Life Sciences Commons^™

Investigating The Age-Dependent Impact Of Lactate Dehydrogenase On Cognition In Flies And Mice, Ariel Khaya Frame

Electronic Thesis and Dissertation Repository

Lactate is a carbohydrate breakdown product typically produced in astrocytes, a type of glial cell, and transported to neurons within the brain. This type of metabolic coupling is commonly referred to as the astrocyte neuron lactate shuttle (ANLS). While numerous studies have shown that the ANLS is involved in cognition in mammals few have taken into consideration sex differences, changes with age, or evolutionary conservation in invertebrates. Lactate metabolism is controlled by the enzymatic interconversion of pyruvate and lactate in a reaction catalyzed by lactate dehydrogenase (LDH). In this thesis I examined cognitive changes across lifespan affected by genetic manipulation …

The Impact Of Progerin On Genome Maintenance In Mammalian Cells, Liza Alexandra Joudeh

Theses and Dissertations

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by accelerated aging. The cause of HGPS is a point mutation in the LMNA gene, which encodes lamins A and the splice variant lamin C. Lamins are components of the nuclear lamina, a complex that plays structural and catalytic roles in the nucleus that are essential to chromatin organization, DNA replication, and DNA repair. The mutation associated with HGPS activates a cryptic splice donor site which alters the lamin A protein in a way that does not allow prelamin A to be fully processed, and ultimately results in the accumulation …

Impacts Of Dietary Restriction On A Drosophila Model Of Werner Syndrome, Eileen Sember

College of Arts & Sciences Senior Honors Theses

Werner syndrome (WS) is an autosomal recessive disorder that results in premature aging and occurs in 1 in 1,000,0000 to 1 in 10,000,000 people. In humans, WS is the result of mutations that render the WRN gene, that contains a helicase and an exonuclease domain, non-functional. Currently, there is no cure for WS in humans, making dietary and lifestyle interventions attractive for increasing the quality and longevity of lives. Diet restriction (DR) has been shown to extend the lifespan of several model organisms, including Drosophila melanogaster, making it a strong candidate for WS treatment. In this thesis, mutant flies …

The G Protein-Coupled Receptor (Gpcr) Fshr-1 And The Sphk-1 Lipid Kinase Regulate C. Elegans Life- And Healthspans Via A Common Pathway, Ryan Dennis Adkins

Undergraduate Honors Thesis Collection

Later years of life are often characterized by reduced cognitive function and mobility. One contributor is the cellular accumulation of reactive oxygen species (ROS), but our understanding of how cells respond to ROS to promote health and survival is incomplete. Follicle stimulating hormone receptor-1 (FSHR-1) and sphingosine kinase-1 (SPHK-1) mediate responses to oxidative stress and regulate life history traits in the roundworm Caenorhabditis elegans. The genes encoding both proteins are conserved in humans where they are implicated in stress responses, cell survival and neuronal function. fshr-1 and sphk-1 work together to mediate responses to intestinal oxidative stress in C. elegans. …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

A Long‐Term Obesogenic High‐Fat Diet In Mice Partially Dampens The Anti‐Frailty Benefts Of Late‐Life Intermittent Fasting, Yoko Henderson, Nazmin Bithi, Jie Yang, Christopher Link, Aili Zhang, Benjamin Baron, Eran Maina, Christopher Hine

Senior Honors Projects

The global obesity pandemic coupled with ever-growing life expectancies equates to hundreds of millions of individuals with potentially longer but not healthier lives. Aging is one of the risk factors for numerous maladies such as metabolic dis- order and frailty, which are exacerbated under obesity. Thus, therapeutic approaches that address obesity to ultimately improve afected individuals’ quality of life and extend their lifespan are needed. We previously reported that the every other day (EOD) fasting initiated late-life improved metabolic, musculoskeletal, and cognitive endpoints in standard rodent diet-fed mice. In the present study, using the same dietary intervention methodology, we tested …

