This research effort investigated the influence of confinement on the physical aging behavior of thin and ultrathin glassy polymer membranes. Membrane permeability changes with time due to physical aging, and for reasons not completely understood, the rate of permeability change can become orders of magnitude faster in films thinner than one micron. Special experimental techniques were developed to enable the study of free standing, ultrathin glassy polymer films using gas permeability measurements. The gas transport properties and physical aging behavior of free-standing glassy polysulfone (PSF) and Matrimid® films from 18-550 nm thick are presented. Physical aging persists in glassy films approaching the length scale of individual polymer coils. The membranes exhibited significant reductions in gas permeability and increases in selectivity with aging time. Additionally, the influence of physical aging on the free volume profile in thin PSF films was investigated using variable energy positron annihilation lifetimespectroscopy (PALS). The films exhibited decreasing o-Ps lifetime during physical aging, while o-Ps intensity remained constant. The o-Ps lifetime was reduced at lower implantation energies, indicating smaller free volume elements near the film surface. Thin films aged dramatically faster than bulk PSF and the PALS results agree favorably to behavior tracked by gas permeability measurements. The physical aging behavior of ultrathin films with different previous histories was also studied. The state of these materials was modulated by various conditioning treatments. Regardless of the previous history, the nature of the aging response was consistent with the aging behavior of an untreated film that was freshly quenched from above Tg, i.e., permeability decreased and pure gas selectivity increased with aging time. However, the extent of aging-induced changes in transport properties of these materials depended strongly on previous history. The properties of these ultrathin films deviate dramatically from bulk behavior, and the nature of these deviations is consistent with enhanced mobility and reduced Tg in ultrathin films, which allows them to reach a lower free volume state more quickly than bulk material. The Struik physical aging model was extended to account for the influence of film thickness on aging, and was shown to accurately describe the experimental data. / text

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Upon acquisition, memories undergo an initial stabilization, or consolidation, process after which they are generally resistant to interference. There is now an abundance of evidence that reactivation or retrieval of a consolidated memory opens up a window of time during which the memory can be strengthened, disrupted, or updated via a process of "reconsolidation". This dissertation is comprised of three experimental studies in rats aimed at investigating previously unexamined aspects of this dynamic memory process. The first study assessed whether spatial memories learned under positively-motivated conditions could be updated with new information following reactivation. Rats that learned a second spatial task in the same environmental context as a previously learned task intruded items from the second episode during recall of the first. This result suggests that the context reactivated the memory for the first task, triggering reconsolidation and updating of the memory. The second study used the memory updating effect obtained in the first study as a behavioral measure to investigate the effects of aging on reconsolidation. Unlike in the young rats, the context reminder did not lead to intrusions of the second learning episode during recall of the first. Older adult human participants in this study also showed a different pattern of results than what had been seen previously in young participants. Therefore, in humans as well as in rats, it appears that aging may lead to changes in spatial memory reconsolidation. The third study piloted an experiment to examine hippocampal network activity associated with the spatial memory reconsolidation task used in the first two studies. Preliminarily, we found that the context reminder manipulation was associated with more place field stability across some spatial tasks and that stability across certain tasks was positively related to our measure of memory updating. Additionally, we found evidence that the context reminder enhanced neural replay of some learning episodes. While preliminary, these results suggest that both place field stability and replay may play roles in this reconsolidation paradigm.

