Oxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and processing bodies (PB) in eliminating abasic RNA in situ. We demonstrated that RNA is a major target of oxidative damage, constituting the majority of OS-induced abasic nucleic acids in HeLa cell. Importantly, the level of abasic RNA is strongly correlated with SG abundance. Furthermore, inhibition of SG/PB formation causes accumulation of abasic RNA, suggesting that SG/PB participates in removing oxidized RNA and protects cells under OS, which offers novel targets for therapeutic intervention in age-related diseases. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

In an effort to determine the metabolic changes that occur in fatty acid oxidation during the rapid growth period, the activity of carnitine palmitoyltransferase was measured in four groups of animals at 4, 8, 12 and 16 weeks of age.Muscle samples were taken from the soleus after animals were anesthesi2ed, and the samples were assayed for CPT activity. The CPT activity was significantly higher at 4 weeks than at 8, 12 and 16 weeks (p0.0001), and the fl week activity was significantly higher that the 16 week animals. It was found that there were two distinct phases of decline in CPT activity. The first occured from 4-8 weeks where a 74% drop in activity was recorded. The second phase was a more gradual decline that occured after 8 weeks. 21% decline in activity occured between 8 and 12 weeks, followed by a 23% decrease after 12 weeks. The first drastic drop in activity can be attributed to the residual heightened enzyme concentration carried over from the suckling period in which the rat was exposed to a high fat diet found in the mother's milk. The second phase of the decline in activity is due to a dietary change which caused a shift in metabolism from fat to glucose as the primary carbon source for fuel. / School of Physical Education

The purpose of this study was to examine the pharmacokinetics of d-xylose in man as a function of age with particular emphasis on its absorption characteristics. This study required the development of a specific and sensitive method for the quantitation of xylose from plasma and urine. Following a clean-up procedure, plasma or urine samples are concentrated and undergo two sequential derivatization steps and then are quantitated by capillary column gas liquid chromatography (GLC). D-Xylose is frequently quantitated by a tedious colorimetric assay involving the use of thiourea, a proven animal carcinogen. We have evaluated a more expedient colorimetric assay employing less toxic reagents. Based upon these comparisons the "phloroglucinol" method has been recommended as a replacement for the currently used clinical method for quantitating d-xylose. The human studies revealed age related changes in some but not all d-xylose disposition parameters. Systemic, renal, and nonrenal clearances all declined with advancing age. The terminal elimination half life increased with age. Age had very little influence on the various volumes of distribution. In general, parameters relating to oral absorption showed no age-related dependence. In contrast to what is generally believed, the bioavailability of d-xylose did not decline with age. Lastly, this dissertation addresses the problem of how infusion data may best be fit. Concentration-time data may be fit by a nonlinear regression algorithm in two ways; (1) concentration-time data may be collected and fit both during infusion and after infusion is terminated, (2) concentration-time data may be collected only after the infusion is terminated and be fit as a bolus. Concentration-time data were computer simulated with random error and we found that fitting the entire curve gave the most accurate estimates of disposition parameters.

