Medicine and Health Sciences Commons^™

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

The Challenges Of Nutrition And Aging, Linda C. Tapsell

L. C. Tapsell

From the time of birth and throughout the lifecycle, the human organism depends on food and nutrients to sustain its growth, development and functionality. With increasing knowledge of biological processes within the human body, the term ‘you are what you eat’, takes on more and more meaning. One of the new levels of understanding relates to the interaction of food components with genes to set off cascades of events that affect health and disease (1). This new understanding provides a detailed view of the dynamic relationship between genes and the environment, represented through food. Our health, our lifespan, can be …

Influence Of A Short-Term, Multicomponent Intervention On Balance And Strength Among The Elderly, Pamela C. Webert

Master's Theses and Doctoral Dissertations

Background: Few studies have combined strength and balance training to assess improvement of activities of daily living among subjects over the age of 65. The purpose of this study was to demonstrate how an eight-week balance and strength training program can lead to improvements in activities of daily living among elderly individuals.

Methods: The subjects consisted of 14 elderly women and 3 elderly men who were all residents of an independent living community. There were 10 subjects in the intervention group and 7 subjects in the control group. The intervention group participated in a supervised balance and strength …

Effects Of Thymus Size And Involution On The Contribution Of Recent Thymic Emigrants To The Peripheral T Cell Pool, Michelle L. Bolner

Dissertations & Theses (Open Access)

The contribution of recent thymic emigrants (RTEs) to the peripheral naïve T cell population is necessary to maintain diversity of the T cell receptor (TCR) repertoire and produce immune responses against newly encountered antigens.

The thymus involutes with age, after irradiation or chemotherapy, and due to severe viral infections. Thymus involution results in decreased thymopoiesis and RTE output leading to a reduced diversity of peripheral T cells. This increases susceptibility to disease and impairs immune responsiveness to vaccines. Therefore, studies aimed at maintaining or regenerating thymic function are integral for maintaining and restoring peripheral TCR diversity.

Mice that express a …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Aging, Neuromuscular Decline, And The Change In Physiological And Behavioral Complexity Of Upper-Limb Movement Dynamics, S. Morrison, K. M. Newell

Rehabilitation Sciences Faculty Publications

Aging is characterized by a general decline in physiological and behavioral function that has been widely interpreted within the context of the loss of complexity hypothesis. In this paper, we examine the relation between aging, neuromuscular function and physiological-behavioral complexity in the arm-hand effector system, specifically with reference to physiological tremor and isometric force production. Experimental findings reveal that the adaptive behavioral consequences of the aging-related functional decline in neurophysiological processes are less pronounced in simple motor tasks which provides support for the proposition that the motor output is influenced by both extrinsic (e.g., task related) and intrinsic (e.g., coordination, …

Role Of Phosphoinositide 3-Kinase – Akt Signaling Pathway In The Age-Related Cytokine Dysregulation In Splenic Macrophages Stimulated Via Tlr-2 Or Tlr-4 Receptors, Mosoka Papa Fallah, R. Lakshman Chelvarajan, Beth A. Garvy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Age-associated defects in both B-lymphocytes and macrophages in elderly result in a reduction in the efficacy of vaccines to many Gram positive bacteria like Streptococcus pneumoniae. Splenic macrophages from aged mice have been shown to have a defect in production of pro-inflammatory cytokines (IL-6, IL-12, IL-1β, TNF-α) but exhibit increased production of IL-10 upon TLR4 ligation. Here we showed that aged macrophages demonstrate similar cytokine dysregulation phenotype upon stimulation with TLR2 ligands, or killed S. pneumoniae. We hypothesized that an age-associated increase in activity of phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway may be playing a causal role in …

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 …

Plasticity Of Brain Networks In A Randomized Intervention Trial Of Exercise Training In Older Adults, Michelle W. Voss, Ruchika S. Prakash, Kirk I. Erickson, Chandramallika Basak, Laura Chaddock, Jennifer S. Kim, Heloisa Alves, Susie Heo, Amanda N. Szabo, Siobhan M. White, Thomas R. Wójcicki, Emily L. Mailey, Neha Gothe, Erin A. Olson, Edward Mcauley, Arthur F. Kramer

Kinesiology, Health and Sport Studies

Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and nonaerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain’s resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction.