Infectious diseases remain amongst leading causes of death in people aged 65 years and older; therefore, much research is focused on determining the immune components that contribute to age-dependent increased susceptibility to, and increased mortality from, infections. CD8⁺ T cells are critical for clearing intracellular pathogens through production of cytokines and direct killing of infected cells. Age-dependent CD8⁺ T cell alterations have been described, including decreased numbers of naïve CD8⁺ T cell precursors and decreased numbers and function during infection. This dissertation explores the mechanisms contributing to these changes. First, we demonstrated that multiple mechanisms contribute to changes in the CD8⁺ T cell pool with age. CD8⁺ T cells from unimmunized T cell receptor transgenic (TCRTg) old mice undergo massive virtual memory (VM) conversion with age; both homeostatic proliferation and cross-reactivity may contribute to the generation and accumulation of VM cells with age. These VM cells exhibit an age-dependent replicative impairment to cognate antigen, which points to possible detrimental functional consequences due to changes in the overall T cell pool. Second, we evaluated the cell intrinsic contribution to the decreased old CD8⁺ T cell response. With in vitro stimulation, old CD8⁺ T cells exhibit decreased ability to enter into late cell divisions and decreased production of effector molecules. In addition, we found that old CD8⁺ T cells have decreased expression of the master transcription factor T-bet, which correlates to decreased effector function and terminal differentiation in vivo. Collectively, these results identify possible cell-intrinsic targets for improving CD8⁺ T cell immunity. Finally, we measured whether a Listera monocytogenes live vaccine model induces protective immune responses in old mice. We found that vaccination conferred little protection in old mice upon pathogen challenge. These results contrast with other vaccine models, which may allow for pinpointing both the vaccine and immune components required for generating strong protective immunity in the elderly. Collectively, this dissertation demonstrates that CD8⁺ T cell precursors, effector cells, and memory cells exhibit profound changes with, age and identifies both possible mechanisms contributing to these alterations as well as possible therapeutic/vaccine targets for improving immunity in the elderly.

The segment of the population that is 65 years and older is undergoing rapid growth. With this growth, there is an increased need for speech-language pathologists (SLPs) to treat cognitive-communicative disorders, most of which are age-related disorders secondary to neurologic disease. To do this effectively, SLPs require an understanding of how healthy aging affects cognition, memory and sensory processing. Although the interactions between sensory and cognitive processing are increasingly being investigated, little attention has been paid to the relationship between modality of information presentation and language comprehension in aging. Language comprehension is affected by component processes such as memory span and processing abilities, but to date there has been no systematic investigation of the effect of presentation modality on the processing of linguistic information across a number of tasks ranging in complexity.The primary purpose of this study was to investigate the effects of presentation modality on language processing. The secondary purposes of the study were to determine whether age affected performance on language processing measures, and whether adults can accurately predict if their performance was better in either the auditory or visual presentation condition. The effects of presentation modality were evaluated on four dependent measures: a digit span task, a word span task, a complex span task and a procedural instruction processing task. The participants were 37 older adults and 41 younger adults, matched for years of education and estimated verbal IQ.Three notable findings emerged from the study. First, both young and older adults recalled more information when it was presented in the auditory modality, regardless of the task. Second, age effects were present on all measures. Third, individuals were generally inaccurate in predicting which modality would result in better processing. Implications for the evaluation and treatment of older adults are discussed.

Perirhinal cortical-dependent behavior and single-unit neuron activity in this brain region were compared between normal aged and young rats. Three different variants of the spontaneous object recognition task were used in these experiments, and the results confirmed previous reports that aged animals are impaired at stimulus recognition. The novel contribution of the present experiments was the identification that the behavioral deficit in the aged rats was due to the old animals treating novel objects as familiar, rather than to forgetting the previously experienced stimuli. This pattern of results in the old animals mirror data obtained from rats with perirhinal cortical lesions and promotes a hypothesis that this area of the brain serves a perceptual-mnemonic function. Additionally, multiple single-unit recordings were obtained from perirhinal cortical cells while young and aged rats traversed a track that contained several objects. Perirhinal neurons exhibited selective increases in their firing rates at object locations. We have called these areas of higher perirhinal cortical cell activity `object fields'. While both young and old rats expressed object fields, a lower proportion of perirhinal neurons showed this type of activity in the aged compared to the young rats. Although familiar and novel objects were placed on the track as part of a systematic design, there was no effect of novelty on the overall firing rates of perirhinal cortical neurons or the proportion of cells expressing object fields under these experimental conditions. These data suggest that the physiological correlate of stimulus recognition is not decrements in perirhinal cortical activity when a stimulus goes from novel to familiar. A final important observation made during these studies in young rats was that place fields in the middle hippocampal CA1 subregion are affected by placing objects in the track. Because this same manipulation increases perirhinal cortical activity, it could indicate that age-related changes in the perirhinal cortex might alter the function of other closely associated structures.

