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The rapid increase in human longevity has raised important questions about what implications this development may have for the variability of age at death. Earlier studies have reported evidence of a historical trend towards mortality compression. However, the period life table model, commonly used to address mortality compression, produces a compressed picture of mortality as a built-in feature of the model. To overcome this limitation, we base our study on an examination of the durations of exposure, in years of age, of birth cohorts and period life tables to selected short ranges of the death rate observed at old age. Overall, old-age mortality has been decompressing, cohort-wise, since the 1960s. This process may further indicate good prospects for ever-decreasing mortality. In the future, deaths may not be concentrated within a narrow age interval, but will instead become more dispersed, though at ever later ages on average.

Plasma cells, the effector stage of the B cell compartment, secrete large amounts of antibody. These cells arise in two waves during T-­‐dependent immune responses; an early wave (extrafollicular plasma cells) generate low-­‐affinity antibodies that provide a first line of defence against invading pathogens. Later, plasma cells emerge from the germinal centre reaction and secrete high-­‐affinity antibodies. These plasma cells have the capacity to migrate to the bone marrow, where they become established as long-­‐lived, non-­‐dividing plasma cells. Here, I show that plasma cells found in the bone marrow of young (5-­‐week-­‐old) mice had a turnover comparable to that seen in the spleen. Long-­‐lived plasma cells accumulated over the ensuing weeks until they came to dominate the bone marrow plasma cell compartment by 30-­‐weeks of age. This accumulation required MHC II, CD40 and a normal B cell receptor repertoire, implying that these cells are generated during T-­‐dependent immune responses. Secondly, I determine the signalling pathways required to generate splenic extrafollicular plasma cell responses in the T-­‐dependent response to sheep red blood cells (SRBC) and in bacterial infection with Salmonella. While T cell help, antigen recognition through the B cell receptor (BCR) and TLR signalling were required for maximal plasma cell responses to SRBC, in Salmonella infection TLR signalling was required for day 4 IgM plasma cell responses, whereas class-­‐ switched responses at day 8 required T cell help. The extrafollicular responses generated in Salmonella persisted for around 35 days, far greater than the 2-­‐3 days seen following SRBC immunisation. This was likely due to both antigen persistence causing the generation of new plasma cells, and the induction of cellular populations that produced the plasma cell survival factor APRIL. Thirdly, I document the failure of chronic immune responses to generate long-­‐ lived bone marrow plasma cells. This was accomplished by measuring the generation and survival of bone marrow plasma cells in models of rheumatoid arthritis (K/BxN mice), long-­‐term infection with Salmonella, and a direct comparison between acute and chronic delivery of the T-­‐dependent protein antigen NP-­‐KLH. In all cases, chronic immune responses generated few bone marrow plasma cells, ostensibly due to a failure to migrate to the organ. Finally, I show the depletion of bone marrow plasma cell populations caused by inflammatory episodes. This was observed in Salmonella infection, Schistosoma mansoni infection and immunisation with protein antigen plus adjuvants. This depletion mediated a reduction of antigen-­‐specific bone marrow plasma cell populations and serum antibody previously established by the secondary response to NP-­‐KLH.

The interest in effective human resource management has increased dramatically as mean age of the workforce has been growing in the developed western countries. A part of this workforce is constituted for by knowledge intensive workers, in which the motivation dif-fers from other groups of workers. Moreover, existing literature on lifespan development research on motivation fails to differentiate sufficiently between types of worker groups; in a like manner literature on motivation of knowledge intensive workers has neglected to in-clude age differences. This results in a shortage of research of how motivation of knowledge intensive workers differs in regards to their age. The purpose of this thesis is to describe how the intrinsic motivational factors autonomy, variety in tasks, learning new things, receiving positive feedback, and the feeling of accom-plishment and value creation influence knowledge intensive workers differently in regards to their age. The thesis’ research method was qualitative and the primary empirical data was collected through a case study in which interviews with IT consultants of two different age groups were conducted. The findings revealed that differences between the age groups are present. The most ap-parent differences lie in preference for autonomy, learning new things and receiving posi-tive feedback. Variety in tasks and the feeling of accomplishment and creating value also displayed age related discrepancies between the groups.

