The phenotypic variability in human populations is partly the result of gene polymorphisms and differential gene expression. Studying the variability of gene expression across human populations is essential to understanding the molecular basis for diversity. However, key issues remain unanswered with respect to human expression variability. For example, the role of gene methylation in expression variability is uncertain, nor is it clear what role tissue-specific factors may have. Moreover, the contribution that expression variability has in aging and development is unknown. Here we classified human genes based on their expression variability in normal human breast and brain samples and identified functional aspects associated with high and low expression variability. Interestingly, both high variability and low variability gene sets are enriched for developmentally essential genes. There is limited overlap between the variably expressed genes of different tissues, indicating that tissue-specific rather than individual-specific factors are at work. We also find that methylation likely has a key role in controlling expression variability insofar as genes with low expression variability are likely to be non-methylated. Importantly, we find that genes with high population expression variability are likely to have age-, but not sex-dependent expression. Taken together, our work indicates that gene expression variability is tissue-specific, methylation-dependent, and is an important component of the natural aging process.

Aging is associated with adverse structural and functional changes in the brain. These changes have been directly linked to declines in certain types of learning and memory, likely due to the negative impact of aging on the hippocampus, a region necessary for cognitive functions such as relational learning, memory, and spatial navigation. Health behaviors and characteristics, like exercise and cardiorespiratory fitness (CRF), are related to better brain and cognitive aging, though more research is needed to better understand which age-sensitive aspects of cognitive function are most benefited by these health characteristics. The purpose of this collection of studies was to examine how exercise and fitness affect older adults’ learning and memory abilities, specifically using tasks that are designed to tax hippocampal binding processes. Further, I aimed to determine whether the volume of the hippocampus plays a key mediating role in this relationship. I answer these questions with three specific aims, each testing part of a model that represents complex interactions between physical activity, fitness, learning, and the potential mediator of hippocampal volume. The first aim examines these relationships using a cross-sectional design of 45 cognitively healthy older adults. The second aim evaluates the effects of a 12-week moderate intensity exercise program on 37 previously low-active older adults’ fitness, hippocampal volume, and relational learning rate. In this aim I first examine the amount of change in multiple variables following the intervention in order to infer causal relations, and then I examine the relationships of change across the different outcome measures. Finally, the third aim evaluates in 40 healthy older adults the role of hippocampal structure in the relationships between fitness and both spatial learning and memory in a virtual navigation task that has been found to be sensitive to age and disease-related changes in the hippocampus. In the first aim I found that higher cardiorespiratory fitness (CRF) was associated with larger hippocampal volume and faster relational learning rate. Larger hippocampal volume was also associated with faster learning rate. This pattern of results supports my hypotheses and provides a novel finding about how CRF relates specifically to older adults’ relational learning, which is thought to place demands on hippocampal binding. In the second aim I found that 12-weeks of regular light and moderate exercise increased CRF and early learning of relational associations. These changes were not larger for moderate intensity stationary cycling compared to light intensity stationary cycling. I also unexpectedly found that hippocampal volume decreased for both exercise groups, which suggests that this exercise intervention did not mitigate potential age-related decline in hippocampal volume. Finally, in the third aim I found that CRF was not related to learning object locations on spatial navigation, but higher CRF was related to fewer memory errors on the delayed recall of object locations in the virtual environment. Additionally, hippocampal volume was positively associated with the number of object locations learned after the first five minutes of free exploration in the virtual environment. Overall I found that higher CRF is related to faster relational learning and better memory of spatial object locations, both of which are expected to tax hippocampal binding processes. As even healthy older adults tend to experience structural and functional decline in the brain, CRF may be an effective health characteristic to target to increase the active life expectancy of our aging population.

Made Up, a body of paintings, expresses my love/loathe relationship with the beauty/fashion industries and the fantasy/deception they instill. Aging amplifies my fear of being rejected or invisible and is assuaged by being made-up. Pages torn from fashion layouts are manually distressed to become the visually striking crumpled images that are the basis for my painting. The wrinkled nature of my source communicates my frustration with aging and never being able to meet the standards of modern beauty ideals. My careful repainting of the disfiguration demonstrates my desire to intimately repair and own the image. In taking my power back through painting, the defiled magazine spread becomes a layout of my ability and power as a painter to create and control the illusion. Paint enables me to accept myself through the virtuosity of its application, scale, and in the resulting illusion, in which cathartic moments of subversive humor play out. / Includes bibliography. / Thesis (M.F.A.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