This qualitative descriptive study described how seven older homeless women with depression characterized their homelessness, depression, and aging. The women, with a mean age of 54 years, were concerned with day-to-day survival, and contemplating aging while remaining homeless was frightening. The women described feeling depressed and most had received treatment for depression; however they did not describe their depression as hindering their ability to find housing. The themes were aging, homelessness, depression, and chronic health conditions. Homelessness contained the subthemes of addictions, loss of relationships, and lack of income. Depression contained the subthemes of history, experience, and treatment of depression. Although chronic health conditions and chronic pain were concerns for all participants, only one woman had access to ongoing health care. The majority of the women had no income. Nearly all the women had attended school beyond high school but this did not translate into better paying employment because most of them had worked at jobs with no benefits. Implications for policy development included expanding the safety net to provide housing options for homeless women in the 50-60 year range. Recommendations for practitioners included the suggestion that older homeless women be viewed as geriatric clients with care provided at that level. Future research should explore the connection between addictions and homelessness for older homeless women, the impact of chronic pain or chronic illness on their daily functioning, and the potential benefits of treating older homeless women according to standards of care developed for the geriatric general population.

Lifespan theories of emotion suggest that the ability to regulate emotion improves with age. The supporting evidence, however, is indirect: older adults pay less attention to negative events, remember less negative information, and report fewer experiences of negative emotion. Few studies directly measure emotion regulation by explicitly instructing older adults to modulate their feelings while exposed to emotion-evoking stimuli. The purpose of this thesis was to directly compare younger and older adults in their ability to modulate feelings to investigate whether aging results in decline, stability, or improvement in emotion regulation and also to examine potential mechanisms underlying regulation skills. The study employed a startle modulation paradigm to measure both emotional reactivity and regulation. Two experimental tasks (Stroop colour-word interference, reversal learning) were also administered to explore the relationship between emotion regulation and two theoretically-relevant processes: (a) cognitive control and (b) modification of learned emotional associations. There were three main findings: (1) emotional reactivity was preserved in older adults. Both age groups showed emotion-modulated startle (negative > neutral) during the pre-regulation viewing period; (2) age-related decline in emotion regulation was evident on an objective measure of emotion regulation (startle eyeblink reflex) but not on a subjective measure (self-ratings). Specifically, for older adults, startle eyeblink was not enhanced or attenuated following increase and decrease instructions, respectively. In contrast, both groups showed similar modulation of valence and arousal ratings by regulation instruction (increase > look > decrease); (3) for older adults, reversal learning performance correlated positively with the degree of reappraisal-related startle attenuation in the decrease condition, suggesting a possible mechanism for impaired down-regulation. These findings suggest that even when emotional reactivity is similar, older adults are less effective at modulating their physiological responses.

Spoken language conveys two forms of information: transactional (content, what is said) and interactional (how it is said). The transactional message shared during spoken communication has been studied extensively in different listening conditions and in people of all ages using standardized tests of speech intelligibility. However, research into interactional aspects of speech has been more limited. One specific aspect of interactional communication that warrants further investigation is the communication of emotion in speech, also called affective prosody. A series of experiments examined how younger and older adults produce affective prosody, recognize emotion in speech, and understand emotional speech in noise. The emotional valence and arousal properties of target words from an existing speech intelligibility test were rated by younger and older adults. New stimuli based on those words were recorded by a younger female and an older female using affective prosody to portray seven emotions (anger, disgust, fear, happiness, pleasant surprise, sadness, neutral). Similar to previous studies, the acoustical parameter that best differentiated the emotions was fundamental frequency (F0). Specifically, discriminant analysis indicated that emotional category membership was best predicted by the mean and range of F0. Overall, recognition of emotion and intelligibility were high. While older listeners made more recognition errors and had poorer intelligibility overall, their patterns of responding did not differ significantly from those of the younger listeners on either measure. Of note, angry and sad emotions were recognized with the highest degree of accuracy, but intelligibility was highest for items spoken to portray fear or pleasant surprise. These results may suggest that there is a complementarity between the acoustic cues used to recognize emotions (how words are said) and those used to understand words (what is said). Alternatively, the effect of emotion on intelligibility may be modulated primarily by attentional rather than acoustical factors, with higher performance associated with alerting emotions.