Age-Specific Differences In The Use Of Thrombolytic Therapy And Hospital Outcomes In Patients With Acute Myocardial Infarction: A Community-Wide Perspective, Omar Ali, Immad Sadiq, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Jerry Gurwitz, Joel Gore

Jorge L. Yarzebski

BACKGROUND: Relatively limited information is available about recent, and trends over time, use of thrombolytic therapy in patients of different ages hospitalized with acute myocardial infarction and the association between use of thrombolytic therapy and hospital outcomes. METHODS: We conducted an observational study of 5601 residents of the Worcester, Massachusetts, metropolitan area (1990 census = 437,000) with confirmed acute myocardial infarction in all local hospitals during 6 one-year periods between 1990 and 1999. RESULTS: Despite relatively stable use of thrombolytic therapy between 1990 and 1995, decreases in the use of thrombolytic therapy in all patients with acute myocardial infarction were …

Algal Biofuel, Feb. 12, 2010, Harry Reid Center, University Of Nevada, Las Vegas

Biofuels

News in Brief

1. Fatty Acids Protect Against Aging (Feb. 8, 2010)

Aging And Endothelial Progenitor Cell Telomere Length In Healthy Men, Erich J Kushner, Gary Van Guilder, Owen J Maceneaney, Jennifer N Cech, Brian L Stauffer, Christopher A Desouza

Health and Nutritional Sciences Faculty Publications

BACKGROUND: Telomere length declines with age in mature endothelial cells and is thought to contribute to endothelial dysfunction and atherogenesis. Bone marrow-derived circulating endothelial progenitor cells (EPCs) are critical to vascular health as they contribute to both reendothelialization and neovascularization. We tested the hypothesis that EPC telomere length decreases with age in healthy adult humans.
METHODS: Peripheral blood samples were collected from 40 healthy, non-obese, sedentary men: 12 young (age 21-34 years), 12 middle-aged (43-55 years) and 16 older (57-68 years). Putative EPCs were isolated from peripheral blood mononuclear cells and telomere length was determined using genomic DNA preparation and …

Increased Strength And Physical Performance With Eccentric Training In Women With Impaired Glucose Tolerance: A Pilot Study, Robin L. Marcus, Paul C. Lastayo, Leland E. Dibble, Laura Hill, Donald A. Mcclain

Human Movement Sciences & Special Education Faculty Publications

Background: Menopause is associated with both a loss of muscle mass and a worsening of insulin sensitivity (IS). Although eccentric resistance exercise (ECC) can effectively improve muscle mass over time, a single bout of ECC can worsen IS. This study assessed the effect of repeated ECC on IS, muscle mass, and function in postmenopausal women with impaired glucose tolerance (IGT).

Methods: Sixteen PM women (aged 56 years +/- 6.4) with IGT were randomly assigned to a 12-week, knee extensor ECC program (n = 10) or a nonexercise control group (CON) (n = 6). Participants underwent hyperinsulinemic-euglycemic clamps, dual-energy …

Effects Of Aging And Gender On Regulators Of Muscle Adaptation In F344/Bn Rat Model, Satyanarayana Paturi

Theses, Dissertations and Capstones

Sarcopenia is the loss of muscle mass and strength that occurs with aging. Here we examine the effects of aging and gender on the regulation of molecules believed to regulate muscle growth and adaptation in the F344/BN rat. In male animals, soleus and EDL muscle/body weight ratio declined continuously with aging while muscle atrophy in female animals plateaued at 26-months and remained constant thereafter. Aging increased the phosphorylation of protein kinase-B (Akt) and the mammalian target of rapamycin (mTOR) in the female but not male soleus muscle. This finding was associated with the attenuation of muscle atrophy observed in female …

