Medicine and Health Sciences Commons^™

Mechanisms Underlying Stem Cell Depletion In Ageing., Mackenzie Hsu

Electronic Thesis and Dissertation Repository

As we age, our bodies lose the ability to repair damaged tissues. This impairment may be due to age-related deficits in our regenerative stem cells. Stem cells reside in specialized areas called stem cell niches. Ageing may cause alterations in the stem cells directly or may alter the stem cell niche to generate deficits. However, systematic studies mapping stem cell deficits and alterations to stem cell niche are lacking. Here, I investigated the bone marrows of young and aged mice to determine age-related changes in the microenvironment that may alter resident stem cells.

To achieve my research objective, I examined …

Facilitation–Inhibition Control Of Motor Neuronal Persistent Inward Currents In Young And Older Adults, Lucas B. R. Orssatto, Gabriel L. Fernandes, Anthony J. Blazevich, Gabriel S. Trajano

Research outputs 2022 to 2026

A well-coordinated facilitation–inhibition control of motor neuronal persistent inward currents (PICs) via diffuse neuromodulation and local inhibition is essential to ensure motor units discharge at required times and frequencies. Present best estimates indicate that PICs are reduced in older adults; however, it is not yet known whether PIC facilitation–inhibition control is also altered with ageing. We investigated the responses of PICs to (i) a remote handgrip contraction, which is believed to diffusely increase serotonergic input onto motor neurones, and (ii) tendon vibration of the antagonist muscle, which elicits reciprocal inhibition, in young and older adults. High-density surface electromyograms were collected …

Identification Of Healthspan-Promoting Genes In Caenorhabditis Elegans Based On A Human Gwas Study, Nadine Saul, Ineke Dhondt, Mikko Kuokkanen, Markus Perola, Clara Verschuuren, Brecht Wouters, Henrik Von Chrzanowski, Winnok H. De Vos, Liesbet Temmerman, Walter Luyten

School of Medicine Publications and Presentations

To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obstructive pulmonary disease (COPD), asthma, rheumatism, Crohn’s disease, malabsorption or kidney disease. Six single nucleotide polymorphisms (SNPs) with unknown function associated with ten human genes were identified as candidate healthspan markers. Thirteen homologous or closely related genes were selected in the model organism C. elegans for evaluating healthspan after targeted RNAi-mediated knockdown using pathogen resistance, muscle integrity, chemotaxis index and the …

Women's Health: Optimal Nutrition Throughout The Lifecycle, Edith J M Feskens, Regan Bailey, Zulfiqar Ahmed Bhutta, Hans-Konrad Biesalski, Heather Eicher-Miller, Klaus Krämer, Wen-Harn Pan, James C. Griffiths

Department of Paediatrics and Child Health

Sex differences are an important consideration when researching and establishing policies for nutrition and optimal health. For women's health, there are important physiologic, neurologic, and hormonal distinctions throughout the lifecycle that impact nutritional needs. Distinct from those for men, these nutritional needs must be translated into appropriate nutrition policy that aims to not only avoid overt nutritional deficiency, but also to promote health and minimize risk for chronic disease. Through a series of webinars, scientific experts discussed the advances in the understanding of the unique nutritional needs, challenges and opportunities of the various life stages for women across the life …

Positive Selection And Enhancer Evolution Shaped Lifespan And Body Mass In Great Apes, Daniela Tejada-Martinez, Roberto A Avelar, Inês Lopes, Bruce Zhang, Guy Novoa, João Pedro De Magalhães, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body …

Associations Of The Lipidome With Ageing, Cognitive Decline And Exercise Behaviours, Maria Kadyrov, Luke Whiley, Belinda Brown, Kirk I. Erickson, Elaine Holmes

Research outputs 2022 to 2026

One of the most recognisable features of ageing is a decline in brain health and cognitive dysfunction, which is associated with perturbations to regular lipid homeostasis. Although ageing is the largest risk factor for several neurodegenerative diseases such as dementia, a loss in cognitive function is commonly observed in adults over the age of 65. Despite the prevalence of normal age-related cognitive decline, there is a lack of effective methods to improve the health of the ageing brain. In light of this, exercise has shown promise for positively influencing neurocognitive health and associated lipid profiles. This review summarises age-related changes …

Endothelial Dysfunction In Hindlimb Arteries Of Old Sprague Dawley Rats, And The Type 2 Diabetic Zucker Diabetic Sprague Dawley Strain., Andrea N. Wang

Electronic Thesis and Dissertation Repository

Ageing, and type 2 diabetes are associated with cardiovascular diseases and endothelial dysfunction. Endothelial dysfunction is characterized by a decline in endothelium-mediated vasodilation. In this thesis, we determined the vascular function of hindlimb arteries supplying skeletal muscle and extremities using isolated arteries and wire myography. For ageing studies, we used Sprague Dawley rats and for type 2 diabetes we used the Zucker Diabetic Sprague Dawley strain. Vasodilation of hindlimb arteries with acetylcholine were impaired in both models. However, protease-activated receptor 2 mediated vasodilation was upregulated in arteries. Evidence of non-nitric oxide mechanisms were also found in peripheral vasculature. These data …

Neuroligin-1 Is Altered In The Hippocampus Of Alzheimer's Disease Patients And Mouse Models, And Modulates The Toxicity Of Amyloid-Beta Oligomers, Julien Dufort-Gervais, Chloé Provost, Laurence Charbonneau, Christopher M. Norris, Frédéric Calon, Valérie Mongrain, Jonathan Brouillette

Pharmacology and Nutritional Sciences Faculty Publications

Synapse loss occurs early and correlates with cognitive decline in Alzheimer’s disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by Aβo, and that it can modulate Aβo toxicity. We found that hippocampal NLGN1 was decreased in patients with AD in comparison to patients with mild cognitive impairment and control subjects. Female 3xTg-AD mice also showed a decreased NLGN1 level …