Inspection Time (IT) is a speed measure that has been primarily investigated in the field of individual differences. However, Nettelbeck and Wilson (2004) proposed that IT could have promise as a biomarker for functional outcomes, particularly cognitive aging. The premise behind biomarker research is that chronological age is simply a proxy for the physiological and cognitive changes that occur in the body with advancing age. Biomarkers are measures that 'mark' the aging process and represent the biological age of an individual rather than the years since his/her birth. Speed of processing tasks offer promise as biomarkers because decline in speed of processing is one of the most robust findings in cognitive aging research. However, traditionally used tasks are problematic because they confound speed and accuracy and some are sensitive to cohort effects. Inspection time is a speed of processing measure that is free from these problems and is therefore a promising candidate for a biomarker. This dissertation presents the first empirical investigation of this proposition. One hundred and fifty elderly participants were assessed on IT, traditionally used biomarkers (e.g. grip strength, visual acuity), a battery of cognitive tasks (e.g. fluid ability and crystallised ability) and measures of everyday functioning (e.g. activities of daily living). These individuals were assessed on three separate occasions over a period of 18-months. For the biomarkers, initial scores, 6-month change scores and 18-month change scores were generated and used to predict final scores and 18-month change scores on the functional outcomes (cognition and everyday functioning). Results revealed that slow IT at the start of the study was associated with dependence in activities of daily living and poorer fluid ability at the end of the study. There was also evidence that slow IT at the start was associated with decline in fluid reasoning over the subsequent 18-months. Moreover, consistent with the major aims of this study, decline in IT over time was associated with more cognitive problems in daily life and poor fluid ability at the end of the study. Given that initial and change scores for IT were independent, due to the methodology used to estimate them, the two measures explained unique variance in the functional outcome measures.These findings are extremely encouraging, particularly given the relatively short time frame for this study. IT has predictive validity for everyday functioning and cognitive aging over an 18-month period, and therefore, it is concluded that IT has promise as a valid biomarker for functional age. Recommendations for further research include investigating the link between IT and mortality, examining the association between IT and a broader range of functional age measures, the replication of these findings in a different sample, and means for improving the sensitivity and specificity of the current IT estimation procedure. / Thesis (Ph.D.) -- University of Adelaide, School of Psychology, 2006.

The normal development of adipose tissue lipolysis as measured by glycerol release was studied in epididymal fat pads of Sprague-Dawley rats between 4 and 16 weeks of age and correlated with changes in fat cell size.For each age group studied, 4 weeks, 8 weeks, and 16 weeks of age, basal (no hormone present) and hormone stimulated lipolytic activity were observed for two concentrations of epinephrine were used, maximal (10,00 nM) and minimal (10 nM). Basal levels of glycerol were not linear. There was an increase between 4 and 8 weeks of age followed by a decrease between 8 and 16 weeks of age. The maximal dosage of hormone evoked a large increase in 9lYcerol production between 4 and 8 weeks, which was followed by a decrease between 8 and 16 weeks of age. The minimal dosage of epinephrine, although not significant, showed a decrease in glycerol production from 4 to 16 weeks of age. Fat cell size continued to increase between 4 and 16 weeks. Both fat cell diameter and volumes underwent a linear increase with age. However, the change was not reflected in epinephrine stimulated glycerol release. Therefore, glycerol release is inversely correlated with fat cell size during early development.The results indicate that age influences hormone stimulated lipolysis and is not dependent on cell size. Although the mechanism for the decreased lipolytic response of the isolated adipocytes was not discovered, it is believed that it may be due in part to a reduced number of receptors and to a reduced sensitivity of the cellular enzymatic system underlying lipolysis. / School of Physical Education

Inspection Time (IT) is a speed measure that has been primarily investigated in the field of individual differences. However, Nettelbeck and Wilson (2004) proposed that IT could have promise as a biomarker for functional outcomes, particularly cognitive aging. The premise behind biomarker research is that chronological age is simply a proxy for the physiological and cognitive changes that occur in the body with advancing age. Biomarkers are measures that 'mark' the aging process and represent the biological age of an individual rather than the years since his/her birth. Speed of processing tasks offer promise as biomarkers because decline in speed of processing is one of the most robust findings in cognitive aging research. However, traditionally used tasks are problematic because they confound speed and accuracy and some are sensitive to cohort effects. Inspection time is a speed of processing measure that is free from these problems and is therefore a promising candidate for a biomarker. This dissertation presents the first empirical investigation of this proposition. One hundred and fifty elderly participants were assessed on IT, traditionally used biomarkers (e.g. grip strength, visual acuity), a battery of cognitive tasks (e.g. fluid ability and crystallised ability) and measures of everyday functioning (e.g. activities of daily living). These individuals were assessed on three separate occasions over a period of 18-months. For the biomarkers, initial scores, 6-month change scores and 18-month change scores were generated and used to predict final scores and 18-month change scores on the functional outcomes (cognition and everyday functioning). Results revealed that slow IT at the start of the study was associated with dependence in activities of daily living and poorer fluid ability at the end of the study. There was also evidence that slow IT at the start was associated with decline in fluid reasoning over the subsequent 18-months. Moreover, consistent with the major aims of this study, decline in IT over time was associated with more cognitive problems in daily life and poor fluid ability at the end of the study. Given that initial and change scores for IT were independent, due to the methodology used to estimate them, the two measures explained unique variance in the functional outcome measures.These findings are extremely encouraging, particularly given the relatively short time frame for this study. IT has predictive validity for everyday functioning and cognitive aging over an 18-month period, and therefore, it is concluded that IT has promise as a valid biomarker for functional age. Recommendations for further research include investigating the link between IT and mortality, examining the association between IT and a broader range of functional age measures, the replication of these findings in a different sample, and means for improving the sensitivity and specificity of the current IT estimation procedure. / Thesis (Ph.D.) -- University of Adelaide, School of Psychology, 2006.

