bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALTERED TRYPTOPHAN DEGRADATION LINKS CHRONIC INFLAMMATION TO FUNCTIONAL DECLINE & FRAILTY IN MICE AND HUMANS
Authors: Westbrook Reyhan , Chung Tae , Lovett Jacqueline , Ward Chris , Khadeer Mohammed , Moaddel Ruin , Walston Jeremy , Abadir Peter 
Published: November 2019

Abstract
Chronic inflammation is associated with frailty and functional decline in older adults but the molecular mechanisms of this linkage are not well understood. We sought to examine metabolic and physiologic states associated with aging and frailty by analyzing the composition of metabolites in the blood of a population of community dwelling young, and older adults. Serum inflammatory cytokines and demographic and physiological covariates were collected in a set of community-dwelling adults age 20-97 (n=166). We then used LC/MS technology to profile 121 metabolites from five substance classes. Associations of the cytokines and metabolites with grip strength, walking speed, falls and outcomes were assessed in young, robust, pre-frail and frail participants. Age and frailty status positively correlated with IL6, TNFα, TNFαR1, IL1β (p&lt;0.0001). Analysis of metabolites revealed significant alterations in tryptophan degradation pathway with aging and frailty. Among the top metabolites to correlate with age and frailty status were kynurenine (p&lt;0.0001) and the kynurenine/tryptophan ratio (p&lt;0.0001). The kynurenine/tryptophan ratio also tightly correlated with serum inflammatory cytokines TNFαR1 (p&lt;0.0001) and IL-6 (p&lt;0.0001). Higher kynurenine/tryptophan levels were associated with weaker grip strength and slower walking speed, even after adjusting for age, gender, BMI and blood pressure. Further dissection of the pathway revealed the accumulation of 3-hydroxykynurenine, a cytotoxic and neurotoxic intermediate from the kynurenine pathway, with frailty. The increased levels of cytotoxic and neurotoxic molecules in this pathway may in part explain the link between inflammation and cognitive and physical decline in frailty.
KEY DIMENSIONS OF OASIS, AN OLDER-ADULT DRIVEN MODEL OF AGING-IN-PLACE IN CANADA
Authors: DePaul Vincent , Donnelly Catherine , Parniak Simone , Collaborative Oasis Study 
Published: November 2019

Abstract
Oasis Senior Supportive Living (Oasis) is an active aging-in-place model created by older adults in a naturally occurring retirement community, such as an apartment building. The program is member-driven so that participating older residents determine the programming and services that best address their needs. The first Oasis program was established in an apartment building in Kingston, Canada and has been running for more than ten years. Preliminary evaluations of the Oasis program demonstrate that its members report feeling more socially connected, are more physically active, and have increased nutrition as a result of participation. In-depth interviews were conducted with Oasis members and key program stakeholders to identify the core dimensions of the Oasis program that has led to its success in supporting active aging in place. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to identify, analyze and report themes. Four themes emerged: (1) nutrition, social and physical activities as critical programming pillars; (2) the importance of active member participation and decision-making; (3) the need for onsite support to facilitate programming; and (4) Oasis as a family. These findings highlight the need for programming that is designed for and by older adults. Supporting older adults to come together and form community is key to healthy and active aging. Identification of these elements is critical to modelling Oasis in other community contexts. Oasis is currently being expanded to seven new communities across Ontario using a participatory action research approach.
AGE, FUTURE TIME PERSPECTIVE, AND EVERYDAY PHYSICAL ACTIVITY AND NUTRITION IN COUPLES POST STROKE
Authors: Garza Elizabeth Zambrano , Pauly Theresa , Linden Wolfgang , Ashe Maureen C , Murphy Rachel , Madden Kenneth , Hoppmann Christiane A 
Published: November 2019

