bluuebunny/crossref_metadata_2025_split huggingface dataset:
IN VIVO ANALYSIS OF REPORTER ALLELES REVEALS INCREASED VARIABILITY OF GENE EXPRESSION IN CELLS AND ANIMALS WITH AGE
Authors: Burnaevskiy Nikolay , Sands Bryan , Yun Soo , Mendenhall Alexander 
Published: November 2019

Abstract
As a major risk factor for a multitude of chronic diseases aging is being increasingly recognized as a necessary therapeutic target for preventive medicine. Yet, despite tremendous progress in our understanding of the genetic determinants of longevity, proximal causes of aging remain incompletely understood. In part, this may be due to a plethora of factors, such as various types of stochastic macromolecular damage that affect individual cells and individual animals. Indeed, recent studies point to an increase of cell-to-cell variability in gene expression within old tissues, supporting the idea that stochastic events contribute to the aging process. Therefore, more single-cell focused studies are needed for a complete understanding of biological aging. Here, we utilized quantitative microscopy for analysis of gene expression in individual aging cells, in vivo in C. elegans. Using transcriptional reporters, fluorescently tagged proteins and a quantitative analytical framework adapted from yeast, we have found that young C. elegans exhibit very little stochastic or signaling noise in gene expression. However, using quantitative microscopy, we directly observed dysregulation of gene expression with age in vivo. Specifically, the stoichiometric ratios of proteins that are tightly regulated among the youthful populace start deviating in a cell autonomous fashion. Importantly, we find that an increase of gene expression variation is a relatively early event in the aging of C. elegans, readily observed before median lifespan. Hence, we suggest that incoherent cell-to-cell variation in gene expression arising with age can be an immediate causal factor for age-related loss of robust tissue function.
IDENTIFICATION OF ADAMTS7 AND CEACAM19 AS CANDIDATE HEALTHY AGING ASSOCIATED GENES
Authors: Evans Daniel S , Cummings Steven R 
Published: November 2019

Abstract
The goals of the Longevity Genomics research group (www.longevitygenomics.org) are to develop translational strategies to promote healthy human aging based on findings from genomic studies of aging. Our investigation began with the previously reported and publicly available GWAS of the top 10% of parental lifespan in the UK Biobank, reported by Pilling et al. From five loci reported by Pilling et al., 61 candidate longevity-associated genes (LAGs) were identified using FUMA software. We then tested the 61 candidate genes for aging-related trait associations with tissue-specific predicted gene expression in cohort studies of elderly participants using PrediXcan. PrediXcan was applied to three longitudinal cohort studies of elderly individuals: Health ABC, MrOS, and SOF with a total N of 9893 participants. Aging outcomes tested for association were in the following categories: survival and lifespan, kidney function, cognitive function, physical performance tests, self-reported health and disability, diabetes-related traits, cardiovascular-related traits, lung function, and markers of inflammation. After correction for multiple testing, two genes were significantly associated with longevity-related outcomes. Predicted expression of CEACAM19 in the aorta was significantly associated with circulating C-reactive protein (CRP) levels. In addition, predicted expression of ADAMTS7 in the spleen was associated with a measure of lung function, the forced expiratory volume in the first second. Biological mechanisms for these associations are proposed, and our project provides funding opportunities for interested scientists to follow-up these results with laboratory studies (www.longevitygenomics.org/funding).
LATE-LIFE TIME-RESTRICTED FEEDING AND EXERCISE DIFFERENTIALLY ALTER HEALTHSPAN IN OBESITY
Authors: Schafer Marissa , Mazula Daniel , White Thomas , Pearsall Vesselina , Aversa Zaira , Miller Jordan , LeBrasseur Nathan 
Published: November 2019

Abstract
Aging and obesity increase multimorbidity and disability risk, and determining interventions for reversing healthspan decline is a critical public health priority. Exercise and time restricted feeding (TRF) benefit multiple health parameters when initiated in early-life, but their efficacy and safety when initiated at older ages are uncertain. Here, we tested the effects of exercise versus TRF in diet-induced obese, aged mice from 20 to 24 months of age. We characterized healthspan across key domains: body composition, physical, metabolic, and cardiovascular function, activity of daily living (ADL) behavior, and pathology. We demonstrate that both exercise and TRF improved aspects of body composition. Exercise uniquely benefited physical function, and TRF uniquely benefited metabolism, ADL behavior, and circulating indicators of liver pathology. No adverse outcomes were observed in exercised mice, but in contrast, lean mass and cardiovascular maladaptations were observed following TRF. Through a composite index of benefits and risks, we conclude the net healthspan benefits afforded by exercise are more favorable than those of TRF. Extrapolating to obese older adults, exercise is a safe and effective option for healthspan improvement, but additional comprehensive studies are warranted before recommending TRF.
GROWTH DIFFERENTIATION FACTOR 15 IS CORRELATED TO MARKERS OF IMMUNOSENESCENCE IN MONOCYTES
Authors: Pence Brandt , Yarbro Johnathan 
Published: November 2019