Circadian Clock Controls Rhythms In Ketogenesis By Interfering With Ppar Alpha Transcriptional Network, Volha Mezhnina, Oghogho P. Ebeigbe, Nikkhil Velingkaar, Allan Poe, Yana I. Sandlers, Roman Kondratov

Biological, Geological, and Environmental Faculty Publications

Ketone bodies are energy-rich metabolites and signaling molecules whose production is mainly regulated by diet. Caloric restriction (CR) is a dietary intervention that improves metabolism and extends longevity across the taxa. We found that CR induced high -amplitude daily rhythms in blood ketone bodies (beta-hydroxybutyrate [beta OHB]) that correlated with liver beta OHB level. Time-restricted feeding, another periodic fasting-based diet, also led to rhythmic beta OHB but with reduced amplitude. CR induced strong circadian rhythms in the expression of fatty acid oxidation and ketogenesis genes in the liver. The transcriptional factor peroxisome-proliferator-activated-receptor alpha (PPAR alpha) and its transcriptional target hepatokine …

Measuring Mtdna In Drosophila, Lola Demurger

WWU Honors College Senior Projects

Mitochondria have long been studied in relation to aging as they are critical to cell operation, and their dysfunction is linked to several age-related factors, such as shortened lifespan and increased innate immunity. In this study, we use a mitochondrially targeted nuclease called UL12.5 to artificially induce mitochondrial dysfunction by degrading the mitochondrial genome in Drosophila. Degraded mitochondrial DNA (mtDNA) has many downstream effects, including mtDNA depletion, mtDNA leakage into the cytoplasm, chronically upregulated innate immune response, and shortened lifespan. We began the process of developing an assay that measured mtDNA depletion as a result of UL12.5-mediated mtDNA degradation in …

Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans, Lindsey N. Barrett

USF Tampa Graduate Theses and Dissertations

The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene …

The Effects Of Aging On Wound Healing And Limb Regeneration In The Axolotl, Hande Sahin

Graduate Masters Theses

The Mexican axolotl is capable of regenerating various parts of its body and maintains this capacity throughout its entire life. Although this ability is sustained through adulthood, multiple regenerative processes appear to be negatively affected by aging. Here, we focus on evaluating the effect of aging on the rate of wound healing and limb regeneration. We have developed new in vivo, and ex vivo assays to characterize wound healing and identify differences between young and aged animals during this process. We have also characterized morphological features of mature skin from both groups of animals and although there are no obvious …

Ocean Quahog (Arctica Islandica) Population Dynamics: Sex-Based Demographics And Regional Comparisons In The Northwest Atlantic, Kathleen M. Hemeon

Dissertations

Arctica islandica (ocean quahog) is the longest-lived bivalve on Earth. Individuals on the deep continental shelf of the Mid-Atlantic (US) can survive for centuries, and when found in the colder, boreal waters of Iceland, ages over 500 years can be reached. The ocean quahog is important in the US, yet very little is known about the resiliency of the ocean quahog stock to fishing activity, and ocean quahog recruitment patterns over time. To quantify and constrain age-reader error prior to age analysis, a triple-method error protocol was developed for A. islandica that included age-reader bias, precision, and error frequency. The …

Reproductive Aging In Caenorhabditis Elegans: From Molecules To Ecology, Andrea Scharf, Franziska Pohl, Brian M. Egan, Zuzana Kocsisova, Kerry Kornfeld

Biological Sciences Faculty Research & Creative Works

Aging animals display a broad range of progressive degenerative changes, and one of the most fascinating is the decline of female reproductive function. In the model organism Caenorhabditis elegans, hermaphrodites reach a peak of progeny production on day 2 of adulthood and then display a rapid decline; progeny production typically ends by day 8 of adulthood. Since animals typically survive until day 15 of adulthood, there is a substantial post reproductive lifespan. Here we review the molecular and cellular changes that occur during reproductive aging, including reductions in stem cell number and activity, slowing meiotic progression, diminished Notch signaling, and …

