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Age- And Sex-Dependent Alterations In Primary Somatosensory Neuronal Calcium Network Dynamics During Locomotion, Sami L. Case

Theses and Dissertations--Pharmacology and Nutritional Sciences

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Indeed, age-dependent Ca2+-mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline. However, much of this work has been done at the single-cell level, mostly in slice preparations, and in restricted structures of the brain. Recently, our lab identified age- and Ca2+-related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to …

Muscle Mass And Immune Function In The Senior Horse, Alisa Christina Herbst

Theses and Dissertations--Veterinary Science

Senior horses (≥ 15 years) represent up to one-third of the global equine population, and the proportion of old horses (≥ 20 years) in the U.S. has been steadily increasing. Aging is associated with a loss of skeletal muscle mass in horses, and while age-related muscle loss is comparingly well characterized in humans, little is currently known concerning underlying mechanisms, adverse outcomes, or the prevalence of low muscle mass in senior horses. One factor proposed to play a role in the development of age-related muscle atrophy in humans is inflamm-aging, a low-grade inflammation that affects elderly people and that has …

The Use Of Mechanotherapy To Promote The Recovery From Disuse Atrophy In Aging Rat Skeletal Muscle, Zachary Hettinger

Theses and Dissertations--Rehabilitation Sciences

The combination of age and disuse-related skeletal muscle atrophy predisposes older adults to reduced mobility, loss of independence, and poor quality of life. Poor health outcomes resulting from periods of disuse in older adults are exacerbated by an inability to fully recover, ultimately accelerating geriatric populations towards further functional decline. Aged-related changes to skeletal muscle viscoelastic properties, specifically of muscle extracellular matrix (ECM) stiffness, may not only impact how muscle responds during recovery, but also to interventions intended to augment recovery. Remodeling of muscle ECM in the aged may therefore benefit muscle mass recovery, yet therapies focused on ECM remodeling …

Myoglobin Post-Translational Modifications And Fresh Beef Color Stability, Yifei Wang

Theses and Dissertations--Animal and Food Sciences

Surface color of fresh beef is the major trait influencing consumers’ purchase decisions. Fresh beef color is determined by the myoglobin (Mb) redox stability. Post-translational modifications (PTMs) play a critical role in regulating Mb structure and functionality. This thesis focuses on the PTMs in Mb and their impact on fresh beef color stability.

In the first experiment, Mb PTMs in beef longissimus lumborum (LL) muscle during postmortem aging and their influence on fresh beef color stability were examined. Beef LL muscle from nine (n = 9) beef carcasses (24 h postmortem) were subjected to wet-aging for 0, 7, 14 …

Divergence In Neuronal Calcium Dysregulation In Brain Aging And Animal Models Of Ad, Adam Ghoweri

Theses and Dissertations--Pharmacology and Nutritional Sciences

Neuronal calcium dysregulation first garnered attention during the mid-1980’s as a key factor in brain aging, which led to the formulation of the Ca²⁺ hypothesis of brain aging and dementia. Indeed, many Ca²⁺-dependent cellular processes that change with age, including an increase in the afterhyperpolarization, a decrease in long-term potentiation, an increased susceptibility to long-term depression, and a reduction in short-term synaptic plasticity, have been identified. It was later determined that increased intracellular Ca²⁺ with age was due to increased Ca²⁺ channel density, elevated release from intracellular Ca²⁺ stores, and decreased Ca²⁺ buffering …

Maladaptive Personality Traits And Health Behaviors, Health Perceptions, And Inflammatory Biomarkers In Older Adults, Joshua R. Oltmanns

Theses and Dissertations--Psychology

Traits from dimensional models of normal-range personality have been shown to predict physical health outcomes including health behaviors, health perceptions, disease, and mortality. Maladaptive traits of personality disorders may predict even more variance in physical health indicators. Dimensional models of maladaptive personality traits are replacing categorical models of personality disorder, and the five-factor model of personality disorder (FFMPD) has been shown to be a useful dimensional model of maladaptive traits. However, there has been little work investigating the criterion validity of the FFMPD for predicting physical health indicators. The present study examines FFMPD scales in the prediction of health behaviors, …

