Dissertations / Theses on the topic 'Ageing-related'
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Lau, Yuet-han Jasmine. "Ageing-related effect on emotion recognition." Click to view E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B37101730.
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Lau, Yuet-han Jasmine, and 劉月嫻. "Ageing-related effect on emotion recognition." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B37101730.
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Khan, Muhammad Tariq. "The effects of ageing on driving related performance." Thesis, University of Southampton, 2009. https://eprints.soton.ac.uk/73700/.
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According to one estimate, about 40 percent of the driving population will be over the age of 60 by the year 2020 in the UK and currently, several hundred thousand drivers with dementia hold driving licenses. The number of motor vehicle crashes per unit distance of automobile travel is “U”-shaped, with risk increasing slightly between the ages of 55 and 60, but risk increasing with each successive five-year interval. Some individuals who have mild dementia possess sufficient driving skills to be designated as fit drivers. The most challenging assessment and decision for the physician/licensing authority as regards fitness to drive lies in drivers who are questionably demented or are in a state of very mild dementia. In the absence of a reliable standard protocol, some clinicians make judgment based on selfreporting, which has risks associated with it as lack of insight and judgment are potential common traits of the population experiencing cognitive decline. Seldom is recourse made by health professionals to on-road assessment as a first alternative as it requires a fee and such testing centers are not readily available everywhere. This research addresses this issue of the identification of cognitive tests that can be used to assess an individual’s ability to drive and especially of those individuals that are questionably demented and are the most difficult to identify. A younger and an older group consisting of 56 drivers in total were administered nine different cognitive tests and two drives (Drive-I and Drive-II) on the STISIM driving simulator. The cognitive test ufov3 (involving the identification of a central target and simultaneously the radial localization of a peripheral target embedded in distracter triangles), which is the third subtest of the UFOV (Useful Field of View) test showed the highest discriminating ability in separating “poor-drivers” from “not-poor-drivers”, with 92.86 % of the drivers correctly classified. The next best discriminating ability in decreasing order of strength was that of dichotic listening test, trail making test, rey-copy test and paper folding test. Also, age was found to be an excellent discriminator of “poor-drivers” and “not-poor-drivers” with 91.07 % of the drivers correctly classified. A composite cognitive measure consisting of the sum of all nine cognitive tests was not a better predictor than the ufov3 test alone; overall it was still an excellent discriminator, classifying 89.29 % of drivers correctly. The commonly recommended Clock Drawing test and the Trail Making test did not emerge as significant predictors of driving ability. A general driving skills linear model for prediction purposes was derived that explained 59 % of the variation in a general driving performance index with the ufov3 test, the dichotic listening test and the rey-recall test as significant predictors. Recommendations are made as to how this test should be used to screen potentially at risk drivers.
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Alatawi, Fatema Suliman. "An investigation of ageing-related genomic effects of resveratrol." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/1943.
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Dietary restriction (DR) increases lifespan robustly in diverse species. Effects of the dietary polyphenol resveratrol consistent with delayed ageing and/or extension of lifespan have been reported. The involvement in the longevity response to DR of the protein Sirt1, which may be activated by resveratrol and deacetylates a range of cellular substrates that includes histone proteins, identifies epigenetic processes as a pathway that may mediate effects of both DR and dietary resveratrol in delaying ageing and/or extending lifespan. Based on a preliminary observation, the hypothesis underlying the study is that some of the beneficial effects of resveratrol on lifespan/aging are mediated through effects on histone expression that oppose changes observed in ageing. A secondary hypothesis, based on a degree of structural similarity between resveratrol and 17β-oestradiol, was that epigenetic effects of resveratrol are mediated through the estrogen receptor (ER). The effect of resveratrol on histone protein expression was investigated in human intestinal Caco-2 cells and human MCF-7 breast cancer cells. Histone H2a, H2b, H3 and H4 expression was decreased in response to resveratrol treatment in both cell lines. In support of our hypothesis that resveratrol affects ageing through reversing ageing-associated changes in histone proteins, higher levels of H2A, H2B, and H4 expression were detected by western blotting in the small intestine of old (38 months) mice than in younger (12 months) mice. To investigate possible consequences of effects of resveratrol, including effects resulting from altered histone expression, we studied the effect of resveratrol on global gene expression in Caco-2 and MCF-7 cells to address several objectives including: (1) investigating if resveratrol has an effect similar to that of DR at the level of gene expression; (2) identifying if genes or pathways affected by resveratrol were also affected by manipulation of the expression level of Sirt1. For both cell types, the number of genes in the intersection between those affected by resveratrol and a compiled list of genes reported in other studies to respond to DR was greater than expected by chance, supporting the view that responses to resveratrol and to dietary restriction have some commonality and that resveratrol may mimic some effects of dietary restriction. We also found that there was very little overlap between genes affected by resveratrol treatment and by knockdown of Sirt1 expression in Caco-2 cells, which adds to accumulating evidence that resveratrol does not act through effects on Sirt1. To investigate if effects of resveratrol - in particular the reduction in histone protein expression - are mediated through the estrogen receptor (ER), Caco-2 and MCF-7 cells were treated with resveratrol in the presence or absence of the ER antagonist fulvestrant, then total cell lysate was analysed by western blotting. The reduction in histone protein (H2a, H2b, H3 and H4) expression was attenuated by fulvestrant, indicating that resveratrol reduced histone expression via an ER-dependent mechanism. For further investigation of effects of resveratrol on histone expression, Caco-2 cells were transfected with a promoter reporter construct comprising the histone H3 promoter upstream of the β- galactosidase reporter gene, and the effect on reporter gene expression of treatment with resveratrol in the presence and absence of the fulvestrant was measured. Resveratrol reduced reporter gene expression and this effect was attenuated by fulvestrant, demonstrating that resveratrol acts to reduce histone H3 expression at the level of transcription through an ER-mediated mechanism. To investigate if the response to resveratrol treatment is through interaction with estrogen response elements (EREs) in the histone H3 promoter we replaced three potential EREs within the histone H3 promoter region included in the promoter-reporter construct with random sequence. Caco-2 cells were then transfected with either original or mutated promoter-reporter construct and treated with resveratrol or the endogenous ER ligand 17-β estradiol in the presence and absence of fulvestrant. Resveratrol and 17-β estradiol both reduced reporter gene expression from both promoter reporter constructs and in all cases responses were attenuated by fulvestrant, indicating that effects of neither compound, although mediated through the ER, are on the specific sequences region we identified and replaced. In conclusion, these data indicate that resveratrol reduces histone expression in both intestinal and breast cancer cells through an ER-mediated mechanism acting at the level of transcription and that this effect may oppose an accumulation of histone proteins (observed in mouse small intestine) that accompanies ageing. With respect to effects on gene expression, resveratrol was found to mimic some effects of dietary restriction but appeared to act through a mechanism independent of Sirt1.
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Soundara, Pandi Sudha Priya. "MicroRNA in retinal ageing and age-related retinal degeneration." Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.675475.
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Ageing is the main risk factor for the sight threatening disease, age-related macular degeneration (AMD) which causes central vision loss. Although the exact pathogenic mechanism underlying this disease is not well known, recent advances in understanding of how gene expression is regulated suggest a role for small nOI1- coding regulatory RNAs called microRNAs. The main aims of this PhD project were to characterise the endogenous microRNAs in retinal tissues and to investigate how they change with age and in a model of AMD. In addition, how do specific microRNAs regulate retinal pigment epithelium (RPE) function. Firstly, I demonstrated that the small RNA population in three month-old C57BLl6J wild type mice retina and RPE/choroid is extremely complex, including novel orthologs and microRNAs, isomiRs, microRNAs synthesized via non-canonical via Drosha-independent pathways and other small RNAs. Secondly, expression of these microRNAs was changed with age. Half of the microRNAs expressed in polycistronic clusters change with age in the same direction. MicroRNAs altered with age were predicted to be targeting age-related pathways, retina specific functions and inflammation-related pathways, especially TGF -β signalling. Thirdly, miR-26a was highly expressed in RPE/choroid, down-regulated with age and was involved in the regulation of TGF-β signalling. Inhibition of miR-26a caused a change in YEGF expression, cell proliferation and migration . Finally, microRNAs altered in the CCLT/-/ CX3CR 1 GrP/GFP animal model of geographic atrophy were predicted to be targeting genes involved in pathways related to AMD pathology. MicroRNAs altered at before an overt phenotype in this model animal also targeted some of these pathways and may be a prelude to this disease pathology. Some of the microRNA changed with age overlap with this animal model suggesting that microRNA changes in retina contribute to .disease progression. Alhough miR-26a expression changes in this model are not significant. Functional changes with miR- 26a inhibition suggest its potential as a future biomarker for ageing and a therapeutic approach for age related macular degeneration. Thus, microRNAs playa major role in ageing and age-related retinal degeneration.
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Tsai, Pei-Chien. "Epigenetic determinants of healthy ageing and age-related disease risk." Thesis, King's College London (University of London), 2015. https://kclpure.kcl.ac.uk/portal/en/theses/epigenetic-determinants-of-healthy-ageing-and-agerelated-disease-risk(8a338def-2d32-4bc3-a0bd-7ced65efc679).html.
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Epigenome-wide association scans (EWAS) of human complex traits are a rapidly growing area of research, in part due to recent advances in technology that have allowed for a deeper coverage of the human methylome. One of the unique features of the human methylome is that it is dynamic and previous studies have shown that age can have a strong impact on DNA methylation patterns. The dynamic nature of DNA methylation also influences EWAS methodology, both from a statistical and biological perspective. In this thesis, I explored EWAS methods and applications to ageing and age-related phenotypes. Firstly, I estimated EWAS power under several simulation scenarios and study designs, and my results suggested that the majority of recent EWAS studies lack statistical power to detect small DNA methylation effect sizes. I then applied EWAS to identify differential methylation CpG sites associated with three phenotypes, including ageing, birth weight and smoking. One of the novel findings from this thesis was that hundreds of genome-wide significant ageing-related hypermethylated regions were identified across multiple tissues in twins. These findings confirm and extend previous work showing that ageing has a strong underlying effect on DNA methylation. Birth weight did not yield significant differential methylation sites, which may be partly explained by low power to detect modest methylation effects. Smoking is a well-known environmental risk factor for disease, and my analyses identified novel impacts of smoking on DNA methylation patterns in adipose tissue, which are of interest to cardiovascular and metabolic disease. I further explored the impacts of smoking by integrating DNA methylation and gene expression profiles in adipose tissue and in whole blood. In addition to identifying novel results, my findings also confirmed that the AHRR and F2RL3 genes showed stable and consistent changes related to smoking in both DNA methylation and gene expression profiles across tissues. My findings explored methodological issues in genome-wide methylation studies and showed that age and smoking have a strong and reproducible effect on DNA methylation across tissues in humans, which suggests that these factors should always be included as covariates in EWAS of human complex traits.
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Perales, Puchalt Jaime 1985. "Health and ageing : Active ageing in older adults and health related quality of life in people with dementia." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/286877.
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The continuing growth of older age groups worldwide needs an increased understanding of the ageing phenomena. For this reason, the present thesis is aimed at two very important outcomes in the elderly, active ageing (AA) in older adults and health-related quality of life (HRQL) in people with dementia. To do this, I have participated in different studies and used different research methodologies. In the first publication of this thesis, I study the distribution and associations with sociodemographic variables of different definitions of AA in a large adult population sample in Spain, Poland and Finland. The next publication reviews the previous literature on HRQL instruments for dementia in order to understand such complex concept and compare the different instruments in terms of for example data collection method or purpose of assessment. In the last publication, I explore the distribution of HRQL in the very old population in Cambridge by creating a new instrument using an already existing conceptual framework.