Quantifying The Heterogeneity Of The Immunoglobulin G N-Glycome In An Ageing Australian Population: The Busselton Healthy Ageing Study, Alyce Russell

Theses: Doctorates and Masters

The use of immunoglobulin G N-glycomics to study chronic non-communicable disorders and other complex phenotypes emerged following the Human Genome Project. The consortium discovered that most phenotypes were too complex to be explained by genetics alone. Thus, the biological importance of epigenetics was recognised; heritable modifications to gene expression rather than the genome itself. Nglycosylation is a form of epigenetic regulation known as a post-translational modification. It stabilises the immunoglobulin G structure and alters downstream responses elicited by the antibody and is extensively studied as a candidate biomarker in the post-genomic era.

The N-glycosylation of immunoglobulin G itself is complex, …

Cortical Beta Oscillations Are Associated With Motor Performance Following Visuomotor Learning, Svenja Espenhahn, Bernadette C.M. Van Wijk, Holly E. Rossiter, Archy O. De Berker, Nell D. Redman, Jane Rondina, Joern Diedrichsen, Nick S. Ward

Brain and Mind Institute Researchers' Publications

© 2019 The Authors People vary in their capacity to learn and retain new motor skills. Although the relationship between neuronal oscillations in the beta frequency range (15–30 Hz) and motor behaviour is well established, the electrophysiological mechanisms underlying individual differences in motor learning are incompletely understood. Here, we investigated the degree to which measures of resting and movement-related beta power from sensorimotor cortex account for inter-individual differences in motor learning behaviour in the young and elderly. Twenty young (18–30 years) and twenty elderly (62–77 years) healthy adults were trained on a novel wrist flexion/extension tracking task and subsequently retested …

Age-Related Reductions Of Motor Unit Discharge Rates In The Human Hamstrings, Eric A. Kirk

Electronic Thesis and Dissertation Repository

Neuromuscular age-related differences of human limb muscles have been widely described with the notable exception of the hamstring muscles. The purpose was to assess contractile function and spinal motor neuron output expressed as motor unit discharge rates in the hamstrings of 11 young (26 ± 4 y) and 10 old (80 ± 5 y) men. Maximal voluntary isometric contractions (MVC), stimulated contractile properties and motor unit discharge rates from sub-maximal to MVC were recorded from the lateral (biceps femoris) and medial (semimembranosus-semitendinosus) posterior thigh. In the old men, knee extension and flexion at MVC were lower (P < 0.05) and voluntary activation as assessed by the twitch interpolation technique was reduced (P < 0.05) compared with the young. Electrically evoked twitches were lower in amplitude and increased in duration of old hamstrings (P < 0.05) compared with the young. At sub-maximal to maximal contraction intensities the old had lower motor unit discharge rates as compared to the young (P < 0.001). At MVC, mean motor unit discharge rates in the biceps femoris and semimembranosus-semitendinosus of old hamstrings were 15.6 ± 6.4 and 15.3 ± 5.9 Hz, as compared to 26.1 ± 10.1 and 27.9 ±7.8 Hz in the young, respectively (P < 0.001). To date, the hamstrings show the greatest age-related reductions in motor unit discharge rates of any major limb muscle. These findings, in relation to motor unit discharge rates from other flexors and extensors support that in ageing, greater reductions are associated with limb flexor muscles.

The Incidence And Aetiology Of Hospitalised Community-Acquired Pneumonia Among Vietnamese Adults: A Prospective Surveillance In Central Vietnam, Kensuke Takahashi, Motoi Suzuki, Le Minh, Nguyen Anh, Luu Thi Huong, Tran Vo Son, Phan Long, Nguyen Thi Ai, Le Tho, Konosuke Morimoto, Paul E. Kilgore, Dang Anh, Koya Ariyoshi, Lay Yoshida

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population.

Methods

A prospective surveillance for hospitalised adult …

Age And Gender Associated Changes In Cystatin C And \Beta 2 -Microglobulin, Zuhal Parildar, Ceyda Gülter, Sara Habi̇f, Işil Mutaf, Nevbahar Turgan, Di̇lek Özmen, Oya Bayindir

Turkish Journal of Medical Sciences

Assessment of renal function in clinical medicine is of great importance. Various studies report that cystatin C (cysC) and \beta 2 -microglobulin are valuable markers of renal function. In this study, serum cysC and \beta 2 -microglobulin were measured in parallel with serum creatinine in a healthy population, and the characteristics of the relationship of cysC and \beta 2 -microglobulin to age and gender were compared. Serum creatinine, cysC and b2-microglobulin were measured in 119 (86 female; 33 male, 6 to 69 years old) healthy subjects. They were divided into five different age groups: group 1 (6-15 years, n = …

The Effect Of Sulfur Dioxide On T-Butyl Hydroperoxide Induced Oxidative Stress In Lung Tissues Of Rats, Saadet Gümüşlü, Di̇jle Ki̇pmen Korgun, Süreyya Bi̇lmen, Gülteki̇n Yücel, Pi̇raye Yargiçoğlu, Aysel Ağar

Turkish Journal of Medical Sciences

In this study, the effects of sulfur dioxide (SO_2) ,a common pollutant in urban air, on t-butyl hydroperoxide-induced oxidative stress in rat lung tissues were examined. Ten young rats and 10 adult rats were exposed to SO_2 while another 10 young rats and 10 adult rats made up the control groups. Ten ppm SO_2 was administered to the animals of the SO_2 groups in an exposure chamber for one hour a day every day for 6 weeks. The control groups were exposed to filtered air in the same chamber for the same period. At the end of the experimental period, …