bluuebunny/crossref_metadata_2025 huggingface dataset:
PHYSICAL THERAPY STUDENTS' ATTITUDES TOWARDS WORKING WITH PEOPLE WITH DEMENTIA AFTER VARIOUS LEARNING EXPERIENCES
Authors: Vincenzo Jennifer L , Bennett Holly
Published: November 2019

Working with people with dementia (PWD) can be challenging even for the most seasoned health professionals. Hence, teaching health professional students how to effectively work with this patient population is of importance. Two cohorts (n=43; aged 23-36 years) of Graduate Physical Therapy students participated in multi-modal learning experiences geared towards working with PWD within a geriatrics course. Modules included: 1) online lectures and readings followed by a team based learning activity, 2) 3 hours of ‘positive approaches to care’ along with a simulated experience of performing Activities of Daily living and Instrumental Activities of Daily Living of PWD, and 3) one-on-one interactions during both lunch and dinnertime with at least three PWD residing in a state veteran’s home. The Dementia Attitudes Scale (DAS) was used to measure attitudes of students at baseline and following each activity. Repeated measures analysis of variance revealed a significant increase in positive attitudes of students working with PWD across each activity (98.2 +/- 10.5 baseline) with the most positive attitudes noted after interactions with PWD in a state veteran’s home (111.2 +/- 15.0), [F (2.0, 83.8) = 19.4, p < .01, partial eta^2 = .32]. However, this difference was not significant when controlling for students who had previous experience interacting with PWD . In conclusion, Doctor of Physical Therapy students’ attitudes towards PWD improve with different learning experiences, with the greatest improvements after one on one interactions with PWD if the student did not have prior experience interacting with PWD.
NOVEL GAMMA-SECRETASE MODULATOR REGULATES APP PROCESSING AND INFLAMMATORY RESPONSES IN NPM-EXPOSED MICE
Authors: D'Agostino Carla , Cacciottolo Mafalda , Sioutas Constantinos , Wagner Steven L , Tanzi Rudolph E , Morgan Todd E , Finch Caleb E
Published: November 2019

Air pollution is associated with accelerated cognitive decline and increased risk of dementia in older populations (Cacciottolo et al 2017; Chen et al 2017). Rodent models of air pollution exposure also show Alzheimer-like changes including glial inflammatory responses and increased levels of endogenous amyloid beta (Aβ) peptides (Cacciottolo et al 2017 Levesque et al 2011). We hypothesized that pharmacological inhibition of Aβ production during nPM exposure would attenuate the amyloidogenic processing of APP and glial inflammatory responses. This hypothesis was tested using the γ-secretase modulator (GSM) (BPN-15606) which decreases Aβ42 levels in wild-type rodents (Wagner et al 2017; Kounnas et al. 2010). After nPM exposure of C57BL/6J male mice for 8 weeks, GSM-feeding attenuated pro-amyloidogenic and microglial inflammatory responses. Cerebral cortex levels of Aβ40 and 42 peptides were decreased by 35% and 45% respectively in mice exposed to filtered air and fed with GSM. Hippocampal levels of microglial Iba1 remained at control levels, a decrement of 50% below GSM treated mice. We suggest the Alzheimer candidate drug BPN-15606 has potential benefits to reducing the possible impact of urban air pollution in cognitive aging and Alzheimer risk. The attenuation of pro-amyloidogenic and microglial inflammatory responses is consistent with a role of endogenous Aβ levels in glial inflammatory responses and cognitive impairments from air pollution. Cacciottolo et al 2017, PMID 28140404; Chen H et al. 2017, PMID: 28917207; Levesque et al 2011, PMID 21864400; Wagner et al 2017, PMID 28416568; Kounnas 2010, PMID 20826309 Funding: P01 AG055367, R21AG050201, Cure Alzheimer’s Fund
PROGRESSIVE CARE OF AN AGING WOMAN: INTERACTIVE VIDEO SIMULATION CASES SPANNING 15 YEARS
Authors: Kennedy-Malone Laurie M , Amirehsani Karen , Zimmer Rachel , Borders Joshua
Published: November 2019

