jacqueline , Harrington Karra , Sliwinski Martin 
Published: December 2021

Abstract
Self-reported cognitive difficulties are common in older adults and may be an early indicator of future cognitive decline or dementia. In past retrospective reports, cognitive difficulties have been linked with differences in social engagement or social relationships among older adults. However, little is known about how self-reported cognitive difficulties in daily life, such as memory lapses, relate to older adults’ daily social experiences. This study examined how self-reported cognitive difficulties were related to older adults’ daily social interactions and loneliness. Data were drawn from 312 community-dwelling older adults (aged 70 to 90 years) who reported their social interactions and loneliness throughout the day (five times) as well as cognitive difficulties (e.g., memory lapses, problems with attention) at the end of each day for 14 days. Multilevel models revealed that participants reported fewer memory lapses on days when they reported more frequent interactions with family members (p=.041). Higher levels of disruptions to daily activities caused by cognitive difficulties, in turn, predicted higher levels of loneliness the next day (p=.006), but not changes in social interactions the next day. At the between-person level, more memory lapses in daily life were associated with less frequent social interactions with friends, but more frequent unpleasant social interactions and higher levels of loneliness on average. These results suggest that older adults’ self-reported cognitive difficulties were dynamically associated with their social interactions and loneliness at the daily level and played an important role in older adults’ social life and well-being.