Abstract
Immunosenescence is an age-associated decrease in function of immune cells precipitated by a variety of mechanisms and affecting nearly every immune cell subset. In myeloid cell subsets, aging reduces numbers of phagocytes and impairs their functional abilities, including antigen presentation, phagocytosis, and bacterial clearance. Recently, we have described an aging effect on several functions indicating immunosenescence in monocytes, including impaired mitochondrial function and reduced inflammatory cytokine gene expression during stimulation with lipopolysaccharide (LPS). We hypothesized that circulating factors altered by the aging process underly these changes. Growth/differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor-beta superfamily that has known anti-inflammatory effects in macrophages and has recently been shown to be highly differentially expressed during aging. We used biobanked serum and plasma samples to assay circulating GDF-15 levels in subjects from our previous studies and examined correlations between GDF-15 levels and monocyte mitochondrial function and inflammatory responses. Monocyte interleukin-6 production due to LPS stimulation was negatively correlated to plasma GDF-15 levels (p = 0.046). Additionally, serum GDF-15 was positively correlated to circulating CD16+ monocyte proportions (p = 0.021) and negatively correlated to monocyte mitochondrial respiratory capacity (p &lt; 0.001). Therefore, our data suggest that GDF-15 is a potential circulating factor affecting a variety of monocyte functions and promoting monocyte immunosenescence, and thus is an attractive candidate for therapeutic intervention to ameliorate this.
AGE-RELATED DIFFERENCES IN IMMUNO-HEMATOLOGIC PROFILES AND THEIR ASSOCIATION WITH ALL-CAUSE MORTALITY
Authors: Dalton Jarrod E , Zidar David A , Krieger Nikolas I , Perzynski Adam T , Gunzler Douglas D 
Published: November 2019

Abstract
Immuno-hematologic function (IHF) is increasingly being recognized as a central component of health status in older age. In this study, we sought to identify homogeneous IHF profiles regarding their relationship to all-cause mortality. We then studied the distribution of these profiles among individuals over age 65. We used data on 30,828 NHANES participants, including 10 baseline complete blood count with differential components [e.g., lymphocytes, leukocytes, red cell distribution width (RDW)] and all-cause mortality. We used latent profile analysis (LPA) to simultaneously optimize intra-cluster homogeneity on CBC components and inter-cluster survival differences. LPA (using MPlus 8.2) allowed for the empirical comparison of different solutions based on goodness-of-fit criteria. After LPA model convergence, a 9-class solution balanced goodness-of-fit criteria and interpretability of the resulting classes. The largest 3 classes accounted for 83.7% of the sample, with classes 1, 2 and 3 comprising 32.1%, 28.6% and 23.6%. Class 2 had lower lymphocytes, monocytes, neutrophils and platelets relative to classes 1 and 3. Survival rates were different between classes 1 and 2 (Cox model hazard ratio, HR=0.85; P=0.012) and 2 vs 3 (HR=1.18; P=0.001). The remaining 6 classes, which generally shared in common characteristics of higher RDW and lower hemoglobin, also were involved with significant survival differences. Multinomial logistic regression revealed that, among the subset of 7,173 participants over 65, older age was significantly associated with membership in class 1 relative to classes 2 (P&lt;0.001) and 3 (P&lt;0.001). These results point toward the possibility of developing immune marker profile indicative of accelerated aging.
LIFETIME EXERCISE ATTENUATES AGE- AND WESTERN DIET-RELATED DECLINES IN PHYSICAL FUNCTION IN MICE
Authors: Clayton Zachary S , Gioscia-Ryan Rachel A , Justice Jamie N , Lubieniecki Kara , Rossman Matthew , Zigler Melanie , Seals Douglas 
Published: November 2019