As a means of enhancing experiential educational opportunities for adult-gerontology nurse practitioner students who are prepared to manage the complex care of older adults, interactive simulation videos were developed using the eLearning authoring tool H5P to create learning experiences for students that can be used either in face to face classroom experiences or embedded in learning management systems. H5P is a web-based authoring tool that helps faculty build interactive course content. H5P activities provide instant feedback to students, allowing them to self-assess their understanding of the dynamic video simulation case. With funding through the Health Resources and Service Administration Advanced Nursing Education Workforce grant, four video simulation cases were developed that address emerging chronic care conditions in an older women who aged 15 years presenting initially with signs of hypothyroidism, progressed to early frailty, through moderate dementia and eventually along with her daughter face end of life health care issues. Partnering with the university instructional design experts, nurse practitioner faculty created questions that were inserted throughout the video as a means of keeping students engaged in problem-solving and decision making. A faculty handbook that described the case scenario with the interactive questions with suggested discussion questions was developed for each video simulation. The adult-gerontology primary care nurse practitioner competencies addressed in each case are identified in the handbook. Recommendations for the interactive question format will be presented and QR codes with access to direct viewing of the videos will be presented on the poster.
MAKING OLD BONES: QUALITY IMPROVEMENT IN OSTEOPOROSIS MANAGEMENT IN A GERIATRIC PRIMARY CARE CLINIC
Authors: Gilliam Meredith , Vereen Sabrina
Published: November 2019

Osteoporotic fractures and their sequelae are a leading cause of morbidity and mortality in older adults. In the United States, nearly 50% of white women and 20% of black women and white men will suffer a fragility fracture in his or her lifetime. Osteoporosis medications reduce the risk of major fragility fracture by 31-62%, but numerous care gaps exist, including screening rates as low as 1-47% and treatment rates as low as 16-30% even after a fracture has already occurred. From January to August 2019, we conducted a multi-faceted quality improvement project at a university hospital-based geriatric primary care clinic, with a goal of improving our rates of osteoporosis screening and treatment. We designed and tested electronic health record-based registries of eligible patients, and developed patient outreach workflows and physician “inreach” workflows. We piloted a bone health clinic. While we did not meaningfully affect the rate of osteoporosis screening, our efforts resulted in an increase in treatment of osteoporosis from 49% to 53%. Documentation of osteoporosis decision making among eligible patients improved from 66% to 80%. In our clinic, ongoing barriers to evidence-based osteoporosis management include competition for time with other medical issues, patient mistrust of medications, and the complexity of decision making around osteoporosis in older adults with polypharmacy and limited life expectancy. Future work must balance the broad application of treatment guidelines via population health tools with the need to individualize treatment decisions for each patient’s overall health and goals of care.
THE ROLE OF RELIGIOSITY IN DEPRESSIVE SYMPTOMS AMONG CHINESE OLDER ADULTS
Authors: Jia Ru , Kong Dexia , Dong XinQi
Published: November 2019

