This thesis aimed to investigate physical education, physical activity and sport (PEPAS) participation and the adoption of health behaviours in Scottish adolescents. To address this topic, I start with a general reflection on the current state of Scottish health, through the lens of the Scottish and nested Glasgow effects. Subsequently, building on this conceptual base, I outline a series of three studies to further investigate the linkages between PEPAS and accumulating life stress and health behaviours. Accordingly, the thesis narrative consists of 4 distinct research outputs (1 desktop study, followed by 3 studies involving the collection of primary data). These studies were arranged as follows: In Chapter 4 (research study 1), I suggest that a confluence of social, environmental, attitudinal and cultural stressors may combine to negatively influence biological health. The core conclusion of this conceptual paper was that PA may provide a highly efficient, and cost-effective means to remediating some of the issues underpinning the Scottish effect. Chapter 5 (research study 2) presents data comparing patterns of PA uptake in adolescents of low socioeconomic status (SES) backgrounds with more affluent age-matched peers. SES is a significant biopsychosocial stress-elevating consideration. These findings add to mounting evidence suggesting excessively accumulating life stress, not only diminishes health, but simultaneously reduces PA uptake in vulnerable populations. The outcomes of this study thus emphasise the negative relationship between excessive life stress and PA, and highlight that there may be a bidirectional relationship between these factors. Chapter 7 (research study 3) qualitatively investigates the barriers and facilitators of PEPAS and exercise in the broad general education (BGE) phase of CfE in Scotland. Focus groups were conducted with 39 secondary school pupils (S1-S2). This study adds context-specific information highlighting the role of self-image, perceived competence and social influence on PEPAS participation. Subsequent findings indicated that the delivery of traditional PE lessons, which prioritise sporting ability, act as a participation barrier to pupils who consider themselves 'non-sporty'. Chapter 8 (research study 4) builds on Chapter 7 by qualitatively investigating why young people in the post 16 phase of CfE discontinue participation in exercise, sport and PA, whilst analysing reasons for this post compulsory education decline in PA. Previous negative PE experiences were perceived as a major barrier to continued PA. Furthermore, this young cohort perceived that PE teachers focused primarily on physically capable students. Respondents also perceived that access to contemporary fitness activities would be a positive option both during PE lessons, and as a tool to promote lifelong PA. Key conclusions emanating from this thesis included: PA levels were significantly lower in those who had experienced greater accumulated life stress. Thereby suggesting that excessively accumulating life stress not only exerts a negative effect on health, but simultaneously reduces PA uptake in vulnerable populations. Activities where individuals felt singled out, such as fitness testing, present significant barriers to PEPAS. Similarly, an overly competitive, performance-based curriculum acted as a barrier for those who self-identified as 'non-sporty'. Many 16-18-year- olds see current cultural fitness trends as preferable to the range of activities traditionally promoted within PE. It was perceived that previous negative PE experiences acted as a barrier to continued PA into adulthood. A core finding arising from this thesis is the recommendation that promoting lifelong PA habits, particularly in those at risk of elevated life stress, should be a fundamental objective of educators. Furthermore, evidence uncovered during this thesis suggests that PE should be structured around pedagogical models promoting self-efficacy and intrinsic motivation. Also, it is suggested that, during the senior phase, PE should be repackaged into an attractive compulsory brand. Finally, the implementation of current fitness and exercise trends, may prove an effective strategy in promoting lifelong activity and health and wellbeing.