Abstract
Physical activity and fruit/vegetable consumption are recommended to help prevent and manage cardiovascular disease. Yet, most people struggle to meet physical activity and nutrition guidelines. This study examined the role of age and future time perspective for these two health behaviors using repeated daily life assessments as well as accelerometry-based step counts from 70 persons living with the effects of stroke and their partners (50% female, M age=69 years). Consistent with previous research, older age and living with stroke were associated with taking fewer steps in everyday life but also with consuming more fruit and vegetables. Furthermore, participants who viewed their future as being filled with many opportunities took more daily steps and ate more fruit and vegetables than participants low in future opportunities. Further analyses will examine dyadic associations in these two health behaviors as well as partner factors that may facilitate or hamper the engagement of the behaviors. It is important to analyze these relationships to gain further insight into the effects partners have on each other.
SOCIAL DETERMINANTS OF HEALTH DRIVE EMERGENCY ROOM AND HOSPITAL USE BY DUAL ELIGIBLE AND DISABLED PENNSYLVANIANS
Authors: Cai Sih-Ting , Degenholtz Howard , Germack Hayley 
Published: November 2019

Abstract
The study examined correlates and consequences of social determinants of health risk factors (SDoH) among dual eligible aged and disabled individuals; Pennsylvania is transitioning this population into a managed care plan with responsibility for care coordination and incentives to prevent hospitalization and nursing home placement. Medicaid and Medicare claims were used to identify people with SDoH based on ICD-10 codes in 2016 in four domains: economic insecurity, life stressors, physical dependence, and potential health hazards. Of 281,918 people, 38.6% had one or more SDoH. Among people with severe mental illnesses (SMI; schizophrenia, psychosis, major depressive disorder, or bipolar disorder), the prevalence of SDoH was 57.9%. Of people with one or more SDoH, 42% visited the ED, compared to only 32% of people with no SDoH. Economic insecurity (OR 1.68; CI 1.59-1.78), life stressors (OR 1.39; CI 1.29-1.48), physical dependence, (OR 2.01; CI 1.97-2.06), and potential health hazards (OR 1.52; CI 1.47-1.56) were independently associated with risk of hospitalization, controlling for age, gender, race, SMI, chronic conditions and disability. The introduction of diagnosis codes for SDoH under ICD-10 has facilitated identifying individuals with deficits that might increase health care use above and beyond their underlying health status. Although the prevalence of these risk factors as captured in diagnosis data is likely an underestimate, the strong association with subsequent ED use and hospitalization lends credence to these indicators. Medicare and Medicaid claims data can be used to identify people with SDoH and target interventions to prevent downstream health services use.
FLAVIN-CONTAINING MONOOXYGENASES (FMOS): LONGEVITY-PROMOTING ENZYMES OR ATHEROSCLEROSIS RISK FACTOR?
Authors: Rossner Ryan J , Kaeberlein Matt 
Published: November 2019

Abstract
Since their discovery in 1970, flavin-containing monooxygenases (FMOs) have been studied as Phase 1 xenobiotic metabolizing enzymes that act on sulfur- and nitrogen-containing small molecules. In 2015, we demonstrated that C. elegans (worm) fmo-2 was not only necessary for hypoxic response and dietary restriction-mediated lifespan extension, but was also sufficient to extend lifespan when overexpressed. Consistenet with a conserved role for FMOs as longevity-promoting enzymes, mouse hepatic Fmo3 transcript is highly upregulated by numerous major lifespan extending interventions. A contrasting series of reports, however, have described mammalian Fmo3-mediated production of trimethylamine N-oxide (TMAO) as a risk factor for atherosclerosis and other major diseases. My thesis research aims to define the regulation and function of worm fmo-2 using genetic and biochemical approaches. My data thus far support the hypothesis that fmo-2 acts on sulfur amino acid pathway intermediates to promote longevity and healthspan.
METABOLOMICS OF DELIRIUM: A CASE-CONTROL STUDY
Authors: Tripp Bridget , Dillon Simon , Vasunilashorn Sarinnapha , Ngo Long H , Fong Tamara G , Marcantonio Edward R , Libermann Towia A , Otu Hasan 
Published: November 2019