Of the three major cell types in bone, osteocytes are considered the major mechanosensors, capable of detecting whole-bone mechanical forces at a cellular level and coordinating tissue-level bone formation and resorption responses. The pathology of age-induced bone loss, a major factor in the development of osteoporosis, is attributed to impaired osteocyte mechanosensing. However, real-time evidence of immediate osteocyte responses to mechanical load to support the blunted tissue-level responses that have been demonstrated thus far is lacking. A ubiquitous cellular response upstream of many functions in all cell types, intracellular calcium (Ca2+) is an early mechanosensitive signal in osteocytes, wherein the response characteristics studied in systems of multiple scales are related to mechanical stimuli. Thus, this phenomenon can be characterized as a real-time measure of osteocyte mechanosensitivity. The objective of this thesis was to utilize an ex vivo model of osteocyte Ca2+ signaling to investigate potentially altered mechanosensitivity of the osteocyte network in two clinical contexts: aging, and a recently-approved therapy for treatment of osteoporosis. Additionally, we aimed to enhance this ex vivo model to identify a functional consequence of this robust Ca2+ signaling response to mechanical load in the context of osteocyte mechanotransduction. We first sought to characterize and compare Ca2+ signaling responses to mechanical load in osteocytes from aged and young-adult mice using an ex vivo model to visualize cell networks in viable mouse tibiae. We found that fewer osteocytes responded to whole-bone cyclic mechanical loading in aged mice tibiae compared to those from young-adult mice and did so in a delayed manner, suggesting a diminished mechanosensitivity to load. Osteocytes from aged mice also lacked the well-correlated relationship between Ca2+ signaling synchrony and cell-cell distance exhibited by young-adult osteocyte networks. Taken together, we have demonstrated, for the first time, a real-time measure of the dampened mechanosensing and lack of signal coordination in aged osteocyte networks in situ, which may contribute to blunted long-term bone formation responses to load. Next, we utilized the ex vivo Ca2+ signaling model to investigate the effect of bone formation in response to treatment with sclerostin antibody (Scl-Ab) on osteocyte mechanosensing. Previous studies have identified two phases of bone formation response to Scl-Ab treatment: an initial period of rapid bone formation with short-term dosing and a return to a steady phase of bone formation response with long-term dosing. Thus, we treated mice according to three groups: vehicle, short-term Scl-Ab, and long-term Scl-Ab. Serum P1NP assays and biweekly micro-CT scans throughout the treatment period confirmed the two phases of bone formation response to Scl-Ab. At the conclusion of treatment, under ex vivo whole-bone loading matched at 10 N, there were no significant differences in osteocyte Ca2+ signaling parameters between treatment groups. However, under strain-matched loading, fewer osteocytes from the short-term group exhibited Ca2+ responses and the initiation of Ca2+ signaling was delayed. We interpreted this as reduced mechanosensing in osteocytes that have been newly-embedded in bone that has been rapidly formed in response to Scl-Ab, as confirmed by alizarin red intensity analysis in the osteocyte field of view ex vivo. This study provides real-time evidence of the cellular responses under the distinct phases of bone formation response to Scl-Ab and demonstrates that osteocyte mechanosensing is maintained with long-term treatment, suggesting that other mechanisms may be responsible for self-regulation of bone formation. Given the robust Ca2+ responses to load characterized in osteocytes by our group and others, we concluded this work by investigating a consequence of this mechanism that may contribute to osteocyte mechanotransduction. A common Ca2+-dependent mechanism that has been demonstrated in osteocytes in vitro with possible implications for cell-cell communication is contraction of the actin cytoskeleton. Therefore, we sought to confirm this mechanism in osteocytes maintained in their native 3D network and morphology using the ex vivo murine tibia model. We successfully enhanced the model to simultaneously image intracellular Ca2+ and the F-actin network of individual osteocytes in situ at high magnification using transgenic Lifeact mice paired with either Ca2+ dye or bred with Ca2+ indicator mice. In both models, using biochemical stimuli, we quantified actin network dynamics over time and identified Ca2+-dependent contractile events. Under mechanical loading, phasic actin network contractions corresponded to individual Ca2+ peaks in single osteocytes. The mechanosensitive nature of these contractions was demonstrated by comparing cellular dynamics in single cells under two paired mechanical loading levels; interestingly, mechanosensitivity was dependent on the order of application of these load magnitudes. In identifying this novel mechanosensitive Ca2+-dependent mechanism, we enhance the understanding of the mechanotransduction pathway in osteocytes and have provided a potential point of intervention in cases where osteocyte mechanotransduction is inhibited, such as in osteoporosis. Taken together, this body of work contributes to knowledge of how osteocytes are sensing mechanical forces in different contexts and transducing signals to effector cells. We provide novel, real-time, immediate measures of osteocyte mechanosensing in situ that may correspond to whole-bone responses, such as age-induced bone loss or the differential responses to Scl-Ab treatment. Future work will focus on ways to recover diminished osteocyte mechanosensing and further connect the cell responses we observe herein to long-term bone formation responses in clinical applications.