This study aims to examine the relationship between religiosity and depressive symptoms in a large cohort of community-dwelling U.S. Chinese older adults living in the Greater Chicago area, which has received relatively little research attention. Cross-sectional self-report data was obtained from the Population Study of Chinese Elderly in Chicago between 2011 and 2013 (N=3,157). Depressive symptoms were measured by the nine-item Patient Health Questionnaire (PHQ-9). A score of 5 and above indicated the presence of clinically significant depressive symptoms. Logistic regression analyses were conducted to examine the association between religiosity and depressive symptoms. Out of 3,157 participants, 20.3% participants had a score of or above 5 on PHQ-9. 35.4% reported religiosity as being “important” (24.7%) and “very important” (10.7%); 16% reported attending organized religious services at least once a month (3.1% reported once a month; 12.3% reported once a week; 0.6% reported almost every day); 23% reported having religious services at home at least once a month (10.3% reported once a month; 3.2% reported once a week; 9.5% reported almost daily). Results showed that recognizing religiosity as important is significantly negatively associated with depressive symptoms (odds ratio [OR]=0.94, 95% confidence interval [CI]=0.89-0.99). However, no significant associations between depressive symptoms and religious activity attendance or religious service at home were observed. Findings suggest that senses of belonging and life meaning may help reduce depressive symptoms, rather than the religious activities per se. Future interventions could reduce depressive symptoms of U.S. Chinese older adults through religiosity.
DOES EXPOSURE TO INFORMATION ABOUT DEMENTIA CHANGE STIGMA? AN EXPERIMENTAL STUDY
Authors: Zhang Fan , Cheng Sheung-Tak
Published: November 2019

Objectives: Educational programs on dementia may backfire, as recipients could feel more negatively about people with dementia after exposure to the alarming symptoms (e.g., behavioral and psychological symptoms of dementia, or BPSD). This study aimed to investigate whether such exposures had any effect on stigma. Methods: 200 adults aged 18-83 years were randomly assigned to three groups. The first group read vignettes describing fictitious older adults with memory impairment. The second group read the same vignettes that were expanded to include descriptions of BPSD (i.e., memory impairment cum BPSD). After reading the vignettes, both groups answered questions about stigma, while the third group directly responded to this questionnaire without reading any vignette (i.e., not exposed to experimental manipulation). ANOVA was performed to analyze the effect of experimental manipulation, as well as that of age, education, whether having relatives with dementia, and belief about treatability of dementia. Results: At posttest, the level of stigma was moderate and was comparable across the three groups, suggesting that exposures to information about cognitive and behavioral symptoms did not change people’s stigmatizing attitude. The absence of group effect in stigma did not vary by age, education, whether having a relative with dementia, or belief about prognosis. Only the main effects of age and education were significant, where younger and least educated participants reported higher stigma. Conclusion: There was no evidence that stigma would be affected by exposure to information about symptoms of dementia, including the more disturbed ones (i.e., BPSD).
AGE DIFFERENCES IN PSYCHOSOCIAL AND HEALTH OUTCOMES AMONG ADULTS EXPERIENCING HOMELESSNESS
Authors: Turturro Carolyn L , Otters Rosalie , Turturro Zeferin
Published: November 2019

Homelessness is a critical social problem for this nation. It takes a tremendous toll on individuals and families who live without stable shelter, adequate food, and personal security, as well as strains the societal resources. The mean age of death for people experiencing homelessness has been reported to be age 50, far less than the 76 years that is the average for Arkansas. This study investigates the sociodemographic, behavioral and health-related data of 331 adults experiencing homelessness in Central Arkansas. Data was collected by structured interviews during recent homeless counts. Participants ranged in age from 18 to 70, with quartiles established for ages 18-35, 36-45, 46-55 and 56 –70. Sociodemographic comparisons of the groups included education, income, months homeless, work and veteran status, behavioral variables included alcohol use and drug abuse, whereas health-related comparisons included reported diabetes, heart disease, diabetes, high blood pressure, heart disease, problems with hearing, vision, walking as well as mental health including anxiety and depression; in addition, medication procurement and available assistance from family and friends were compared. Preliminary results suggest significant differences, as well as some similarities, among the four age quartiles. Analyses are on-going.
PROVIDING QUALITY ASSURANCE IN ONLINE GERONTOLOGY COURSES THROUGH A PEER REVIEW NETWORK
Authors: Murray Louise M , Park Enoch
Published: November 2019