Abstract
Postoperative delirium complicates 15-50% of major surgery in older adults, resulting in poor patient outcomes and increased healthcare costs. Basic mechanisms of delirium are largely unknown. In this study we implemented a protocol that uses high-throughput metabolomics to explore potential biological mechanisms of delirium. We profiled the plasma metabolome of 10 delirium cases and 10 matched controls from the SAGES cohort of older adults without dementia undergoing major non-cardiac surgery. We used targeted mass spectrometry to measure 302 metabolites (features) preoperatively (PREOP) and on postoperative day 2 (POD2). Metabolomics studies are challenged by inherent technical variability and signal noise. With a small sample and a large feature count, signal noise diminishes statistical power and masks true biological signals. To address these challenges, we implemented quality control sample-based signal correction and normalization to internal standards (ISs). ISs were screened from a pool of 6 potential candidates, resulting in the removal of 3 that failed to perform well, while 3 were retained for our experiments. ISs also enabled successful concatenation of experiments run at different times. Prior to implementing quality control samples and customized ISs, no metabolites were identified as differentially expressed. After implementation, we identified one metabolite that was significantly differentially expressed at PREOP and 17 metabolites that were significantly differentially expressed at POD2 between delirium and controls (BH-corrected p-value &lt; 0.05). In conclusion, integration of quality controls and normalization to internal standards enabled us to detect metabolites associated with postoperative delirium. Such methods should be considered for future metabolomics studies.
SOCIAL RELATIONS AND FRAILTY TRAJECTORY IN LATER ADULTHOOD: EVIDENCE FROM HEALTH AND RETIREMENT STUDY
Authors: Lee Ji Hyun 
Published: November 2019

Abstract
Frailty is a state of heightened vulnerability due to the cumulative declines across multiple physiological systems. Growing attention is given to identifying social environmental factors associated with the risk of frailty. It is not yet known how different aspects of social relationships (structure and quality) are linked to frailty, and whether the strength and directions of links may differ by relationship types. Current study aims to 1) to identify sub-populations that follows distinctive trajectory of frailty and 2) to examine the multidimensional social relationship predictors of frailty trajectory. Data came from six waves of the Health and Retirement Study (2006-2016). Sample was older adults aged over 65 (n = 8,892; Mage = 74, SD = 6.96). Frailty index was created using 32 items each wave. Network size, frequency of contact, support, and strain with each relationship type (spouse, children, family, friends) was measured at baseline. Growth mixture model identified three distinctive subpopulations of older adults who share similar frailty trajectory, namely the average, high, and steep increase frailty group. Multinomial logistic regression results showed that frequent contact with friends were associated with lesser frailty. Perceived strain with the spouse, children, and family members all had additive influence on the membership to the higher or steep increase frailty group, compared to the average frailty group. Total network size or perceived support from ties were not significant factors for frailty progression. Interventions can target friendships and stress with kin members as modifiable factors to reduce the risk of frailty progression.
CORRELATES OF MENTAL HEALTH PROBLEMS AMONG OLDER AFRICAN AMERICANS WITH CHRONIC ILLNESS
Authors: Yoon Eunkyung , Spence Susie 
Published: November 2019

Abstract
Prior epidemiologic studies have established that high rates of comorbidity of diabetes and depression is common. The aim of this study is to examine prevalence and correlates of mental health conditions among older African Americans with chronic health conditions The sample (n=1,399) from the first round of the NHATS includes older African Americans living in their community: 60% women, 35% married, 39% less than HS, 57% from the South. A two-way MANCOVA was conducted to determine the effect of diabetes and high blood pressures on four DV (no interest, depressed, anxious, worry) while controlling for age. Data indicated that 37% are with diabetes and 80% with high blood pressure and showed that 10% no interest, 4.4% depressed, 3.6% anxious, and 6.4% constantly worry for nearly every day. The main effects of high blood pressure [Wilk’s Λ = .983, F= 2.322, p =.010, η 2 = .015)] and diabetes [Wilk’s Λ = .975, F= 3.526, p =.010, η² = .024] indicate significant effect on combined mental health DV. The covariate significantly influenced the combined MH DV [Wilks’ =.983, F = 3.697, p = .003]. Univariate ANOVA results showed that only anxiety and worry were significantly affected by diabetes and high blood pressure except “depressed” and “no interest” These results partially support that older African Americans with chronic illness are at high risk for general mental health. However, anxiety and worry were more prevalent than just ‘be depressed’. Greater attention should be paid to specific mental expressions of minority older patients.
LONGEVITY OVER THE COUNTER: INVESTIGATING THE EFFECTS OF COMMON DIETARY SUPPLEMENTS ON AGING
Authors: Blue Ben , Vayndorf Elena , Kaeberlein Matt 
Published: November 2019