Recent neuropsychological research has stressed the sensitivity of the Prefrontal Cortex, mostly the Dorsolateral region, in relation to aging (Darowski et al., 2008). Prefrontal Cortex functions, such as Inhibitory Control (IC), are thought to wane steadily after the ages of 60-65 (Craik & Bialystok, 2006). Little is known about what changes occur between the stages of prefrontal optimal performance (i.e., ages 20-25), and the later periods of functional decline. The present study aimed to investigate performance differences between younger (ages 30-40; n=9), middle-aged (ages 50-60; n=10), and older adults (ages 70 and up; n=13), on five tasks of Executive Functions (EFs); specifically, assessing the abilities of problem representation, shifting, updating working memory, inhibition, and integrating valence and rewards into pursuing a goal. It was hypothesized that (a) quantitative age trends differentiating the three groups on the tasks would be found, (b) IC would be particularly targeted by the hypothesized age trends, and (c) the devolution of IC across the adult lifespan would be linear. MANOVA tests with all tasks of EFs representing the Dependent Variables and age serving as the Independent Variable revealed no significant main effect. Follow-up separate ANOVA tests however, suggested a statistically significant difference between the means of Groups 2 and 3 for the Updating Working Memory task, F(2,29)=5.374, p=.010, Scheffe (p=.012) and Bonferroni (p=.010). The contributions of interactions among EFs to the present results, recruitment challenges, and potential age effects are discussed. / Graduate / 0622 / emiliecq@uvic.ca

abstract: The present study aimed to advance the current understanding of the relation between disability and subjective well-being by examining the extent to which different facets of subjective well-being (life satisfaction, positive affect, and negative affect) change before and after disability onset, and the extent to which age and type of disability moderate such changes. Multiphase growth-curve models to prospective longitudinal survey data from Waves 1-16 of the Household, Income and Labour Dynamics in Australia (HILDA) survey (N = 3,795; mean age = 50.22; age range: 16-99; 51% women). On average, life satisfaction remained relatively stable across the disability transition, whereas positive affect declined and negative affect increased the year surrounding disability onset; in the years thereafter, neither positive affect nor negative affect returned to pre-onset levels. Individuals who acquired disability in old age were more likely to report sustained declines in subjective well-being than were individuals who became disabled in midlife or young adulthood. Psychological disability was associated with the strongest declines across each indicator of subjective well-being at disability onset but also greater adaptation in the years thereafter. The findings provide further evidence against the set-point theory of hedonic adaptation and for a more moderate viewpoint that allows for processes of adaptation to vary based on the outcome examined, the type of stressor, and individual characteristics. The discussion focuses on possible mechanisms underlying the moderating roles of age and type of disability. / Dissertation/Thesis / Masters Thesis Psychology 2019