In health care and senior housing and care, the challenge of meeting diverse regional workforce needs is increasingly important in higher education. Educators within gerontology are rising to this challenge using multiple platforms, including online education (Carter, Solberg, & Solberg, 2017; Nadash, Miller, Porell, Birchander, Glickman, & Burr, 2014). This poster presents the life cycle of a traditional face to face introductory level graduate gerontology course which was transitioned to a fully online course. This transition was achieved using a structured course development process based on nationally recognized online course quality standards by Quality Matters (QM). Utilizing a team approach, the process incorporated faculty (subject matter experts and course developers), instructional designers, and professional staff in distance education, faculty teaching support, and online learning specialists. QM standards serve to assure quality online instruction, with the goal of providing students with a positive and successful online learning experience. Analysis of this case highlights the role of Certified (QM) peer reviewers who have expertise in Gerontology and can serve as the connector of online gerontology courses offered within programs, between institutions, and globally. Recommendations are presented to improve the pedagogical quality of online courses to attract and retain students in gerontology and aging studies courses. The case for building an initial network of online course peer reviewers to strengthen online teaching and learning within the gerontology profession will be made.
DO INTRA-PROXY GAPS EMERGE WHEN FAMILY CAREGIVERS ASSESS QOL FROM DIFFERENT PERSPECTIVES?
Authors: Egan Patricia
Published: November 2019

Dementia family caregivers are routinely enlisted as proxy assessors of care recipients’ quality of life (QOL). This study explored whether prompts to change perspective during QOL assessment could elicit an intra-proxy gap. The intra-proxy gap was hypothesized to be any difference between those assessments made from the caregiver’s own perspective and those made from the adopted perspective of the care recipient, as the care giver imagined it to be (Pickard and Knight, 2005). Thirty-six dementia family caregivers were recruited from senior service agencies. Subjects completed the Quality of Life-Alzheimer Disease (QOL-AD), Caregiver Version under two conditions: First, from an unprompted perspective and second, from the adopted perspective of the care recipient, as the family caregiver imagined it to be. T-testing indicated intra-proxy gaps emerged for eleven of the QOL-AD’s thirteen domains. For these domains, QOL scores were higher when assessed from the care recipient’s perspective, as the family caregiver imagined it to be. The sample was then repeatedly bisected using caregivers’ personal, relational, and health factors. T-testing indicated that family caregivers’ personal factors were associated with intra-proxy gaps across more QOL-AD domains than their relational or health factors were. Three personal factors, being of older age, having more empathetic concern, and having more empathetic distress, were associated with intra-proxy gaps more frequently than other personal factors were. Findings suggest that clinicians should be alert for perspective employed by proxy assessors and for the possibility of intra-proxy gaps. Recognition of these gaps could help improve interpretation of QOL scores.
SENIOR COMMUNITY CENTER AS A SOCIAL ENGAGEMENT PLATFORM FOR OLDER ADULTS IN NEPAL: AN ADAPTATION OF WESTERN CONCEPT
Authors: Shrestha Sabita , Colson Tina
Published: November 2019

Older adults around the world are living longer. Similarly, in Asian countries longevity of older adults have significantly altered the demographics shift as well as the cultural landscape and needs of the society. These changes have compounded with challenges and needs as a community grapples with how to best take care of aging population. Nepal, a developing country, is also faced with a similar demographic shift among the geriatric population. This shift has brought challenges and needs to communities such as health care, daily living needs, social support systems, economic needs, etc. The geriatric population will require social support systems as they age. Historically, older adults have relied on traditional family support systems for their care and needs maintaining cultural values and norms which may burden immediate or extended family members. Recently, traditional family structures along with social support systems are breaking away from their family trees due to community advancement and modernization, and many are leaving for better economic opportunities. This trend has left many older adults alone in social isolation. Despite challenges in the community, Nepal government doesn’t offer infrastructure for social engagement for older adults. One solution to prevent isolation and loneliness is to establish “senior community centers” (western based concept) for social engaging older adults. Based on ecological framework, this presentation proposes a need of “Senior Community Centers” for older adults where they can become involved in social engagements and receive social supports outside traditional family support systems; thus, optimizing their health and well-being.
FALL PREVENTION IN RURAL COMMUNITIES OF NORTH DAKOTA
Authors: OConnor Melissa L , Strommen Jane , Estepp Philip , Hay Megan , Fuller Heather , Grace Rachel , Brotherson Sean
Published: November 2019

