Medicine and Health Sciences Commons^™

The Impact Of Access To Oral Health Care On Inadequate Oral Health And Multimorbidity, Luis Limo

Electronic Thesis and Dissertation Repository

The connection between oral health and other non-communicable chronic conditions—commonly referred in the dental literature as the oral-systemic health connection—emphasizes the role of oral health care on both oral diseases and chronic conditions, particularly in vulnerable populations like the elderly. This thesis comprises 2 studies: the first is a systematic review on the impact of oral health care interventions, as an indicator of access to oral health care, on chronic conditions of which their co-existence would result in multimorbidity; the second study is a cross-sectional investigation of the associations between oral health, access to oral health care, and multimorbidity among …

Effects Of Age On Amplitude-Modulated Cvemp Temporal Modulation Transfer Function, Raghav H. Jha

Dissertations, 2020-current

With the aging population on the rise, the need for effective assessment tools to identify risk factors for falls among the elderly is paramount. One independent risk factor for falls is vestibular impairment, but the available vestibular diagnostic tests have limitations. A promising new methodology: amplitude-modulated tones to elicit a vestibular-evoked myogenic potential (AMcVEMP), offers a more detailed examination of vestibular (sacculo-collic reflex) functions. This method assesses non-linearities, synchrony, and magnitude, providing a more thorough evaluation compared to the conventional transient cVEMP. So far, AMcVEMP has only been utilized in young adults.

The current study aimed to investigate the impact …

Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD⁺) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD⁺ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPR^mt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD⁺ and through increasing levels …

Stromal Vascular Fraction Restores Vasodilatory Function By Reversing Mitochondrial Dysfunction And Oxidative Stress In Aging-Induced Coronary Microvascular Disease., Evan Paul Tracy

Electronic Theses and Dissertations

Background: Coronary Microvascular Disease (CMD) presents in aging post-menopausal women with chronic angina due to microvascular hyperconstriction. The objective was to identify mechanisms of adipose stromal vascular fraction’s (SVF) restorative effects on vasodilation. We hypothesize aging-induced CMD is caused by a) abrogated flow-mediated dilation (FMD) due to loss of nitric oxide signaling and b) ROS-dependent βADR desensitization & internalization, reversible by ameliorating mitochondrial dysfunction and oxidative stress with SVF. Methods: Coronary microvessels were isolated from female rats either young, old, or old with SVF tail-vein injection (OSVF). Pressure myography, RNA-sequencing, immunofluorescence, Western blotting, and morphological analysis were performed to …

Knockdown Of C. Elegans Nad Kinases Nadk-1 Or Nadk-2 Induces An Antioxidant Response Without Affecting Lifespan, Henry Gong

Electronic Theses and Dissertations

Nearly all multicellular organisms show changes in redox balance with aging leading to oxidative damage of macromolecules. This study investigated the role of the [NADP⁺]/[NADPH] redox couple in aging. This redox couple plays an important role in maintaining tissue redox balance and becomes slightly more oxidized in aged tissues. NADPH is a major source of reducing equivalents for enzymes that detoxify hydrogen peroxide. However, catalase detoxifies hydrogen peroxide independently of NADPH. But catalase is absent from mitochondria, a major source of hydrogen peroxide, where instead glutathione plays the major role in hydrogen peroxide detoxification in an NADPH-dependent manner. …

Adipose-Derived Stromal Vascular Fraction Therapy Improves Age-Related Adrenergic Mediated Microvascular Dysfunction And Increases Revascularization Potential Following Injury., Gabrielle Brown

Electronic Theses and Dissertations

The role of the microcirculation is to balance blood flow and oxygen delivery to meet local metabolic and oxygen demands. With advancing age, the health of the endothelium declines leading to improper augmentation of the microcirculation; decreasing vasoreactivity and angiogenic potential which can further increase the risk of ischemia. The multiple contributing factors that drive the decline in endothelial health with age make traditional pharmacological interventions challenging whereas cell-based therapies can exert multifactorial gains. Adipose-derived stromal vascular fraction (SVF) is an emerging therapeutic for its easily accessible, autologous, anti-inflammatory, and angiogenic properties. It is a heterogenous population comprised of leukocyte …

Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos

Graduate Theses, Dissertations, and Problem Reports

Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …

The Role Of Protein Translation And Degradation In Aging And Alzheimer Disease Pathogenesis, Harper S. Kim

