Browsing by Subject "aging"

Now showing 1 - 12 of 12
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    Atrial Fibrillation In Older Adults: Relation To Proteomics, Risk Prediction, And Urban/Rural Disparities In Treatment And Outcomes
    (2020-07) Norby, Faye
    Atrial fibrillation (AF), a cardiac arrhythmia, is a major public health problem. AF is largely a disease of advancing age and contributes to other cardiovascular complications. Identification of novel protein biomarkers could advance understanding of AF mechanisms and may improve the prediction of incident AF. Additionally, it is unknown if disparities exist in AF treatment and outcomes in rural versus urban areas of the US. For manuscripts 1 and 2, we used data from the Atherosclerosis Risk in Communities (ARIC) study, a cohort of older-aged adults in the US. For manuscripts 3 and 4, we used a sample of Medicare beneficiaries enrolled from 2011-2016 with residential zip code categorized into 4 rural/urban areas. In the first manuscript, we examined the association of plasma proteins and identified 40 novel protein biomarkers associated with incident AF. These biomarkers provide insight into mechanistic pathways of AF development. In the second manuscript, we derived and validated a series of 5-year incident AF prediction models that are better targeted and calibrated to older populations. Incorporating biomarkers, including proteomics data, into the models improved AF risk prediction. In the third and fourth manuscripts, we examined the initiation of anticoagulation use and compared the risks of subsequent stroke, heart failure, myocardial infarction, and mortality in newly-diagnosed AF patients in rural versus urban areas. Patients in rural areas were more likely to initiate anticoagulant treatment; however, they were less likely to initiate a newer class of anticoagulants compared to those in urban areas. Those in rural areas had modestly higher risk of cardiovascular outcomes and mortality compared to those in urban areas. Proteomics aids in understanding AF mechanisms and improves risk prediction. Future research should validate our prediction models, develop meaningful ways to incorporate protein biomarkers in clinical practice, and focus on improving AF treatment in rural areas.
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    CURA Research Reports on Underrepresented Groups: Reports Based on CURA Research Projects, 1968-2000
    (University of Minnesota: Center for Urban and Regional Affairs, 2001-04) Wolfe, Margaret R.
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    Estrogen Deficiency-Induced Phosphoproteomic Alterations In Skeletal Muscle Of Female Mice
    (2022-08) Peyton, Mina
    Dynapenia, the age-related loss of muscle strength without the loss of muscle mass, significantly impacts the physical function and overall quality of life in older adults, thereby decreasing their health span. Skeletal muscle strength loss has been shown to occur earlier and is greater in aging females than males. Furthermore, clinical and preclinical studies have measured associations between skeletal muscle strength loss and the age at which circulating estrogen begins to decline in females. Despite copious years of skeletal muscle research, the molecular mechanisms underlying muscle strength loss in aging females remain poorly understood. Age-related protein phosphorylation changes have been reported in skeletal muscle of males, and protein phosphorylation alterations have been shown in cardiac muscle across age and sex. However, the extent and magnitude of these changes in the skeletal muscle phosphoproteome of females in response to estrogen deficiency have yet to be determined. This dissertation aims to further our molecular understanding of how estrogen deficiency impacts skeletal muscle function (i.e., the force-generating capacity of muscle) in females by investigating the skeletal muscle phosphoproteome using high-throughput mass spectrometry coupled with bioinformatic analyses and computational modeling. First, using an ovariectomy model, we determined the physiological remodeling of the skeletal muscle phosphoproteome associated with estrogen deficiency. Next, due to the controversies related to using an ovariectomy model to implicate estrogen-related changes in aging females and because the primary function of skeletal muscle is contraction (i.e., molecular force generation), we sought to discern estrogen deficiency-associated protein phosphorylation alterations in contracted skeletal muscle via evoked electrical stimulations in ovariectomized and natural aging ovarian-senescent female mice compared to their respective controls. Examining the phosphoproteomic alterations in resting, non-contracted, and contracted skeletal muscle of estrogen-deficient females, we identified novel phosphosites, candidate kinases and phosphatases, as well as illuminated key pathways that are sensitive to estrogen levels that may contribute to the loss of skeletal muscle strength. This dissertation provides new avenues for further research and novel targets for the development of therapeutics and interventions to mitigate the loss of skeletal muscle strength in females.