Abstract
C. elegans has been a workhorse within the field of aging biology for several decades due to its short lifespan, easy culturing, and robust genetic tools. However, the limiting factor in using C. elegans has been that throughput was constrained by the time and effort needed to manually check the worms for signs of life during longitudinal studies. By using the WormBot, a robotic image capture platform, we are able to successfully screen a wide array of compounds for their effects upon C. elegans lifespan. A single WormBot can monitor 144 individual experiments simultaneously and allows for accurate time of death calls. Here we present data generated with the WormBot that includes a screen of compounds from a wide array of natural and synthetic products that are often available as over-the-counter supplements. In order to better examine the effects of these widely-used compounds upon the aging process and an age-associated disease we examined longevity in a wildtype strain of C. elegans as well as an engineered strain that expresses human Aβ protein in the body wall muscle. The age-related pathogenesis of the Aβ-expressing strain is a progressive paralysis that can be halted with treatment of known effectors of Alzheimer’s disease. As such, we screened our battery of compounds with this strain to determine which compounds have a significant affect on delaying Aβ-associated paralysis. Lastly, using the WormBot’s ability to capture video recording, we examine how each compound affects mobility as animals age.
EFFECT OF CALORIC RESTRICTION AND RAPAMYCIN ON OVARIAN AGING IN MICE
Authors: Garcia Driele , Saccon Tatiana , Rincon Joao , Pradiee Jorgea , Mondadori Rafael , Masternak Michal , Bartke Andrzej , Schneider Augusto 
Published: November 2019

Abstract
The ovarian follicular reserve of primordial follicle declines with aging in female mammals. Caloric restriction (CR) has been shown to increase the preservation of the ovarian follicular reserve. Likewise, rapamycin has similar effects to CR on the ovarian reserve. Therefore, the aim of our study was to evaluate the effects of rapamycin and CR on the metabolism and ovarian follicular reserve and gene expression in mice. Thirty-six female mice were used, and allocated into 3 groups: control, rapamycin (4mg/kg body weight every other day) and 30% CR. At 85 days of treatment, an insulin tolerance test (ITT) and glucose tolerance test (GTT) was performed. At 93 days ovaries were collected for analysis. CR females had lower body weight (P&lt;0.05) and were more insulin sensitive (P=0.003), while rapamycin treated females did not change body weight (P&gt;0.05) and were more resistant to insulin (P&lt;0.05). Females from the CR and rapamycin groups had a twice higher number of primordial follicles (P=0.02 and 0.04) and half the number of primary, secondary and tertiary follicles (P&lt;0.05). Both CR and rapamycin females had increased ovarian gene expression of Foxo3a mRNA (P&lt;0.05). In conclusion, female mice from rapamycin and CR groups had an increased ovarian follicular reserve associated to higher expression of Foxo3a mRNA, despite divergent metabolic effects of the treatments.
EFFECT OF TLR4 INHIBITION IN FAT-INDUCED INSULIN RESISTANCE IN HUMAN SUBJECTS
Authors: Liang Hanyu , Sathavarodom Nattapol , Colmenares Claudia , Ganapathy Vinutha , Orsak Beverly , Musi Nicolas 
Published: November 2019

Abstract
Older and obese subjects have increased levels of free fatty acids (FFA) in plasma that may mediate the inflammation and insulin resistance seen in these individuals. Data generated mostly in cells and rodents suggest that toll like receptor 4 (TLR4) mediates the inflammatory and insulin resistant states induced by FFA. In the present study, we tested the hypothesis that pharmacologic blockade of TLR4 would prevent lipid-induced insulin resistance. We recruited 10 lean, healthy subjects (Age: 51 ± 1 y, Sex: 6M/4F, BMI: 23.8 ± 0.7 kg/m2, Fasting plasma glucose (FPG): 5.5 ± 0.1 mmol/l). They were randomized to receive the following 72 h long i.v. treatments on separate occasions: saline (30 ml/h)+placebo (12 mg every 12 h); Intralipid (30 ml/h)+placebo; Intralipid (30 ml/h)+eritoran (12 mg every 12 h). After these infusions, insulin sensitivity was measured with an hyperinsulinemic clamp. Infusion of Intralipid significantly decreased insulin sensitivity (M value) by 14%. FPG and fasting plasma insulin concentrations increased with Intralipid infusion by 7% and 22%, respectively. Intralipid also caused a low-grade inflammatory state, evidenced by increases in plasma levels of TNFa (32%), lipopolysaccharide (14%), LPS binding protein (21%), and blood monocytes counts (15%). However, metabolic and inflammatory outcomes were not different between the Intralipid+placebo and the Intralipid+eritoran groups. We conclude that short-term TLR4 inhibition with eritoran fails to prevent lipid-induced inflammation and insulin resistance. Studies with longer acting TLR4 inhibitors may be needed to clarify the role of TLR4 on the pro-inflammatory and insulin resistant states seen with aging and obesity.
CLONAL HEMATOPOIESIS IN A CENTENARIAN COHORT
Authors: Bhutkar Aparna , Gurinovich Anastasia , Perls Thomas T , Sebastiani Paola , Monti Stefano 
Published: November 2019