All ETDs from UAB

Protein translation (PT) is an essential cellular process playing crucial roles in growth and development. PT precipitously declines with age in multiple animal species, including humans. It has been implicitly assumed that elevated PT at young ages is beneficial to health while PT ends up dropping as a passive byproduct of aging. However, whether this holds true and how dynamic fluctuations in PT over time impact aging remain unknown. In Drosophila, we show that a transient PT spike in early-adulthood drives aging by triggering dysfunction in protein homeostasis (proteostasis) at old ages. We propose the early-adulthood spike in PT to …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

Protein Misfolding Toxicity And Inclusion Formation In Cellular Models Of Neurodegeneration, Sonja E. Di Gregorio

Electronic Thesis and Dissertation Repository

Protein misfolding characterizes most neurodegenerative diseases. Protein misfolding is the conversion of specific proteins from their normal, often soluble, and native three-dimensional conformation into an aberrant, often insoluble, non-functional conformation. Protein inclusions and aggregates are among the major pathological hallmarks of protein misfolding associated with many neurodegenerative diseases. Yet, the role of aggregates and inclusions is not clearly defined and heavily debated. This study utilizes powerful genetic approaches in yeast and verification in mammalian neuronal cell lines to address the misfolding and toxicity of three proteins, the Rho Guanine Nucleotide Exchange Factor (RGNEF), Matrin3, which are involved in amyotrophic lateral …

The Role Of Ms-818 In Altering Age-Related Characteristics Of An In Vitro Model Of Senescence In Neural Stem Cells, Sandeep Sreerama

Honors Undergraduate Theses

Aging of the brain is the leading risk factor for neurodegenerative diseases and brain cancers and has deleterious effects on brain functions. It follows that attempts to reverse the aging process may be therapeutically valuable. Neural stem cells (NSC) have been shown to play a critical role in maintaining brain functions, and their number is severely decreased with age. The development of senescence-like characteristics and declining functions in NSCs have been proposed to be responsible for brain aging and tumorigenesis. MS-818 is a pyrrolopyrimidine that has been shown to increase the NSC population and reverse the decline of behavioral function …

Immune Modulation As A Therapeutic Target In An Α-Synuclein Model Of Parkinson’S Disease, Meena Subhashini Subbarayan

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting about 1.5 million people in the United States with more than 60,000 people diagnosed each year. It is classically characterized by four major symptoms: tremor, postural instability, stiffness in joints, and slow movement (bradykinesia). Pathologically PD is characterized by up to 70% loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) of midbrain and accumulation of presynaptic protein called α-synuclein (α-syn) within dopaminergic neurons that extend to the striatum. This disrupts the nigrostriatal pathway leading to the motor symptoms seen in PD patients. Microglia, the innate immune cells …

Indicators Of Mild Cognitive Impairment Associated With Language Processing And Production, Diana Julbe-Delgado

USF Tampa Graduate Theses and Dissertations

The research purpose of the present study was to (1) examine cognitive-linguistic features related to processing and production across a series of tasks that are representative of everyday discourse and (2) compare older adults with and without mild cognitive impairment (MCI) across linguistic features. Twenty-seven participants, including 12 individuals with- and 15 individuals without MCI, were enrolled from a larger study (Hudak et al., 2019). Cognitive status was initially assessed as part of the larger study using the Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005). Participants who scored ≤ 25 on the MoCA received a standardized neuropsychological evaluation and …

Mass Spectrometry Discovery-Based Proteomics To Examine Anti-Aging Effects Of The Nutraceutical Nt-020 In Rat Serum, Samantha M. Portis

USF Tampa Graduate Theses and Dissertations

Aging is a complex physiological process that leads to the deterioration of all cells and tissues throughout the body. Aging is a major risk factor for the onset of many degenerative diseases in both the central nervous system (CNS) and the periphery, but even nonpathological aging (“normal” aging) is associated with chronic inflammation, oxidative stress, and decreased stem cell proliferation and regenerative capacity. This decreased regenerative capacity in stem cell niches is thought to be a key component underlying the aging process and many disease states associated with aging.