Note: data from Courage Project (http://www.courageineurope.eu/) used for the thesis.El continuo envejecimiento de la población mundial hace que sea necesario entender mejor este fenómeno. Por esta razón, la presente tesis doctoral tiene como objetivo estudiar dos variables muy importantes en la gente mayor, envejecimiento activo (AA) en la gente mayor y calidad de vida relacionada con la salud (HRQL) en gente con demencia. Para ello, he participado en diferentes estudios y he utilizado diferentes metodologías de investigación. En la primera publicación de esta tesis, estudio la distribución y asociación de diferentes definiciones de AA con variables sociodemográficas en una amplia muestra poblacional de España, Polonia y Finlandia. En la siguiente publicación llevo a cabo una revisión de la literatura sobre instrumentos para medir HRQL en demencia con tal de entender este complejo concepto y comparar los diferentes instrumentos en cuanto al método de recogida de información o al motivo de evaluación, por ejemplo. En la ultima publicación, exploro la distribución de HRQL en la población de gente muy mayor de Cambridge, creando un nuevo instrumento utilizando un marco conceptual ya existente. Nota: se usan los datos del Proyecto Courage (http://www.courageineurope.eu/).
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Sacitharan, Pradeep. "Linking ageing and arthritis : the role of the longevity-related SIRT1 molecule in age-related cartilage degeneration and osteoarthritis." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:cb519867-d184-44ff-b17f-bee1974f430b.
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Osteoarthritis (OA) is the most common form of arthritis worldwide and is characterised by the progressive degradation of articular cartilage. Ageing is the primary risk factor associated with OA. However, the roles of ageing-related mechanisms in cartilage homeostasis are poorly understood. The class three histone deacetylase, Silent mating type information regulation 2 homolog (SIRT1) has been extensively shown to regulate lifespan in lower organisms and signalling pathways linked to mammalian ageing. My thesis explores the role of Sirtuin 1 in cartilage homeostasis and OA. I used in vitro experiments with chondrocyte cell lines, human clinical samples, novel genetically modified cartilage specific and whole body SIRT1 deficient mice alongside molecular biological tools to investigate my research questions. Human OA cartilage showed decreased SIRT1 compared to healthy cartilage. Mice with cartilage-specific SIRT1 deletion showed greater cartilage degradation during ageing and in an experimental OA model. In vitro and in vivo studies showed SIRT1 to directly regulate autophagy in chondrocytes. More importantly, the activation of autophagy using spermidine protected against experimental OA in wild-type mice but not in cartilage-specific SIRT1 deficient mice. In addition, my data revealed whole body SIRT1 deficient mice had increased early joint inflammation in repose to injury but displayed less cartilage loss over time in an experimental OA model. Together I have shown that SIRT1 declines with age and contributes to OA due to dysregulated autophagy. However, chronic low grade inflammation caused by SIRT1 loss was protective. My data suggest these pathways can be targeted to treat OA.
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Zierer, Jonas. "Integrative analysis of the metabolic signatures of ageing and age-related diseases." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/integrative-analysis-of-the-metabolic-signatures-of-ageing-and-agerelated-diseases(b76bf26f-2cc0-4aff-b02a-d5805316697a).html.
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Ageing is a complex process and is the strongest risk factor for many diseases. To elucidate processes underlying biological ageing, many studies have investigated the associations of individual metabolites or genes with age and age-related phenotypes. While these studies improved our understanding of the pathogenic mechanisms for many diseases, they have their limitations. Analysing phenotypes separately in classical association studies typically neglects relationships and interactions between and across different phenotypes (e.g. comorbidities), genes (e.g. pleiotropy), and metabolites (e.g. through shared biochemical pathways). The aim of this thesis was to better understand age-related phenotypes and their interdependencies through exploring shared underlying processes. To this end, I first identified biomarkers of ageing and age-related diseases, focusing on chronic kidney disease, using metabolomics and glycomics technologies. I identified several metabolites associated with leukocyte telomere length, a common marker of biological ageing. Then I investigated the associations of molecular phenotypes with renal disease. Analysing metabolomic profiles associated with renal function in diabetic and non-diabetic cohorts illustrated similarities between the different aetiologies of kidney disease, such as the lack of renal conversion of amino acids, but also differences, particularly of lipid and energy metabolism. Subsequent analyses identified changes of Immun-oglobin G glycosylation as a novel inflammatory pathway involved in renal disease. Then, I assessed the potential of the faecal metabolome as a functional readout of the gut microbial community to investigate its association with biological ageing. While faecal metabolites were only moderately associated with age and renal function, they showed great potential as novel profiling method for studying the microbiome, particularly with respect to obesity. Next, I integrated metabolomics data from plasma, urine, and saliva to model cross-fluid metabolism individually for kidney disease patients and healthy controls. By comparing both models, I identified metabolic key processes impaired in kidney disease. Finally, I integrated metabolomic and glycomic biomarkers of ageing with other omics markers as well as extensive phenotypic data to investigate their multivariate interdependencies, underlying the comorbidities of age-related diseases. This comprehensive integration of age-related phenotypes highlighted several molecular mechanisms that potentially cause the joint occurrence of diseases with age. Con-sidering the complex aetiologies of different diseases and their dependencies will be needed to facilitate personalised healthcare. In conclusion, I have shown the future potential of sys-tems and network biology approaches for understanding disease mechanisms and precision medicine.
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Harris, Mathew Alan. "Navigational strategy switching in ageing." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/10066.
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With advancing age, many cognitive faculties deteriorate, and navigation abilities may be among those most affected. The majority of previous work investigating navigation impairments in ageing has focused on allocentric processing, attributing deficits to hippocampal dysfunction. However, real-world navigation is dependent upon numerous different strategies, as well as the ability to flexibly switch between them. Outside the context of navigation, it has been demonstrated that strategy switching, thought to be coordinated by regions of prefrontal cortex and the locus coeruleus-noradrenergic system, is also susceptible to the effects of ageing. Deficits in navigational strategy switching, and prefrontal or noradrenergic dysfunction, are therefore also likely to contribute to age-related navigation impairments. The work presented in this thesis aimed to explore age-related impairments in strategy switching within the context of navigation, and the underlying neural mechanisms in terms of a prefrontal-noradrenergic model of switching. The studies presented in Chapter Three assessed the use of allocentric and egocentric navigational strategies by young and older people. Older participants tended to use an egocentric strategy where an allocentric strategy was required, possibly due to a difficulty in switching to the appropriate allocentric strategy. In Chapter Four, I provide an account of two studies directly assessing navigational strategy switching, using two different tasks based in virtual reality. The first study utilised a virtual adaptation of the plus maze task, involving switching between an allocentric place strategy and an egocentric response strategy, and demonstrated that older participants were specifically impaired at switching to the place strategy. The second study used a more realistic task set in a virtual town environment, which involved switching from an egocentric route-following strategy to an allocentric wayfinding strategy, and also demonstrated an age-related deficit in switching to an allocentric strategy. In Chapter Five, I begin to explore the mechanisms underlying impaired navigational strategy switching in ageing. Firstly, I describe a further behavioural study that used variants of the virtual plus maze and a navigational gambling task to demonstrate a contribution of impaired decision making to the deficit in switching to an allocentric strategy. This indicates that the deficit can be attributed, at least in part, to prefrontal dysfunction. A second study presented in the same chapter demonstrated that practising orienteering does not protect against decline in navigational strategy switching ability with ageing. Chapter Six provides an account of my direct assessment of the neural bases of navigational strategy switching using functional magnetic resonance imaging. In young subjects, I found some evidence in support of the roles of prefrontal regions in navigational strategy switching. However, I was unable to complete development of a task suitable for assessing age differences in functional activation of brain regions involved in navigational strategy switching. The final experimental study, included in Chapter Seven, assessed pupil size and heart rate as physiological correlates of noradrenergic activity during performance of the virtual plus maze. Both young and old participants demonstrated a noradrenergic response to all strategy changes, suggesting that impairments are more likely attributable to dysfunction of prefrontal cortex than of the locus coeruleus, although some subtle effects suggested that noradrenergic dysfunction does have some effect on navigational strategy switching deficits. In the same chapter, I report the results of a meta-analysis of data from five of the preceding studies, suggesting that deficits in both strategy switching and allocentric processing combine to produce a greater impairment in switching to an allocentric strategy. The main finding of this series of studies is that navigational strategy switching is impaired in ageing, which may contribute to the more widely reported difficulties that older people have with navigation. My work also provides evidence in support of a prefrontal-noradrenergic model of navigational strategy switching, and suggests that dysfunction of prefrontal cortex and, to a lesser extent, the locus coeruleus-noradrenergic system is responsible for decline in navigational strategy switching ability with ageing. In conclusion, this thesis draws attention to the important role of deficient executive processing and dysfunction of extra-hippocampal brain regions in age-related navigation impairments.
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Miller, Veronica M. "Medullary pathology in ageing-related autonomic disorders : carotid sinus hypersensitivity and orthostatic hypotension." Thesis, University of Newcastle Upon Tyne, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435568.
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Dreder, Abdouladeem. "Machine learning based approaches for identifying sarcopenia-related genomic biomarkers in ageing males." Thesis, Northumbria University, 2017. http://nrl.northumbria.ac.uk/36184/.
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Sexual dimorphism of skeletal muscle can occur due to age and many of these age-related changes in skeletal muscle appear to be influenced by gender. In humans, the muscle mass peaks in the second decade while loss of muscle mass (sarcopenia) starts between the third and the fifth decade of life. In system biology, the function of genes still needs to be understood and understanding gene function remains a significant challenge. Several machine learning and computational techniques have been used to understand. However, these previous attempts have not produced enough interpretation of the impact of age on skeletal muscle mass across both gender. Although there are several thousands of genes, very few differentially expressed genes play an active role in understanding the age and gender differences. The core aim of this thesis is to uncover new biomarkers that can contribute towards the prevention of sarcopenia progress in humans according to the gene expression levels of skeletal muscle tissues. The main contributions are the development of machine learning methods based on majority voting of multi-evaluation methods and multi-feature selection methods in order to analyse microarray data and identify subsets of genes related to muscle mass loss in ageing males and females. Previously, statistical methods were used to find important genes related to the impact of age on muscle mass loss. Multi-filter and multi- wrapper based systems are proposed in this thesis to identify different and common sarcopenia-related genes in males and females based on human skeletal muscle. Genes are first sorted using three different evaluation methods (t-test, Entropy and Receiver operating characteristic). Then, important genes are obtained using majority voting based on the principle that combining multiple models can improve the generalization of the system. Experiments were conducted on three different microarray gene expression datasets and results have indicated a significant increase in classification accuracy up to 10% associated with sarcopenia when compared with existing systems.
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Birch, Jodie. "Telomere dysfunction and senescence in the ageing lung and age-related lung disease." Thesis, University of Newcastle upon Tyne, 2015. http://hdl.handle.net/10443/3927.
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Cellular senescence, the irreversible loss of replicati ve capacity of somatic cells, bas been associated w ith diseases of accelerated lung ageing, including Chroni c Obstructive Pulmonaty Disease (COPD). However, the mechanisms und erl ying senescence of a irway epithelial cell s, parti cula rl y the role of telomere dysfunction in this process, are poorly understood . The aim of this work was to investigate senescence and telomere dysfunction in airway epithelial cells from pati ents with COPD and bronchiectasis, in the ageing murine lung and in the context of cigarette smoke exposure. DNA dam age foci (yH2A.X) and foci associated with telomeres (telomere-associated foci (TA F)), a long with other senescence-associated m arkers, were increased in small airway epith elial cells from patients with COPD, wi thout significant telomere shottening. With age, TAF increased in large and sm all aitway epithelial cells of the murine lung and predicted age-dependent lung emphysema, independen tly oftelomere length . M oreover, fomth generation telomerase-null mi ce showed early-onset emphysema. Exposure to cigarette smoke was found to increase TAF in large and small ai1way epithelial cells of the murine lung and in epith elial cells and fibrobla sts in vitro. Cigarette smoke m ay accelerate telomere dysfunction via reactive oxygen species (ROS) and contribute to Ataxia telangiectasia mutated (ATM)-dependent secretion of pro-inflammatory cytokines interleukin (lL)-6 and IL-8. Inhibition of mechan istic target of rapa myc in complex I (mTORC I ) by rapa mycin alleviated age-assoc iated increases i n TAF in vivo and supressed cigarette smoke-i nduced increases in TAF and in flammatory cytokine release in vitro. Cigarette smoke increases mitochondrial-derived ROS, which is supressed by culturing cell s at low oxygen pressure and by treating cell s w ith rapam ycin. These results suggest that activation of a DN A damage response at telomeres may be induced by oxidative stress from altered mTOR signalling ancl/or dysfu nctional mitochondri a. Telomere dys function could conttibut e to inflamm atory processes and the functional decline that occurs in the ageing lung and in the context of cigarette smoke induced accelerated lung ageing.