Exploring The Role Of Insulin Receptor Signaling In Hippocampal Learning And Memory, Neuronal Calcium Dysregulation, And Glucose Metabolism, Hilaree N. Frazier

Theses and Dissertations--Pharmacology and Nutritional Sciences

In the late 90’s, emerging evidence revealed that the brain is insulin-sensitive, highlighted by broad expression of brain-specific insulin receptors and reports of circulating brain insulin. Contemporary literature robustly supports the role of insulin signaling in normal brain function and suggests that insulin-related processes diminish with aging, evidenced by decreased signaling markers, reduced insulin receptor density, and lower levels of insulin transport across the blood-brain barrier. In the context of pathological cognitive decline, clinical trials using intranasal insulin delivery have reported positive outcomes on memory and learning in patients with mild cognitive decline or early-stage Alzheimer’s disease. However, while the …

Livable For All Ages: Evaluating Perceptions Of Community In An Intergenerational Context, David L. Ferrell

Theses and Dissertations--Social Work

Aging-friendliness work uses a model of eight core domains to assess and achieve communities in which people are more equipped to age well, and remain in their community as they age. These domains are broken into the built environment (i.e., Housing, Transportation) and the social environment (i.e., Communication, Social Inclusion, Employment). This dissertation is centered on the efforts to make communities more aging-friendly, and focuses specifically on the Livable Lexington initiative. This dissertation utilized an exploratory study of a pre- and posttest evaluative design to pilot intergenerational discussion groups as a potential intervention. Intergenerational discussion groups were developed with the …

Maintenance Of Positive Affect Following Pain In Younger And Older Adults, Ian Andres Boggero

Theses and Dissertations--Psychology

Socioemotional selectivity theory posits that as people age, they become motivated and successful at maximizing positive emotions and minimizing negative ones. Yet, 70% of older adults report physical pain, which is associated with negative affect. The strategies and resources that older adults use to maintain positive affect in the face of pain remain largely unknown. Specific positivity-enhancing strategies include recalling, recognizing, and responding to positive stimuli and prioritizing close over knowledgeable social partners. Executive functions (EF, i.e., task-switching, working memory, and inhibition) and heart rate variability (HRV) may be important resources for coping with pain. The current project used two …

Lymphocyte-Mediated Inflamm-Aging In The Horse, Melissa Hope Siard

Theses and Dissertations--Veterinary Science

Senior horses (≥20 years) exhibit inflamm-aging, or chronic, low-grade inflammation that occurs systemically with aging, similarly to humans. Inflamm-aging has previously been characterized in the horse in circulation as well as specifically being mediated by lymphocytes and monocytes. In humans, inflamm-aging has been associated with increased morbidity and mortality. However, in the horse, relatively little about inflamm-aging is known regarding clinical effects or factors influencing severity. The contribution of lymphocytes to inflamm-aging of senior horses was examined, specifically through determining the relationships of inflamm-aging with various other health parameters, effects of seasonality, and the extent to which inflamm-aging can be …

Insulin Actions On Hippocampal Neurons, Shaniya Maimaiti

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aging is the main risk factor for cognitive decline. The hippocampus, a brain region critical for learning and memory formation, is especially vulnerable to normal and pathological age-related cognitive decline. Dysregulation of both insulin and intracellular Ca2+ signaling appear to coexist and their compromised actions may synergistically contribute to neuronal dysfunction with aging. This dissertation focused on the interaction between insulin, Ca2+ dysregulation, and cognition in hippocampal neurons by examining the contributions of insulin to Ca2+ signaling events that influence memory formation. I tested the hypothesis that insulin would increase cognition in aged animals by altering Ca2+-dependent physiological mechanisms involved …

Testing A Values-Based Approach To Healthcare Decision-Making In Older Adults, Paul Jefferson Geiger

