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Evaluating The Occurrence Of Age-Related Peripheral Neuropathy In Het3 Mice And Development Of A Whole Tissue Imaging Technique For Analyzing Total Innervation In The Subcutaneous Adipose Depot, Jake Willows

Electronic Theses and Dissertations

Adipose tissue can be characterized as either being a white (energy storing) depot or a brown (energy expending) depot and both have been found to contain dense networks of neural innervation. This adipose nerve supply regulates numerous metabolic functions and likely plays an important role in the function of adipose blood vessels. Recently our lab has shown in the C57BL/6 mouse model that peripheral neuropathy, or the dying back and dysfunction of the nerves in the superficial tissues such as the skin, can extend into the subcutaneous adipose tissue in conditions commonly associated with the neuropathic phenotype (i.e. diabetes, obesity, …

Identification Of Chromatin Regulators Perturbed In Hematopoietic Stem And Progenitor Cell Aging, Eraj S. Khokhar

Electronic Theses and Dissertations

As lifespan is increasing globally, there is a critical need to identify strategies to extend healthspan and prevent chronic diseases into older age. The long-term goal of my research is to identify novel strategies to ameliorate aging-induced decline in hematopoietic stem cell (HSC) function. HSCs give rise to all mature blood and immune cells. With age, HSCs undergo defects in their differentiation ability which correlates with a decline in immune function. Comprehensive knowledge of gene regulatory and epigenetic mechanisms underlying this defect is a barrier to developing therapies to ameliorate aging-associated decline in HSC function. Therefore, my project focuses on …

Age And Seasonal Change In The Chronobiology Of A Spider With An Exceptionally Long-Period Circadian Clock, Shae Crain

Electronic Theses and Dissertations

This study examines locomotor activity in samples of Frontinella pyramitela collected over its active season (April-October) to investigate whether seasonality and/or age may help explain the exceptional variability typically found in spider clock systems. Despite its noteworthy variability (%CV= 7.7), we have found that Frontinella has a mean free-running period of 28.4±2.18 hours that does not significantly vary over time. There is no correlation between day length and free-running period, indicating that varying length of FRP is not a function of photoperiod length. In LD 12:12 h, the window of activity is significantly smaller in April, gradually widening as the …

Serum Myostatin And Igf-1 As Biomarkers Of Sarcopenia: A Proof-Of-Concept Design, Ashley Binns

Graduate Theses and Dissertations

The population comprising older adults is growing exponentially, as are healthcare related costs. Nearly $20 billion is annually expensed by older adults for health-related issues affiliated with age-related decline in skeletal muscle mass. Yet, diagnostic criteria are not readily utilized in clinical practice. PURPOSE: Therefore, the purpose of this study was to provide evidence for use of blood biomarkers (myostatin, IGF-1) to predict appendicular skeletal muscle mass (ASM) among middle-aged and older adults. METHODS: A cross-sectional study was conducted among 106 individuals (n = 68 females; n = 38 males) aged ≥ 40 years of age (60.1 ± 11.1 y) …

Comparing Independent Approaches To Estimate Age At Size Of The Jonah Crab (Cancer Borealis): Corroborating Gastric Mill Band Counts As A Direct Aging Method, Carlton Huntsberger

Electronic Theses and Dissertations

Knowing the age of an organism is essential in understanding the dynamics and management of wild populations. Age determination has been an especially long-standing challenge in the study of crustaceans, since they posed a unique challenge, shedding all calcified structures with each molt. The Jonah crab (Cancer borealis), is one of many commercially harvested crustaceans for which no absolute aging method has yet been established. It is an ecologically important species and a newly managed fishery in New England and Atlantic Canada. The recent increase of commercial fisheries for this species has highlighted the large data gap of …

One Year Change In Cognitive Function In Male And Female Common Marmosets (Callithrix Jacchus), Brianna Healey

Masters Theses

Long term cognitive studies in humans and nonhuman primates such as macaques are difficult because of their long lifespan. The common marmoset (Callithrix jacchus) is a non-human primate who shares with humans many features characteristic of primates, including a complex brain and cognitive function. They also have a short lifespan (~10 years) that makes them a great model in studies of cognitive aging. This study focuses on the rate of decline in cognitive function in male and female marmosets based on performance on reversal learning tasks over 2 years of testing.

We found that marmosets improved their overall …

Effects Of Life-Long Wheel Running Behavior On Plantar Flexor Contractile Properties, Alexander Nicholas Beechko

Electronic Theses, Projects, and Dissertations

Aging in skeletal muscle is characterized by a loss in muscular performance. This is in part related to the direct loss of muscle mass due to senescence, known as sarcopenia. With age, skeletal muscles lose force production, contractile speed, and power production. The force velocity relationship of muscle is a product of force production and contraction speed, both of which decline with age; however, the mechanisms and trajectory of this decline are not well understood. Exercise has positive effects on muscle, and thus may assist in maintaining performance in old age. However, few long-term studies have been performed to examine …

Mechanics Of Phenotypic Aging Trajectories In C. Elegans And Humans, William Zhang

