Date of Award

Spring 2012

Degree Type

Thesis

Degree Name

Master of Science (MSc)

Department

Biology

Supervisor

CD Rollo

Co-Supervisor

G Parise

Language

English

Committee Member

GB McClelland

Abstract

Aging involves the progressive decline of physical performance and effective metabolic regulation. To date, dietary interventions to slow this deterioration have shown limited success. I tested the effectiveness of a complex dietary supplement (that targets five key mechanisms of aging) for ameliorating age-related declines in physical activity, metabolism and energetic efficiency in mice. Supplemented mice maintained youthful levels of daily physical activity in old age, compared with a progressive decline in untreated controls. The diet also influenced aspects of metabolic rate, as supplemented mice showed age-related increases in fasting oxygen consumption and respiratory quotient compared to declines in these biomarkers in untreated mice. Furthermore, oxygen consumption over 24-h was significantly lower in supplemented mice in spite of being more active than untreated mice. Taken in conjunction with higher resting respiratory exchange ratios across age, this suggests that supplemented mice may utilize more carbohydrate than lipid as an energy substrate and they may express increased metabolic efficiency. These results hold promise for augmenting youthful athleticism and extending geriatric functionality. I also assessed the impact of the supplement on age- related changes in biomarkers of oxidative stress in heart and kidney samples from normal (Nr) and transgenic (Tg) mice that over-express growth hormone. Measures of whole-tissue H2O2 in the heart showed no significant changes in Nr or Tg mice, but catalase activity was ~33% higher in supplemented Nr and Tg compared to untreated controls. Kidney tissue from Nr mice showed significant and opposite age-related trends of H2O2, increasing in supplemented mice and decreasing in untreated controls, however, no changes were observed in Tg mice. Catalase activity in kidney tissue remained unchanged in both genotypes regardless of diet. Furthermore, the ratio of reduced to oxidized glutathione was 43% higher in urine from older (>12 months-old) supplemented mice, indicative of substantially lower whole-body oxidative status. Lastly, older supplemented mice showed improved whole-body glucose tolerance compared with untreated counterparts. These results confirm that the supplement reduces aspects oxidative stress and improves insulin sensitivity, two of the key design criteria for formulating the supplement. This work represents proof of principle that complex dietary supplements can extend functional capacities associated with metabolism and energetic efficiency into older ages.

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