The hypothesis that the right cerebral hemisphere declines more quickly than the left cerebral hemisphere in the normal aging process was tested in two studies using a facial recognition and a response time task. In Study 1, subjects (N=60) were asked to identify facial affect fram 50 standardized photographs of 5 affective categories: Happy, Neutral, Sad, Angry, and Fearful, and were asked to rate the intensity of each photograph. The results of the analysis indicate that the elderly group was significantly less accurate at identifying negative and neutral affective expressions than the younger group, with no significant differences seen between groups in the identification of positive affect. The results also indicate that the elderly rated the affective expressions as being significantly more intense than the younger group. Study 2 (N=60) investigated response times for the recognition of the affective stimuli as 4 function of visual field of presentation and valence of the stimuli, using the same subject population. The results of this analysis reveal that the elderly show an increase in cerebral lateralization in comparison to the younger group. The elderly exhibited increased response times to negative affect presented to the left hemisphere. The results of this study also indicate that both groups had faster response times to positive affect, and that both groups had a response bias in favor of positive affect when neutral facial affective slides were presented to the left hemisphere. The results are interpreted as partially supporting the right hemi-aging theory. The elderly showed a diminished ability to identify negative affect across both studies, suggestive of lowered right hemisphere functioning. However, the increased rather than decreased cerebral asymmetry in the response time task, and slower response times to negative affect presented to the left hemisphere are suggestive of bilateral changes in affective processing for the elderly. Overall, these findings suggest that the elderly have more difficulty processing negative affect, while their ability to process positive affect remains intact. This finding has implications for research using facial affective paradigms designed for use with younger subjects, and suggests the need for more studies of emotional aging processes in normal populations. / Ph. D.