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Farooq, Muhammad Akmal. "Potential of omega-3 EPA/DHA 6/1 to ameliorate ageing-related endothelial dysfunction." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ107/document.
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La présente étude évalue la capacité de la formulation d’oméga-3 EPA:DHA 6:1, une formulation capable d’induire la formation continue de monoxyde d’azote par la NO synthase endothéliale, à améliorer la dysfonction endothéliale liée à l’âge établie chez le rat. La dysfonction endothéliale liée à l’âge est caractérisée par une altération des composantes de la relaxation et une augmentation des réponses contractiles dépendantes de l’endothélium. L’âge augmente le stress oxydant vasculaire, l’expression de la NADPH oxydase, COX-2, eNOS, ACE, AT1R, et des marqueurs de senescence, alors que la COX-1 est sous-exprimé. La formulation EPA:DHA 6:1 améliore la composante NO, diminue l’EDCF et le stress oxydant vasculaire, et normalise l’expression des protéines cibles. En conclusion, la consommation chronique de EPA:DHA 6:1 améliore la dysfonction endothéliale liée à l’âge chez le rat, probablement en prévenant l’activation du système angiotensine locale et le stress oxydant en résultantEPA:DHA 6:1 omega-3 formulation has been shown to induce a sustained endothelial NO synthase-derived formation of nitric oxide. This study examined if the intake of EPA:DHA 6:1 improves an established ageing-related endothelial dysfunction. Ageing-related endothelial dysfunction was characterized by a blunted NO-mediated component of relaxation, abolished EDH-mediated component and increased COX-derived endothelium-dependent contractile responses. Ageing increased vascular oxidative stress, expression of NADPH oxidase subunits, COX-2, eNOS, ACE, AT1R, and senescence markers, whereas COX-1 was down-regulated. Chronic intake of EPA:DHA 6:1 improved the NO-mediated relaxations, reduced EDCFs, vascular oxidative stress and normalized the expression of protein markers. In conclusion, chronic intake of EPA:DHA 6:1 prevented the ageing-related endothelial dysfunction in old rats, most likely by preventing activation of the local angiotensin system and the subsequent vascular oxidative stress
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Killen, Claire V. "Ageing and episodic memory : combining neuropsychological and event-related potential approaches to investigate strategic retrieval." Thesis, University of Stirling, 2009. http://hdl.handle.net/1893/1722.
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This thesis investigates the effect of normal ageing on the strategies adopted during episodic memory retrieval, using a combination of neuropsychological profiling and neuroimaging data measured during performance on a source memory exclusion task. The exclusion task is a type of source memory task where participants distinguish between targets (studied items from one source e.g. female voice), non-targets (studied items from another source e.g. male voice) and new items. Unlike a source memory task where three separate buttons are pressed for each item at test, in the exclusion task one button is pressed for targets and a second for non-target and new items. As this task is more complex than a normal source memory paradigm and also allows participants to perform the task in more than one way, it places high emphasis on the use of strategies to facilitate retrieval and is therefore ideal for investigating strategic retrieval. Previous source memory studies have shown that while older adults are reasonably good at recognising whether items are old or new, they show marked impairments at remembering the source in which items were presented at study. Dual process theories propose that the age-related decline in source memory occurs because recollection becomes impaired with ageing whereas familiarity remains relatively spared. The results reported in this thesis support dual process theory. Experiment 2a showed that, behaviourally, as expected, the young outperformed the elderly. Event-related potentials (ERPs), recorded while a source memory exclusion test was performed, revealed that both young and older adults showed bilateral frontal and left parietal old/new effects, thought to index familiarity and recollection respectively. Importantly, the magnitude of the left parietal effect was significantly reduced in the older adults. The ERP findings also suggested that dual process theories represent an oversimplification of episodic memory decline with age. In Experiment 1a, three temporally and topographically distinct late frontal old/new effects were present in the younger adults: a bilateral anterior frontal effect (450-900ms post stimulus), a right prefrontal effect (900-1300ms) and a right frontal effect (1300-2000ms). Significant positive correlations between the magnitude of these effects and performance on neuropsychological tests of executive functioning in Experiment 1b, revealed that the bilateral anterior frontal effect was related to working memory, strategy use and planning; the right prefrontal effect was related to working memory and planning while the right frontal effect was related to planning. By contrast, the older adults in Experiment 2a only produced the right frontal effect, which correlated with planning across all three time windows in Experiment 2c. Post-retrieval monitoring in older adults therefore appeared to be qualitatively different than their younger counterparts. Performance on the neuropsychological tests in Experiment 2b, revealed that the older adults’ working memory and strategy use was impaired compared to the young, whereas planning was relatively intact, suggesting that age-related differences in post retrieval processing may be due to reduced executive functioning in older adults. Identifying distinct late frontal effects and demonstrating a relationship between these effects and specific executive functions is a novel finding. The presence of a left parietal target greater than non-target difference in the young adults from Experiment 1a and 2a was interpreted as the young reducing recollection of irrelevant non-target information. The modulation did not differ in magnitude for targets and non-targets in the elderly adults from Experiment 2a, suggesting they were less able to reduce activation of goal irrelevant non-target information. The results in the young adults from Experiment 1a also highlight the importance of considering the context of source information on the processes engaged at retrieval. The bilateral frontal effect was significant for the retrieval of the intrinsic context (source information inherent to the studied item), but not the extrinsic context (source information not inherent to the studied item). This finding was interpreted within a unitisation framework, where the intrinsic context became unitised with the item and enhanced familiarity based remembering. The findings also highlight that in order to fully understand post retrieval processing in both young and old adults, focus should move away from examining quantitative differences in the right frontal effect over long time periods and instead identify qualitatively distinct late frontal effects that may reflect the engagement of various executive functions over time.
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Elewa, Rana [Verfasser]. "Ageing-related molecular changes of the skin on the protein level : an immunohistochemical study / Rana Elewa." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1228859868/34.
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Cahill-Smith, Sarah K. "Oxidative stress in ageing-related metabolic syndrome, endothelial dysfunction and neurodegeneration: a crucial role of Nox2." Thesis, University of Surrey, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608376.
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Chronic oxidative stress and oxidative damage has become one of the most convincing theories in ageing pathology. NADPH oxidase 2 (Nox2) is a reactive oxygen species (ROS) generating enzyme expressed constitutively in the vasculature and the central nervous system, however the role of this enzyme in ageing-related cardiovascular dysfunction and neurodegenerative diseases remains unclear. Therefore, the overall aim of this PhD research project is to investigate the role of Nox2-induced oxidative stress in ageing-associated metabolic syndrome, endothelial dysfunction and neurodegeneration using age-matched littermates of wild-type (WT) versus Nox2 null (Nox2-/-) mice on a (5781/6 background at young (3 -4 months), middle aged (10-12 months) and ageing (20•22 months). Compared to young mice, there were ageing-related increases in bodyweight and fasting insulin levels along with impaired glucose tolerance, hyperlipidaemia and hypertension in WT ageing mice (p<0.05). These metabolic syndrome risk factors were accompanied by significant increases in aortic ROS production and Nox2 expression and a significant decrease in the endothelium-dependent relaxation to acetylcholine (Emax 75 % for young and 64 % for ageing, p<0.05) , ). However, all these ageing-related metabolic and endothelial abnormalities were significantly reduced in Nox2-1- ageing mice. We then examined the role of Nox2 in ageing-related neurodegeneration and found that compared to young mice, there was a significantly reduced locomotor activity and dopaminergic neuron firing frequency accompanied by increased brain ROS production in WT but not in Nox2-/- mouse brain. Ageing-associated increases in brain ROS production was further confirmed using human post-mortem brain tissues. In conclusion, Nox2-derived oxidative stress plays an important role in ageing-associated metabolic syndrome, vascular dysfunction, and neurodegeneration. Targeting Nox2 represents a valuable therapeutic strategy to treat these ageing-related diseases.
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Foster, Vincent. "A pathological investigation of the frontal lobe in post-stroke dementia and other ageing-related dementias." Thesis, University of Newcastle upon Tyne, 2015. http://hdl.handle.net/10443/2931.
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Approximately 30% of elderly stroke survivors develop post-stroke dementia (PSD). The mechanisms underlying this cognitive decline following stroke are unclear. Vascular pathology is associated with the frontal lobe, damage to which may result in executive dysfunction; a common clinical outcome of PSD. Previous pathological studies in PSD subjects have found that pyramidal neurons in the CA1 region of the hippocampus were particularly vulnerable, with atrophy of these cells associated with cognitive impairment. In this study we test the hypothesis that similar changes in pyramidal neurons in the three prefrontal circuits which control executive function may be related to executive dysfunction. The three circuits are; the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC). Histological and immunohistochemical staining with three dimensional morphometric analysis and quantitative image analysis was carried out in fixed paraffin-embedded prefrontal brain sections from the MRC funded CogFAST study (a long-term prospective study designed to investigate delayed dementia after stroke) as well as frontal brain tissue from aged-matched controls and pathologically defined dementia groups: vascular dementia (VaD), Alzheimer’s disease (AD), and those with mixed Alzheimer’s disease and vascular dementia (mixed). Pyramidal neuron volumes were significantly reduced in PSD, VaD, mixed, and AD when compared to aged-controls and post-stroke non demented (PSND) subjects in layer III, with layer V following a similar pattern. The neuronal changes in PSD correlated with global and executive function scores and were associated with markers for mitochondrial function, though did not correlate with tau or amyloid burden. Neuronal volumes in the ACC and the OFC did not significantly vary between groups; however pyramidal neurons within the OFC were significantly smaller in all groups (controls and disease) when compared to controls in dlPFC and ACC. There were no significant changes in pyramidal neuron densities between PSND and PSD in any of the three frontal regions. Analysis of the interneuronal densities revealed no significant differences between inhibitory neurons in PSND and PSD subjects. Pyramidal neuron ii volume changes did not appear to be associated with white matter (WM) pathology in post-stroke subjects. These findings suggest that pyramidal neuronal volume loss in the dlPFC is associated with cognitive decline in post-stroke and ageing-related dementia. The lack of relationship between AD type pathology, WM pathology, or interneuronal changes suggests dysfunction of the pyramidal neurons in the dlPFC play an important role in the development of executive dysfunction in PSD.
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Wan, Cen. "Novel hierarchical feature selection methods for classification and their application to datasets of ageing-related genes." Thesis, University of Kent, 2015. https://kar.kent.ac.uk/54761/.
