bluuebunny/crossref_metadata_2025_split huggingface dataset:
MICROGLIA MAY INSTRUCT SYNAPTIC FATE VIA SIRPα IN MOUSE RETINA
Authors: Jiang Danye , Samuel Melanie 
Published: November 2019

Abstract
As we age, our nervous system undergoes many deleterious alterations: cognitive and sensory functions decrease while the risk of disease increases. Synapses are responsible for neural information processing, and the decline of these structures via microglia-mediated remodeling is thought to underline many age-related neural changes. However, the molecular pathways responsible for microglia-mediated synapses removal in development and old age remain unknown. To begin to elucidate these pathways, we leveraged the precisely organized murine retina where neurons form synapses in distinct lamina. Using this system, we screened 102 lacZ reporter lines available through the Knockout Mouse Project (KOMP) and uncovered a unique synapse regulatory candidate, SIRPα. We show that SIRPα is present in microglia prior to synapse formation but becomes selectively enriched in neural synapse terminals as these connections mature. Further, the levels of SIRPα decrease in the context of age-related neural decline. In ongoing studies, we are testing the hypothesis that neuronal SIRPα regulates its receptor CD47 to modulate refinement by microglial SIRPα. Together, these studies will resolve the molecular cues through which microglia prune synapses in development and dissect how these programs may go awry in the context of aging and disease.
ANTICHOLINERGIC DRUGS: CUT-OFF FOR IMPAIRED COGNITION AND MOBILITY IN SENIORS
Authors: ATTOH-MENSAH Elpidio K , Loggia Gilles , Morello Remy , Schumann-Bard Pascale , Descatoire Pablo , Marcelli Christian , Chavoix Chantal 
Published: November 2019

Abstract
Background and Objectives: Anticholinergic drugs are commonly prescribed in older adults despite growing evidence of their adverse outcomes. We aimed to improve knowledge about deleterious effects of anticholinergic drugs on both cognition and mobility, in particular whether there is a threshold value for the number of anticholinergic drugs or for the anticholinergic burden leading to mobility or cognitive impairment. Methods: 177 community-dwelling individuals aged 55 years or over, with a fall history in the previous year, took part in the study. Anticholinergic drugs were identified using the Anticholinergic Drug Scale (ADS), and global cognition and mobility were assessed using the Mini Mental State Examination (MMSE) and the Time-Up-and-Go (TUG) test, respectively. Results: ROC (Receiver Operating Characteristics) curve analysis indicated that consumption of a single anticholinergic drug per day was a risk factor for impaired MMSE (p &lt; .05) and TUG scores (p &lt; .05). There was also a cut-off of anticholinergic burden of one for impaired MMSE scores (p &lt; .05). Logistic regressions showed that impaired cognition induced by anticholinergic drugs were independent of confounding factors including comorbidities, while impaired mobility would be influenced by age and cardiac comorbidities. Conclusion: Daily consumption of a single anticholinergic drug, regardless of its anticholinergic burden, impairs both cognition and mobility community-dwelling seniors. Alternative solutions to anticholinergic drug prescription should thus be considered whenever possible.
USEFUL FIELD OF VIEW AND DRIVING SIMULATION ACROSS TWO AGE GROUPS
Authors: Dunterman Rebecca A , Intrieri Robert C , Guernsey Marisa 
Published: November 2019