We are the first lab to report the occurrence of a diet-induced transsulfuration (TS) blockade associating with elevated S-adenosylmethionine (i.e. SAM) synthesis, enhanced lifespan and enhanced reproductive capacity, in a vertebrate animal model. In this paradoxical study, we used LC-MS/MS-derived metabolomics data to report the effects of flaxseed (Linum Usitatissimum) on one-carbon metabolism in White Leghorn laying hens (Gallus gallus). Flaxseed contains a vitamin B6-antagonizing molecule called ‘linatine’ that is particularly effective at reducing vitamin B6 levels in small rodents and poultry. Linatine reduces TS flux through its inhibition of the vitamin B6-dependent enzymes cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE). In this study, our flaxseed-fed hens displayed decreased 4-pyridoxic acid and decreased pyridoxamine, concomitant with 15-fold elevated cystathionine. Homocysteine levels were stable in flaxseed-fed hens despite such highly elevated cystathionine. This is an astonishing finding, because mammalian models would predict the induction of hyperhomocysteinemia (i.e. elevated homocysteine) when cystathionine is so highly elevated (1). We are therefore reporting a phenomenon that might be unique to birds. Our metabolomics data indicate increased consumption of one-carbon donor molecules (e.g. choline, betaine, dimethylglycine, serine, etc) in flaxseed-fed hens, probably as a means of fueling the betaine homocysteine methyltransferase (BHMT) and methionine synthase-B12 (MS-B12) reactions. This modeling approach provides a rationale that flaxseed-fed hens increase their rate of homocysteine remethylation via BHMT and MS-B12, and in turn this would maintain stable homocysteine levels in the animal. We observed that the culminating outcome is elevated synthesis of SAM and an elevated SAM:SAH ratio. The associated biological outcomes are extended lifespan and increased reproductive capacity (i.e. increased daily egg laying) in flaxseed-fed hens. Our data further indicate that flaxseed tremendously stimulates a glucagon-like phenotype in hens. Specifically, flaxseed-fed hens exhibit 3-fold elevated glycated hemoglobin (HbA1c), 2-fold elevated serum free fatty acids (FFAs), 10 to 14% reduced body weight, and slightly reduced plasma pyruvate. These phenotypic markers suggest that glucagon might also play a large role in extending lifespan and enhancing reproductive capacity in flaxseed-fed hens. We predict that the anti-vitamin B6 effects of flaxseed are responsible for stimulating this glucagon-like phenotype in hens. Therefore, we conclude that the vitamin B6-antagonizing effects of linatine (via flaxseed dieting) improve liver function, body leanness, egg laying and survival, in a manner associated with increased SAM synthesis, increased blood FFA levels and increased blood glucose levels, in laying hens. The second part of this dissertation is used to test the hypothesis that polyunsaturated fatty acids (PUFAs) regulate lipid metabolism, increase mitochondrial respiration and decrease E-cadherin expression, in laying hen ovarian tumors. Researchers are unaware of the mitochondrial effects of PUFAs within laying hen ovarian tumors, and only a few publications exist regarding the analysis of E-cadherin in laying hen ovarian cancer. The results of this present work suggest that dietary PUFAs accumulate within laying hen ovarian tumors, and these same tumors exhibit decreased gene transcripts that govern de novo lipogenesis (i.e. FASN). Simultaneously, these tumors exhibit elevated transcripts for oxidative phosphorylation (OXPHOS) and decreased transcripts for phase 2 antioxidant enzymes. These patterns associated with decreased transcript levels of CDH1 (the gene for E-cadherin) in ovarian tumors, but no effect on full length 120kDa protein was observed by PUFAs versus our control diet. Interestingly, the effect of PUFAs on E-cadherin occurred at the level of the cleaved 37kDa and 80kDa E-cadherin fragments, such that PUFAs reduced their levels in hen ovarian tumors. We therefore developed a system for depleting the 80kDa E-cadherin fragment from hen ascites fluid (i.e. fluid from a hen that had ovarian cancer), so that we could test our hypothesis that the 80kDa E-cadherin fragment is important for supporting mitochondrial respiration in normal ovarian surface epithelial cells (IOSE80s). Mitochondrial membrane potential was decreased in IOSE80s when the 80kDa fragment was removed from the ascites; however, there was no effect on basal oxygen consumption in subsequent tests using extracellular flux analysis with Seahorse XFp. During our analysis of microRNA-200a-3p (miR-200a) we did not observe any effect of diet on miR-200a within hen ovarian tumors; however, we did observe that miR-200a levels increased within the tumor when going from stage 2 to stage 4 disease. Overall, we observed reduced risk of ovarian cancer, stage 4 ovarian cancer, multiple peritoneal tumor involvement and cancer-associated mortality, in laying hens that consumed a diet that was supplemented with PUFAs.

Terror management theory (TMT) seeks to understand religious worldview adherence, positing that worldview beliefs can abate existential threats such as mortality salience. Most research on TMT has employed young samples, so influences on older adults' experiences of mortality salience are unclear. Simultaneously, research on death anxiety shows that older people may view their own death more favorably than younger individuals do. Guided by the lifespan development perspective, I investigated whether the range of life experiences and interpretation of them might account for perceptions of death in old age. A multi-phase content analysis of in-depth interview transcripts from 16 adults aged 65+ focused on narratives of life events, religious worldviews, and death. The findings suggested how lifespan adversity, such as the death of a loved one, promoted growth in self and religious belief that enhanced participants' reported relationship with the sacred. In turn, participants' views of and beliefs about death were without fear, indicating the influence of highly individualized and deeply spiritual religious worldview beliefs on the abatement of death fear. These findings support extension of TMT to older people by identifying the impact of lifespan experiences with trauma and adversity as contributing to less superficial, more individualized conceptions of religious worldviews. Such worldviews, contingent upon growth from adaptation to lifespan experiences, may indeed lead to less death anxiety and reduce the effects of mortality salience in old age. / Master of Science