Abstract
Aging is associated with progressive declines in physical function. However, it is unknown if consumption of a western-style diet (WD; high-fat and sucrose, low fiber), compared with a non-WD (healthy diet), accelerates declines in physical function over the adult lifespan, and whether regular voluntary exercise attenuates age- and WD-associated declines in function. To determine this, we studied 4 cohorts of male C57BL/6 mice that consumed either normal chow [NC] or WD with or without access to voluntary running [VR] wheels beginning at 3 mo of age and assessed strength (grip strength normalized to body mass) and endurance (rota-rod distance) every 3 mo throughout life. WD decreased average lifespan by 30% (WD: 18.6±0.5 vs. NC: 26.7±0.8 mo); therefore, function was compared from 3-18 mo of age in all groups. Age-related declines (% change over 3-18 mo) in physical function were accelerated by WD (strength: WD -61.2±10.1%, NC -43.2±10.2%; endurance: WD -97.4±5.1%, NC -65.1±6.3%; all p&lt;0.05 WD vs. NC). VR attenuated declines in physical function within the same diet group (strength: WDVR -34.7±5.1%, NCVR -18.6±5.2%; endurance: WDVR -48.5±5.2%, NCVR -41.4±4.7%; all p&lt;0.05 versus same diet non-VR group). These unique data obtained from a lifelong study of aging in mice, indicate that: 1) consuming a WD reduces lifespan and accelerates age-related declines in physical function by 40-50% vs. a non-WD; regular voluntary exercise (wheel running) prevents this effect of WD on physical function; and 2) regular voluntary exercise also attenuates the age-associated decline in physical function by ~60-130% when consuming a healthy diet.
LEFT VENTRICULAR REMODELING PROCEEDS FROM YOUNG ADULTHOOD INTO MIDLIFE IN INTRAUTERINE GROWTH RESTRICTION BABOONS
Authors: Clarke Geoffrey D , Huber Hillary , Li Cun , Kuo Anderson , Nathanielsz Peter 
Published: November 2019

Abstract
Previous cross-sectional studies have shown young adult baboons (~5-6 y.o.), subjected to intrauterine growth restriction (IUGR) by maternal calorie restriction during pregnancy and lactation, exhibit ventricular remodeling with mildly impaired heart function relative to age/sex-matched controls (CTL). METHODS: In this longitudinal study cardiac MRI was performed on male IUGR baboons (n=7). A 3 Tesla, Siemens TIM Trio MRI system was used with phase-array coils with parallel imaging acquisition and breath-holding during the scan. Studies of IUGR animals occurred at 4.7 + 0.1 yr. intervals; the first scan (scan1) at 5.8 + 1.2 y (human equivalent - HE ~24 years) and the second (scan2) at 10.4 + 1.2 yr (HE~40 y). Scans on the CTL animals (N=4) occurred at 5.3 + 1.4 years and 10 + 1.4 years. RESULTS: Change in body weight over 4.7 years was less in the IUGR group (Δwt=6.3 + 6.1 kg) than in the control group (Δwt =11.5 + 8.2 kg). Left ventricular (LV) ejection fraction (EF) was significantly greater in IUGR animals for scan2 (+10.7%, p=0.03) but not in normal controls (+1.8%, p=0.75). Stroke volume and end-diastolic LV volume were normalized to body surface area (BSA). SV/BSA (17.6 + 4.9, 31.5 + 12.3 mL/sq.m; p=0.016) and EDV/BSA (47.3 + 13.6, 64.5 + 18.8 mL/sq.m; p=0.045) were also significantly increased in IUGR animals but not controls. In IUGR subjects, Δweight was significantly and positively correlated with ΔEF (r=0.86, p=0.01). CONCLUSIONS: In IUGR, but not in CTL baboons, cardiac function adaptations continue into midlife and are related to increases in body weight with aging. We conclude that IUGR programs cardiovascular function and that programmed changes continue into midlife.
METABOLIC CONSEQUENCES OF METHIONINE REDOX IN METHIONINE RESTRICTION
Authors: Thyne Kevin , Liu Yuhong , Salmon Adam B 
Published: November 2019