Abstract
The Insurance Information Institute (2017) reports that drivers aged 65 and older have the second highest rate of fatal car crashes. Research with the useful field of view (UFOV) assessment has predicted crashes in older drivers (Ball, 2006). “UFOV is defined as the area from which an individual can extract information quickly without head or eye movement” (Posit Science, 2019). Research demonstrates that older drivers are limited by poorer vision, divided attention and the inability to ignore distractions, and slower reaction time to critical stimuli (Owsley et al. 1998). As a result UFOV is an effective variable in assessing driver safety. We hypothesized that older compared to younger drivers would be less likely to inhibit attention to task irrelevant visual stimuli while engaged in a simulated driving task. Participants were community dwelling older adults and students recruited from a research pool and through word of mouth. Participants completed a series of demographic and health questions, Snellen visual acuity test a series of cognitive measures (e. g., Trails 1 and 2, digit symbol, digit span) and the UFOV assessment. Participants completed a driving simulation task while information on driving performance: number of collisions, speed limit deviations, turn signal use, time spent tailgating another vehicle, and braking reaction times. ANOVA demonstrated that as hypothesized, younger participants had significantly lower UFOV risk scores (p = .000). Older adults’ (M = 2.15, SD = .945) and younger adults’ (M = 1, SD = 0).
DNA METHYLATION CLOCKS IN MOUSE
Authors: Meer Margarita , Gladyshev Vadim 
Published: November 2019

Abstract
One of important limiting factors in aging research is the time required to measure the effect of an intervention on lifespan. But this situation is now changing due to a recent discovery of DNA methylation-based markers (DNAm clocks). We developed a whole lifespan multi-tissue DNAm clock for mice with R2 =0.89. We also carried out comparative analyses of the available mouse DNAm clocks (single- or multi-tissue, based on different number of sites, based on one genomic locus or multi-loci). In general, tissue specific clocks are more accurate than muti-tissue clocks. We applied these tools to a variety of experimental systems, ranging from interventions to rejuvenation approaches, and analyzed various mouse tissues and public datasets. We further applied DNAm clocks to newly sequenced sets of blood and liver samples. Multi-loci blood clock outperforms other clocks when applied to blood samples, and the liver and multi-tissue clocks show similar precision on liver.
HOW THE IMPACT OF CHRONIC PAIN ON COGNITION VARIES BY POLYGENIC RISK SCORE (PRS)
Authors: Song Jieun 
Published: November 2019

Abstract
While prior research has found associations between chronic pain and cognition and genetic risk of cognitive decline, little research examined moderating effects of genetic risk on the association between chronic pain and cognition. This study investigate whether genetic risk of accelerated cognitive decline, assessed by polygenic risk score (PRS) of Alzheimer disease (AD), moderates the association between severe chronic pain and cognitive decline. The data are drawn from Midlife in the US (MIDUS), a survey of a nationally representative sample of US adults. The analytic sample consists of two groups: 201 individuals who reported severe chronic pain (116 women, 85 men) and 404 individuals without severe chronic pain (215 women, 189 men) who completed MIDUS 2 (2004-06) and MIDUS 3 (2013-14) surveys and participated in biomarker data collection. The findings showed that men who suffered from severe chronic pain were more vulnerable to genetic risk of cognitive decline than men who did not experience severe chronic pain. Specifically, men who suffered from severe chronic pain and had higher level of PRS of AD experienced a greater decline of episodic memory than men who experienced chronic pain with lower level of PRS of AD. This association was not found in women sufferers. For both men and women who did not have chronic pain, cognitive change was not a function of the level of genetic risk of cognitive decline. Findings suggest that genetic risk of cognitive decline would be manifested contingent on life circumstances as well as gender of individuals.
SYSTEMS BIOLOGY OF HUMAN AGING - NETWORK MODEL 2019
Authors: Furber John D 
Published: November 2019

Abstract
This network schema is presented to aid in conceptualizing the many processes of aging, the causal chains of events, and the interactions among them, including feedback and vicious cycles. Contemplation of this network suggests promising intervention points for therapy development. This diagram is maintained on the Web as a reference for researchers and students. Content is updated as new information comes to light. www.LegendaryPharma.com/chartbg.html At first glance the network looks like a complicated web. However, as a conceptual summary, in one view, we can see how the many biogerontological processes relate to each other. Importantly, examination of these relationships allows us to pick out reasonably plausible causal chains of events. Within these chains, we can see age-related changes or accumulations that appear to be promising targets for future therapy development. Especially harmful is damage to the body's regeneration and repair systems, because they normally repair damage to other structures and systems. The many observable signs of human senescence have been hypothesized by various researchers to result from several primary causes. Inspection of the biochemical and physiological pathways associated with age-related changes and with the hypothesized causes reveals several parallel cascades of events that involve several important interactions and feedback loops. This network model includes both intracellular and extracellular processes. It ranges in scale from the molecular to the whole-body level. Effects due to externalities, lifestyle, environment, and proposed interventions are highlighted around the margins of the network.
BUILDING H.O.U.S.E. (HEALTHY OUTCOMES USING A SUPPORTIVE ENVIRONMENT) FOR LGBTQ OLDER ADULTS
Authors: Rosenwohl-Mack Amy , Beld Matt , Greene Meredith , Skultety Karyn , Dubbin Leslie , Deutsch Madeline B , Flatt Jason D 
Published: November 2019