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Hierarchical Feature Selection (HFS) is an under-explored subarea of data mining/machine learning. Unlike conventional (flat) feature selection algorithms, HFS algorithms work by exploiting hierarchical (generalisation-specialisation) relationships between features, in order to try to improve the predictive accuracy of classifiers. The basic idea is to remove hierarchical redundancy between features, where the presence of a feature in an instance implies the presence of all ancestors of that feature in that instance. By using an HFS algorithm to select a feature subset where the hierarchical redundancy among features is eliminated or reduced, and then giving only the selected feature subset to a classification algorithm, it is possible to improve the predictive accuracy of classification algorithms. In terms of applications, this thesis focuses on datasets of ageing-related genes. This type of dataset is an interesting type of application for data mining methods due to the technical difficulty and ethical issues associated with doing ageing experiments with humans and the strategic importance of research on the biology of ageing - since age is the greatest risk factor for a number of diseases, but is still a not well understood biological process. This thesis offers contributions mainly to the area of data mining/machine learning, but also to bioinformatics and the biology of ageing, as discussed next. The first and main type of contribution consists of four novel HFS algorithms, namely: select Hierarchical Information Preserving (HIP) features, select Most Relevant (MR) features, the hybrid HIP–MR algorithm, and the Hierarchy-based Redundancy Eliminated Tree Augmented Naive Bayes (HRE–TAN) algorithm. These algorithms perform lazy learning-based feature selection - i.e. they postpone the learning process to the moment when testing instances are observed and select a specific feature subset for each testing instance. HIP, MR and HIP–MR select features in a data pre-processing phase, before running a classification algorithm, and they select features that can be used as input by any lazy classification algorithm. In contrast, HRE–TAN is a feature selection process embedded in the construction of a lazy TAN classifier. The second type of contribution, relevant to the areas of data mining and bioinformatics, consists of two novel algorithms that exploit the pre-defined structure of the Gene Ontology (GO) and the results of a flat or hierarchical feature selection algorithm to create the network topology of a Bayesian Network Augmented Naive Bayes (BAN) classifier. These are called GO–BAN algorithms. The proposed HFS algorithms were in general evaluated in combination with lazy versions of three Bayesian network classifiers, namely Naïve Bayes, TAN and GO–BAN - except that HRE–TAN works only with TAN. The experiments involved comparing the predictive accuracy obtained by these classifiers using the features selected by the proposed HFS algorithms with the predictive accuracy obtained by these classifiers using the features selected by flat feature selection algorithms, as well as the accuracy obtained by the classifiers using all original features (without feature selection) as a baseline. The experiments used a number of ageing-related datasets, where the instances being classified are genes, the predictive features are GO terms describing hierarchical gene functions, and the classes to be predicted indicate whether a gene has a pro-longevity or anti-longevity effect in the lifespan of a model organism (yeast, worm, fly or mouse). In general, with the exception of the hybrid HIP–MR which did not obtain good results, the other three proposed HFS algorithms (HIP, MR, HRE–TAN) improved the predictive performance of the baseline Bayesian network classifiers - i.e. in general the classifiers obtained higher accuracies when using only the features selected by the HFS algorithm than when using all original features. Overall, the most successful of the four HFS algorithms was HIP, which outperformed all other (hierarchical or flat) feature selection algorithms when used in combination with each of the Naive Bayes, TAN and GO–BAN classifiers. The difference of predictive accuracy between HIP and the other feature selection algorithms was almost always statistically significant - except that the difference of accuracy between HIP and MR was not significant with TAN. Comparing different combinations of a HFS algorithm and a Bayesian network classifier, HIP+NB and HIP+GO–BAN were both the best combination, with the same average rank across all datasets. They obtained predictive accuracies statistically significantly higher than the accuracies obtained by all other combinations of HFS algorithm and classifier. The third type of contribution of this thesis is a contribution to the biology of ageing. More precisely, the proposed HIP and MR algorithms were used to produce rankings of GO terms in decreasing order of their usefulness for predicting the pro-longevity or anti-longevity effect of a gene on a model organism; and the top GO terms in these rankings were interpreted with the help of a biologist expert on ageing, leading to potentially relevant patterns about the biology of ageing.
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Persson, Joanne K. "Perceptions of older adults in an ageing world : content, structure, and consequences of age-related auto-stereotypes." Thesis, University of St Andrews, 2014. http://hdl.handle.net/10023/7056.
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The current thesis explored participants' stereotypes and auto-stereotypes of old age within the UK, and the consequences of auto-stereotype activation on older adults' memory performance and well-being. Study 1 employed a questionnaire design to explore young (aged 17-25 years) and older adults' (aged 60-75 years) experiences and stereotypes of ageing. Older participants demonstrated high subjective age bias, reporting subjective ages significantly below their chronological age. Older adults also demonstrated a greater understanding of positive aspects of old age than young adults, although no significant differences emerged between cohorts over the valence of generated stereotype content. Study 2 modified the questionnaire to further differentiate between more positive versus less negative aspects of ageing. Findings indicated that although older adults displayed less negative perceptions of old age than young adults, they did not demonstrate more positive representations. Study 3 explored the structure (as opposed to content) of age-related stereotypes using a free-sorting task, and included old-old adult participants (aged 75-91 years). Confirming previous findings, subtype structure formed two high level clusters, consisting of positive or negative categories. Old-old adults demonstrated the most complex subtype structure from the three groups, with no significant differences emerging between young and older adults. Finally, Study 4 employed a subliminal priming paradigm to examine the impact of positive or negative auto-stereotype activation on older adults' memory performance and well-being. Findings suggested that negative auto-stereotype activation had a detrimental impact on participants' memory performance, although the low power of the study means additional work is required to confirm this effect pattern. No significant effects of priming emerged for young adults. In summary, the current findings suggest that stereotypes and auto-stereotypes of old age are complex, consisting of both positive and negative elements, and point to the importance of considering subjective, rather than chronological age when assessing age-related identity.
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Peel, Nancye M. "The protective effect of healthy ageing on the risk of fall-related hip fracture injury in older people /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19388.pdf.
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Geng, Li. "The role of NADPH oxidase 2 in ageing-related brain oxidative stress, cerebral endothelial damage and brain dysfunction." Thesis, University of Reading, 2018. http://centaur.reading.ac.uk/80438/.
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The average age of our population continues to grow as a result of increasing longevity. Indeed, according to WHO, by the year 2100, nearly one third of the global population will be 60+ years old. However, the key factors and signalling pathways involved in cellular ageing remain largely unknown. Our hypothesis is that oxidative stress generated by the activation of a Nox2-containing NADPH oxidase plays a key role in ageing-related vascular and neuro-degenerative disorder. Therefore, the overall aim of this PhD research project is to investigate the role of Nox2 activation in ageing-related brain oxidative stress and cerebral endothelial damage using littermates of age-matched wild-type (WT) and Nox2 knockout (KO) mice (C57BL/6J background) at young (3-4 months, similar to human ~20-30 years old) and old age (21-22 months, similar to human ~70-80 years old). I have found a significant increase in the levels of reactive oxygen species (ROS) production in multiple organs of WT ageing mice in comparison with WT young mice, and this can be significantly inhibited by knockout of Nox2. There was a significant reduction of locomotor function in WT ageing mice but not in Nox2 KO ageing mice. Increased ROS production in the WT ageing brain was accompanied by (1) significant decreases in brain endothelia cells and neurons; (2) significant increases in microglial cells and brain Nox2 expression; and (3) an activation of stress signalling pathways such as ERK1/2. Once again, these ageing-related changes were inhibited significantly by knockout of Nox2. The crucial role of ageing related Nox2 activation in oxidative damage of endothelial function was further investigated in vitro using coronary microvascular endothelial cells isolated from WT versus Nox2KO mice stimulated with high glucose plus insulin, and this was further confirmed using brain tissues of endothelial specific Nox2 overexpression mice at young and old ages. Furthermore, ageing-associated increases in brain ROS production and Nox2 activation was confirmed using human post-mortem brain tissues. In conclusion, Nox2-derived oxidative stress plays an important role in ageing-associated systemic oxidative stress, cerebral endothelial damage, neurodegeneration and loss of locomotor function. Targeting Nox2 represents a valuable therapeutic strategy to treat these ageing-related diseases.
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Devarajan, Gayathri. "Activation of microglia in ageing retina and in age-related macular degeneration and their role in RPE degeneration." Thesis, University of Aberdeen, 2012. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192261.
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Wiley, Laura. "Exploring the potential of oxidative stress-related biomarkers of ageing in a population-based study of the very old." Thesis, University of Newcastle upon Tyne, 2014. http://hdl.handle.net/10443/2695.
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There are considerable differences in the timing, type and extent of age-related decline between individuals who share the same chronological age, which may be driven by a combination of genetic, stochastic and environmental factors. Biomarkers of ageing (BoA) that can discriminate between individuals who differ in their biological age will therefore be useful to understand biological mechanisms, develop and test interventions and allow the prediction of age-related events so interventions can be implemented. In recent years, a variety of mechanistic candidate BoA have been discovered on the basis of a greatly improved understanding of the cellular and molecular biology of ageing. These include various measures of oxidative stress, which is thought to contribute causally to the ageing of organisms via its acceleration of cellular senescence. However, their reliability and validity as BoA, especially within population based cohorts are scarce. This study therefore focused on various oxidative stress-related measures as candidate BoA including: reactive oxygen species (ROS) production from dysfunctional mitochondria, by measuring superoxide levels, mitochondrial mass and mitochondrial membrane potential in blood mononuclear cells by flow cytometry; and also markers of lipid peroxidation, F2-isoprostanes, by measuring 8-iso Prostaglandin F2 by Automated Dissociation Enhanced Lanthanide Fluorescence Immunoassay (AutoDELFIA). Despite providing evidence of experimental reliability for all measures and also some evidence of construct validity for ROS production from dysfunctional mitochondria in terms of: associations with chronological age, associations with some markers of oxidative stressinduced cellular senescence, validation in a dietary restricted animal model of ageing and a role in an immunosenescent phenotype; there was no evidence of predictive validity in terms of longevity or age-related health outcomes in a population based cohort of the very old, the Newcastle 85+ study. This questions the predictive validity of these parameters as candidate BoA in the very old population.
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Collins, D. P. "Towards an understanding of how hip musculature modifies fall-related stress patterns in the ageing femur : a computer simulation approach." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3021537/.
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Pattison, Mari Anne. "The effects of ageing on murine NKT cell and macrophage populations." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/29559.
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The immune system is a complex network of tissues, cells and proteins which protects us against infections and invading pathogens we encounter every day. Immunosenescence refers to age-related impairments in immune function which may contribute to increased prevalence and severity of infectious disease in the elderly. How and why ageing affects the immune system is not fully understood. Using a naturally aged mouse model, work in this thesis shows that the abundance of a rare type of lymphocyte, known as NKT cells, increased across multiple immune organs. Additionally, macrophage abundance was also altered in the lymph nodes of aged mice. Invariant NKT (iNKT) cells express an invariant T cell receptor (TCR) which recognises lipids presented on the CD1d molecule. iNKT cells can be activated and respond to invading pathogens either by recognition of antigens through TCR-CD1d interactions or cytokine-dependent means. Less is known about NKT-like cells, which also express NK cell-associated surface markers, such as CD49b, but lack an invariant TCR. Data within this thesis show that both iNKT and NKT-like cell populations are abundant in the spleen and liver of aged mice. iNKT and NKT-like cells can be divided into subpopulations based on their expression of surface markers or transcription factors, and data suggests that not all subpopulations of these cells are affected by age equally. For instance, flow cytometry showed that while spleen-derived iNKT cells are significantly increased in aged mice, within the iNKT cell population the percentage representation of CD4+ cells are significantly reduced with age. Additionally, data indicates that both iNKT and NKT-like cells from aged mice show compromised responses to in vitro stimulation compared to young controls. Using bone marrow chimeras, where either young cells are reconstituted within an aged mouse or old cells are reconstituted within a young mouse, provided the opportunity to determine whether the aged environment contributes to this diminished response. Data demonstrates that the aged environment plays at least a partial role in these age-related changes to response to stimulation, however the young environment seems unable to reverse these changes. Macrophages are phagocytes which are found within all organs of the body. Studies in this thesis show that CD169+ macrophages have diminished numbers in the lymph nodes of aged mice, but this did not seem to affect the capture of the model antigen, dextran. Further studies revealed ageing affects macrophage populations differently in the different tissues within the body. For example, macrophage numbers remain constant in the spleen with ageing, but appear to increase in density in the lungs. To conclude, ageing can cause dramatic changes to the numbers and function of different cells of the immune system across multiple organs. Furthering our understanding of the ageing immune system and the underlying mechanisms which cause age-related decline in immune function is important to design strategies to improve the quality of the lives of the elderly.
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Al-Saaidy, Haydar Raheem Hmoud [Verfasser]. "Effects of Recycling Process on Performance-Related Properties of Recycled Asphalt Mixtures Before and After Ageing / Haydar Raheem Hmoud Al-Saaidy." Wuppertal : Universitätsbibliothek Wuppertal, 2020. http://d-nb.info/1221969013/34.
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Shadforth, Audra M. "Development of a cultured tissue substitute to repair the ageing retina." Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/90058/12/Audra_Shadforth_Thesis.pdf.
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This project provides a foundation for the use of silk membranes in a tissue engineered therapy for the treatment of devastating retinal diseases such as age-related macular degeneration. The three-dimensional tissue model described in this thesis has great potential for use in basic research of retinal pathologies, and the potential to be implemented into clinical approaches after appropriate refinement.
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Hariton, Florence A. G. "Anti-stress gene response in cell and tissue ageing : role of transcription factor NF-E2-related factor-2 and effect of dietary activators." Thesis, University of Warwick, 2014. http://wrap.warwick.ac.uk/66553/.