Fall-related injuries are common sources of morbidity and mortality for adults aged 65 and older. Thus, interventions for preventing falls can have substantial public health benefits. One promising fall prevention program is the Stepping On program, which involves seven community-based workshops. In these workshops, older adults learn about risk factors for falls, as well as safety-conscious behaviors. Stepping On has been offered in several states, and outcomes have been positive. However, research in rural areas has been lacking. To address this issue, the current study examined 508 older adults who participated in the Stepping On program across 53 rural communities in North Dakota through May of 2019. Most participants were female (82%), with an average age of 79 years (range 65-98). Participants completed baseline and post-test assessments of their knowledge regarding health, mobility, and safety issues. At baseline, 46% of participants reported falling at least once during the previous year. Repeated-measures ANOVAs showed that participants had improved significantly in the following areas at post-test: understanding how vision influences safety; knowledge of balance and strength exercises; recognizing hazards in the home; choosing safe footwear; confidence in mobility; understanding how medications affect fall risk; and the importance of bone health (p<0.001 for all). Just 14% of participants reported falling during the year following the workshops, and 62% felt that the program reduced their risk of falls “to a big extent.” These findings suggest that the Stepping On program is feasible to administer in rural areas and benefits older adults in such communities.
MTOR-DRIVEN ALTERATIONS IN THE BRAIN MICROVASCULAR PROTEOME IN ALZHEIMER’S DISEASE
Authors: Banh Andy , Pomilio Carlos , Hussong Stacy A , Galvan Veronica
Published: November 2019

Therapeutic interventions for Alzheimer’s disease (AD) remain limited due to an incomplete understanding of the molecular mechanisms of its onset and progression. Cerebrovascular dysfunction occurs early during disease development. Attenuation of mTOR, a key regulator of aging, attenuates and reverses cerebrovascular deficits by restoring cerebral blood flow, brain vascular density, neurovascular coupling, and vascular amyloid-β clearance in hAPP(J20) mice expressing human amyloid precursor protein carrying two FAD-associated mutations. The mechanisms by which mTOR attenuation alleviates AD pathology are poorly understood. This study defined changes in the microvascular proteome of hAPP(J20) mice arising from mTOR attenuation. At 7 months of age, hAPP(J20) mice were fed vehicle- or rapamycin-supplemented diet (2.24 mg/kg/day) for 4 months. Mass spectrometry of collected brain microvasculature identified significant changes in 840 of 3361 proteins (p<0.05). mTOR attenuation led to significant changes in 26 of these proteins, some of which are involved in pathways including tight junction regulation, calcium signaling, and actin cytoskeleton regulation. Candidate mediators of mTOR-driven cerebrovascular dysfunction were identified by selecting proteins that were aberrantly altered in hAPP(J20) microvasculature and normalized by rapamycin. Examples include members of the heterogeneous nuclear ribonucleoprotein family (hnRNPA/B, hnRNPD) which regulate the mRNA stability of genes related to cellular cycle arrest and inflammatory cytokines as well as localization of crucial mRNA involved in nitric oxide signaling. Also included are nucleoporin 54 and vacuolar ATPase assembly factor, both of which are altered in aging and neurodegeneration. Subsequent studies will elucidate the role of these proteins in mTOR-driven cerebrovascular dysfunction in AD.
THE ROLE OF RIBOSOMAL COMPOSITION IN SELECTIVE TRANSLATION OF LONGEVITY GENES UNDER DIETARY RESTRICTION
Authors: Rollins Jarod A
Published: November 2019