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    MNREAD Baseline Data for Normal Vision Across the Lifespan
    (2017-08-30) Calabrèse, Aurélie; Cheong, Allen M. Y.; Cheung, Sing-Hang; He, Yingchen; Kwon, MiYoung; Mansfield, J. Stephen; Subramanian, Ahalya; Yu, Deyue; Legge, Gordon E.; acalabre@umn.edu; Calabrèse, Aurélie; Minnesota Laboratory for Low-Vision Research, Psychology Department, University of Minnesota
    The continuous-text reading-acuity test MNREAD is designed to measure the reading performance of people with normal and low vision. This test is used to estimate maximum reading speed (MRS), critical print size (CPS), reading acuity (RA), and the reading accessibility index (ACC). The present data contains MNREAD data from 645 normally sighted participants ranging in age from 8 to 81 years. The data were collected in several studies conducted by different testers and at different sites in our research program, enabling evaluation of robustness of the test. The data allows to: 1) study the age dependence of reading performance for normally sighted individuals; 2) provide baseline data for MNREAD testing.
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    The Social Pattern and Causes of Dementia Prevalence Decline in the United States
    (2022-07) Lee, Mark
    Age-adjusted dementia prevalence has significantly declined in the United States over the last 25 years, despite little advancement in the biomedical treatment of Alzheimer’s Disease or improvement in proximal dementia risk factors. In this dissertation, I analyze data from the Health and Retirement Study (HRS) to improve current understanding of the descriptive trends and causal mechanisms underlying dementia prevalence decline. In my first study, I rebut the argument that dementia decline in the HRS is an artefact of unmeasured panel conditioning. I show that practice effects do not bias the estimated secular trend in dementia prevalence after accounting for selective panel attrition. In my second study, I argue that cohort trends in early life risk factors offer a more plausible explanation of the observed dementia improvement than period trends, which have been emphasized in previous research. In my third study, I empirically test the contribution of early life risk factors to cohort trends in dementia prevalence. I find that age- and sex-adjusted dementia prevalence declined 2.3 percentage points per 10-year increase in birth year for cohorts born 1892-1952. The majority (72%) of this trend was explained by increases in educational attainment for more recent cohorts. Proximal risk factors had little influence net of education and other early life factors. The trend in dementia decline was steeper for Black than White Americans, and the causal mechanisms also differed by race. In my fourth study, I document cohort trends in midlife cognitive aging. I find that, compared with those born 1942-1947, those born 1954-1959 entered midlife with lower cognitive function, but exhibited greater maintenance of cognition over time. This suggests that dementia prevalence may continue to improve as this latter-born cohort ages. Overall, this research reinforces the importance of social improvement (especially educational expansion) across the 20th century for cognitive health improvements in the 21st century. This work indicates that interventions to reduce or delay dementia and ameliorate racial disparities should be expanded to include social determinants of health across the life course.
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    Soil Matric Suction Changes With Time in Pressed Soil Briquettes
    (Water Resources Research Center, University of Minnesota, 1971-05) Fuentes, Victor C.
    Soil metric suctions were measured with time in soil samples in which the water content was varied in a series to obtain information on the processes occurring as stable structural units develop during aging. Soil metric suctions of Clarion loam surface soil were measured by tensiometers. It is concluded that water stability of synthetic soil aggregates increase with time. At flow water contents (0 < 0.258 g/g) there was a rapid decrease in soil metric suction with time after pressing that indicates an increase in the free energy state of water in the system. At higher water contents the rate of decrease in metric suction was smaller. At 0w = 0.258 g/g suction remained constant with time. At water contents over 0.258 g/g soil metric suction increased with time.