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The concept of cellular senescence is based on the notion that proliferation of normal diploid cells can only occur for a limited period of time after which cells slowly cease to divide and die. This limitation of lifespan for in vitro cell cultures was first described by Leonard Hayflick in 1961, going against the theory formulated by Alexis Carrel claiming that cells kept in culture have an unlimited potential for division (Carrel and Ebeling, 1921). Evidence from cell senescence studies have been used to explain the basis of healthy ageing as well as develop food supplements promoting the delay of ageing. Since these discoveries, there has been marked expansion of anti-stress gene response research with relation to the role of the transcription factor NF-E2-related factor-2 as well as healthy ageing with regards to dietary activators intake. This study examined the effects of sulforaphane (SFN) and hesperetin (HESP) on MRC-5 cell senescence in vitro as well as characterized gene expression and cell metabolism in cells escaping senescence by treatment with SFN and HESP and the mechanism of decrease glucose metabolism by SFN and HESP action linked to delay of fibroblast senescence. The effects of treatment of MRC-5 with the dietary bioactivators SFN and HESP was studied and shown to delay cellular senescence in these cells in vitro. Similar findings for SFN treatment of BJ cells were found previously by studies of the host team. Caloric restriction mimetic mechanisms by treatment with 1 μM SFN and 5 μM HESP was shown due to the decrease in culture glucose consumption increase with senescence in these treatment groups and this CR restriction mimetic effect and decrease in the flux of formation of D- and L-lactate in the SFN-treated group was consistent with previous studies done in CR and ageing in mice models (Hargopan, Ramsey and Weindruch, 2003). Moreover, in this study, SFN was shown to act as a CRM dietary bioactive through cellular contents of glycolytic intermediates with SFN-treatment (Bensaad et al., 2006). Finally, the mechanism by which SFN induces delay of senescence through CR was shown to be due to the extraction of Mondo A from the cell nucleus to the cytoplasm.
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Drake, Carolyn M. "Protecting and promoting the health and safety of older workers : opportunities and challenges." Thesis, Loughborough University, 2017. https://dspace.lboro.ac.uk/2134/25535.
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As the 21st century proceeds, individuals are increasingly working into later years to support themselves and maintain their quality of life. This changing pattern of employment has implications for workers, employers and society alike. Although older workers have much to contribute, individuals may experience health issues or physical, sensory or psychological changes related to ageing. Health and safety statistics indicate that older workers are a vulnerable group. Employers then, have a responsibility to examine the working environment and protect those with reduced capabilities. For society to function, older workers need to be able to remain in work, otherwise this will impact on both the economy and older individuals quality of life. This thesis aimed to understand the opportunities and challenges employers encounter when trying to protect and promote the health and safety of older workers. The research used qualitative approaches, combining interviews and focus groups to provide rich data on the circumstances of older workers. Triangulation was used, collecting data over different time periods, from different sources, to help balance out any weaknesses across the studies. Data were analysed using thematic analysis. A review of the literature found that there is no consistent definition of ageing or older worker. Many researchers have used chronological age and, therefore, this thesis used 50 as a threshold. The literature highlights that older workers have a wealth of knowledge and skills to bring to the workplace. Negative perceptions, however, regarding natural ageing and adaptability exist. Other authors have argued that organisations need to provide a safe environment for older workers and implement measures to mitigate changes in abilities, whilst recognising that there is no one size fits all strategy. First, an initial scoping study was undertaken with employers, which sought to understand their perceptions concerning the ageing workforce. The study also collected information on the health and safety age management strategies that have been implemented within the organisations. Interviews with employers (senior managers who influence health and safety management strategies) (n=41) revealed that, in line with literature, there is recognition that older workers bring benefits to the workplace. However, some comments demonstrated inaccurate stereotyping. The interviews found that these employers were uncertain how to proceed with implementing actions to protect the health and safety of their older workers. Two subsequent studies, consisting of focus groups (n=10) and interviews (n=50) were then conducted, which explored older workers experiences of working into later life and their views on the issues identified by the employer interview study. The older worker interviews also examined their perceptions regarding their health and capabilities, appropriate health and safety measures in response to this and interviewees anticipated future in the workforce. Older workers explained that they do not feel supported or engaged. They are fearful of reporting capability changes that may affect their ability to perform work tasks, as they believe this may have negative consequences for their future employment. During discussions, they suggested various measures that may help them remain in the workforce for longer. The information gathered during the literature review and the findings from the first three studies, were then used to develop examples of good practice health and safety measures that organisations could implement to help protect and promote the health and safety of older workers. A final interview study with key employer representatives (n=16) was conducted, to understand whether the health and safety good practice measures might be considered beneficial and achievable. This study found that although organisations recognised the benefits of health and safety measures tailored for older workers, the feasibility of some of the suggestions was in doubt. Budgetary constraints, insufficient time and lack of necessary knowledge were seen as particular obstacles to implementation. This thesis has identified that although research evidence exists in relation to measures to support the health and safety of older workers, e.g. the benefits of health promotion, improved work scheduling, workplace assessments etc, this is rarely translated into practice. Within organisations, there is uncertainty about age management for older workers and limited understanding of the divergent needs as workers capabilities change. The default position then becomes to cater for a typical worker. A coordinated multi-disciplinary approach between health and safety, occupational health, human resources and operational management is required. This thesis argues for an integrated age management strategy, with an emphasis on proactive prevention, in the interests of protecting and promoting the health and safety of older workers.
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Long, Madeleine Rebecca Anne. "Lifelong interplay between language and cognition : from language learning to perspective-taking : new insights into the ageing mind." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31398.
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A fundamental question in language research is the extent to which linguistic and cognitive systems interact. The aim of this thesis is to explore that relationship across new contexts and over the entire adult lifespan. This work centers on two branches of empirical research: the first is an investigation into the impact of later-life language learning on cognitive ageing (chapters 2-4), and the second examines the cognitive mechanisms underlying communicative perspective-taking from young adulthood into old age (chapter 5). The results of these chapters demonstrate that changes to one's linguistic environment can affect cognitive functions at any age, and similarly age-related changes to cognition can affect linguistic abilities, shedding light on the extent to which language and the brain are intricately connected over the lifespan. In the discussion (chapter 6), I consider how this work contributes new insights to the field, opening the door for future research to explore methods of improving cognitive abilities and linguistic behavior in old age.
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Williams, Owen A. "The application of a diffusion tensor image segmentation technique in healthy ageing and cerebral small vessel disease : microstructural changes in the cerebrum related to cognitive decline." Thesis, St George's, University of London, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.719394.
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Brain changes and cognitive decline are observed in healthy ageing and cerebral small vessel disease (SVD), an age-related disease. This thesis describes the optimisation and application of a diffusion tensor image segmentation technique (DSEG) to measure microstructural changes in healthy ageing and SVD in order to predict cognitive decline and dementia risk. Neuropsychological and magnetic resonance imaging data were collected in two prospective cohorts. 112 healthy ageing participants (aged 50-90), tested up to four years. 120 SVD patients (aged 43-89) tested annually for MR! and neuropsychological data for up to five years. Cognitive domains tested included executive functions (EF), working memory (WkM), information processing speed (IPS) and episodic memory (EM). DSEG provides a vector of 16 segments, describing brain microstructure of healthy/damaged tissue. A novel, whole-brain diffusion metric of microstructural change was calculated using the dot-product of each DSEG vector compared to a reference brain (e.g. oldest/youngest) to generate an angle-of-difference (#), describing microstructural differences of each brain compared to the reference brain. Conventional imaging was used to assess normalised brain volume, white-matter hyperintensity volume, lacunes, cerebral microbleeds, and white-matter microstructural changes. DSEG measures were associated with age-related differences in cognition (p < .05) but not longitudinal changes due to a lack of decline in cognition, in healthy ageing. In SVD, changes in individual DSEG segments and 6 were associated with decline in EF, IPS and global cognition (p < .05) over 3-5 years. DSEG accurately identified individuals who developed dementia. DSEG consistently provided more stable models for predicting cognitive decline, compared to conventional MRI parameters. This thesis shows for the first time that DSEG is a stable measure of whole-brain microstructural changes associated with cognitive differences in healthy ageing and cognitive decline in SVD. DSEG can predict who will have the most severe declines in cognition and develop dementia.
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Simoni, Michela. "Age-related white matter changes in patients with TIA and stroke : population-based study on aetiological and prognostic significance." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:d3e55744-5cc1-44e9-a33f-589abbc50c93.
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White matter changes (WMC) seen on CT and MRI brain scans of healthy subjects and of vascular or dementia patients are strongly associated with age. Their pathogenesis is still under debate, and associations with vascular risk factors have varied according to studies. Their prognostic meaning, both in the general population and in stroke patients, is also not completely established. I systematically reviewed the literature on prevalence and associations of WMC and then evaluated CT and MRI scans of the first 8 years of a population-based study of all strokes and TIA in Oxfordshire (OXVASC). In this population I researched sex and age-specific associations between WMC and different types of strokes (TOAST), different components of blood pressure, and possible vascular risk factors. I also looked into their prognostic meaning for stroke recurrence and outcome, cognitive performance and mortality. 1840 patients were assessed by MRI (520) and/or CT (1717). White matter changes were independently associated with the lacunar type of stroke. The association with hypertension was confirmed (using 10 years of pre-morbid blood pressure readings), and it was particularly strong in the younger patients, mainly for diastolic hypertension. There was no association with blood pressure variability and peripheral pulse pressure. Hypercholesterolaemia, diabetes, smoking, ischaemic heart disease, carotid stenosis and atrial fibrillation were not associated with white matter changes. There was also no association with gender. Severe WMC posed a higher risk of disability and cognitive impairment at one year from the stroke, and of death in the following 10 years. This is the first study on white matter changes associations and on their prognostic meaning, to be set in a large population-based cohort of stroke and TIA. I confirmed the association between white matter changes and higher blood pressure, in particular diastolic hypertension. I also showed the association with lacunar type of stroke to be independent from vascular risk factors, and WMC to reduce life expectancy and functional and cognitive outcome of patients with stroke.
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Eriksson, Arlene, and Annie Hejdström. "Förekomst av tal-, språk- och sväljsvårigheter på geriatrisk avdelning." Thesis, Linköpings universitet, Logopedi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68884.
Full textAbstract:
Normalt åldrande innebär förändringar hos individen som kan påverka tal, språk och sväljning. Ökad känslighet för inre och yttre påverkan hos den åldrande individen samt sjukdomsbild kan skapa problematik, vilken kan ge upphov till svårigheter med tal, språk och/eller sväljning, som i sin tur påverkar den upplevda livskvaliteten. Geriatriska patienter karaktäriseras av nedsatt funktionsnivå och kroniska sjukdomar, därför ställs krav på specialkompetens för vård och rehabilitering av dessa patienter. Syftet med föreliggande studie var att genom screening undersöka förekomst av tal-, språk- och sväljsvårigheter på geriatriska avdelningar i två städer i södra Sverige. Därtill undersöktes även orofacial påverkan och hälsorelaterad livskvalitet. Totalt 42 patienter från geriatriska avdelningar med inriktningarna allmängeriatrik, strokerehabilitering och ortopedi deltog. Screeninginstrument som användes var Nordiskt Orofacialt Test – Screening (NOT-S) för screening av orofaciala funktioner. Screening av tal baserades på delar ur NOT-S samt talade delar ur språklig screening. Delar ur Neurolingvistisk Afasi-undersökning (A-ning) valdes för screening av språk och Standardised Swallowing Assessment (SSA) användes för klinisk undersökning av sväljning. Hälsoenkäten the Short Form – 12 (SF-12) användes för skattning av hälsorelaterad livskvalitet. Identifierade svårigheter i patientgruppen var talsvårigheter hos 33 % (14 av 42), samt 40 % (16 av 40) och 37 % (15 av 41) språkliga svårigheter respektive sväljsvårigheter. Bland deltagarna hade 64 % svårigheter med en eller flera av de undersökta funktionerna. Förekomst av dessa svårigheter hade signifikant samband med nedsatt orofacial funktion. Lågt skattad hälsorelaterad livskvalitet hade signifikant samband med språkliga svårigheter och med orofacial dysfunktion.Changes occur during the normal ageing process that can interfere with speech-, language- and swallowing functions. An increased occurrence of diseases increases the frailty in the ageing individual and may cause disordered speech, language and/or swallowing, in which case the health related quality of life may be negatively affected. The geriatric population is characterized by functional impairment and chronic diseases. This therefore poses special demands on specialist care and rehabilitation of these patients. The aim of this study was to examine the occurrence of speech, language and swallowing disorders in geriatric wards in two cities in the southern part ofSwedenusing screening. The orofacial influence on these functions and health related quality of life were also examined. In total 42 patients participated, from geriatric wards with general, stroke rehabilitation and orthopedic specialty. The instruments used for screening of orofacial functions was the Nordic Orofacial Test – Screening (NOT-S) and perceptual parameters for screening of speech based on speech parts from NOT-S and speech production from Neurolingvistisk Afasi-undersökning (A-ning). Parts of A-ning were also used for screening of language. Standardised Swallowing Assessment (SSA) was used for clinical examination of swallowing. The Short Form – 12 Health Survey (SF-12) was used to estimate the health related quality of life. Results showed that 33 % (14 of 42) had difficulties with speech, 40 % (16 of 40) and 37 % (15 of 41) showed difficulties with language and swallowing respectively. Of the participants, 64 % had difficulties with one or more of the examined functions. Occurrence of these difficulties associated significantly with impaired orofacial function. Language difficulties were associated with decreased mental health status and orofacial dysfunction with decreased physical health status, measured with the SF-12.