The Challenges Of Nutrition And Aging, Linda C. Tapsell

Faculty of Health and Behavioural Sciences - Papers (Archive)

From the time of birth and throughout the lifecycle, the human organism depends on food and nutrients to sustain its growth, development and functionality. With increasing knowledge of biological processes within the human body, the term ‘you are what you eat’, takes on more and more meaning. One of the new levels of understanding relates to the interaction of food components with genes to set off cascades of events that affect health and disease (1). This new understanding provides a detailed view of the dynamic relationship between genes and the environment, represented through food. Our health, our lifespan, can be …

Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. …

Effect Of Dietary Protein On Prepubertal Mammary Development In Rapidly Growing Dairy Heifers, Brian K. Whitlock, M J. Vandehaar, L F. Silva, H A. Tucker

Brian K Whitlock, PhD, DVM, DACT

The objective was to determine whether increased dietary protein would enhance mammary development in prepubertal heifers fed for rapid body growth (1.2 kg/d). Fifty-four Holstein heifers (weighing approximately 134 kg) were assigned to one of three treatments. Heifers were fed a total mixed ration with metabolizable energy at 2.85 Mcal/kg and metabolizable protein at low, standard, or high concentrations (37, 41, or 44 g/Mcal of metabolizable energy, respectively) from 3.5 mo of age until slaughter at approximately 46 d after puberty. Heifers fed low, standard, and high protein gained 1130, 1170, and 1180 g/d, respectively. Dietary protein did not affect …

Effect Of Dietary Protein On Prepubertal Mammary Development In Rapidly Growing Dairy Heifers, Brian K. Whitlock, M J. Vandehaar, L F. Silva, H A. Tucker

Faculty Publications and Other Works -- Large Animal Clinical Sciences

The objective was to determine whether increased dietary protein would enhance mammary development in prepubertal heifers fed for rapid body growth (1.2 kg/d). Fifty-four Holstein heifers (weighing approximately 134 kg) were assigned to one of three treatments. Heifers were fed a total mixed ration with metabolizable energy at 2.85 Mcal/kg and metabolizable protein at low, standard, or high concentrations (37, 41, or 44 g/Mcal of metabolizable energy, respectively) from 3.5 mo of age until slaughter at approximately 46 d after puberty. Heifers fed low, standard, and high protein gained 1130, 1170, and 1180 g/d, respectively. Dietary protein did not affect …

Cellular Basis Of Decreased Immune Responses To Pneumococcal Vaccines In Aged Mice, Manju Garg, Wei Luo, Alan M. Kaplan, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152: 1589-1596, 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studies showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell …

Restaurant Dining Strategies: Attracting Nutrition-Conscious Future Seniors, Elizabeth B. Pederson, Frederick J. Demicco

Hospitality Review

Senior Customers pose some unique challenges to operators due to some of the physiological changes associated with aging. In an effort to make food and beverage managers more cognizant of these changes, the authors examine these areas and also discuss strategies to attract and enhance the dining experience of the viable senior market segment.

Age Differences In Bimanual Coordination, Paul Amrhein, George Stelmach, Noreen Goggin

Department of Psychology Faculty Scholarship and Creative Works

A bimanual coordination experiment was conducted in which two groups of 10 male and female participants, elderly (67 to 75 years of age) and young (21 to 25 years of age), produced unimanual, bimanual symmetrical (equal extent amplitude), and bimanual asymmetrical (unequal extent amplitude) movements. In addition to an overall increase in performance latency, the elderly group exhibited a linear increase in response initiation (RT) with increases in task complexity similar to that of the young group. However, the elderly participants showed a proportional increase over the young participants in response execution latency (MT). Further, the elderly group had a …