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    Synergistic Effects of Multiple Aging Stressors on HDPE and HDPP
    (2020-12) Finke, Adam
    The service life for power cables in our nation’s nuclear power plants have been extended beyond 40 years, however no reliable test has been found for determining the remaining lifetime of a cable in service. With experimental data and simulated models, a test and material lifetime prediction are being developed based on changes in electrical, mechanical, and chemical properties as a function of service conditions, temperature, aqueous exposure, material, and time. While it may be next to impossible to test every condition or environment for a material lifetime study, analytical models based on accelerated aging can attempt to predict both tested and untested conditions. By using models obtained from experimental data produced during accelerated aging studies, changes in mechanical properties, chemical properties, and even visual properties can be combined to better understand and more accurately predict aging.The first step to understanding insulation degradation is to understand how environmental conditions like water, temperature, and mineral or an aqueous environment affects polymer aging and how that might accelerate or decelerate aging. The aim of this thesis is to cover what effects combining these conditions might have on polyethylene and polypropylene tensile samples at a moderately elevated temperature. Additionally, how might cycling of conditions age or degrade these samples differently from samples continuously submerged. Tensile properties, hardness measurements, and surface chemical characterization of carbonyl formation through the attenuated total reflection were measured and calculated to determine the synergistic effects of aging polyethylene and polypropylene in distilled water, a copper sulfate solution, and Harrison’s solution at 90ºC through common mechanical properties and aging indicators. Additional studies were started aging both materials at elevated temperatures and oxygen partial pressures, and submersion in water. Results suggest that at 90ºC these mixed conditions did not accelerate aging over dry aged samples within a 16-week period and more time or a greater temperature would be required to create a greater difference between conditions.
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    Toughening Poly(lactide) with Diblock Copolymers
    (2021-11) McCutcheon, Charles
    With the rapid expansion of the plastic industry, plastic waste is generated at an alarming rate. Currently, only a small fraction of waste is recycled, leading to a buildup of plastic in landfills and the environment. Poly(lactide) (PLA), a bio-derived and industrially compostable polymer, provides an alternate approach to plastic disposal. Although PLA displays several advantageous mechanical properties, it is brittle and thus cannot be readily used in many applications. In this work, we blended PLA with a diblock copolymer poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) using industrially relevant preparation methods to produce tough blends. The incompatibility of the PBO block with PLA promotes phase separation, while the PEO block decreases the interfacial tension between the two phases, leading to well-dispersed PEO-PBO particles with uniform size in PLA. Melt mixing of 1.8 wt % PEO-PBO into amorphous PLA (PDLLA) led to a 20-fold increase in tensile toughness without affecting the modulus or transparency. The deformation mechanism was investigated by small angle X-ray scattering (SAXS), revealing that the particles cavitate and act as stress concentrators for craze deformation followed by necking, where the deformation mechanism transitions to shear yielding. As a result of the craze deformation mechanism, these blends remain tough after 114 days of aging, displaying a 10-fold increase in elongation at break compared to neat PDLLA. Semi-crystalline PLA (PLLA) was also blended with PEO-PBO, resulting in a unique combination of properties which can expand the applications of PLLA as a sustainable plastic. The blends were annealed at different temperatures, resulting in a range of crystallinities. Addition of 5 wt % PEO-PBO led to a minimum 5-fold reduction in the time required to achieve 50% of the final extent of crystallinity compared to neat PLLA. The blends exhibit a 7-15-fold increase in tensile toughness compared to neat PLLA, scaling