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Foottit, Jenneke Anna. "Wellness in older adults." Thesis, Queensland University of Technology, 2009. https://eprints.qut.edu.au/35655/1/Jenneke_Foottit_Thesis.pdf.
Full textAbstract:
Understanding perception of wellness in older adults is a question to be understood against the backdrop of concerns about whether global ageing and the ‘bulge’ of ageing baby boomers will increase health care cost beyond what modern economies can deal with. Older adults who age in a healthy way and who take responsibility for their own health offer a positive alternative and change the perception that older adults are a burden on their society’s health system.
The concept of successful ageing introduced by Rowe and Kahn (1987; 1997) suggested that older adults age successfully if they avoid disease and disability, maintain high cognitive and physical functioning and remain actively engaged with life. This concept, however, did not reflect older adults’ own perceptions of what constitutes successful ageing or how perceptions of wellness or health-related quality of life influenced the older adult’s understanding of his or her own health and ageing.
A research project was designed to examine older adults’ perceptions of wellness in order to gain an understanding of the factors that influence perception of their own wellness. Specifically, the research wanted to explore two aspects: whether belonging to a unique organisation, in this instance a Returned Services Club, influenced perceptions of wellness; and whether there are significant gender differences for the perception of wellness. A mixed method project with two consecutive studies was designed to answer these questions: a quantitative survey of members of a Returned Services Club and of the surrounding community in Queensland, Australia, and a qualitative study conducting focus groups to explore findings of the survey. The results of the survey were used to determine the composition of the focus groups.
The participants for the first study, (N=257), community living adults 65 years and older, were chosen from the membership role of a Returned Services Club or recruited by personal approach from the community surrounding the Services Club. Participants completed a survey that consisted of a perception of wellness instrument, a health-related quality of life instrument, and questions on morbidities, modifiable life style factors and demographics.
Data analysis found that a number of individual factors influenced perception of wellness and health-related quality of life. Positive influences were independent mobility, exercise and gambling at non-hazardous levels, and negative influences were hearing loss, memory problems, chronic disease and being single. Membership of the Services Club did not contribute to perception of wellness beyond being a member of a social group. While there may have been an expectation that members of an organisation that is traditionally associated with high alcohol use and problematic gambling may have lower perceptions of wellness, this study suggested that the negative influences may have been counteracted by the positive effects of social interaction, thus having neither negative nor positive influences on perception of wellness. There were significant differences in perception of wellness and in health-related quality of life for women and men. The most significant difference was for women aged 85-90 who had significantly lower scores for perception of wellness than men or than any other age group. This result was the impetus for conducting focus groups with adults aged 85-90 years of age.
Focus groups were conducted with 24 women and four men aged 85-90 to explore the survey findings for this age group. Results from the focus groups indicated that for older adults perception of wellness was a multidimensional construct of more complexity than indicated by the survey instrument. Elite older women (women over 85 years of age) related their perception of wellness to their ability to do what they wanted to do, and what they wanted to do significantly more than anything else, was to stay connected to family, friends and the community to which they belonged.
From the focus group results it appeared that elite older women identified with the three elements of successful ageing – low incidence of disability and disease, high physical and cognitive functioning, and active engagement with life – but not in a flat structure. It appears that for elite older women good physical and mental health function to enable social connectedness. It is the elements of health that impact on the ability to do what they wanted to do that were identified as key factors: independent mobility, hearing and memory - factors that impact on the ability to interact socially. These elements were only identified when they impacted on the person’s ability to do what they wanted to do, for example mobility problems that were managed were not considered a problem. The study also revealed that older women use selection, optimisation and compensation to meet their goal of staying socially connected. The shopping centre was a key factor in this goal and older women used shopping centres to stay connected to the community and for exercise as well as shopping. Personal and public safety and other environmental concerns were viewed in the same context of enabling or disabling social connectedness. This suggested that for elite older women the model of successful ageing was hierarchical rather than flat, with social connectedness at the top, supported by cognitive functioning and good physical and mental health.
In conclusion, this research revealed that perception of wellness in older adults is a complex, multidimensional construct. For older adults good health is related to social connectedness and is not a goal in itself. Health professionals and the community at large have a responsibility to take into account the ability of the older adult to stay socially connected to their community and to enable this, if the goal is to keep older adults healthy for as long as possible. Maintaining or improving perception of wellness in older adults will require a broad biopsychosocial approach that utilises findings such as older adults’ use of shopping centres for non-shopping purposes, concerns about personal and environmental safety and supporting older adults to maintain or improve their social connectedness to their communities.
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Anderson, Rhonda Laurelle. "Exercise and dietary behaviour change in a sample of midlife Australian women." Thesis, Queensland University of Technology, 2008. https://eprints.qut.edu.au/18573/1/01Thesis.pdf.
Full textAbstract:
The purpose of this study was to understand the factors that encourage midlife women to make exercise and dietary changes, the prevalence of those changes, the process by which women make them, the factors that support or impede them, and how we can enhance women’s capacity to make health behaviour changes in midlife. Since the literature highlighted the importance of self-efficacy in changing health behaviour, and of health-related quality of life as a widely recognized measure of women’s mental and physical wellbeing, the study sought to understand the relationship between exercise and dietary self-efficacy, health behaviour change and health-related quality of life (SF-36), by testing a modified version of Bandura’s 1977 and 2002/2004b models of self-efficacy.
The methodology involved postal surveys as well as semi-structured interviews with a subsample of the women who completed the survey. Surveys were sent to 866 women aged 51-66 years from rural and urban locations in Queensland, Australia. Five hundred and sixty-four (69%) were completed and returned. Survey data was analysed using descriptive and bivariate statistics and structural equation modeling. Thematic analysis was used to analyse interviews.
The results confirmed that midlife is a significant time for women to make positive health behaviour changes. Almost 40% of women made a change to their exercise and around 60% made a dietary change since turning 40. The main exercise change was doing more walking and the most common dietary change was reducing fat intake. Self-efficacy was shown to be a key influence on whether women made positive changes to their health in midlife. In the relationship between health behaviour change and health-related quality of life, making a positive change to exercise was significantly related to physical but not mental health, and making a dietary change was not related to either physical or mental health. Body mass index was shown to be an important influence on both self-efficacy and health-related quality of life (particularly physical health).
Interviews were conducted with 29 of the participants. Interview data reinforced that the main motivations to make a positive health behaviour change among midlife women were being overweight, having an injury or being diagnosed with an illness or health condition. Witnessing the hardship experienced by others with a degenerative disease could also prompt a positive behaviour change. Successful changes mainly involved modifying existing practices and repeating new behaviours until they became part of the daily routine. The main facilitators of health behaviour change were having positive role models, having more time due to retirement, and having support from significant others (such as husbands), health professionals and organizations such as Weight Watchers. The main obstacles to making changes were work, care giving, illness and injury.
Bandura’s (1977, 2000/2004b) model was partially supported, but the cross-sectional nature of the study may have been a limitation in demonstrating all aspects of the self-efficacy process.
In summary, women are willing to make positive health behaviour changes in midlife, but they need education and support to have those changes be effective. It is anticipated that this research will lead to a greater understanding of the significance of midlife as a time for making healthy lifestyle changes that have the potential to improve women’s health and quality of life in later years.
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Anderson, Rhonda Laurelle. "Exercise and dietary behaviour change in a sample of midlife Australian women." Queensland University of Technology, 2008. http://eprints.qut.edu.au/18573/.
Full textAbstract:
The purpose of this study was to understand the factors that encourage midlife women to make exercise and dietary changes, the prevalence of those changes, the process by which women make them, the factors that support or impede them, and how we can enhance women’s capacity to make health behaviour changes in midlife. Since the literature highlighted the importance of self-efficacy in changing health behaviour, and of health-related quality of life as a widely recognized measure of women’s mental and physical wellbeing, the study sought to understand the relationship between exercise and dietary self-efficacy, health behaviour change and health-related quality of life (SF-36), by testing a modified version of Bandura’s 1977 and 2002/2004b models of self-efficacy.
The methodology involved postal surveys as well as semi-structured interviews with a subsample of the women who completed the survey. Surveys were sent to 866 women aged 51-66 years from rural and urban locations in Queensland, Australia. Five hundred and sixty-four (69%) were completed and returned. Survey data was analysed using descriptive and bivariate statistics and structural equation modeling. Thematic analysis was used to analyse interviews.
The results confirmed that midlife is a significant time for women to make positive health behaviour changes. Almost 40% of women made a change to their exercise and around 60% made a dietary change since turning 40. The main exercise change was doing more walking and the most common dietary change was reducing fat intake. Self-efficacy was shown to be a key influence on whether women made positive changes to their health in midlife. In the relationship between health behaviour change and health-related quality of life, making a positive change to exercise was significantly related to physical but not mental health, and making a dietary change was not related to either physical or mental health. Body mass index was shown to be an important influence on both self-efficacy and health-related quality of life (particularly physical health).
Interviews were conducted with 29 of the participants. Interview data reinforced that the main motivations to make a positive health behaviour change among midlife women were being overweight, having an injury or being diagnosed with an illness or health condition. Witnessing the hardship experienced by others with a degenerative disease could also prompt a positive behaviour change. Successful changes mainly involved modifying existing practices and repeating new behaviours until they became part of the daily routine. The main facilitators of health behaviour change were having positive role models, having more time due to retirement, and having support from significant others (such as husbands), health professionals and organizations such as Weight Watchers. The main obstacles to making changes were work, care giving, illness and injury.
Bandura’s (1977, 2000/2004b) model was partially supported, but the cross-sectional nature of the study may have been a limitation in demonstrating all aspects of the self-efficacy process.
In summary, women are willing to make positive health behaviour changes in midlife, but they need education and support to have those changes be effective. It is anticipated that this research will lead to a greater understanding of the significance of midlife as a time for making healthy lifestyle changes that have the potential to improve women’s health and quality of life in later years.
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Pilling, Luke C. "Human population studies of transcriptome-wide expression in age-related traits." Thesis, University of Exeter, 2015. http://hdl.handle.net/10871/17471.