Abstract
Lesbian, gay, bisexual, transgender, and queer (LGBTQ) older adults face unique challenges in finding affordable, inclusive, and supportive housing. These challenges may be due to discrimination, income disparities, and higher rates of health problems compared to cisgender heterosexual seniors. To our knowledge, this is the first longitudinal study of the health and wellbeing of older adults who move into LGBTQ-welcoming, affordable senior housing. Participants completed a brief baseline survey at the time of their housing lottery application. Questions focused on physical, psychological, and social health and current health service use. We calculated descriptive statistics on health status at baseline. 184 participants completed the baseline survey, mean age was 68 years (SD 5.2), and nearly 75% reported an annual income under $30,000. Almost half reported a diagnosis of hypertension, 40% depression, 27% anxiety, and 25% HIV/AIDS. Around 70% reported their health as good to excellent, 21% fair, and 9% poor or very poor. However, 58% reported their physical activities were at least somewhat limited by their physical health, 43% reported difficulties with balance or walking, and 32% reported memory problems. Nearly 3% had been admitted into the hospital and 10% had visited the emergency room in the past 30 days. In terms of social wellbeing, 63% felt isolated from others at least some of the time. In summary, LGBTQ older adults seeking affordable senior housing report relatively good health, although they also experience functional and social difficulties. New forms of housing that are explicitly LGBTQ-welcoming may help address these health challenges.
QUALITY IMPROVEMENT IN DEMENTIA CARE: EFFECTIVENESS OF IMPLEMENTING STAR-VA IN A VA COMMUNITY LIVING CENTER
Authors: Chacko Thomas , Curyto Kim , Maller Marc , Eddy Connie 
Published: November 2019

Abstract
Staff Training in Assisted Living Residences adapted for Veterans Affairs (STAR-VA) is an evidence-based, interdisciplinary behavioral intervention to manage challenging Behavioral Symptoms of Dementia (BSD) at VA Community Living Centers (CLCs). Components of STAR-VA included creating realistic expectations for individuals with dementia, effective communication, using a behavioral problem-solving approach, and increasing resident-centered pleasant events. STAR-VA was implemented at VA Western New York CLC to help staff manage Veteran BSD. The purpose of the study was to examine the effectiveness of STAR-VA implementation in 17 CLC Veterans with Dementia who demonstrated BSD distressing to themselves, other Veterans and/or staff and documented in 2017-2018. STAR-VA was facilitated by the behavioral coordinator and nurse champion in partnership with the CLC behavior team during weekly rounds and as needed modeling and debriefing. The team included the medical provider, recreation therapist, social worker, and all levels of nursing. On average, the intervention involved four assessments over 75 days. Outcome measures at baseline and post-intervention included assessments of target behavior frequency and severity, direct care tracking of behaviors, and the Minimum Data Set distress behavior indicator. Compared to baseline scores, clinically meaningful reduction was documented using team assessment and direct care ratings of BSD frequency and severity, and overall inappropriate utilization of antipsychotic medication. CLC clinical staff tailored implementation of STAR-VA to be feasible and effective. Ongoing evaluation of STAR-VA implementation using routine measures promotes measurement based care, providing feedback to the team to improve care quality.
RESILIENCE OF CHINESE OLDER COUPLES LIVING WITH CHRONIC ILLNESSES
Authors: Chow Esther O 
Published: November 2019

