Medicine and Health Sciences Commons^™

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 …

Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in …

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 …

Endothelial Function Is Associated With White Matter Microstructure And Executive Function In Older Adults, Nathan F. Johnson, Brian T. Gold, Christopher A. Brown, Emily F. Anggelis, Alison L. Bailey, Jody L. Clasey, David K. Powell

Physical Therapy Faculty Publications

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI …

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Kevin M Rice

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. …

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Eric Blough

No abstract provided.

Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, Srinivasarao Thulluri, Miaozong Wu, Eric R. Blough, Nandini D.P.K. Manne, Ashley B. Litchfield, Bin Wang

Nandini Manne

Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase I (HOI), iron-regulatory protein I (IRPI), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model, …

Epigenetic Age Acceleration Assessed With Human White-Matter Images, Karen Hodgson, Melanie A. Carless, Hemant Kulkarni, Joanne E. Curran, Emma Sprooten, Emma E. Knowles, Samuel R. Mathias, Harald H. H. Goring, Nailin Yao, Rene L. Olvera, Laura Almasy, Ravindranath Duggirala, John Blangero, David C. Glahn

School of Medicine Publications and Presentations

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n = 628; age = 23.28-93.11 years), epigenetic …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

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 …

Age-Dependent Absolute Abundance Of Hepatic Carboxylesterases (Ces1 And Ces2) By Lc-Ms/Ms Proteomics: Application To Pbpk Modeling Of Oseltamivir In Vivo Pharmacokinetics In Infants., Mikael Boberg, Marc Vrana, Aanchal Mehrotra, Robin E. Pearce, Andrea Gaedigk, Deepak Kumar Bhatt, J Steven Leeder, Bhagwat Prasad

Manuscripts, Articles, Book Chapters and Other Papers

The age-dependent absolute protein abundance of carboxylesterase (CES) 1 and CES2 in human liver was investigated and applied to predict infant pharmacokinetics (PK) of oseltamivir. The CES absolute protein abundance was determined by liquid chromatography-tandem mass spectrometry proteomics in human liver microsomal and cytosolic fractions prepared from tissue samples obtained from 136 pediatric donors and 35 adult donors. Two surrogate peptides per protein were selected for the quantification of CES1 and CES2 protein abundance. Purified CES1 and CES2 protein standards were used as calibrators, and the heavy labeled peptides were used as the internal standards. In hepatic microsomes, CES1 and …

Adolescent Cannabinoid Exposure Induces A Persistent Sub-Cortical Hyper-Dopaminergic State And Associated Molecular Adaptations In The Prefrontal Cortex., Justine Renard, Laura G Rosen, Michael Loureiro, Cleusa De Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette

Brain and Mind Institute Researchers' Publications

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. …

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 …

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. …

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 …

The Relationship Between Physical Fitness And Falling Risk And Fear Of Falling Incommunity-Dwelling Elderly People With Different Physical Activity Levels, Mehmet Duray, Arzu Genç

Turkish Journal of Medical Sciences

Background/aim: The aim of this research was to determine the effects of physical activity level (PAL) and physical fitness on falling parameters in community-dwelling elderly people. Materials and methods: Seventy-six elderly people were grouped as low PAL group (group 1, n: 38) and high PAL (group 2, n: 38) according to their PAL scores. PAL was measured by the Physical Activity Scale for the Elderly and muscle strength, muscle endurance, aerobic endurance, and flexibility tests were applied; body mass index (BMI) was calculated for physical fitness measurement. Fall assessment included falling risk (Berg Balance Scale), dynamic balance (Time Up and …

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 …