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This thesis presents novel investigations of three common ageing phenotypes in human population studies, using microarray technology to assess ‘transcriptome-wide’ expression in whole blood to identify mechanisms and biomarkers. Muscle strength is related to frailty and is predictive of disability in older persons. I assessed the association between transcript abundance in the InCHIANTI peripheral blood samples (N=695) and muscle strength. One gene (CEBPB) passed the multiple testing criteria, and is involved in macrophage-mediated repair of damaged muscle. I extended this work with a meta-analysis of over 7,781 individuals in four collaborating cohorts; expression of over 222 genes were significantly associated with strength, less than half of which have previously been linked to muscle in the literature. CEBPB did not replicate in these younger cohorts. I then performed the first human analysis of gene expression and cognitive function (and separately with decline in cognitive ability over nine years) in the InCHIANTI cohort (N=681), and one gene was identified; CCR2, a chemokine receptor. Evidence in mice has implicated this gene in the accumulation of β-amyloid and cognitive impairment. Finally, in a collaborative project with the Framingham Heart Study I studied age-related inflammation – another hallmark of ageing - using a novel approach to ‘transcriptome-wide’ analysis; each transcript was assessed for the proportion of the association between age and interleukin-6 (IL6) that it statistically mediated. Very few of the genes associated with IL6 alone also mediated the relationship with age. Findings include; SLC4A10, the strongest mediator, not previously linked to inflammation, and interleukin-1 beta and perforin, a cytokine and cytotoxic protein, respectively. These novel analyses highlight key molecular pathways associated with age-related phenotypes in whole blood and provide links between mouse models and humans. They provide biological insight and directions for future research.
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Hackett, G. I. "The management of erectile dysfunction and related disorders in primary care." Thesis, Keele University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323722.
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Edwards, Carolyn Anne. "The role of the frontal cortex in normal age-related memory performance." Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389161.
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Sjölinder, Marie. "Age-related cognitive decline and navigation in electronic environments." Doctoral thesis, Stockholm University, Department of Psychology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1038.
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The older population is increasing, as is life expectancy. Technical devices are becoming more widespread and used for many everyday tasks. Knowledge about new technology is important to remain as an active and independent part of the society. However, if an old user group should have equal access to this technology, new demands will be placed on the design of interfaces and devices. With respect to old users it is and will be important to develop technical devices and interfaces that take the age-related decline in physical and cognitive abilities into account. The aim of this work was to investigate to what extent the age-related cognitive decline affects performance on different computer-related tasks and the use of different interfaces. With respect to the use of computer interfaces, two studies were conducted. In the first study, the information was presented with a hierarchical structure. In the second study the information was presented as a 3D-environment, and it was also investigated how an overview map could support navigation. The third study examined the age-related cognitive decline in the use of a small mobile phone display with a hierarchical information structure. The results from the studies showed that the most pronounced age-related difference was found in the use of the 3D-environment. Within this environment, prior experience was found to have the largest impact on performance. Regarding the hierarchical information structures, prior experience seemed to have a larger impact on performance of easy tasks, while age and cognitive abilities had a larger impact on performance of more complex tasks. With respect to navigation aids, the overview map in the 3D-environment did not reduce the age-differences; however, it contributed to a better perceived orientation and reduced the feeling of being lost.
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Marioni, Riccardo Emilio. "Inflammation and cognition : the association between biomarker levels, their genetic determinants, and age-related cognitive decline." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4436.
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Chronic in ammation and variations in blood flow have been implicated in the pathogenesis of cardiovascular disease. It is also possible that inflammatory and rheological processes are involved in the development of mild cognitive impairment and dementia, either through their association with vascular disease or via some other, more direct effect on the brain. Evidence is increasing for a causal relationship between Alzheimer's disease and inflammation, possibly related to inflammatory activation of microglia. Inflammatory processes may also be involved in the pathogenesis of cerebral small vessel disease, which in turn has been linked to cognitive impairment and dementia. There is also evidence showing that rheological factors affect cerebral blood flow. However, despite these findings, the associations between inflammatory and rheological markers and cognitive ability have not been extensively studied in large groups of ageing people. The primary aim of this thesis was to test for associations between late-life levels of inflammatory and rheological markers (C-reactive protein (CRP), fibrinogen, tumor necrosis factor (TNF)-α, interleukin (IL)-6, plasma viscosity, and haematocrit) and cognitive ability. A genetic analysis was then performed to model single nucleotide polymorphisms (SNPs) in the genes encoding the markers against cognition in an attempt to determine the weight of evidence for a causal inflammation-cognition association. Four studies were used to test these aims with the majority of the analysis being performed on the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 3,350), and the Edinburgh Type 2 Diabetes Study (ET2DS) (n = 1,066). The Edinburgh Artery Study (n = 534), and the 1936 Lothian Birth Cohort (n = 1,091), were used as replication cohorts for the genetic analysis. All cohorts comprised community-dwelling, elderly citizens (aged around 70 years) living in central Scotland. With the exception of the ET2DS, all data used were for secondary analyses. Cognitive ability was assessed in all studies using comprehensive batteries of neuropsychological tests that included a measure of crystallised intelligence in the form of a vocabulary test. As performance on such tests varies little across a lifespan, adjusting for these scores in the late-life models enabled the determination of estimated lifetime cognitive change. In the case of the 1936 Lothian Birth Cohort an actual age-11 IQ measure was available in addition to the cognitive follow-up scores recorded at age-70. Linear regression showed small but significant associations between CRP, fibrinogen, and plasma viscosity, and cognition and estimated lifetime cognitive decline in the AAA Trial. Similar results were observed in the ET2DS for CRP, IL-6, and TNF-α. These associations tended to be of a magnitude whereby the markers explained 1% of the variance of the cognitive test scores. The cognitive domains most consistently associated with the markers were processing speed, and a data derived general intelligence factor. A novel genetic analysis was then undertaken to model SNPs against cognitive ability and decline. Most of the results generated were null findings. However, strongly significant associations were found between the rs2227412 fibrinogen beta gene SNP and the cognitive test scores in the ET2DS. Furthermore, the genotype associated with the lowest cognitive scores was also related to higher levels of plasma fibrinogen. Whilst replication of the association between the fibrinogen SNPs and cognition was not found across all cohorts, these results still indicate a potentially causal role for this haemostatic/inflammatory marker. To date, the majority of inflammation-cognition associations have focussed on the acute-phase protein CRP. The main outcomes from this thesis suggest that its close correlate, fibrinogen, is an equally, if not more important factor in the complex process of cognitive ageing.
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Ribeiro, Karen Tokuhashi. "Fatores associados à qualidade de vida relacionada à saúde de idosos residentes no município de São Paulo - Estudo SABE: Saúde, Bem-Estar e Envelhecimento." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/6/6132/tde-20122011-114524/.
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Introdução: O envelhecimento populacional, decorrente do aumento da expectativa de vida, foi, sem dúvida, uma importante conquista em nível global. Contudo, discute-se atualmente a necessidade premente de agregar qualidade aos anos de vida ganhos. Objetivo: Identificar fatores associados à Qualidade de Vida Relacionada à Saúde (QVRS) de idosos não institucionalizados do Município de São Paulo, em 2006. Método: Este estudo faz parte do Estudo Longitudinal SABE Saúde, Bem-Estar e Envelhecimento. Os dados foram coletados em 2006, de uma amostra representativa composta por 1.160 idosos (idade 60 anos) que responderam ao Short-Form 12 (SF-12), questionário genérico que avalia QVRS. As variáveis dependentes foram os Componentes Físico (PCS) e Mental (MCS) do SF-12 e as análises foram conduzidas separadamente segundo sexo. Buscou-se a associação com variáveis demográficas, socioeconômicas, estado de saúde, incapacidade funcional, estilo de vida e relacionamento social, utilizando o método de regressão logística múltipla. Resultados: Entre as idosas, estiveram associados a baixos escores no PCS: idade 80 anos, multimorbidade, internação, ter incontinência urinária, ter depressão, ter dificuldades para executar atividades instrumentais e básicas da vida diária (AIVD e ABVD) e não praticar atividades físicas. Baixos escores no PCS dos homens associaram-se a idade 80 anos, renda insuficiente, multimorbidade, tomar dois ou mais medicamentos, ter dificuldades para ABVD e não praticar atividades físicas. Baixos escores no MCS das mulheres estiveram associados a ser fumante, auto-percepção negativa de saúde geral e saúde bucal, ocorrência de queda no último ano e ter depressão. Baixos escores no MCS entre os homens idosos associaram-se à auto-percepção negativa de saúde, ter incontinência urinária e ter depressão. Homens mais velhos (idade 70 anos) apresentaram melhores escores no MCS em relação aos mais jovens (60-69 anos). Discussão: No PCS, as únicas variáveis coincidentes entre homens e mulheres foram idade, prática de atividades físicas, multimorbidade e dificuldade para ABVD; enquanto no MCS foram auto-percepção de saúde e depressão. A análise separada por sexo possibilitou a identificação de modelos distintos de determinantes da QVRS de idosos. Conclusão: Os fatores que se associaram significativamente ao PCS-SF12 de idosos de ambos os sexos foram: auto-percepção de saúde, multimorbidade, dificuldades para desempenhar ABVD e prática de atividades físicas. Enquanto suficiência de renda e número de medicamentos associaram-se apenas para o sexo masculino e internação, incontinência urinária, depressão e dificuldades para desempenhar AIVD, apenas para o sexo feminino. Ao MCS-SF12 de ambos os sexos associaram-se apenas auto-percepção de saúde e depressão; enquanto para o sexo masculino associaram-se também faixa etária e incontinência urinária. Já para as mulheres também apresentaram associação significativa o tabagismo, a auto-percepção de saúde bucal e quedasBackground: The world had experienced a high increased in life expectancy during the last decades, which has been undoubtedly considered as a major achievement. Because the increase of elderly population, that presents highest prevalence of chronic conditions, besides other single characteristics, several researches have been developed due to determine ways to add quality to the gained years of life. The aim of this study was to identify factors associated with elderly health-related Quality of Life (HRQoL), in São Paulo. Methods: This study is part of the Longitudinal Study SABE - Health, Welfare and Ageing (from Portuguese: Saúde, Bem-Estar e Envelhecimento). Data were collected in 2006. The sample consisted of 1,160 elderly (age 60 years) who answered the Short-Form 12 (SF-12), a generic HRQoL questionnaire. Dependent variables were Physical (PCS) and Mental Components (MCS) of SF-12. All analysis were separated by sex and the independent variables approached demographic, socioeconomic, health status, functional disability, lifestyle and social networking conditions, using the multiple logistic regression. Results: Among old women, lower PCS scores were associated with age 80 years, multimorbidity, hospitalization, urinary incontinence, depression, difficulty to perform basic and instrumental activities of daily living (BADL and IADL) and lack of physical activities. Among old men, lower PCS scores were associated with age 80 years, insufficient income, multimorbidity, taking two or more medications, difficulty to perform BADL and the lack of physical activities. Among the women, lower MCS scores were associated with being a smoker, negative self-perception of general health and oral health, occurrence of falls in the last year and depression. Among the men, lower MCS scores were associated with negative self-perception of health, urinary incontinence and depression. Older men ( 70 years) had better MCS scores than younger (60-69 years). Conclusion: Significantly associated factors with the PCS-SF12 for both male and female elderly were: self-perceived health status, multimorbidity, incapacity for BADL and physical activity; while income and number of drugs were associated only for males. Hospitalization, urinary incontinence, depression and incapacity for IADL were associated only for females. To the MCS-SF12 of both sexes were associated only self-perceived health and depression, while age and urinary incontinence were associated for males. Females MCS-SF12 also had significant association with tobacco, self-perception of oral health and falls
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Kilgour, Alexandra Helen Middleton. "Sarcopenia and cognitive ageing : investigating their interrelationship, biological correlates and the role of glucocorticoids." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/14231.
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Background Sarcopenia and age-related cognitive decline (ARCD) are important age-related conditions which significantly impact upon the quality of life of older adults. ARCD is a well-established research area, whereas sarcopenia is a relatively new field. Research into the inter-relationships between them and possible common underlying mechanistic processes is lacking. Methods Several research techniques were used: a large systematic review; the development of an image analysis technique to measure neck muscle size on volumetric MR brain scans; the subsequent use of the technique in elderly cohort studies; statistical modelling to investigate the role of glucocorticoids in sarcopenia; and an invasive clinical study to develop a novel technique to measure the activity of 11beta-hydroxysteroid dehydrogenase (11βHSD1) in the human brain in vivo. Results I consistently found a relationship between: some measures of brain structure and muscle size; markers of brain structure and muscle function, mostly grip strength and gait speed; and cognition and muscle function. However, I found no relationship between current cognition and muscle size in any of the above studies. Cortisol was identified as a possible explanatory factor in the relationship between both cognition and brain volume with gait speed. I found an association between markers of immunosenescence and sarcopenia (neck muscle CSA and grip strength) and an association between expression of the cortisol amplifying enzyme 11βHSD1 and quadriceps strength. I developed a technique to measure 11βHSD1 activity across the human brain, which found that the amount of cortisol produced within the brain was not detectable and highlighted the asymmetries within the cerebrovascular venous system. Conclusions Further longitudinal studies looking at the association between sarcopenia and ARCD are now required to investigate these important relationships further and hopefully this will lead to improved therapeutic options.