Abstract
Applying theories of lifelong psycho-social growth and life course principles of human development, older couples generally possess rich and valuable resources from diverse aspects of life. However, empirical evidence, on whether these supports are fully transferred to benefit themselves as they age, remains uncertain due to inevitable physiological decline and increasing caregiving strains. The present study explicated the underlying processes of the older Chinese couples in forming a dyadic resilience model as they age with chronic illnesses. Using in depth interviews, 15 pairs of older Chinese couples were interviewed twice through home visits. The conversations were transcribed and analyzed using thematic analysis. Eight themes related to resilience and challenges of spousal caregiving were identified: 1) insights and acceptance of the chronicity of illnesses, 2) a sense of purpose and commitment as being the spouse in providing care for each other, 3) mastering skills and resources to handle the duties, 4) mixed feelings when the spouse was functioning changes, 5) realizing the importance of self-care and life-management, 6) cultivating positive meanings amidst difficult circumstances, 7) accepting things that cannot change, and cherishing on those aspects which are still functioning well, 8) working closely with other formal and informal support for common good. Findings have both practice and policy implications to health and social care practitioners in understanding different patterns of resilience as experienced by older Chinese couples in mitigating the developmental challenges from individual, relational and societal levels, and research implications in examining actor-partner interdependence practice in addressing caregiving challenges.
PARASYMPATHETIC INFLUENCE ON COGNITIVE AGING IS MODERATED BY SYMPATHETIC ACTIVITY, ESPECIALLY IN EARLY MIDLIFE
Authors: Knight Erik L , Giuliano Ryan , Shank Sean , Clarke Megan , Almeida David M 
Published: November 2019

Abstract
The two branches of the autonomic nervous system (ANS) have been individually linked to age-related changes in cognitive functioning: The parasympathetic nervous system (PNS) is thought to support healthy cognitive aging, whereas the sympathetic nervous system (SNS) has been linked to heightened cognitive decline. Despite these separate findings and despite the integrative nature of the ANS, little work has examined the two branches simultaneously to better understand their interactive effects on age-related cognitive changes. We examined cognitive change in two waves of the MIDUS cognitive project and indexed PNS and SNS activity from heart rate variability and epinephrine levels (respectively) from the MIDUS biomarker project (n = 764, 56% female, mean age = 54.1 years). Our findings indicate that higher PNS levels attenuate cognitive decline, but only among individuals with low SNS levels; at higher SNS levels, the beneficial effects of the PNS are blocked. Further, lower PNS levels can be somewhat compensated for by increased SNS levels. This pattern was most robust among individuals transitioning to mid-life (i.e., 35-40 years old at the initial cognitive test). These results suggest that interventions targeting the ANS as a modifiable factor in cognitive aging should consider both ANS branch’s effects simultaneously, particularly in the early stages of midlife.
A GENERIC METHODOLOGY FOR EFFECTIVE CREATION OF LABORATORY-TEST-BASED FRAILTY INDICES
Authors: Stubbings Garrett M , Mitnitski Arnold , Rutenberg Andrew 
Published: November 2019

Abstract
Laboratory test-based frailty indices (FI) are known to be highly predictive of adverse health outcomes and mortality. However, these FI depend on the proper classification of continuous valued health measurements into binary deficits (healthy or unhealthy). This classification is not standardized and is often done by using thresholds for medical intervention or maximally predictive values from statistical tests. This work proposes a simple and generic methodology for the creation of FI from laboratory values and measures its performance against existing methods. The methodology is as follows: a direction of risk is determined for each measurement, individuals are then assigned a score based on their relative standing in the population, binarization is then done using a global cut-point which binarizes all measures based on a given quantile. This method is shown to outperform FI created with medical risk thresholds for a range of global cut-points in both the NHANES and CSHA studies. Furthermore, our method is shown to be more robust to cohort effects than FI created using cut-points determined by maximum information measures, such as maximal separation of survival curves.
COMBINING MACHINE LEARNING WITH AUTOMATED NEMATODE LIFESPAN ANALYSIS TO IDENTIFY MODIFIERS OF ALZHEIMER’S DISEASE
Authors: Russell Joshua , Kaeberlein Matt 
Published: November 2019