Loneliness is a risk factor for premature mortality but the mechanics of this relationship remain obscure. A potential mechanism is sleep disturbance. The present study aimed to examine the association between loneliness and sleep disturbance, evaluate loneliness as a risk factor for sleep disturbance and vice-versa, model effects between loneliness and sleep disturbance over time, and evaluate a mediation model of loneliness, sleep disturbance, and health. Data came from the 2006-2012 waves of the Health and Retirement Study, a nationally-representative study of older Americans; participants > 65 were included (n=11,400). Analyses included (i) linear regressions accounting for complex sampling and (ii) path analysis (cross-lagged panel and mediation models). Loneliness and sleep disturbance were correlated and were risk factors for one another. Cross-lagged panel models showed reciprocal effects between loneliness and sleep disturbance. Cross-lagged mediation models showed that loneliness predicted subsequent sleep disturbance, which in turn predicted poor self-reported health. Moreover, there was evidence of a direct and indirect effect of loneliness on sleep disturbance. All associations were weakened— but remained—when accounting for demographics, isolation, and depression. Collectively, these findings are consistent with the theory that sleep disturbance is a mechanism through which loneliness damages health. However, effects between loneliness and sleep are reciprocal, rather than unidirectional. Moreover, longitudinal effects were very small. Further research is necessary to speak to causality, assess daily associations between loneliness and sleep, assess a comprehensive model of the mechanics of loneliness and health, and examine loneliness and sleep in the context of other factors.

The migration of keratinocytes across wound beds is a key step in dermal wound healing. In aged human skin, wound healing rates decrease, and reactive oxygen species damage accumulation increases, but it is unclear if these factors relate specifically to migration of human skin keratinocytes (HSKs). In this study, two concentrations of oxygen (4% and 21%) were used to model low and high oxidative stress to produce varying levels of reactive oxygen species. When migration of HSKs from young and old primary skin were compared by scratch assay, those from old skin migrated faster in high oxygen tension than did young HSKs, which was an opposite trend from that seen in young skin. An intense increase in reactive oxygen species at margins immediately after scratching was seen in both young and old HSKs, but reactive oxygen species disappeared from young skin at 21% oxygen most quickly. These cells also had the slowest migration. These findings suggest that old and young keratinocytes respond differently to oxidative stress, and that migration of keratinocytes--a key step in re-epithelialization of wounds, is effected by the efficacy of reactive oxygen species removal.

The paraoxonase gene family consists of three members (PON1, PON2, and PON3) with both distinct and overlapping roles in human health. These enzymes influence oxidative stress, inflammation, and bacterial infections, along with a large number of diseases and disorders, such as atherosclerosis. The wide-reaching effects of the PON gene family make them an important and highly advantageous subject of study. Their ability to be modified by diet, lifestyle, and environmental exposures, as well as various polymorphisms and genetic influences, provide for a complex, highly modifiable internal form of individual protection. The overall goal of this project was to determine what factors affect individual variations in paraoxonase activity, as well as the influence of individual PON members on health and exposure outcomes. The initial study in this project provided the first data about intra-individual PON1 variations over a time of about 15 years, showing levels remain relatively stable in an agricultural population. This study also contributed data regarding the polymorphic distributions of influential PON SNPs and the influence of lifestyle factors on PON1 activity. The use of a twin population for the next study allowed for examination of the heritability of PON1 activity and antioxidant capacity, and provided novel data regarding the influence of genetic variations on PON1 activity. To further attempt to eliminate the complexity of influences on these genes and individual polymorphisms, the third study in this project characterized an innovative transgenic Drosophila melanogaster model with the goal of analyzing the influence of individual PON family members on exposure and disease outcomes without the effects of compensation from other PONs. By further elucidating the effects of the PONs at the individual level, human populations will be able to be advised regarding the most at-risk individuals and modifiable changes to improve PON levels, and therefore overall health.