While the exact biological mechanisms underlying impaired stem cell proliferation and …

Age Differences In Hippocampal Glutamate Modulation During Associative Learning And Memory: A Proton Functional Magnetic Resonance Spectroscopy (1h Fmrs) Study, Chaitali Anand

Wayne State University Dissertations

Episodic and associative memory decline is one of the earliest cognitive impairments in normal aging and among the defining cognitive features of Alzheimer’s disease (AD). Since, age-related cognitive decline gradually devolves into AD, with neuropathology preceding cognitive changes by many years, the identification of biomarkers of early disease progression is crucial. Reduction in glutamate, the main excitatory neurotransmitter involved in associative memory, in key brain regions such as the hippocampus, has been theorized as one of the cellular mechanisms underlying cognitive decline in aging and AD. A few neuroimaging studies that demonstrated a link between older adults’ weaker cognitive performance …

Using Genetic Diversity To Understand Susceptibility To Cognitive Decline In Aging And Alzheimer’S Disease, Sarah M. Neuner

Theses and Dissertations (ETD)

An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging and transition to dementia such as Alzheimer's disease (AD). Identifying the specific genetic variants that contribute to cognitive aging and AD may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we turned to genetically diverse mice from the BXD genetic reference panel (GRP) to overcome some of the …

Axon Initial Segment Integrity In Aging And Traumatic Brain Injury, Mazen M. Gouda

Theses and Dissertations

According to the Center for Disease Control’s (CDC) report to the Congress, there are 2.2 million emergency department visits; 80,000 hospitalizations; and 50,000 deaths each year due to traumatic brain injury. Adults 65 years and older account substantially for the majority of the hospitalization and deaths. Over 70% of the traumatic brain injuries of the older adults are classified as mild to moderate; however, even with these milder injuries, older adults present with a significantly higher morbidity and mortality compared to all other age groups (LeBlanc et al., 2006). With that in mind, it seems essential to develop a deeper …

Context Fear Memory Formation Is Regulated By Hippocampal Lncrna-Mediated Histone Methylation Changes, Anderson Alan Butler

All ETDs from UAB

The post-translational modification of histones regulates gene expression and is critical for the formation and maintenance of hippocampus-dependent long-term memories. Changes in gene-specific expression of various epigenetic marks during the aging pro-cess are sufficiently consistent as to be used as an aging landmark or epigenetic clock in both humans and other species; however, the molecular mechanisms which govern the application of these marks aging are poorly explored. Recently, long noncoding RNAs (lncRNAs) have been implicated as regulators of histone methyltransferases and other chromatin-modifying enzymes (CMEs). Despite the relevance of such mechanisms to both aging and memory formation, the behavioral relevance …

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.

Astaxanthin Attenuates Mptp Induced Neurotoxicity And Modulates Cognitive Function In Aged Mice, Beth Grimmig

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease is the second common neurodegenerative disease and is most frequently diagnosed in individuals over 60. There are no available medications that can prevent or restore the loss of neurons that correspond to motor impairments in patients. Identifying novel therapeutic compounds that are capable of slowing and reversing the extensive neurodegeneration that occurs in PD remains an important goal of the field. While basic research has identified potential therapeutic agents, studies often use young model organisms to demonstrate efficacy of the target compound. This approach ignores the impact of the aged CNS on the disease process, and likely contributes …

Effects Of Aging And Dietary Phytoestrogens On Sperm Production In Sprague Dawley Rats, Brian Cutler

Masters Theses

Estrogens, in addition to testosterone, are physiologically relevant to normal sperm production in the testis and sperm maturation in the epididymis. Previous studies from our lab demonstrated that daily sperm production declines from 15 to 18 months of age in Sprague Dawley rats, and treatment with estrogen during this period attenuated the age-associated decline. Phytoestrogens are present in standard rodent diets at high levels (350-650 mg/kg) and may be potential endocrine disruptors. The purpose of this study was to investigate the effect of removing dietary phytoestrogens during aging on sperm production. Retired breeder Sprague Dawley rats were obtained at 9 …

Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers

USF Tampa Graduate Theses and Dissertations

The last century has seen a steady increase in the extension of the average lifespan. This has concomitantly produced higher incidences of age-related chronic degenerative diseases like Alzheimer’s and Parkinson’s diseases. Age is the single greatest risk factor for the development of not just these degenerative conditions but cancer as well. The aged niche undergoes a number of maladaptive changes that allow underlying conditions to present and progress. Exactly which changes, contribute to the progression of which disease is currently an area of intense study. However, these answers often present therapeutic targets for disease prevention. Age is characterized by a …

Change In Processing Speed And Its Associations With Cerebral White Matter Microstructure, Muzamil Arshad

Wayne State University Dissertations

The decline of cognition with age is one of the most feared aspects of aging, while the slowing of responses, or reduced processing speed, is one of the most reliable aspects of aging. Slowing of processing has been hypothesized to affect other domains of cognition as well. Despite the well-known slowing-age relationship and central position processing speed plays in theories of cognitive aging the neurobiological mechanisms which underpin slowing is unclear. If we could identify the biology associated with processing speed we could then attempt to develop interventions to mitigate the effects of age on those variables. In turn we …