Dietary restriction influences longevity through changes in gene expression on the level of transcription and translation. Our lab is investigating the changes occurring under dietary restriction in C. elegans on the level of individual ribosomal proteins (RPs) and changes in RP phosphorylation and how they shape gene expression and longevity. To look at the impact of changes in RP expression we used RNAi knockdowns starting at adulthood and assayed lifespan and health span. Two RPs knockdowns that increased longevity, rpl-7A and rpl-22, were then subjected to transcriptome and translatome analysis using polysome profiling and mRNA-seq. Both knockdowns resulted in similar transcriptomic changes with an up-regulation of genes related to translational fidelity and mitochondrion organization. In contrast, the translatome analysis showed minimal changes upon loss of rpl-7A and rpl-22 suggesting that they are not responsible for increase in selective translation previously observed under DR. To look at impact of changes in phosphorylation of rps-6 on DR, we generated mutant lines incapable of being phosphorylated by TOR signaling. These mutants were assayed for changes in lifespan, health span and selective translation. While phenotypically similar to controls under well fed conditions, the mutants were longer lived under DR. Furthermore, preliminary results indicated that the selective translation of the anti-longevity microchondrial electron transport genes cytochrome c oxidase and ubiquinol-cytochrome c reductase binding protein was repressed when rps-6 is not phosphorylated. In summary, our preliminary results that ribosomal protein phosphorylation but not protein composition is responsible for guiding selective translation pf longevity genes under DR.
SENESCENCE-ASSOCIATED SECRETOME COMPONENTS AS BIOMARKERS FOR AGING
Authors: Zhang Xu , Schafer Marissa , White Thomas , Jachim Sarah , LeBrasseur Nathan
Published: November 2019

Cellular senescence is a state of stable growth arrest in response to stress, which is a fundamental process of biological aging. They secrete products, the Senescence-Associated Secretory Phenotype (SASP), which consists of inflammatory cytokines, chemokines, growth factors and matrix remodeling proteins. Senescent cells accumulate with advancing age and partial elimination of senescent cells can reverse age-related dysfunction and increase mean lifespan in mice. However, it is not clear whether components of the SASP can be measured in human plasma and serve as aging biomarkers. Here we generated a candidate panel of senescence markers based on a multiplexed bead-based assay of proteins secreted by senescent preadipocytes, endothelial cells, fibroblasts, myoblasts, preadipocytes, and epithelial cells compared to non-senescent controls. The SASP undoubtedly varies by cell type; however, we observed that multiple components of the SASP are conserved. We then assessed circulating SASP components in human plasma samples from Mayo Clinic Biobank participants (n=280, 20 male and 20 female per decade, age 20-90) using the same method. We confirmed that components of the SASP can be quantified in human plasma with the multiplexed bead-based assay and observed several SASP components robustly increase with chronological age in humans. Our study illustrates that senescence-associated secretome components are detectable in human plasma and could potentially serve as biomarkers of systemic aging and senescent cell burden.
SENESCENCE SECRETOME: BIOMARKERS OF BIOLOGICAL AGING AND POSTOPERATIVE OUTCOMES
Authors: Schafer Marissa , Zhang Xu , Kumar Amanika , White Thomas , Atkinson Elizabeth , Burning Michelle , LeBrasseur Nathan
Published: November 2019