Abstract
While caloric restriction (CR) provides highly robust improvements to longevity and health, dietary restriction of the essential amino acid methionine can provide similar benefits including improved metabolic function and increased longevity. Despite these similarities between CR and methionine restriction (MR), there is growing evidence to suggest they may be mediated by different mechanisms that require further elucidation. The sulfur side-chain of methionine is highly prone to oxidation, even in vivo, with redox changes of these residues potentially altering protein function and interfering with its use as a substrate. An entire family of enzymes, methionine sulfoxide reductases, have evolved in aerobic organisms to regulate the redox status of methionine. We tested the role of methionine sulfoxide reductase A (MsrA) in the physiological and metabolic benefits of MR. After three months of MR, mice lacking MsrA (MsrA KO) showed significant loss of weight, including both fat and lean mass, in comparison to wild-type mice under MR. Both MsrA KO and wild-type mice responded to MR with improvements to both glucose and insulin tolerance. However, MR MsrA KO mice showed lower HbA1c and reduced leptin compared to MR wild-type mice. Overall, our results show mice lacking MsrA have a stronger response to MR suggesting that methionine redox may play an important role in some of the mechanisms responsible for these metabolic outcomes. Further studies clarify whether MsrA could also be a potential regulator of the longevity benefits of MR.
AGE-RELATED PRESERVATION OF MOTOR NERVE CONDUCTION VELOCITY IN NEURONAL MTORC1 KNOCKDOWN MICE
Authors: Hussong Stacy A , Galvan Veronica 
Published: November 2019

Abstract
With age, peripheral nerves undergo demyelination along with overall decrease in peripheral nerve conduction velocity in both sensory and motor nerves. Loss of innervation in muscles is thought to be a major factor in causing age-related sarcopenia including a decrease in muscle function. Dietary restriction attenuates the detrimental effects of aging in mice. Reduction of mTOR signaling is hypothesized to have overlapping mechanisms with dietary restriction. Furthermore, inhibition of mTOR via rapamycin treatment is known to extend lifespan in mice as well as improve peripheral nerve myelination. Therefore, I hypothesized that reducing mTORC1 signaling in neurons would be able to ameliorate the deleterious effects of aging in peripheral nerves. An overall decrease in nerve conduction velocity was observed in both tail sensory and sural nerves with age (15 vs. 30 months). In neuronal mTORC1 KD animals, there was an age-related preservation of both sural and sciatic nerve conduction. Rapamycin treatment produced similar effects with a trend towards increased sciatic nerve conduction velocity in rapamycin-treated wild-type mice at 19 months. The preserve sciatic nerve conduction velocity could be partially explained by preserved myelination. Neuronal mTORC1 knockdown animals had more myelin in the sciatic nerve at 30 mo. as compared to age-matched controls. Overall, these data indicate that mTORC1 signaling plays a role in the age-related decline in peripheral nerve myelination as well as nerve conduction velocity. Future therapeutics could utilize rapamycin or other rapalogs to combat the decline in peripheral nerve function associated with age and other diseases as well.
BEHAVIORAL ACTIVATION FOR FAMILY CAREGIVERS OF PEOPLE WITH DEMENTIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Xu Xinyi , Kwan Rick , Leung Angela Y M 
Published: November 2019

Abstract
Behavioural activation (BA) aims to increase positive response-contingent environmental reinforcement and help caregivers to engage in pleasant and constructive activities, and therefore improve psychological and physical health among family caregivers of people with dementia (PWD). However, knowledge of the effectiveness of BA in this population remains limited. The current study applied a systematic review and meta-analysis in order to determine the effectiveness of BA among family caregivers of PWD. Literature was searched in PubMed, Medline, CINAHL, Cochrane, Embase and PsycINFO published from March 1988 to March 2018. Seven Randomized Control Trials (RCT)s evaluating the effects of BA in family caregivers of PWD were eligible to be included in this review. Cochrane’s guideline was used in order to measure risk of bias and extract data. A random effects model was used to pool the effect size. Family caregivers of PWD receiving BA that only for caregivers demonstrated a statistically significant reduction in depression (n=3; 311 participants; Cohen’d=0.55; 95% CI: 0.30 to 0.81; P&lt;0.001). BA also had a positive impact on interlukin-6, negative affect of caregiving, relationship satisfaction, dysfunctional thoughts and distress related to neuropsychiatric symptoms of PWD for family caregivers. The available evidence suggests that future studies are needed to focus on better ways of administering BA to family caregivers of PWD, to improve their physical and psychological health. Meanwhile, more RCTs to investigate the effects of BA on psychological and physical health for family caregivers of PWD is needed.
EVALUATION OF THE RESCUE PROGRAM FOR REDUCING STROKE CAREGIVER STRESS AND IMPROVING PROBLEM-SOLVING ABILITIES
Authors: Jordan Meggan , Freytes I Magaly , Orozco Tatiana , Dang Stuti , Uphold Constance R 
Published: November 2019