Changes in cognitive status occur with aging and significant attention has been placed on developing interventions to possibly delay cognitive decline and identifying risk factors that exacerbate cognitive deficits. One issue that arises when studying interventions is that they do not always effectively translate from animal models to human subjects. When testing potentially modifiable risk factors related to cognitive impairment, more sensitive metrics could help in identifying targets for intervention at earlier time-points. Therefore, the aims of the current dissertation were twofold. The first study examined the ability to translate between species using a common behavioral paradigm, the Morris water maze (MWM). The second study evaluated human MWM performance and commonly used neuropsychological test performance in relation to a marker of glucose regulation, HbA1c. The first study tested translation between rats and humans using the MWM paradigm. Using secondary data sources from a study of nutrition, inflammation, and aging among rats and the Czech Brain Aging Study among humans, differences in average performance and across trial learning were examined between young (3 months; n=10) and aged (20 months; n=13) rats as well age young-old (age 53-70; n=47) and old-old (age 71-85; n=30) human subjects. The cumulative distance was measured in rats and distance error to the hidden goal was measured in human subjects. Results indicated that age-related deficits in performance are greater in magnitude for rats than human subjects. Further, the across trial learning data is more sensitive to change in performance than average performance metrics. Across learning trials indicated poorer performance for aged rats than young rats. Significant effects of age were also observed for human subjects using with the allocentric and egocentric subtests. The second study examined the influence of a measure of glucose regulation (HbA1c) on commonly used neuropsychological tests and a test of spatial navigation abilities among human subjects. Participants classified as cognitively normal, subjective cognitive decline, amnestic mild cognitive impairment (aMCI), and Alzheimer’s disease (AD) were evaluated on verbal memory, nonverbal memory, working memory, visuospatial skills, and executive function in addition to the virtual and real space versions of a human MWM paradigm. A total of 116 participants were included in the complete data sample and 133 participants were included in the multiple imputation sample. Results indicated that HbA1c influenced executive function but not any other measures of cognition. Higher HbA1c levels were associated with poorer performance. A significant interaction was observed between cognitive status and HbA1c. Those with cognitive impairment and higher HbA1c levels had poorer executive function performance. This effect, however, was not observed with the imputation sample. Results of the first study indicated that the MWM paradigm serves as a good tool to assess translation between rats and human subjects. This would be helpful in examining interventions designed to improve normal age-related changes in cognition. It is important to note, however, that the differences observed among animals tend to be greater than human subjects. Therefore, the margin of improvement may be greater following treatment with studies utilizing animals rather than human subjects. The second study indicated that glucose levels may have an impact on cognitive abilities, particularly those related to executive function. Targeting blood glucose levels may be one effective way to keep executive function abilities more intact with age. Taken together, these studies will better inform future work related to delaying cognitive decline among older adults.

Older adults of the 21st century have not grown up with information and communication technology and may not have used computers in their working lives. However, they have experienced the many technological changes of the 20th century. Some changes have fundamentally altered communication, entertainment, and the kinds of knowledge and skills that are sought and valued. These changes are difficult to ignore because of their pervasiveness. In order to actively participate in their lifeworlds older adults face an imperative to adapt and meet new challenges. The purpose of this research was to investigate and interpret the lived experience of laterlife computer learners in non-formal learning environments. The research focused on the interpretation and understanding of the learning experience from the perspective of participants. Hence there is an ontological thread that is grounded in the lifeworld of older adults in Sydney, Australia. A hermeneutic phenomenological methodology was considered suitable because of its emphasis on understanding the lived experience of humans. A qualitative method was used in this study because it enabled existential insights into the learning experience from the perspective of learners and privileged their voices. Fourteen older adults volunteered to participate and were interviewed. Participants identified themselves as laterlife beginning computer learners. Interviews were audio-taped and analysed using an interpretative case study approach. Other analytic tools used were grounded theory, thematic analysis and narrative inquiry. Existential themes were identified and interpreted within a framework of wellbeing. The research found that participants engaged in learning optimistically and that they believed in their abilities and also in the worth of the learning they were undertaking. The learners believed the outcomes from learning would lead to greater opportunity for participation in their lifeworld. Without computer skills and knowledge they believed they would be ignored and relegated to a peripheral position as observers in their lifeworld. By undertaking learning they believed they were taking control of their current and future lives, acting in defiance of developmental theories that suggested ageing was a stage of life and not a process. However, the sense of agency and purpose was not without its pressures and hurdles and learning was perceived to be difficult, dynamic, frustrating and immensely satisfying. Their purposes and expectations were situated in the changing nature of the world and a desire to continue to live their lives authentically, as participants and not spectators. Laterlife computer learners in this study were seen to be learning and growing their lives into a future of their making.