The purpose of this study was to determine if a relationship existed in healthy older adults between two psychological and physiological variables. The conceptual framework suggested that a relationship of psychological and physiological functions would facilitate positive adjustment to the stressors of aging. Life satisfaction represented psychological functioning; body temperature represented physiological functioning; body temperature represented physiological functioning. Because some evidence exists that normal temperature for older adults is lower than 98.6°F, an additional purpose was to determine if the sample had a normal body temperature lower than 98.6°F. Subjects were 174 healthy Caucasians aged 60-97. None were taking antibiotic, phenotiazine, cortisone, or reserpine containing drugs. Life satisfaction was measured using Neugarten's Life Satisfaction Index A (LSIA); body temperature was measured with an IVAC 821 oral electronic thermometer. Subjects rated perceived health on the Health Status Scale (HSS), and enumerated the past year's stressful life events on a modification of Holmes and Rahe's Social Readjustment Rating Questionnaire (SRRQ). Data were collected in winter and summer to determine if body temperature was different based on season. Statistical significance was p = .05. An ANOVA revealed no significant differences between winter and summer groups. The Pearson product-moment revealed no correlation between LSIA and TEMP. LSIA was significantly correlated with HSS and AGE; that is, subjects who were more satisfied with their lives considered themselves healthier, and were younger than other subjects. TEMP was significantly related only to SEX, indicating that females had higher temperatures than males. The mean temperature for all subjects, 98.24°F, was statistically different from 98.6°F, as were winter (98.32°F) and summer (98.17°F) group means. No difference was found between winter and summer mean temperatures, indicating that season of the year did not affect body temperatures in this sample. It was concluded that no psychophysiological relationship was found because body temperature may index only illness, not health. The mean temperature was not clinically different from 98.6°F most likely because these subjects were not taking drugs known to affect body temperature. A recommendation was that nurses evaluate each older client's temperature against his own normal, versus a universal normal.

While a great deal of research has been directed towards investigating the age-related decline in V02max, the effect of physical activity on the age-related decline in V02max has not been clearly established. Therefore, the purpose of this study was to examine the relationship between physical activity and the age-related decline in maximal oxygen consumption (VO2max) in apparently healthy individuals. In order to assess the effects of physical activity on the age-related decline in V02max, physiological data was obtained from 142 former participants (116 men and 26 women) (40 ± 8.0 years), in the Ball State University Adult Physical Fitness Program across an average of 12 ± 4.5 years. The subjects were divided into three physical activity group categories depending on their self-reported physical activity status at the time of the first and follow-up test. Those subjects who were sedentary at the first and last test were designated as SED-SED. Those who reported sedentary at the first test and active at the last test were designated as SEDACT and those who were physically active at the time of both tests were designated as ACT-ACT. The data from the analysis revealed that the rate of decline in V02mx expressed as change per year among adult men varied as a function of their reportedphysical activity habits. Those men designated as SED-SED and ACT-ACT experienced a statistically significant decline (p<0.05) in V02max during the follow-up period, while, those men designated as SED-ACT maintained their V°2max. The rates of the change in V02max (ml-kg- 1•min-1) for the men were -0.45, 0.03 and -0.22 ml•kg-l-min-1•yr1 for the SED-SED, SED-ACT and ACT-ACT groups respectively. The percent decline in V02max were 6%, 11% and 2% respectively. A statistical comparison of the rate of change among physical activity groups indicated a difference between the SED-SED and SED-ACT groups (p<0.05). Within the limitations of this study, these data suggested that there was no statistically significant difference in the rate of change in V02max (ml•kg-1•min-1-yr1) between the SED-SED and ACT-ACT physical activity groups. However, when presented as percent change per decade, the decline for those men who were sedentary at both time points was twice that of those men who reported an active lifestyle at both time points. Although the rates of change were not different for the SED-SED and ACT-ACT physical activity groups, those men with a physically active lifestyle maintained their aerobic power advantage as compared to sedentary men who remained sedentary. Furthermore, sedentary men who took up an active lifestyle had offset the decline in V02max (ml•kg-1•min-1) attributed to physical inactivity.The rates for the change in V02max (ml•kg-1•min-1-yr1) for the women were -0.36, 0.20 and -0.21 (ml•kg-1•min-1-yr1) for the SED-SED, SED-ACT and ACT-ACT groups respectively. While these changes were similar in direction and magnitude to those observed for the men, there were no statistically significant differences among the female groups (p>0.05). Therefore the results from the present study were inconclusive for women possibly due to the low sample size (n=26). / School of Physical Education