<p>Physical activity (PA) in preschool children (3- to 5-year olds) is characterized by short bouts of intermittent movement, generally accumulated during free play activities. Little is known about how the amount of PA or the patterns of PA accumulation are related to health in preschoolers. Ninety-six healthy preschool children (46 boys, 50 girls; 4.4 ± 0.9 years) participated in assessments of PA, body composition, health-related fitness, blood pressure, and motor proficiency. PA data were collected for 7 consecutive days using Actigraph accelerometers. PA prevalence was assessed by the amount of total and moderate-to-vigorous PA (MVPA) in min/day and as a % of wear; PA patterns were assessed by the frequency and duration of MVPA bouts and by the duration of breaks between MVPA. Younger preschoolers engaged in less PA than older preschoolers, according to measures of prevalence and patterns (<em>p </em>< 0.05). Girls participated in less PA, less frequent MVPA, and longer breaks between bouts of MVPA compared to boys (<em>p </em>≤ 0.001, for all). Health-related fitness was higher in preschoolers who engaged in more total PA, more frequent bouts of MVPA, longer bouts of MVPA, and shorter breaks between bouts of MVPA (<em>p </em>< 0.05, for all). Blood pressure was higher in preschoolers taking longer breaks between bouts of MVPA (<em>p </em>< 0.05). Motor proficiency was poorer in preschoolers who participated in shorter bouts of MVPA (<em>p </em>< 0.001). Preschoolers who met current PA recommendations of 180 min of total PA and 60 min of MVPA daily had better body composition and health-related fitness, respectively, compared to their peers who did not meet recommendations (<em>p </em>< 0.05). To the best of our knowledge, these data are the first to provide support for new PA guidelines and to demonstrate relationships between PA and health-related fitness and blood pressure in preschoolers. Our findings indicate that PA patterns are just as important as PA prevalence in describing relationships between health measures in preschool children.</p> / Master of Science in Kinesiology

<p>Skeletal muscle exhibits a remarkable capacity for growth and regeneration in response to physiological stimuli. This extensive plasticity is, in part, due to a tissue-resident stem cell called the satellite cell. Satellite cells respond to myotrauma by upregulating a class of transcriptional networks which orchestrate myogenic specification. This process is controlled by four main transcription factors known as the myogenic regulatory factors: Myf5, MyoD, MRF4 and Myogenin. Satellite cells respond to molecular cues released from the muscle fiber or inflammatory cells in response to muscle damage. Although several regulators have been implicated in the control of the satellite cell response to exercise or damage, very few of these have been examined in humans. Insulin-like growth factor-1 (IGF-1) and Interleukin-6 (IL-6) have been demonstrated to enhance satellite cell proliferation in animal and cell culture models. IGF-1 has also been shown to induce myogenic differentiation, however little is known about IGF-1 and IL-6 in humans, in response to physiological levels of muscle damage. Myostatin has been identified as a negative regulator of muscle growth and an inhibitor of satellite cells in mice. To date no data exists regarding the relation of myostatin to the satellite cell response to exercise and in the context of aging. The work outlined in this thesis provides support for the proposed divergent effects of the IGF-1 splice variants on satellite cell function. IGF-1 appears to be preferentially spliced as IGF-1Ec during the proliferative phase of the myogenic program while IGF-1Ea and Eb appear as the predominant splice variants during the initiation of differentiation based on the expression of the MRFs. Furthermore, the localization of IGF-1 with Pax7 in muscle-cross sections in the post-exercise time-course lends support to the importance of IGF-1 in the myogenic response to myotrauma. This thesis also provides novel evidence to support the role of IL-6 in the regulation of satellite cell proliferation in response to acute muscle damage in humans. These data confirm that IL-6 imparts its action on the satellite cell via the JAK2/STAT3 pathway. In addition, for the first time, myostatin is demonstrated to be altered by acute exercise in both young and older adults and this effect is most notable in the satellite cell compartment. In addition, these data implicate myostatin as a contributing factor to age-related satellite cell dysfunction in response to exercise (or myotrauma).</p> / Doctor of Philosophy (PhD)