Arts & Sciences Electronic Theses and Dissertations

Overall, my dissertation integrates longitudinal measurements of physiology to investigate the aging process. In the first half, I examine the surprising and largely unexplained degree of variation in lifespan within even homogeneous populations. I sought to understand how physiological aging differs between long- and short-lived individuals within a population of genetically identical C. elegans reared in a homogeneous environment. Using a novel culture apparatus, I longitudinally monitored aspects of aging physiology across a large population of isolated individuals. Aggregating several measures into an overall estimate of senescence, I find that long- and short-lived individuals start adulthood on an equal physiological …

Does Acute Preprandial Exercise Modify Postprandial Inflammation After A High Fat Meal In Young And Older Adults?, William Wisseman

Masters Theses, 2010-2019

A single high-fat meal (HFM) can increase systemic inflammation (postprandial inflammation; PPI) and may be attenuated by recent exercise. However, the effect of preprandial exercise on PPI in older adults (OA) is not clear. Purpose: To determine if preprandial exercise attenuates PPI in YA and OA. Methods: 12 YA (23.3±3.9 years n= 5 M/7 F) and 12 OA (67.7±6 years, n= 8 M/4 F) completed two HFM challenges in a randomized order. During HFM alone, participants abstained from exercise 48 hours prior to the HFM session (except for the exercise session) and adhered to a 12 hour overnight …

Rejuvenation Of The Epigenetic Landscape Of The Aged Brain Through Manipulation Of Circulating Factors, Edward Koellhoffer

Dissertations & Theses (Open Access)

The aging population of the United States is expanding at an alarming rate. The Center for Disease Control and Prevention estimates that the population of those age 65 years and older will reach over 50 million by 2020 and will double to 100 million by 2060. This will not only put a massive strain on national healthcare resources, but will also increase the number of those who are not able to live and function independently. It is becoming increasingly vital to understand how the brain changes with age and mechanisms to possibly protect and rejuvenate the aged brain to a …

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

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 …

The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks

Dissertations

This study examined the relationship between distress and the development of Type 2 diabetes mellitus (T2DM) in the presence of established risk factors. Distress secondary to mental health disparities, stressful life events, and work conditions has been shown to promote insulin resistance and the development of T2DM.

Subjects (N=79) diagnosed with T2DM within the previous six months were recruited from SSM Health Centers and VA Medical Centers in the greater St. Louis area. They completed the Recent Life Changes Questionnaire, ENRICHD Social Support Instrument, and a demographic survey and analyses were conducted to determine differences between the veteran …

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Amelioration Of Alzheimer's Disease Pathology In 12-Month-Old Happ(Sweind) Transgenic Mice After Treatment With A Cysteine Rich Whey Supplement, Immunocal®, Srivalli Puttagunta

Electronic Theses and Dissertations

Deficits in Reelin expression and signaling play a pathogenic role in Alzheimer’s disease (AD). Thus, strategies aimed at correcting Reelin deficits may provide a novel therapeutic approach to treating AD. The cysteine-rich, whey protein supplement, Immunocal®, has recently been shown to rescue Reelin expression in a mouse model of Schizophrenia. Given that Reelin-expressing neurons of the entorhinal cortex region are a highly vulnerable population of cells that are lost early in AD, we examined the effects of Immunocal® in the hippocampal-entorhinal cortex formation in a mouse model of AD. Glutathione levels and Reelin expression in the hippocampal-entorhinal cortex formation (entorhinal …

Qualitative And Quantitative Fitness Consequences Of Advanced Maternal Age, Claudia Jean Hallagan

Electronic Theses and Dissertations

Parental age can affect offspring fitness across taxa and through various mechanisms. However, the effect(s) of advanced maternal age on offspring, particularly in insects, has not been comprehensively reviewed making it difficult to draw conclusions about the effects of advanced maternal age on offspring in insects. In my first chapter, I reviewed maternal age literature and found overall negative effects of advanced maternal age on offspring fitness. However, results vary depending on which fitness measures were used, the life stages at which offspring were measured, and the experimental design of the study. In my second chapter, I conducted an experiment …

Transgenerational Effects Of Maternal Age On Offspring Fitness In Crickets, Jacob D. Wilson

Electronic Theses and Dissertations

Advanced parental age is an important aspect of parental condition that can have both positive and negative effects on offspring fitness, and thus, parental age can be considered a parental effect. As a parental effect, parental age may affect a variety of offspring traits and may cascade to influence several generations of offspring. Given the complexities of studying both paternal and maternal age, we studied the effects of maternal age only. Using the Pacific field cricket, Teleogryllus oceanicus, we asked 1) does maternal age have influences over several generations of offspring and 2) does maternal age influence the reproductive …

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …

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 …

The Role Of Sirt1 In Skeletal Muscle Function And Repair Of Older Mice, Matthew John Myers

Graduate Theses, Dissertations, and Problem Reports

Human skeletal muscle is a highly metabolic tissue necessary for mobility and coordination. Responsible for approximately one-fifth of the resting human metabolism, skeletal muscle is also an important regulator of metabolites like glucose and contributes to the regulation of body temperature. Although there is a gradual decline in muscle mass associated with aging, a certain percentage of the population suffer from severe muscle mass and strength deterioration, classified as sarcopenia (5-13% for people aged 60-70 years old, 11-50% for those 80 or older). Sarcopenia is linked to increased morbidity and mortality rates in the elderly population, while annual healthcare costs …