Theses and Dissertations--Psychology

Despite natural declines in physical and cognitive function, older adults maintain good emotion regulation abilities, leading to emotional wellbeing and resilience. This phenomenon can partially be explained by socioemotional selectivity theory (SST), which posits that when time is perceived as a limited resource, older adults focus attention on positive environmental stimuli to regulate emotions. Although this positivity effect maintains emotional wellbeing, it may disrupt information processing related to healthcare decision-making. Older adults request less information from their doctors, are less likely to ask for a second opinion, make their decisions more quickly, and devote more attention to positive medical information, …

Optimism And Pain Interference In Aging Women, Stephanie T. Judge

Theses and Dissertations--Psychology

Pain interferes with people's daily lives and often limits the extent to which they can pursue goals and engages in activities that promote well-being. The present study test how optimism affects and is affected by pain interference and activity among older women. Every three months for two years, middle- and older-age women (N = 199) complete daily diaries at home for a seven-day period, reporting their daily pain, pain interference, and activity. Optimism was measured at baseline and end-of-study. Multilevel models test the between- and within-person relationships among pain, optimism, pain interference and activity. Pain best predicted pain interference …

The Default Mode Network And Executive Function: Influence Of Age, White Matter Connectivity, And Alzheimer’S Pathology, Christopher A. Brown

Theses and Dissertations--Neuroscience

The default mode network (DMN) consists of a set of interconnected brain regions supporting autobiographical memory, our concept of the self, and the internal monologue. These processes must be maintained at all times and consume the highest amount of the brain’s energy during its baseline state. However, when faced with an active, externally-directed cognitive task, the DMN shows a small, but significant, decrease in activity. The reduction in DMN activity during the performance of an active, externally-directed task compared to a baseline state is termed task-induced deactivation (TID), which is thought to ‘free-up’ resources required to respond to external demands. …

Deep Sleep, Cognition, Body Weight, Body Temperature, And Behavioral Distress Responses To New Onset Psychosocial Stressors Are Blunted With Age In Male F344 Rats, Kendra E. Hargis

Theses and Dissertations--Pharmacology and Nutritional Sciences

Complaints associated with aging, including cognitive deficits and sleep loss, are highly prevalent and negatively impact quality of life. Further, with increased age, humans are also more likely to experience new-onset psychosocial stressors, such as divorce, loss of a spouse, and social isolation. Stress has detrimental consequences that in many ways parallel the effects of aging on sleep and cognition. The long-standing stress/ glucocorticoid hypotheses of brain aging posit that stress exposure exacerbates aging symptoms, and extensive prior studies have shown that early life stress exposure does worsen phenotypic aging symptoms. However, despite its prevalence in aged humans, little basic …

Sex, Dementia, And Long-Term Care: Public Perspectives, Erin L. Yelland

Theses and Dissertations--Family Sciences

The current mixed methods study utilized an ecological framework to examine public perspectives toward sexual behaviors among long-term care residents with dementia. Analyzing attitudes of the public is an integral component of understanding the entire ecological system that affects the development and overall well-being of a long-term care resident. Attitudes were examined using a multiple segment factorial vignette with a probability sample of 329 respondents from a southern state. Results indicate that attitudes were not statistically affected by sex or the elapsed time since diagnosis, and age, spousal disposition, and degree of intimacy predicted attitudes. A respondent’s education level also …

Self-Regulation In Older Adults: The Prioritization Of Emotion Regulation, Daniel R. Evans

Theses and Dissertations--Psychology

Despite having fewer cognitive resources, older adults regulate their emotions as well as, if not better than, younger adults. This study aimed to (1) test the limits of older adults’ emotion regulation capacity and (2) gain a better understanding of how older adults use their more limited resources to regulate their emotions. Participants included 48 healthy older adults aged 65-85 from the community and 50 healthy younger adults aged 18-25 from the student population. They were randomly assigned to one of four experimental groups involving an initial activity that was high or low in self-regulatory demand followed by a test …

Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel

Theses and Dissertations--Pharmacology and Nutritional Sciences

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors …

Effect Of Estradiol Supplementation On Blood Estradiol And Metabolite Levels, And Hepatic Protein Expression, In Growing, Mature, And Senescent Beef Cattle, Edwena D. Miles

