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Elderly residents of nursing homes are at high risk of respiratory viral infection, mortality and frailty. It is a widely held view that the dysfunctional changes to the immune system that arise from ageing, known as immunosenescence are responsible for the increased risk of infection, mortality and frailty; however only sparse data exist to substantiate this. Furthermore, the majority of studies investigating these associations have excluded elderly nursing home residents, thus little is known about immune phenotypes in this group. In this thesis, I first characterized immune phenotypes in elderly nursing home residents by comparing immune phenotypes in an elderly nursing home cohort to a group of younger healthy adults. I then explored how age, sex, frailty and nutrition influence immune phenotypes in the elderly group. I subsequently used different statistical analyses, including Cox proportional hazards modeling, hierarchical cluster analysis and multi-level modelling to identifying immune biomarkers predictive of clinical outcomes in elderly nursing home residents including respiratory viral infection, mortality and frailty. We found that high cytomegalovirus (CMV)-reactive CD4+ T-cells were associated with an increased risk of respiratory viral infection and high T-regulatory cells (T-regs) were associated with a reduced risk of respiratory viral infection. High CMV-reactive CD4+ T-cells were also associated with an increased risk of mortality within the subsequent 1-year in those aged 65-84 years but had no differential effect in those aged 85-104 years. Other immune phenotypes were not predictive of mortality. Higher naïve CD4+ T-cells and effector memory CD8+ T-cells predicted lower levels of frailty and higher central memory CD8+ T-cells predicted higher levels of frailty. These findings may help provide more focused care through targeted prevention. Furthermore, knowledge of these immune biomarkers provides insight into how immunosenescence may contribute to these clinical outcomes and will help guide future research into novel prevention strategies. / Thesis / Doctor of Philosophy (PhD)

OBJECTIVES: In older age, body composition changes as fat mass increases and redistributes. Due to this, the current body mass index (BMI) classification proposed by the World Health Organization (WHO) may not accurately classify older adults (65+) by health risk. The objectives of thesis were to: 1) conduct a scoping review of the literature to investigate the association between BMI and mortality in older adults, 2) define age-specific BMI cut-offs for older adults with regards to health outcomes using data from the Canadian Longitudinal Study on Aging (CLSA), and 3) test the performance of the age-specific BMI thresholds in comparison to WHO thresholds. METHODS: The Ovid MEDLINE and EMBASE databases were searched for English language observational studies examining the association between BMI and all-cause mortality in older adults (objective 1). CART decision tree analysis was then used to define age-appropriate BMI cut-points in relation to health outcomes (i.e. cardiovascular (CV) conditions and frailty) (objective 2). Logistic regression models were utilized to determine the association between BMI and health outcomes, and area under the receiver operating characteristic curve (AUC) and sensitivity/specificity were used to test the performance of new BMI cut-offs (objective 3). RESULTS: The scoping review found that older adults classified as overweight had reduced mortality compared to normal BMI, thereby necessitating a need for revised cut-offs. In our analyses, age-specific cardiovascular- and frailty-BMI groups were created. Compared to the BMIFrailty- Risk groups, the BMI-CV-Risk groups demonstrated the most improvement in classification from the WHO groups. When evaluating the association between cut-points and outcomes, the model performance and specificity both improved for the new age-specific cut-points compared to the original WHO thresholds, suggesting improved classification with use of these revised groups. The results propose increased overweight thresholds (25.9-27.1) and lowered obese thresholds (28.7-30.9) for older adults. CONCLUSIONS: This novel analysis is the first attempt at revising the WHO-BMI thresholds for older Canadian adults. The age-specific BMI-CV-Risk groups offered improvements in classification of older adults from the WHO-BMI groups, and these findings suggest that a higher overweight but lowered obese thresholds may be best suited to older adults. Further work must be done to validate these thresholds in other populations and ethnicities, as well as in the context of other health outcomes. / Thesis / Master of Science (MSc)

Aging is associated with attenuated sweat gland function, which has been suggested to occur in a peripheral-to-central manner. However, evidence supporting this hypothesis remains equivocal. We therefore revisited this hypothesis by evaluating sweat rate across the limbs and trunk in young and older men during whole-body, passive heating. A water-perfused suit was used to raise and clamp esophageal temperature at 0.6°C (low-heat strain) and 1.2°C (moderate-heat strain) above baseline in 14 young (24 [SD 5] years) and 15 older (69 [4] years) men. Sweat rate was measured at multiple sites on the trunk (chest, abdomen) and limbs (biceps, forearm, quadriceps, calf) using ventilated capsules (3.8 cm²). Sweat rates, expressed as the average of 5 min of stable sweat rate at low- and moderate-heat strain, were compared between groups (young, older) and regions (trunk, limbs) within each level of heat strain using a linear mixed-effects model with nested intercepts (sites nested within region nested within participant). At low-heat strain, the age-related reduction in sweat rate (older-young values) was greater at the trunk (0.65 mg/cm²/min [95% CI 0.44, 0.86]) compared to the limbs (0.42 mg/cm²/min [0.22, 0.62]; interaction: p=0.010). At moderate-heat strain, sweat rate was lower in the older compared to young (main effect: p=0.025), albeit that reduction did not differ between regions (interaction: p=0.888). We conclude that, contrary to previous suggestions, the agerelated decline in sweat rate was greater at the trunk compared to the limbs at lowheat strain, with no evidence of regional variation in that age-related decline at moderate-heat strain.

Visual accommodation plays a critical role in one's visual perception and activities of daily living. The age-related accommodation loss poses a greater risk to older adults' safety and independence. Although extensive effort has been made to study the effects of aging on accommodation, the relationship between aging and the dynamic aspects of accommodation is still unknown. Furthermore, since light is the carrier of external stimuli for accommodation, it is of value to assess the influences of light on the age-related accommodation loss. Therefore, a study was conducted to investigate the age-related dynamic accommodative characteristics under various conditions of the intensity and chromaticity of light. To ascertain the effects of aging, ten individuals from each of three age groups (i.e., younger group: 20 to 29 years old, middle-aged group: 40 to 49 years old, and older group: 60 to 69 years old) were recruited, and their dynamic accommodation responses were examined. Laboratory experiments were designed to measure accommodation in a simulated condition where a person must alternate from viewing outside to reading the dashboard while driving. It was hypothesized that the advancing of age will lead to the deterioration of one's dynamic accommodative performance, and light of different intensities and chromaticities will interact with the effects of aging on accommodation. The results of the study supported the above hypotheses. It was found that the advancing of age, the decrease of light intensity, and the change of light chromaticity all led to the alteration of one's dynamic accommodative performance. The present study concluded with a biomechanical and neural model elaborating the mechanism of an accommodation process within the scope of the study. / Ph. D.