<p>Radiation is a prominent source of environmental oxidative stress that can have deleterious consequences for health. Despite its well-known negative effects, radiation is commonly employed clinically for disease treatment and diagnosis. Bone marrow transplantation (BMT), used in the treatment of a variety of diseases, is preceded by a myeloablative regimen that usually involves radiation. Mortality associated with BMT is quite high and the aggressive radiation pre-treatment regimen contributes to these high rates of mortality. Interventions that inhibit the negative consequences of irradiation and promote BMT success would have significant implications for public health. Exercise-induced adaptations in numerous body tissues have been associated with amelioration of a variety of pathologies, particularly those associated with oxidative stress, and an overall improvement in health. Whether these adaptations can protect from damage induced by an external source of oxidative stress, such as a high dose of radiation, or promote BMT success is unknown. The purpose of this thesis was to determine if the adaptive response to exercise training could inhibit the negative effects of irradiation in skeletal muscle and bone marrow, and promote BMT success. To apply these adaptations to BMT, we examined the response of hematopoietic stem cells (HSC) and their niche to exercise. We report that muscle from exercise trained mice exhibits an enhanced response to radiation characterized by increased antioxidant and mitochondrial metabolic enzyme activity. Extending these findings to cells in the bone marrow, we demonstrated that exercise training inhibited radiation-induced genotoxicity and cytotoxicity. With respect to BMT, exercise training increased HSC quantity with no effects on HSC function; however, preconditioning BMT recipients with exercise training resulted in improved probability of survival and enhanced hematopoietic regeneration. Collectively, results from the studies presented herein suggest that exercise training may be a successful therapeutic intervention to inhibit the damaging effects of radiation and improve BMT outcomes.</p> / Doctor of Philosophy (PhD)

<p>There is a prevalent belief that acute hormone responses to resistance exercise mediate adaptations in skeletal muscle hypertrophy; however, there is little supporting evidence. We conducted studies to examine the relationship between acute hormonal increases after resistance exercises and subsequent changes in muscle anabolism.</p> <p>We tested the hypothesis that exercise-induced responses of anabolic hormones—growth hormone (GH) and testosterone—would enhance rates of myofibrillar protein synthesis (MPS) after an acute bout of resistance exercise, and would augment muscle hypertrophy after training. We concluded, however, that resistance exercise-induced increases in putative anabolic hormones do not enhance MPS or hypertrophy.</p> <p>We also examined whether rates of MPS would be attenuated in women (compared with men) after resistance exercise, due to their lack of post-exercise testosteronemia. We reported similar increases in MPS in men and women; post-exercise testosterone responses in women, which were 45-fold lower than men, did not attenuate elevations in MPS.</p> <p>Collectively, our work leads to the conclusion that the acute rise in hormones such as testosterone and GH has very little bearing on MPS and hypertrophy responses to resistance exercise. Instead, the rise in these hormones appears to be a non-specific response to exercise stress rather than a response that is important for muscle anabolism. Contrary to widely used principles, our data suggests that exercise programs should not be designed based on nuances in the post-exercise hormonal milieu. Alternatively, understanding local mechanotransduction, which is directly linked to muscle fibre loading, will reveal the processes that drive human exercise-mediated muscle hypertrophy.</p> / Doctor of Philosophy (PhD)

<p>Aerobic exercise can stimulate mixed muscle protein synthesis (MPS) acutely post-exercise; however, the types of proteins synthesized as a result of aerobic exercise are not known by studying changes in mixed MPS. We aimed to study the effect of aerobic exercise intensity on the 4 and 24 h post-exercise fractional synthesis rate (FSR) of myofibrillar proteins. Using a within-subject design, eight males (21 ± 1 years, VO_{2 peak}: 46.7 ± 2.0 mL kg^-1 min^-1) underwent 2 trials with a primed constant infusion of L-[<em>ring</em>-¹³C₆]phenylalanine in the fasted state for each work-matched exercise intensity (LOW: cycling for 60 min at 30% W_max and HIGH: 30 min at 60% W_max). Muscle biopsies were obtained to determine resting, 4 and 24 h post-exercise myofibrillar FSR. We also studied the phosphorylation of signaling proteins involved in protein synthesis at each time point using immunoblotting methods. Phospho-p38^{Thr180/Tyr182} was greater at 4.5 h after exercise compared to 0.5, 24 and 28 h post-exercise (<em>p</em> < 0.05). Additionally, a strong trend was present for phospho-mTOR^Ser2448 (<em>p</em> = 0.056) with 0.5 h post-exercise phosphorylation significantly higher after HIGH than after LOW exercise (<em>p </em>< 0.05). Myofibrillar protein synthesis was stimulated 1.5–fold 0.5 – 4 h post-exercise (<em>p</em> < 0.05), returning to rest in the LOW condition 24 h post-exercise, while 6 out of 8 subjects maintained increased myofibrillar FSR 24 h post HIGH exercise (<em>p</em> < 0.05). The increase in myofibrillar FSR 0.5 – 4 h post-exercise was correlated with phospho-mTOR^Ser2448 0.5 h post-exercise (r = 0.698, <em>p</em> < 0.01), indicating the role of this signaling pathway in myofibrillar protein synthesis. It is concluded that aerobic exercise has an effect on myofibrillar protein synthesis and intensity may play a role in the duration of this response.</p> / Master of Science in Kinesiology