Abstract
Mosaicism, the presence of two or more genotypically or karyotypically distinct populations of cells in a single individual, plays an important role in human disease. Mosaicism can result in mutations and/or chromosomal alterations such as loss, gain, or copy-number neutral loss of heterozygosity. Clonal mosaicism and its relationship to aging and cancer, has been previously studied, and earlier work suggests that clonal mosaicism tends to increase with age. The aim of our research is to use genotype data of centenarians to explore the relationship between extreme longevity and mosaic chromosomal alterations (mCAs). To this end, we analyzed genome-wide genotypes from blood-derived DNA of 338 individuals from the New England Centenarian Study. The participants in this dataset ranged from 45 to 112 years of age. For the detection of mCA events, we used MoChA (https://github.com/freeseek/mocha), a bcftools extension, that predicts mCAs based on B-allele frequency (BAF) and log2 intensity(R) ratio (LRR), and uses long-range phase information to increase sensitivity. Chromosomal alteration events, including whole chromosome events, were detected in 180 out of the 338 individuals. A total of 165 duplications, 97 deletions, and 9 copy-number neutral loss of heterozygosity were detected. Additionally, there were 42 events whose copy number state could not be determined with high confidence. 236 events out of the 313 were detected in individuals aged 100 and older. Our analysis of chromosomal alteration frequency by age indicates that, within centenarians, the proportion of individuals with mCAs significantly decreases with increased age (p &lt; 0.05, correlation -0.73).
AGE-ASSOCIATED INCREASE IN KYNURENINE SUPPRESSES AUTOPHAGY AND PROMOTES APOPTOSIS IN MESENCHYMAL STEM CELLS
Authors: Kondrikov Dmitry , Elmansi Ahmed , Bragg Robert T , Mobley Tanner , mcGee-Lawrence Meghan , Hamrick Mark , Isales Carlos , Hill William D 
Published: November 2019

Abstract
The age-related increase of the tryptophan metabolite, kynurenine (KYN), has been associated with osteoporosis progression. Increased activity of by Indoleamine-(2,3)-dioxygenase(IDO), are responsible for the elevation of KYN levels in bone tissue. IDO activity is elevated with age and could be a promising therapeutic target forosteopenia and osteoporosis. Previously, our group has shown that the serum level of KYN is elevated with age and correlates with bone loss in vivo. Kynurenine suppress the expression and activity of chemokine CXCL12 essential for osteogenesis, bone marrow stem cells homing. Bone Marrow Stem Cells (BMSC) cultured in 1% FBS were treated with CXCL12 (100ng/ml) in the presence of saline control or the autophagic flux-inhibition agent chloroquine (CQ). CXCL12 treatment increased autophagy by upregulating the degree of LC3B-II by 20%. CXCL12 treatment also significantly increased co-localization of LC3B and LAMP-2 in serum starved cells. In the present study, we tested the theory that kynurenine plays an opposite role to CXCL12 by suppressing the autophagy cell survival pathway and by inducing apoptosis. Treatment of nutrient-deprived murine BMSCs with 10 or 100 µM of KYN suppresses autophagy in a dose dependent fashion while increasing cellular apoptosis. Treatment of BMSCs with KYN downregulated autophagic flux in BMSC preventing CQ-induced CL3B/LAMP-2 colocalization. KYN treatment prevented conversion of LC3B-I to LC3B-II in CQ-treated cells by 30 percent. At the same time, KYN treatment induces apoptosis, by increasing TUNEL-positive cells number by more than 50 percent. Additionally, KYN treatment significantly increased the levels of cleaved isoforms of PARP and caspase-3.