The Impacts Of Aging, Sedentarism, And Exercise On Neurotrophic Factor Expression And Innervation In The Heart And The Effects Of Treatment With Α-Cgrp On Heart Function, Gabriel Almeida Alves

Dissertations

Neurotrophic factors (NFs) are important molecules responsible for development, differentiation, regeneration, and maintenance of new and mature neurons. Neurotrophic factors act as neurocytokines and may assist with the regulation of axonal and dendritic arrangements and synaptic plasticity between neurons themselves or with other non-neural target tissues. In this study, we analyze the levels of two NFs: glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). Cardiomyocytes produce these neurotrophic factors which assist with the innervation pattern of the heart. The heart is innervated by the two branches of the autonomic nervous system; namely the sympathetic nervous system and …

Dna Damage And Aging In Progeria Compared To Healthy Cells., Ashtyn Marie Hill

Chancellor’s Honors Program Projects

No abstract provided.

The Validation Of Predicted Biological Age Of Drosophila Melanogaster From Combined Statistical Modeling, Lauren Francis

Masters Theses

"Sleep is essential for maintaining a healthy body and mind and is associated with aging and aging related diseases. There are individual differences in fly as well as human sleep behavior and lifespan. Between and within individuals, sleep varies in characteristics including consolidation, rhythmicity, continuity, duration, and more. Various evidence in the literature suggests there are many molecular pathways involved with aging and they may be different for individuals. Our research is interested in a possible restorative mechanism of sleep and the ramifications of that mechanism to aging. We have developed two predictive models of aging using the fruit fly …

Early Life History Of Tarpon (Megalops Atlanticus) In South Carolina Estuaries: Assessment Of Juvenile Recruitment And Validity Of Aging And Back-Calculation Methods, Garrett M. Elmo

Electronic Theses and Dissertations

No abstract provided.

Molecular And Cellular Mechanisms Of Aging In Hematopoietic Stem Cells And Their Niches, Lei Zhang, Ryan Mack, Peter W. Breslin, Jiwang Zhang

Biology: Faculty Publications and Other Works

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of …

Spiny Mice (Acomys) Exhibit Attenuated Hallmarks Of Aging And Rapid Cell Turnover After Uv Exposure In The Skin Epidermis, Wesley Wong, Austin Kim, James R. Monaghan, Ashley W. Seifert, Malcolm Maden, Justin D. Crane

Biology Faculty Publications

The study of long-lived and regenerative animal models has revealed diverse protective responses to stressors such as aging and tissue injury. Spiny mice (Acomys) are a unique mammalian model of skin wound regeneration, but their response to other types of physiological skin damage has not been investigated. In this study, we examine how spiny mouse skin responds to acute UVB damage or chronological aging compared to non-regenerative C57Bl/6 mice (M. musculus). We find that, compared to M. musculus, the skin epidermis in A. cahirinus experiences a similar UVB-induced increase in basal cell …

Investigating The Regulation And Role Of P38 Mapk In Collagen-Related Limb Girdle Muscular Dystrophy, Briseida Oceguera-Perez

Theses and Dissertations

Aging is an expected and normal process across living organisms. It is characterized as a loss of stress resistance, degeneration of tissues, and decline in motor function that happen gradually across lifespan. Susceptibility to neurodegenerative and dystrophic conditions also increase, and unlike aging, are not a normal aspect of lifespan. Discerning the difference between normal and aberrant aging states will give insight into the mechanisms behind the progressive dysfunction shared among organisms. Previous work in our lab has shown that the aging gene p38 MAPK in Drosophila melanogaster plays a significant role in the aging process through its downstream effects …

How Can We Change Gut Microbiota For Healthy Lives?, Elizaveta Shmakova

Scientific Communication News

No abstract provided.