Chapter 1 Abstract: We examined the impact of sampling interval on fine root production and mortality estimates by comparing data from a weekly minirhizotron sampling regimen to subsets of the same data representing biweekly, monthly, bimonthly, and quarterly sampling regimens. We also investigated possible sources of error involved in the root tracing technique and estimated root herbivory using the full weekly sampling regimen. Data were collected for eleven months from a Pinus palustris Miller woodland in southwest Georgia. As sampling interval increased, estimates of production and mortality declined, while estimates of mean fine root lifespan increased. Annual production values ranged from a maximum of 1.26 mm/cm2 for weekly sampling to 0.83 mm/cm2 for quarterly sampling. Total mortality varied from 0.97 mm/cm2 to 0.53 mm/cm2. Bias increased at a decreasing rate when sample interval was increased from weekly to monthly. The root tracing protocol added some small, random error to growth measurements; re-measuring roots returned values 0.16% smaller than initial measures. We also observed a root mortality and regrowth phenomenon that may be measurement error or short-term fluctuation in root length. Herbivory accounted for greater than 20% of fine root biomass produced. Our study suggests that increases in sampling frequency from monthly to weekly can provide substantial gains in accuracy for estimates of root dynamics. Chapter 2 Abstract: We examined the impact of soil environmental variables (soil temperature, moisture, and available nitrate (NO3-) and ammonium (NH4+)) on the production, mortality, standing crop, turnover, and lifespan of Pinus palustris Miller fine roots using the minirhizotron technique. Data were collected for a full year from a P. palustris woodland in southwest Georgia. Mean soil temperatures appeared to have little influence on root processes, while temperature variance had a strong effect. More thermally variable microsites had increased root turnover and reduced root lifespans. Soil resources had a significant impact on demography; in particular, soil moisture and nitrate stimulated production, mortality, and turnover. High levels of soil resource availability also significantly reduced lifespan. Root lifespan was variable among individual roots based on root width, depth in the soil volume, and season of root production. Soil moisture had the strongest overall influence on root demography. This may result from the nature of our ecosystem (deep sands and subtropical climate); in addition, severe drought during our study may have enhanced the role of soil moisture, allowing environmental controls to increase in strength relative to within-plant controls on root demography. / Master of Science

This thesis investigates the roles of the Axin homolog PRY-1 and the Insulin/IGF-1 signaling (IIS) pathways in Caenorhabditis nematodes to elucidate their influence on aging, stress responses, and metabolic regulation. Comparative analyses between C. elegans and C. briggsae highlight conserved and divergent genetic mechanisms within the IIS pathway that regulate lifespan and metabolic processes. Transcriptome profiling reveals novel genes downstream of the daf-2-daf-16 pathway, furthering our understanding of the underlying genetic networks. PRY-1, a key component of the Wnt signaling pathway, plays a significant role in regulating axis formation, lipid metabolism, neuron and vulva development, cell polarity, and lifespan. This research examines PRY-1’s interactions with BAR-1 (a β-catenin homolog), and how these interactions influence lipid metabolism, vitellogenin expression, lifespan, and vulva development. This work extends our understanding of the IIS and Wnt pathways, emphasizing these signaling axes' evolutionary importance in aging, metabolic regulation, and stress response. / Thesis / Master of Science (MS) / This thesis explores how specific biological pathways control aging and stress responses in two species of tiny roundworms, Caenorhabditis elegans and Caenorhabditis briggsae. The research focuses on two key pathways: the Insulin/IGF-1 signaling (IIS) pathway, which regulates lifespan and metabolism, and the PRY-1/Axin component of Wnt signaling pathway, which is crucial for regulating development and lifespan. The study aims to understand how these pathways influence stress response and lifespan and identify new molecular candidates functioning downstream of these pathways. These findings could provide new insights into the biological processes behind aging and help inform potential treatments for age-related diseases in humans.