Older women and men were participants in this qualitative research of three case studies of community theatre. Their stories, gathered through in-depth interviews and participant observation of the theatre projects over a four year period, informed the development of a theoretical model of leisure as process. Through devising and presenting their theatre pieces, 50 older people, ranging in age from 45-8 5 years, with differing cultural and socio-economic backgrounds, reflected on personal experiences, negotiated their own processes for working collaboratively, and presented the stories of theft lives publicly in a way which affirmed their actions and understandings of themselves and theft world. Interviews with more than 30 of these people allowed an analysis of the ways in which older people negotiated the processes of play-building and constructed meaning in their lives at a time when the social structures of paid work and family were becoming less central as people moved into their third age. This research has located the study of individual agency through leisure in the context of the social structures which shape constraints to leisure and in turn limit individual agency. As such, the research has been concerned both with the self and with social relationship and has theorised leisure as a process of negotiation. Since process implies change over time, the research methods used and the leisure context selected for study were also process oriented. The research methodology was emergent and took on qualities of action research as the study progressed. By focusing on community theatre as the social context for leisure, the nexus between community development, community theatre and action research was examined and found to inform a broader understanding of leisure as process. The research has also expanded knowledge of community theatre as a collaborative process which draws on individual and collective reflections to build public presentations of issues of concern to participants. The processes of community theatre have received no attention to date in the leisure literature. The negotiation of self takes place in different social contexts for women and for men, for Aboriginal and non-Aboriginal Australians, for old and young, and for people from different socio-economic backgrounds. This research demonstrated that changes in personal situations as a result of the aging process, changes in family context and changes in work context are associated with changes in the negotiation of self, and these changes are expressed through leisure activity as well as other involvements less clearly classified as leisure. Purposive aspects of leisure assumed greater significance as people grew older and this was expressed in the culture of busyness and a pride in 'never being home'. Older women, in particular, developed friendships and community networks outside the family unit as relationships with husbands and children changed. These social connections were found to facilitate difficult transitions such as divorce or the death of a spouse. Community theatre supported the development of community networks, and presented an opportunity to claim a voice in the public arena and challenge the invisibility of older age. The research added to knowledge about constraints on leisure involvement by older people, and identified personal, social and material constraints. The most significant of these were the personal constraints of fear and of ill-health. However, participants in this research continued to negotiate a path through constraint in order to live their lives to the full. Analysis of their stories indicated that whilst constraint sometimes operated as a hierarchical process of control pushing people into isolation, people who were supported in their efforts to negotiate constraint through the development of community networks gained self-confidence and a heightened sense of agency. The processes of community development used in community theatre were found to facilitate the negotiation of constraint by developing personal skills and strengthening social support. The constructivist orientation of the research acknowledged the dialectical nature of knowledge construction and the possibility of social change through research. Aspects of action research were demonstrated in the processes of community theatre, which also seeks social as well as personal change. The research has a political motivation in that it seeks to strengthen the position of participants. Concern with the power relationship between researcher and researched facilitated a deeper understanding of the role of power in the process of leisure. The research opens up one small window on the processes whereby people may continue to live life to the full through active engagement in life and leisure.

High temperature composite materials used in aerospace applications are exposed to extremely harsh conditions and must be able to withstand moisture and extremes of temperature. For example, the surface of an aircraft flying at Mach 2.4 has been estimated to reach around 177°C as a result of aerodynamic heating. This thesis has examined the effect of isothermal aging on two high temperature composite materials, a novel CSIRO composite and a commercial composite, both based on bismaleimides. Changes in mechanical properties and resin chemistry at two different temperatures were measured in order to assess the validity of accelerated aging tests. ¶ Delamination is a major cause of failure in materials, therefore, the Mode I interlaminar fracture toughness (GIC) of both materials was measured using the double cantilever beam (DCB) test. After aging at 250°C, the CSIRO CBR 320/328 composites exhibited better retention of GIC than the CIBA GEIGY Matrimid® 5292 composites. After 6 weeks of aging at this temperature, the CBR 320/328 material retained 100% of its initial interlaminar fracture toughness, however the Matrimid® 5292 material retained only 64% of its initial GIC. This trend was reversed at the lower aging temperature, when after 30 weeks of aging at 204°C, GIC was measured at 13% of its original value for the CSIRO composites, whereas it was measured at 64% in the case of the Matrimid® composites. When the fracture surfaces of these specimens were examined using scanning electron microscopy (SEM), the commercial material was observed to show an increasing degree of porosity with aging at 204°C. It was concluded that the good property retention at the temperature, despite this observed porosity, was a result of the excellent fibre/matrix adhesion exhibited by this material. ¶ Chemical degradation of the matrix of the composites was monitored by Fourier Transform Infrared (FTIR) and Raman Spectroscopy. Chemical changes at the core of both of these materials were found to occur concurrently with the observed changes in interlaminar fracture toughness. FTIR analysis of both matrix materials revealed the predominant degradation mechanism to be oxidation, specifically the oxidation of the methylene group bridging two aromatic rings common to the structure of both resins, was substantiated by the ingrowth of a broad peak centred at 1600cm-1. In addition to this, the pyromellitic anhydride unit present only in the CBR 320/328 composites was found to be highly resistant to the effects of aging, whereas the saturated imide, common to the cured structures of both materials, was observed to degrade. ¶ Raman spectroscopy showed an increase in the intensity of a peak at 1646 cm-1 in the Matrimid® 5292 composites aged at 250°C towards the centre of the sample as a result of increased reaction of the allylic carbon-carbon double bond. At 204°C, the degree of reaction increased towards the surface of the material, possibly as a result of a reverse Diels-Alder reaction. The glass transition temperatures of both materials were found to decrease with aging, with the exception of the CSR 320/328 composites aged at 204°C, which initially increased due to continued crosslinking of the resin. ¶ It is concluded that the degradation mechanisms at the two aging temperatures are very different. The reliability of results from accelerated (elevated temperature) aging tests has been drawn into doubt.