inversely with crystallinity. The deformation mechanism was investigated by SAXS and wide-angle X-ray scattering (WAXS), indicating that the particles cavitate and induce craze deformation, while the crystal structure displayed minimal changes. These blends also remained ductile over time, and after 85 days of aging, the blends fail at > 50% strain while PLLA fails at 4% strain after 2 days of aging. The previous findings were applied to the final study, focusing on PLA and PEO-PBO/PLA films (both amorphous and semi-crystalline) with aligned chains, a common result of film processing techniques used to produce plastic packaging. Isotropic PDLLA and PEO-PBO/PDLLA samples were uniaxially stretched to various stretching ratios (λ). Both neat PDLLA and PEO-PBO/PDLLA films are tough when examined parallel to chain orientation (machine direction (MD)). At λ = 6, neat PDLLA and PEO-PBO/PDLLA display an 8- and 14-fold increase in toughness, respectively, compared to isotropic PDLLA. However only the PEO-PBO/PDLLA films are tough when examined perpendicular to chain orientation (transverse direction (TD)), exhibiting a minimum 10-fold increase in toughness. In the MD, the PDLLA films deform by shear yielding and the PEO-PBO/PDLLA blends deformation mechanism depends on λ. At λ ≤ 2 the films deform by crazing and at λ ≥ 4 the films deform by shear yielding. In the TD, the PEO-PBO blends deform by uniform crazing. When examined in the MD, both PDLLA and PEO-PBO/PDLLA films remain tough through 155 days of aging. The deformation mechanism of the PEO-PBO/PDLLA films changes with aging, and the propensity of the material to deform by crazing increases. Alternatively, the PEO-PBO/PDLLA films tested in the TD are more sensitive to aging, displaying a reduction in ductility with time. However, the films still exhibit a 5-fold improvement in toughness compared to neat PDLLA films in the TD after 155 days of aging. Film stretching of PLLA and PEO-PBO/PLLA films resulted in tough, transparent semi-crystalline blends. The PEO-PBO particles increase the crystallization kinetics and ductility in the TD. This work provides a framework to manufacture tough PLA blends by the addition of a diblock copolymer, addressing the main property limitation of PLA. The blends are processed through industrially relevant procedures and require low mass loadings of additive to achieve sustained toughness, independent of aging time. These results will greatly advance the applications of sustainable PLA, further supporting a more sustainable future.
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    Understanding The Role Of Pentraxin 3 In Adipose Tissue Inflammation And Aging
    (2022-01) Lin, Te-Yueh
    Obesity and aging are often accompanied by chronic low-grade inflammation in adipose tissue. Metabolic endotoxemia (elevated circulating lipopolysaccharide [LPS] level) is the inducer of systemic and adipose tissue inflammation and dysfunction, which is developed during obesity and aging. As a soluble pattern recognition receptor, Pentraxin 3 (PTX3) plays a vital role in innate immunity and can be induced by inflammatory stimuli in adipose tissue and adipocyte. Altered PTX3 levels have been observed in adipose tissue and blood during obesity and aging, while the role of PTX3 in adipose tissue during inflammation and aging is not fully understood. My Ph.D. research attempts to understand the role of PTX3 in adipose tissue inflammation and aging. In the first project, we investigated how PTX3 regulates inflammation in adipose tissue, and we found that PTX3 plays an anti-inflammatory role partially by regulating miR-21 expression and secretion in brown adipocytes. In the second project, we explored PTX3 secretion from adipose tissue and adipocyte and found that PTX3 is secreted mainly through conventional protein secretion, while a small percentage of PTX3 is released in exosomes from LPS-stimulated adipocytes. In the third project, we examined the physiological role of PTX3 in adipose tissue during aging, and we showed that PTX3 deficiency induced senescence and inflammation in adipose tissue and promoted lipid transport and oxidation in white adipose tissue of old female mice. In summary, my doctoral research reveals that adipose-derived PTX3 plays an essential role in regulating LPS-stimulated inflammation and cellular senescence during aging, and adipocyte-derived PTX3 is secreted via conventional protein secretion and exosomes.