Abstract
Research shows that caregiver interventions that combine problem-solving with psycho-education are the most effective for addressing stroke caregiver concerns. The Resources and Education for Stroke Caregivers’ Understanding and Empowerment (RESCUE) program, designed to reduce caregiver stress, depression, and burden, developed as a result of this evidence. A 4-week telephone and web-based clinical demonstration project led by registered nurses was established as part of the VHA Office of Geriatrics and Extended Care’s Non-Institutional Long Term Care Initiative. The goals of this clinical demonstration were to improve problem-solving skills and provide individualized support for stroke caregivers. A single-group pre and post-test design was used and 72 caregivers of veterans with stroke completed the intervention; qualitative and quantitative methods were used for evaluation. The outcome variables were caregiver depressive symptoms, problem-solving abilities, burden, health-related quality of life and care recipient functional abilities. Post-tests were conducted 2-6 weeks after the intervention. The evaluation found that there were statistically-significant decreases in caregiver depressive symptoms and burden from pre- to post-test assessments. Caregivers’ negative problem orientation significantly decreased. The other components of problem-solving abilities did not change. Qualitative data revealed how the program increased caregivers’ confidence in problem-solving which led to new strategies to relieve stress. Interviews also revealed how the intervention affected caregivers in unexpected ways, such as improved intimate relationships and new perspectives on caregiving. The preliminary effectiveness and barriers and facilitators of implementing a stroke caregiver program will be discussed.
DYADIC INTERVENTION FOR PEOPLE WITH DEMENTIA AND THEIR FAMILY CARERS AFTER THE DIAGNOSIS
Authors: Prins Marleen , Veerbeek Marjolein , van der Velden Claudia , Willemse Bernadette 
Published: November 2019

Abstract
Adaptation to and coping with the diagnosis dementia is a complex process. The right support in this phase is important to find the right care and to (self-)manage future care wishes. However, people with dementia (PWD) and their family carers (FC) often experience support directly after the diagnosis as inadequate. Support is not provided until problems start to accumulate and available support is not focused on continuation of their life and the emotional impact of the diagnosis. Therefore, the intervention SHARE [Support, Health, Activities, Resources, Education] was developed and studied in the US and adjusted to and pilot-tested in the Netherlands with positive results. SHARE is innovative because it is designed for dyads dealing with early-stage dementia to enhance communication between PWD and their FC and to prepare them for the future. In this study, the Dutch SHARE intervention was adjusted because of new insights and an RCT is being conducted to evaluate the (cost)effectiveness of this version of the Dutch SHARE. The primary outcome measurement for the PWD is quality of life and self-efficacy for the FC. Secondary outcomes are stress, communication in the relationship and perspective taking (only FC). The design and procedures of the RCT will be presented in this poster session as well as the demographic characteristics of participating dyads. This study contributes to knowledge about psychosocial interventions for PWD and FC with special attention for preventive empowerment of the ability to cope with the disease and the capacity to deal with the situation.
NEEDS AND EXPERIENCES OF CAREGIVERS TO PERSONS WITH DEMENTIA WHO HAVE LOST THEIR DRIVING PRIVILEGES
Authors: Yamin Stephanie , Gratton Cassandre 
Published: November 2019

Abstract
The ability to drive a motor vehicle for most older adults is associated with a sense of independence, well-being, quality of life and identity. For many older adults, driving cessation eventually becomes inevitable. This is especially the case for older adults with a diagnosis of dementia. Driving cessation has been shown to negatively impact individuals’ mobility and, consequently, quality of life. Informal caregivers (i.e., family caregivers) can mitigate the negative consequences associated with driving cessation in persons with dementia (PWD) by meeting their mobility needs and by offering emotional support. The purpose of this study was to examine the experience and needs of informal caregivers of PWD who had recently lost their driving privileges. Ten informal caregivers of PWD were recruited from a tertiary memory disorders clinic. Semi-structured interviews were conducted and transcribed. Transcripts of interviews were thematically analyzed using a grounded theory approach. The major themes emerging from the experience of caregivers included being overwhelmed by responsibility, overwhelmed by the emotional response of their care recipient and feeling resentment towards their care recipient. Similarly, the major themes emerging from the needs of caregivers included having the need for mobility training, psychoeducation on how to best attend to the emotional needs of their care recipient and the need for coping strategies. These experiences and needs expressed by caregivers indicate that driving cessation of the care recipient is a difficult experience for caregivers and that a therapeutic intervention based on the reported needs may be beneficial.