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Pidgeon, Laura Marie. "Encoding contributions to mnemonic discrimination and its age-related decline." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15739.
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Many items encoded into episodic memory are highly similar – seeing a stranger’s car may result in a memory representation which overlaps in many features with the memory of your friend’s car. To avoid falsely recognising the novel but similar car, it is important for the representations to be distinguished in memory. Even in healthy young adults failures of this mnemonic discrimination lead relatively often to false recognition, and such errors become substantially more frequent in older age. Whether an item’s representation is discriminated from similar memory representations depends critically on how it is encoded. However, the precise encoding mechanisms involved remain poorly understood. Establishing the determinants of successful mnemonic discrimination is essential for future research into strategies or interventions to prevent recognition errors, particularly in the context of age-related decline. A fuller understanding of age-related decline in mnemonic discrimination can also inform basic models of memory. This thesis evaluated the contribution of encoding processes to mnemonic discrimination both in young adults and in ageing, within the framework of two prominent accounts of recognition memory, the pattern separation account (Wilson et al., 2006) and Fuzzy Trace Theory (FTT; Brainerd & Reyna, 2002). Firstly, a functional magnetic resonance imaging study in young adults found evidence for differences in regions engaged at encoding of images according to the accuracy of later mnemonic discrimination, consistent with both pattern separation and FTT. Evidence of functional overlap between regions showing activity consistent with pattern separation, and activity associated with later accurate recognition was consistent with a role of cortical pattern separation in successful encoding, but there was no direct evidence that cortical pattern separation contributed to mnemonic discrimination. This first evidence of cortical pattern separation in humans was supported by findings that in the majority of pattern separation regions, response functions to stimuli varied in their similarity to previous items were consistent with predictions of computational models. Regional variation in the dimension(s) of similarity (conceptual/perceptual) driving pattern separation was indicative of variation in the type of mnemonic interference minimised by cortical pattern separation. Further evidence of encoding contributions to mnemonic discrimination was provided by an event-related potential study in young and older adults. Older adults showed less distinct waveforms than young adults at encoding of items whose similar lures were later correctly rejected compared to those falsely recognised, supporting the proposal that age-related encoding impairments contribute to the decline in mnemonic discrimination. Finally, a set of behavioural studies found that older adults’ mnemonic discrimination deficit is increased by conceptual similarity, supporting previous findings and consistent with FTT’s account of greater emphasis by older adults on gist processing. However, older adults required greater reduction in perceptual or conceptual similarity in order to successfully reject lures, as uniquely predicted by the pattern separation account. Together, the findings support the notion that encoding processes contribute directly to mnemonic discrimination and its age-related decline. An integrated view of the pattern separation account and FTT is discussed and developed in relation to the current findings.
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Rodríguez, Pérez Juan Antonio 1985. "Testing two evolutionary theories of ageing by using public genome-wide data." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/565860.
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Old age comes coupled with frailty and disease and, thus, the ageing of the World’s population have spurred the interest on the causes and mechanisms of senescence. Senescence has long been a mystery, with no single universally accepted theory accounting for its ultimate evolutionary causes (if indeed these causes exist). Perhaps two of the most popular evolutionary explanations proposed so far are the Mutation Accumulation Theory of Senescence proposed by Peter Medawar in 1951 and the Antagonistic Pleiotropy Theory of Senescence, suggested by George C. Williams in 1957. The large amount of data derived from Genome-Wide Association Studies (GWAS) obtained over the last decade allows testing of both theories, provided that they can make predictions in terms of the genetic architecture of complex disease. However, if we want to take advantage from GWAS data, we need to assure that they are sound, replicable and that they contain information that is useful for our purposes. This PhD thesis deals with both goals: we first assess the quality and replicability of information on genome-disease associations and then we use it to explore the Mutation Accumulation and Antagonistic Pleiotropy theories of senescence. Knowledge about the impact of these theories will be important for an increasingly ageing population.La época de la vejez suele venir acompañada con debilidad y enfermedad y, por tanto, este envejecimiento global de la población ha estimulado el interés en las causas y mecanismos de senescencia. La senescencia ha sido un misterio desde hace tiempo, sin ninguna teoría universalmente aceptada para explicar las causas evolutivas finales (si es que de hecho existen estas causas). Quizás dos de las explicaciones evolutivas más plausibles propuestas hasta la fecha son la Teoría de la Acumulación de Mutaciones, propuesta por Peter Medawar en 1951 y la Teoría de la Pleiotropía Antagonista sugerida por George C. Williams en 1957. La gran cantidad de datos derivada de los estudios de asociación de genoma completo (GWAS) obtenidos durante la última década nos permite, por primera vez, testar ambas teorías usando estos datos, dado que a partir de ellos se pueden hacer predicciones acerca de la arquitectura genética de las enfermedades complejas. Sin embargo, si queremos aprovechar estos datos de GWAS, necesitamos verificar que sean replicables y que contengan información útil para nuestros propósitos. Esta tesis doctoral se ocupa de ambos objetivos: en primer lugar evaluar la calidad y la replicabilidad de datos procedentes de GWAS, que luego usaremos para explorar las teorías de Acumulación de Mutaciones y de la Pleiotropía Antagonista de la senescencia. El conocimiento sobre el impacto de estas teorías, será importante para una población cada vez más envejecida.
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Natrajan, Muktha Sundar. "Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and CNS remyelination." Thesis, University of Cambridge, 2015. https://www.repository.cam.ac.uk/handle/1810/252692.
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Remyelination is a regenerative process that occurs through the formation of myelin sheaths by oligodendrocytes, which are recruited as oligodendrocyte progenitor cells (OPCs) after demyelination in diseases such as Multiple Sclerosis (MS).A key environmental factor regulating OPC differentiation is the fate of myelin debris generated during demyelination. Myelin debris contains inhibitors of OPC differentiation and thus its clearance by phagocytic macrophages is an important component of creating a lesion environment conducive to remyelination. The efficiency of debris clearance declines with age, contributing to the age-associated decline in remyelination. Therefore, understanding the mechanisms of the age-related decline in myelin debris phagocytosis is important for devising means to therapeutically reverse the decline in remyelination. The aim of this study was to determine the functional/molecular differences between young and old phagocytes involved in myelin debris clearance, thereby identifying therapeutically modifiable pathways associated with efficient myelin debris phagocytosis. In this study, we show that expression of genes involved in the retinoid X receptor (RXR) and peroxisome proliferator-activated receptor (PPAR) pathways are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages. Disruption of RXR and PPAR using synthetic antagonists in young macrophages mimics ageing by reducing myelin debris uptake. Macrophage-specific RXR? knockout mice revealed that loss of RXR function in young mice caused delayed myelin debris uptake and slowed remyelination. Alternatively, receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The FDA-approved agonists bexarotene and pioglitazone, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profiles in MS patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. Activation of these pathways also enhances immunoregulatory markers on monocytes from MS patients, further suggesting the regeneration-promoting capacity of activating these pathways in phagocytes. These results reveal the RXR/PPAR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.
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Yokoyama, Akira. "Age-related remodelling of oesophageal epithelia by mutated cancer drivers." Kyoto University, 2019. http://hdl.handle.net/2433/244517.
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Linnet, Elisabeth. "Age-related differences in visuomotor integration as measured by object affordance effects : a combined behavioural and neurophysiological investigation." Thesis, University of Plymouth, 2016. http://hdl.handle.net/10026.1/4584.
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Visuomotor behaviour – from handling simple objects to operating complex devices – is of fundamental importance in our everyday lives, yet there is relatively little evidence as to how healthy ageing affects these processes. A central role is played by the human capacity for reaching and grasping. Grasping an object requires complex visuomotor transformations, including processing of the object’s extrinsic features (it’s spatial location) and intrinsic features (such as size and shape). It has been documented that action relevant intrinsic object properties automatically facilitate specific motor actions despite being task-irrelevant, the so-called object affordance effect. These effects have been demonstrated for (1) grasp type (precision and power grips being facilitated by small and large objects) and (2) object-orientation (whereby right and left handed grasps are facilitated by object-orientation), and might underlie the effortlessness with which humans can interact with objects. Yet, these paradigms have not previously been employed in the study of healthy ageing, and little is known concerning how these processes change over the life span. Elucidating these changes is of particular importance as age-related degeneration of white matter integrity is well documented. Consequently, if successful visuomotor behaviour relies on white matter integrity, age-related reductions in affordance effects should be observed. This prediction was tested in a series of experiments. Experiment 1 investigated age-differences in object-size compatibility effects, and results corroborated our prediction of age-related reductions in object-size effects. Experiment 2 investigated age-differences in (1) spatial compatibility effects versus object-orientation effects, and (2) the locus of the effects (facilitation versus interference effects). Results revealed (1) some evidence of larger affordance than spatial effects in both age-groups, and (2) interference effects in the younger group and both facilitation and interference effects in the older group, showing a potential change in processing modes or strategies. Experiments 3 and 4 addressed the main competing account, the attention-directing hypothesis (according to which attentional shifts are responsible for the generation of automatic response codes, rather than the affects arising from afforded actions), by using a novel stimulus set in which such attentional differences can be ruled out. Results provided strong evidence in favour of the object-size affordance hypothesis. A final neuroimaging experiment investigated age-differences in the object-size effect and its neural correlates by combining behavioural, functional MRI and diffusion tensor imaging (DTI) data. Results revealed evidence of age-differences, both on the behavioural and functional level. For the DTI data, we investigated all four diffusion metrics (something which is not frequently reported in the healthy ageing literature), and found widespread age-related differences in white matter integrity. The empirical findings presented in this thesis offer a significant contribution to ageing research, by further elucidating the relationship between age-related neurophysiological changes and visuomotor behaviour. The overall picture which emerged from this series of experiments was consistent with our prediction of age-related reductions in affordance effects. Furthermore, it is likely that these age-differences may have, at least in part, a neurophysiological basis.
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Gilbertson, Terri. "Industry attitudes and behaviour towards web accessibility in general and age-related change in particular and the validation of a virtual third-age simulator for web accessibility training for students and professionals." Thesis, Loughborough University, 2014. https://dspace.lboro.ac.uk/2134/16597.
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While the need for web accessibility for people with disabilities is widely accepted, the same visibility does not apply to the accessibility needs of older adults. This research initially explored developer behaviour in terms of how they presented accessibility on their websites as well as their own accessibility practices in terms of presentation of accessibility statements, the mention of accessibility as a selling point to potential clients and homepage accessibility of company websites. Following from this starting point the research focused in on web accessibility for ageing in particular. A questionnaire was developed to explore the differences between developer views of general accessibility and accessibility for older people. The questionnaire findings indicated that ageing is not seen as an accessibility issue by a majority of developers. Awareness of ageing accessibility documentation was also very low, highlighting the need for raising awareness of accessibility practices for ageing. Current age-related documentation developed by the Web Accessibility Initiative was then examined and critiqued. The findings show a tension between the machine-centric Web Content Accessibility Guidelines 2.0 (WCAG 2.0) and the needs of older people. Examination of guidelines when compared to research-derived findings reveal that the Assistive Technology (AT) centric structure of the documentation does not appropriately highlight accessibility practices in a context that matches the observed behaviour of older people. The documentation also fails to appropriately address the psycho-social ramifications of how older people choose to interact with technology as well as how they identify themselves in relation to any conditions they have which may be considered disabling. The need for a novel, engaging and awareness-raising tool resulted in the development of what is essentially a "Virtual third-age simulator". This ageing simulator is the first to combine multiple impairments in an active simulation and uses eye-tracking technology to increase the fidelity of conditions resulting in partial sightedness. It also allows for developers to view their own web content in addition to the lessons provided using the simulations presented in the software. The simulator was then validated in terms of its ability to raise awareness as well as its ability to affect web industry professionals' intentions towards accessible practices that benefit older people.