Dietary Fish Oil Supplement Induces Age-Specific Contractile And Proteomic Responses In Muscles Of Male Rats, David W. Russ, Kalina Dimova, Emily Morris, Marguerite Pacheco, Sean M. Garvey, Stylianos P. Scordilis

Biological Sciences: Faculty Publications

Background: Dietary fish oil (DFO) has been identified as a micronutrient supplement with the potential to improve musculoskeletal health in old age. Few data are available for effects of DFO on muscle contractility, despite the significant negative impact of muscle weakness on age-related health outcomes. Accordingly, the effects of a DFO intervention on the contractile function and proteomic profile of adult and aged in an animal model of aging were investigated.

Methods: This preliminary study evaluated 14 adult (8 months) and 12 aged (22 months) male, Sprague-Dawley rats consuming a DFO-supplemented diet or a control diet for 8 weeks (7 …

Is Rapamycin An Effective Anti-Aging Drug?, Basya Aboud

The Science Journal of the Lander College of Arts and Sciences

Scientific and pharmaceutical advancements have revolutionized medicine. Many once- debilitating or fatal diseases can now be managed with medication. However, the search for a cure for the inevitable aging diseased state remained futile until recently. Rapamycin has been studied for its possible longevity effects, providing promising results for the development of anti-aging therapies. This paper evaluates the benefits and risks of rapamycin use. While rapamycin cannot be supported as a safe anti-aging drug, rapamycin studies have elucidated parts of the aging pathway, providing a breakthrough for anti-aging research.

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 …

The Effects Of Aging On Sleep Parameters In A Healthy, Melatonin-Competent Mouse Model, Jiffin K. Paulose, Chanung Wang, Bruce F. O'Hara, Vincent M. Cassone

Biology Faculty Publications

Background: Sleep disturbances are common maladies associated with human age. Sleep duration is decreased, sleep fragmentation is increased, and the timing of sleep onset and sleep offset is earlier. These disturbances have been associated with several neurodegenerative diseases. Mouse models for human sleep disturbances can be powerful due to the accessibility to neuroscientific and genetic approaches, but these are hampered by the fact that most mouse models employed in sleep research have spontaneous mutations in the biosynthetic pathway(s) regulating the rhythmic production of the pineal hormone melatonin, which has been implicated in human sleep.

Purpose and method: The present study …

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 …

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 …

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 …

The Effects Of Aging On Skeletal Muscle Atp Production, Chaya Abboudi

The Science Journal of the Lander College of Arts and Sciences

The study of the aging process and its prevention is an incredibly popular field; the natural course of the human body is to age and theories abound on how to avoid it. Age affects every system and pathway of the body and alters many of the bodily functions. This paper, using articles from Touro’s library database examines the different areas in which aging negatively affects ATP production. The multifaceted process associated with the production of ATP in the human body was analyzed. Several features such as the mitochondria, physical activity, and hormones are linked to ATP production and the relationship …

Caloric Restriction Effects On Liver Mtor Signaling Are Time‐Of‐Day Dependent, Richa Tulsian, Nikkhil Velingkaar, Roman Kondratov

Biological, Geological, and Environmental Faculty Publications

The regulation of mechanistic target of rapamycin (mTOR) signaling contributes to the metabolic effects of a calorie restriction (CR) diet. We assayed the effect of CR on the activity of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) in the liver of mice at six different times across the day. CR effects on mTORC1 and mTORC2 activities were time-of-day dependent. CR induced mTORC1 activity at one time, reduced at two times and has no effect during other times. CR induced mTORC2 activity at one time of the day and has no effects at other times. Circadian clocks are implemented …

Determining The Relationship Between Aging And Oxidative Stress In A Drosophila Melanogaster P38 Kb Framework, Aleksandra J. Majewski

Theses and Dissertations

Aging is inevitable for all organisms and can be characterized by degeneration of tissue, adecrease in motor function, and impaired stress response. In humans, it is often accompanied by an increased propensity for age related diseases. While all adults experience biological aging (senescence) not all adults experience age-associated disease. Thus, we claim these are not normal prospects of aging. Although the implications of aging are well understood, the molecular underpinnings for these processes remain elusive. As advances in medical science have been successful at prolonging lifespan, they concurrently extend the amount of time spend in diseased states. If we wish …