Theses and Dissertations--Animal and Food Sciences

Estradiol (Compudose®, COM) implants are extensively used in beef cattle production systems to alter body composition and feed efficiency. Little information exists about the physiological mechanisms affected by COM treatment in growing, mature, and senescent female cattle. Moreover, no reports describe the level of blood estradiol resulting from COM treatment. The effect of COM on levels of plasma estradiol and blood metabolites and proteins, and relative content of glutamine synthetase (GS) and other amino acid nitrogen-metabolizing enzymes in liver tissue, was studied using three experimental models relevant to cow-calf production regimens: senescent cows (Trial 1), young mature (young) versus senescent …

Getting To The Other Side: An Exploration Of The Head And Neck Cancer Treatment Experience, Heather M. Wallace

Theses and Dissertations--Gerontology

Diagnosis of head and neck squamous cell carcinoma (HNSCC) presents a multifarious problem. Late stage diagnosis, uncertainty regarding appropriate clinical treatment, as well as the high potential for disfigurement and functional loss resulting in diminished quality of life, contributes to anxiety, stress, fear, and uncertainty throughout the cancer treatment experience. This qualitative study sought to explore the cancer treatment experience of adults with newly diagnosed HNSCC, including laryngeal, esophageal, and oral cancers. Study participants were recruited from the University of Kentucky Ear Nose and Throat Clinic in Lexington KY. Participants agreed to be interviewed after receipt of their cancer diagnosis …

Memory, Cognition, And The Effect Of A Music Intervention On Healthy Older Adults, Shannon L. Bowles

Theses and Dissertations--Gerontology

Music is a powerful modality that can bring about changes in individuals of all ages. This research employed both an experimental and quasi-experimental design to identify the effects of music as it influenced psychological well-being, memory, and cognition among older adults. Specifically, it addressed three aims: (a) To determine to what extent learning to play a music instrument later in life influenced psychological well-being and cognitive function of non-institutionalized healthy seniors, (b) To determine the effects of the amount of music involvement on psychological well-being and cognitive function (c) To determine the benefit of music for those with limited/no music …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

The Role Of Macrophages In Exercise And Insulin Resistance In Human Skeletal Muscle, Jason S. Groshong

Theses and Dissertations--Physiology

Muscle biopsies were taken at baseline, post eccentric exercise, post aerobic training, and after training followed by eccentric exercise from adults with different health status. In Cell Western analysis of pAkt/Akt ratio suggests that muscle cells isolated from baseline biopsies respond to insulin in a dose dependent manner that tracks with sensitivity to insulin of the host; however, this is uncoupled from glucose disposal in vitro. Nitrotyrosine (NY), a marker of free radical damage, was employed to assess the efficacy of the exercise paradigm. NY immunohistochemistry on muscle cross-sections revealed that eccentric exercise significantly increased damage in older ( …

Nigrostriatal Dopamine-Neuron Function From Neurotrophic-Like Peptide Treatment And Neurotrophic Factor Depletion, Ofelia Meagan Littrell

Theses and Dissertations--Neuroscience

Trophic factors have shown great promise in their potential to treat neurological disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has been identified as a potent neurotrophic factor for midbrain dopamine (DA) neurons in the substantia nigra (SN), which lose function in Parkinson’s disease (PD). GDNF progressed to phase II clinical trials, which did not meet proposed endpoints. The large size and binding characteristics of GDNF have been suspected to contribute to some of the shortcomings of GDNF related to delivery to target brain regions. Smaller peptides derived from GDNF (Dopamine-Neuron Stimulating Peptides – DNSPs) have been recently investigated …

Gene Expression Regulators Lin-11 And Let-711, In Modulating The Rate Of Aging And Lifespan, In C. Elegans., Tseten Yeshi Jamling

University of Kentucky Doctoral Dissertations

lin-11 and let-711 are early-developmental gene expression regulators with no previously known roles in aging regulation. Yet, they show strong aging-correlated expression profiles (Lund, Tedesco et al. 2002). lin-11 is strongly upregulated in very old worm populations, and let-711 is progressively downregulated in aging worm populations. Microarray studies were performed to identify their genome-wide targets, which were then subjected to further lifespan and genetic analysis to investigate their role in C. elegans aging.