Senescent cells drive age-related tissue dysfunction through their potent secretome, termed the senescence associated secretory phenotype (SASP). Circulating concentrations of SASP factors may reflect biological age and serve as clinically useful biomarkers of surgical risk and ultimately, surrogate endpoints in clinical trials. However, they remain largely uncharacterized. We tested associations between circulating concentrations of SASP proteins and biological age, as determined by the accumulation of age-related health deficits, and/or postoperative outcomes in a sample of residents in Olmstead County, MN, age 60-90 years (n = 115) and cohorts of older adults undergoing surgery for severe aortic stenosis (prospective; n = 97) or ovarian cancer (case-control; n = 36). Circulating concentrations of SASP factors were associated with biological age and adverse postoperative outcomes, including risk of any adverse event or rehospitalization within the year following surgery (aortic stenosis group) or admission to an intensive care unit within 30 days of hospital discharge (ovarian cancer group). Gradient boosting machine modeling revealed a panel of SASP factors that predicted adverse outcomes across both surgical groups better than biological age or chronological age and sex. This suggests that the circulating SASP is a robust indicator of age-related health status and may help guide clinical decision making. Furthermore, circulating SASP factors may be harnessed as a readily quantifiable biomarkers in senescence-targeting interventional human studies.
INCREASED HSP25 DRIVES THE TRANSITION FROM PROTEASOME TO AUTOPHAGY-MEDIATED DEGRADATION UNDER PROTEOTOXIC STRESS
Authors: Scheirer Jessica L , Rodriguez Karl
Published: November 2019

Accumulation of protein aggregates are a common pathology in many neurodegenerative disorders. This accumulation may be due to a function decline in the protein homeostasis network known to occur during the aging process. Small heat shock proteins are a class of molecular chaperones that assist in protein folding and ameliorates the degradation activity of the proteasome and autolysosome thereby decreasing disease-associated aggregates. Prior work in rodents and C. elegans has shown expression levels of the small heat shock protein 25 (HSP25) correlates with maximum lifespan potential. Increased levels of HSP25 extends lifespan in a transgenic C. elegans model. This lifespan extension is dependent on skn-1 with evidence suggesting an enrichment in several skn-1-related pathways, such as lysosomal genes. Concomitantly, proteasome activity declines while autolysosome activity increases. This observation might suggest a switch from proteasome degradation to autophagy as the main driver of protein degradation in C. elegans in this transgenic model. To investigate if a reduction of proteasome function and elevated lysosomal gene activation during aging and under proteotoxic stress are modulated by HSP25 we have crossed our HSP25-transgenic worm with an aggregating and non-aggregating tau worm model. This work will elucidate a possible mechanism that explains the change in the protein degradation response pathways potentially modulated by HSP25 during increased protein misfolding.
AGE-RELATED CHANGES IN THE MUSCLE SECRETOME
Authors: Zhang Ning , Weintraub Susan , Musi Nicolas
Published: November 2019

Skeletal muscle is one of the most abundant tissues in the body. In addition to its key roles in body support, movement and metabolic homeostasis, muscle also functions as an endocrine/secretory organ producing and releasing proteins into the circulation that modulate distant tissues (i.e. myokines). Considering that muscle mass and function changes with advancing age, here we tested the hypothesis that aging alters the muscle secretome profile. After euthanasia, soleus muscles from sedentary young and old mice were dissected, and incubated in oxygenated KRB buffer for 2 h. The buffer was subjected to in-gel trypsin-digestion and peptides analyzed by mass spectrometry. The concentration of 36 proteins were significantly (P<0.05) elevated in the young vs. the old group. In contrast, only 7 proteins were significantly elevated in the old group. Some notable differences include those in HSPA1B and HSPA5 that were detected only in the young group. HSPA8 also was significantly elevated by 1.8-fold (P<0.05) in the young versus the old group. Another prominent difference between groups involved translationally controlled tumor protein (TCTP), a critical regulator of apoptosis/carcinogenesis, that was elevated by 7-fold in the young vs. the old group (P<0.05). These results indicate that aging alters the muscle secretion profile. Identified differences in the muscle secretome could reflect intrinsic changes in muscle cells with age. Because these myokines are released into the circulation, it is also possible that myokine secretion is a regulated cellular process by which muscle communicates and modulates the aging process in distant tissues.
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

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

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

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

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 < 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

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<0.001) and 3 (P<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

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<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<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

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

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

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.