<p><strong>Introduction:</strong> Mitochondria are important organelles for skeletal muscle function. Mitochondria are susceptible to many forms of stress that alters their morphology, energy generation and reactive oxygen species (ROS) production, which collectively promote degeneration and dysfunction in skeletal muscle. These processes are implicated in many health disorders, particularly in the aging process itself. Exercise is well established to increase muscle mitochondrial content and thus may attenuate several aspects of mitochondrial deterioration. <strong>Methods:</strong> Both human and animal models of mitochondrial stress (aging, ROS) were utilized in order to determine their effects on mitochondrial and muscle function. Additionally, exercise training was used in order to assess its therapeutic potential in ameliorating defects in oxidative capacity, muscle atrophy and metabolic adaptation in skeletal muscle. <strong>Results:</strong> Aging resulted in reduced strength, aerobic capacity, larger intramyocelluar lipid droplets and fewer mitochondria in skeletal muscle. These changes were related to suppressed lipid metabolism, mitochondrial dynamics and organelle turnover. Habitual aerobic exercise partially attenuated the age-related loss of muscle strength and aerobic capacity, presumably due in part to improved mitochondrial function. Persistent mitochondrial oxidative stress prevented mitochondrial adaptations to exercise training in mice, a phenomenon that may explain why exercise cannot fully counteract the effects of aging in skeletal muscle. <strong>Conclusions and significance:</strong> This work furthers our knowledge of the mitochondrial consequences of aging and the therapeutic potential of aerobic exercise within skeletal muscle. These results can be applied to other differentiated tissues that are severely affected by aging (brain, heart) and the effects described here are likely relevant to other conditions that result in muscle atrophy and energetic insufficiency.</p> / Doctor of Philosophy (PhD)

<p>Introduction: Mitochondrial dysfunction and oxidative stress increase with aging and may contribute to age-associated muscle atrophy (sarcopenia). Resistance exercise (RE) can promote the accretion of muscle mass, increase strength, and ultimately improve function in the elderly. Such beneficial effects are thought to be mitigated solely by increased muscle mass and strength; however, the contribution of the mitochondria to the beneficial effects of RE in aging have not been thoroughly characterized. While mitochondrial benefits have been established separately in both young and aged adults following chronic RE, the acute effects have not been well characterized. Methods: Sedentary young and aged adult males completed either an acute bout of fatiguing RE or endurance exercise (EE), and muscle biopsies were obtained at 3, 24 and 48 h post- exercise depending on the study. Results: Despite equivalent lean-body mass, increased age was associated with elevated mtDNA deletions, indicating potential for mitochondrial dysfunction. RE was associated with reduced mitochondrial content (transcripts, protein, and mtDNA copy number) at 48 h post-exercise, a response that did not differ with increasing age. Paradoxically, reduced mitochondrial content occurred alongside elevated total peroxisome proliferator-activated receptor γ coactivator one α (PGC-1α) mRNA; however, RE altered only the PGC-1α4 isoform post-exercise, a transcript that regulates myostatin and insulin-like growth factor one (IGF1) signalling and ultimately muscle hypertrophy and not mitochondrial adaptations. In addition, PGC-1α modulates the unfolded protein response (UPR), and RE was subsequently shown to elevate endoplasmic reticulum stress and elicit the UPR. Conclusion: PGC-1α mRNA increases regardless of exercise mode; however, differential expression or regulation of alternate PGC-1α isoforms or transcriptional binding partners co-activated by PGC-1α may dictate the specific phenotypic adaptations that occur following divergent modes of exercise. Furthermore, RE acutely decreases mitochondrial content despite elevated PGC-1α mRNA, and this response is not influenced by age.</p> / Doctor of Philosophy (Medical Science)