The results indicate that the target pools of both lin-11 and let-711 are enriched for aging genes, since a significant number of tested genes increased lifespan. This …

Role Of Pi3k-Akt Pathway In The Age Associated Decline In Tlr Mediated Activation Of Innate And Adaptive Immune Responses, Mosoka Papa Fallah

University of Kentucky Doctoral Dissertations

Immunosenescence results in reduced immune response to infections with Streptococcus pneumoniae as well as to pneumococcal polysaccharide vaccines. The antibody response to the capsular polysaccharide (CPS) provides protection against S. pneumoniae infection. CPS immunoresponse is T cell independent and needs the macrophage-derived cytokines such as IL-12, IL-6 and IL-1β to elicit an antibody response. We showed a cytokine dysregulation, i.e. a decrease in IL-12, IL-6 and TNF-α but an increase in IL-10, in the aged (18-24 months old comparable to >65 years in human) compared to young adult mouse (8-12 weeks less than 65 years old) splenic macrophages (SM) or …

Studies Of The Effects Of Dopamine Neuron Stimulating Peptides In Rodent Models Of Normal And Dysfunctional Dopaminergic Systems, Joshua Lee Fuqua

University of Kentucky Doctoral Dissertations

A theoretical post-translational processing model of the proprotein form of glial cell line-derived neurotrophic factor (GDNF) likely produces three biologically active peptides. The three prospective peptides formed are 5, 11, and 17 amino acid peptides, entitled dopamine neuron stimulating peptide -5 (DNSP-5), -11 (DNSP-11), and -17 (DNSP-17), respectively. The DNSPs were hypothesized to increase dopaminergic neuron function because of their relationship to GDNF: a molecule with established neurotrophic actions on dopaminergic neurons. The DNSPs have the potential to provide a therapeutic molecule similar to GDNF, but with increased ease of delivery and improved bioavailability.

Neurochemical effects of DNSPs were examined …

Accelerated Aging Of Mwcnt Filled Electrically Conductive Adhesives, Ashwanth Reddy Vangala

University of Kentucky Master's Theses

Electrically conductive adhesives (ECA) are discussed and studied with everincreasing interest as an environmentally friendly alternative to solder interconnection in microelectronics circuit packaging. They are used to attach surface mount devices (SMD), Integrated Circuits (IC) and Flip chips in electronic assembly. The use of ECAs brings some benefits like flexibility, mild processing conditions and process simplicity. Multi walled carbon nanotubes (MWCNT) are used instead of metal fillers because of their novel properties such as light weight, high aspect ratio, corrosion resistant, reduced processing temperature, lead free, good electrical conduction and mechanical strength.

The purpose of the present work is to …

Age May Be Hazardous To Outcome Following Traumatic Brain Injury: The Mitochondrial Connection, Lesley Knight Gilmer

University of Kentucky Doctoral Dissertations

Older individuals sustaining traumatic brain injury (TBI) experience a much higher incidence of morbidity and mortality. This age-related exacerbated response to neurological insult has been demonstrated experimentally in aged animals, which can serve as a model to combat this devastating clinical problem. The reasons for this worse initial response are unknown but may be related to age-related changes in mitochondrial respiration.

Evidence is shown that mitochondrial dysfunction occurs early following traumatic brain injury (TBI), persists long after the initial insult, and is severitydependent. Synaptic and extrasynaptic mitochondrial fractions display distinct respiration capacities, stressing the importance to analyze these fractions separately. …

Genetic Regulation Of Hematopoietic Stem Cell Aging, Erin J. Oakley

University of Kentucky Doctoral Dissertations

It is well documented that both quantitative and qualitative changes in the murine hematopoietic stem cell (HSC) population occur with age. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting genetic regulation plays a role in HSC aging. In C57BL/6 (B6) mice, the HSC population steadily increases with age, whereas in DBA/2 (D2) mice, this population declines. Our lab has previously mapped a quantitative trait locus (QTL) to murine chromosome 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In these dissertation studies, I first aim to …