The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk

All ETDs from UAB

Klotho is an anti-aging protein that when upregulated, extends lifespan and enhances cognition. Klotho knockout mice age prematurely and die by ~8 weeks of life after developing cognitive impairment. Klotho function outside of the brain is well established but the protein’s action within the brain remains unknown. As klotho regulates peripheral stem cell populations, I sought to determine whether klotho contributes to cognition through a role in the maintenance of the adult hippocampal neurogenic niche. I examined adult mouse neurogenesis using global klotho-deficiency or global klotho overexpression models. Klotho knockout brains show reduced progenitor proliferation and granule cell production while …

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 …

Phenomic And Metabolomic Analysis Of Chronological Aging In Saccharomyces Cerevisiae, Haley Albright

All ETDs from UAB

Systematic investigation of chronological lifespan (CLS) in the Saccharomyces cerevisiae yeast gene knockout and knockdown (YKO/KD) strains reveals genes, path-ways, and interactions of potential relevance for aging of all eukaryotic cell types. Growth curves obtained by quantitative high-throughput cell array phenotyping (Q-HTCP) of the entire YKO/KD strain collection provide comprehensive snapshots of the influence of each individual gene on CLS. Yeast CLS is also influenced by media com-position, auxotrophic background, and media buffering. We used Q-HTCP to analyze CLS of the YKO/KD libraries, focusing on the interaction between gene networks and media buffering, with respect to their influence on CLS. …

Multi-Nuclear Magnetic Resonance Imaging Of Obstructive Lung Disease, Khadija Sheikh

Electronic Thesis and Dissertation Repository

Obstructive lung diseases such as chronic-obstructive-lung-disease (COPD), bronchiectasis, and asthma are characterized by airflow obstruction. They affect over six million Canadians costing the economy $12 billion/year. Despite decades of research, therapies that modify obstructive-lung-disease progression and control are lacking because patient diagnosis, monitoring, and response to therapy are currently made using airflow measurements that may conceal the independent contributions of underlying pathologies. One goal of obstructive-lung-disease research is to develop ways to identify patients with specific underlying pathological phenotypes to improve patient care and outcomes. Thoracic computed-tomography (CT) and magnetic-resonance-imaging (MRI) provide ways to regionally identify the underlying pathologies associated …

Motor Unit Remodeling During Neuromuscular Degeneration In Aging And Parkinson's Disease, Neil Anthony Kelly

All ETDs from UAB

The human neuromuscular system deteriorates progressively with age and disease. This results in denervation events and ultimately motor unit remodeling, which is revealed by abnormal “groups” of myofibers expressing the same myosin protein isoform – a phenomenon described as myofiber type grouping. Despite the acceptance of myofiber type grouping as a hallmark indicator of motor unit remodeling, traditional techniques of detecting it lack quantitative parameters and therefore comparative data in aging and disease are scarce. The purpose of this dissertation is to establish a statistically-driven, quantitative method for detecting myofiber type grouping and to use it to characterize the effects …

Age Related Decline In Memory: Examining The Mediation Effect Of Processing, Executive Functioning And Intelligence In Normal Adults, Jada J. Stewart

Theses and Dissertations

Multiple mediation analyses that collectively examine the prominent theories of cognitive aging (i.e., Common Cause, Processing, and Executive Decline Hypotheses) along with other cognitive domains that are sensitive to aging are rare. Moreover, having identified that cognition begins to decline as early as 30 years old, few studies have examined the mechanisms that underlie memory change among younger aging individuals. As a result, it is unclear whether relevant mediating variables have been excluded from early research on age-related memory decline, or to what extent rehabilitative strategies are applicable as early interventions for maintaining cognitive functioning into late life.

The present …

The Alpha-Glucosidase Inhibitor Acarbose As A Calorie Restriction Mimetic To Modify Metabolic Outcomes In Mice, Rachel Ann Brewer

All ETDs from UAB

Age-related diseases continue to be a leading cause of death. One of the only replicable methods proven to decrease age-related morbidity and mortality in multiple species is calorie restriction (CR). CR is difficult for human populations to implement, and has a number of associated risks and side effects. A CR mimetic could provide the healthspan- and lifespan-extending benefits of CR without the limitations. Acarbose (ACA), an α-glucosidase and α-amylase inhibitor approved to treat type 2 diabetes in humans, was recently identified as able to extend lifespan in healthy mice. The purpose of this research was to determine the effects of …