Abstract
Here we present new computational and experimental methods to leverage the gene expression and neuropathology data collected from several large-scale studies of Alzheimer’s disease . These data sets include diverse data types, including transcriptomics, neuropathology phenotypes such as quantification of amyloid beta plaques and tau tangles in different brain regions, as well as assessments of dementia prior to death. This meta-analysis is a complex undertaking because the available data are from different studies and/or brain regions involving study-specific confounders and/or region-specific biological processes. We have therefore taken neural network and probabilistic computational approaches that reduce the data dimensionality, allowing statistical comparison across all brain samples. These approaches identify gene expression changes that are significantly associated with clinical and neuropathological assessment of Alzheimer’s disease. We then conduct in vivo validation of the genes through genetic screening of C. elegans models of Alzheimer's disease utilizing our automated robotic lifespan analysis platform. This approach allows for the greater leverage of existing Alzheimer’s disease biobank data to identify deep genetic signatures that could help identify new clinical gene-expression markers and pharmacological targets for Alzheimer’s disease.
NEURONAL-SPECIFIC PROTEASOME AUGMENTATION VIA EXTENDS LIFESPAN AND REDUCES AGE-RELATED NEURODEGENERATION
Authors: Pickering Andrew M 
Published: November 2019

Abstract
Cognitive function declines with age throughout the animal kingdom and increasing evidence shows that disruption of the proteasome system contributes to this decline. The proteasome has important roles in multiple aspects of the nervous system, including synapse function and plasticity, as well as preventing cell death and senescence. We report that augmentation of proteasome function, using overexpression of the proteasome β5 subunit, enhances proteasome assembly and function. Significantly, we go on to show neuronal-specific proteasome augmentation slows age-related declines in measures of learning, memory, and circadian rhythmicity. Surprisingly neuronal specific proteasome augmentation of proteasome function also produces a robust increase of lifespan in Drosophila melanogaster. Our findings appear specific to the nervous system; ubiquitous proteasome overexpression increases oxidative stress resistance but does not impact lifespan and is detrimental to some healthspan measures. These findings demonstrate a key role of the proteasome system in brain aging.
A SYSTEM TO IDENTIFY INHIBITORS OF MTOR SIGNALING USING HIGH-RESOLUTION GROWTH ANALYSIS IN S. CEREVISIAE
Authors: Kiflezghi Michael , Kaeberlein Matt 
Published: November 2019

Abstract
Age is the main risk factor for cancer, cardiovascular disease, neurodegeneration and other diseases prevalent in the world’s aging population. These diseases increase the pain and suffering and result in billions of dollars in healthcare costs. Addressing the common risk factor may allow for simultaneous amelioration of these diseases providing personal and economic relief to people and societies around the globe. The mTOR signaling pathway has been shown to be a robust target in the aging process with its inhibition resulting in increased lifespan in model organisms from yeast to mice. Rapamycin is an FDA approved drug for use in transplant patients and is a potent and specific inhibitor of mTOR complex 1. Rapamycin’s use as an anti-aging therapeutic in otherwise healthy individuals is complicated by the occurrence of side effects. As such, groups studying inhibition of the mTOR pathway are searching for alternative inhibitors that may be able decouple the deleterious effects of rapamycin administration from the lifespan extending effects. To address this issue, we have developed a high-throughput yeast-based assay for the identification of novel mTOR inhibitors. By utilizing mutant strains with differential sensitivity to mTOR inhibition, comparative growth kinetics of microcultures exposed to an inhibitor can be used to discern the mTOR inhibitory status of a compound. Furthermore, the assay can provide mechanistic insight on a compound’s mode of inhibition providing a rich, fast readout of a compound’s potential for inhibiting mTOR. This approach allows for the screening of large libraries of compounds speeding the discovery process.