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    Variability in Exercise Responsiveness Among Older Adults: An Examination of Predictors and Patterns of Nonresponse to Exercise in Peripheral Artery Disease
    (2019-07) Whipple, Mary
    Background: Despite the significant inter-individual variability observed in outcomes of aerobic exercise programs among older adults, little is known about the prevalence of nonresponse to exercise in this population. Supervised exercise therapy (SET) is the primary guideline-recommended therapy for the treatment of symptomatic peripheral artery disease (PAD), yet variability in response to outcomes in this population is not well understood. Previous research suggests that individuals with PAD and comorbid diabetes may be less likely to see a benefit in physical function and quality of life outcomes following SET, yet few studies have been designed to directly compare outcomes in these populations, and no studies have examined the potential role of changes in sedentary time during the course of SET in SET outcomes. Additionally, it is unknown if patterns exist in inter- and intra-individual response across a variety of outcomes. Findings of such research could enable informed tailoring of exercise therapy programs to maximize an individual’s potential benefit. Aims: This dissertation aimed to (1) determine the prevalence of nonresponse to aerobic exercise among older adults participating in studies of aerobic exercise programs, and identify factors related to nonresponse that have been examined in the literature; (2) quantify changes in sedentary behavior among older adults with PAD, with and without diabetes, engaging in SET for the management of symptomatic PAD and examine how diabetes and changes in sedentary time are related to SET outcomes; and (3) examine the prevalence of nonresponse to SET among individuals with PAD and explore patterns of nonresponse across of a variety of relevant objective and self-reported outcomes. Methods: Aim 1. A critical review of published studies in which the authors examined variability in response, poor response, or lack of response to aerobic exercise interventions in older adults was conducted. Methods of defining nonresponse, the prevalence of nonresponse, and factors associated with nonresponse are discussed. Aim 2. A pre-test post-test study of older adults (n = 44) initiating a 12-week SET program for symptomatic PAD was conducted in a midwestern hospital system. Participants completed assessments of physical function (six-minute walk test, Short Physical Performance Battery, Walking Impairment Questionnaire), and physical activity and sedentary behavior (assessed objectively via wrist-worn accelerometer) at the time of SET initiation, 6 weeks, and 12 weeks. Changes in sedentary time overall and between participants with and without diabetes were examined. Multiple linear regression was used to examine the influence of diabetes and changes in sedentary time during SET on functional and self-reported outcomes. Aim 3. A secondary analysis of data collected as part of Aim 2 was performed to determine the prevalence of nonresponse to SET in functional and quality of life outcomes using different methods of defining nonresponse reported in the literature. Inter- and intra-individual patterns of response were also examined. Results: Aim 1. A total of 17 articles representing 12 unique studies with 5116 unique participants were eligible for inclusion. Nonresponse to aerobic exercise interventions was prevalent among older adults (1.4-63.4%); age, sex, race, and body mass index were not found to be critical determinants of nonresponse, but there was some evidence to suggest that baseline fitness, health status, and exercise dose were important predictors of nonresponse. Aim 2. On average, sedentary time did not change following the 12-week SET program, although there was substantial inter-individual variability (40% decrease to a 38% increase in average daily minutes of sedentary time). While on average, participants with diabetes reduced their average daily sedentary time, participants without diabetes tended to increase their average sedentary time. In multiple linear regression, neither changes in sedentary time in the first six weeks of SET nor diabetes were significant predictors of changes in total distance attained on the six-minute walk test from baseline to 12 weeks. Aim 3. The prevalence of nonresponse in walking distance when defined as no change or a decline in walking distance was 35.3%, and when defined as the lack of a clinically meaningful improvement (20 meters), the prevalence of nonresponse was 55.9%. Similar patterns of response were observed in both the objective and self-reported measures of physical function. All participants improved in at least one study outcome; however only one participant improved in all measured outcomes. Conclusion: Nonresponse to a single study outcome following participation in aerobic exercise is a common phenomenon among older adults, both with and without PAD. Neither diabetes nor changes in sedentary time were significant predictors of response to SET among individuals with PAD. Exercise studies should include a variety of performance based and patient-reported outcomes, as nonresponse likely represents a failure in just one potential positive adaptation to exercise. Additional research should examine potentially modifiable predictors of response prior to the initiation of or during exercise training (e.g., motivation to exercise, social support), which would foster inquiry and efforts to modify and tailor programming to maximize an individual’s potential benefit from exercise therapy.