<p>Energy restriction-induced weight loss results in the loss of both fat mass (FM) and fat free mass (FFM). Declines in FFM, comprised mostly of skeletal muscle, have the potential to impair metabolic health. A recent meta-analysis demonstrated higher protein hypo-energetic diets (≥ 1.25 g/kg/d) can help retain FFM (Weinheimer, Sands, & Campbell, 2010). This effect is attributed to protein ingestion induced stimulation of muscle protein synthesis (MPS), which is dependent on protein source (Tang, Moore, Kujbida, Tarnopolsky, & Phillips, 2009). However, protein source on modulating FFM preservation during ER remains understudied. In a double blind investigation, 40 adults (BMI 28-40) undertook a moderate 14 day hypo-energetic diet. Subjects were randomized to be supplemented twice daily with whey (WHEY) or soy (SOY) protein, or a carbohydrate (CHO) powder as part of their ER diet. Preliminary and post diet intervention testing included skeletal muscle biopsies, blood samples and DXA measures. Absolute changes in body mass (-2.3 ± 0.18 kg), FM (-1.2 ± 0.16 kg) and FFM (-0.8 ± 0.24 kg) did not significantly differ between groups. Basal serum cortisol was unchanged in WHEY but increased significantly in SOY and CHO (p</p> / Master of Science in Kinesiology

<p>What a ride it has been. The ups and downs of the McMaster graduate program has been a sweet one. It has been a pleasure working with the Exercise Metabolism Research Group for the past 2 years, and I will miss being around the work that goes on in the trenches around the lab. I have leaned on many people for all types of guidance through this journey, and would like to thank everyone for their unprecedented support. I have grown as a person and student and will use everything I have learned at this fine establishment I’m sure at one point or another along the great path of life. I must thank my amazing parents, family, friends and of coarse Ashley for putting up with my work ethic throughout my studies; the long days that I would go missing. Without their support none of this would have been possible. I have to specially mention Melanie Wolfe for recommending myself, and ultimately Stu Phillips for presenting this opportunity that is coming to a close. I have had great senior support from Cam Mitchell, Tyler Churchward-Venne, Todd Prior and Michaela Devries in putting this document together, and would not be submitting this without their selfless assistance. It’s been a journey getting to this point, but I wouldn’t change it for the world, to the next chapter in life, cheers and God Bless.</p> / <p>Higher dietary protein intake, greater than the Recommended Dietary Allowance (RDA; 0.8 g protein/kg/d), coupled with resistive exercise has been shown to aid in preservation of muscle mass during hypocaloric diet-induced weight loss. We examined the impact of dietary protein supplementation at two levels (1.2 and 2.4 g/kg/d) on body composition during a 4wk hypocaloric dietary intervention that included 6d/wk of high intensity resistance exercise and interval training. In a single blind study, forty young men consumed 33±1.1 kcal/LBM (~40% reduction versus estimated energy requirements), and were randomly assigned to a group that consumed either 1.2g/kg/d protein or 2.4g/kg/d. Body composition was determined using DXA, Bod Pod, and Bio-impedance pre- and post-intervention to derive a 4-compartment model for body composition. Both groups retained lean mass (LM), but retention was greater in the higher protein group (p</p> / Master of Science (MSc)