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Dietary restriction (DR) is the only known nutritional manipulation that can increase both lifespan and healthspan in a variety of species. Underlying these increases are improvements in metabolic health and reductions in cancer incidence. Despite these physiological improvements, the regulation of skeletal muscle mass is extremely sensitive to alterations in nutrients [reviewed in (Sharples et al., 2015)] and as such has been reported to reduce regenerative potential and increase atrophy in skeletal muscle cells and myotubes. Interestingly, the activation of Sirtuin1 (SIRT1) has been reported during DR and its reduction abrogates lifespan extension. Importantly, SIRT1 activation via resveratrol treatment has been indicated to be important in the presence of inflammatory stress (TNF-α) (Saini et al., 2012). Resveratrol supplementation has also improved survival and regeneration of skeletal muscle cells as well in muscle cell remodelling following oxidative stress (Bosutti and Degens, 2015). We therefore sought to create an in-vitro physiological model of DR by mimicking levels of glucose in the circulation and interstitium in-vivo in response to DR (Chapter 3) as well as optimising the activation and inhibition of SIRT1 using resveratrol and SIRT1 inhibitor, EX-527 respectively (Chapter 4). With our ultimate aim to investigate the potential role and mechanisms of the activation/inhibition of SIRT1 in ameliorating the degenerative/atrophic effect of DR in both differentiating myoblasts (Chapter 5) and mature myotubes (Chapter 6). Indeed, in Chapter 3 we present two models of reduced glucose; one reduced (medium/ MED) and the other blocked (LOW) differentiation and myotube hypertrophy. The former represented circulatory glucose blood levels (MED 1.13 g/L or 6.25 mM) and the latter interstitial represented glucose levels (LOW 0.56 g/L or 3.12 mM) of rodents under DR. In Chapter 4 we also suggest that within the in vitro muscle cell model, activation/inhibition of SIRT1 phosphorylation (western blot analysis) was thought to be most effective at 10 μM of resveratrol and 100 nM of EX-527 respectively. In chapter 5, we observed that resveratrol treatment did not improve fusion when administered to differentiating myoblasts. Resveratrol did however evoke increases in myotube hypertrophy under normal glucose conditions. Importantly resveratrol enabled improved myotube hypertrophy over an acute 24 h period when administered to existing mature myotubes in low glucose environments. If this finding translates to whole organisms and human populations it could provide healthspan improvements via reductions in fragility associated with loss of muscle mass in individuals undergoing dietary restriction. After this 24 h period resveratrol was unable to reduce myotube atrophy and the myotubes continued to atrophy, suggestive of a need for repeated resveratrol treatment to enable continued protection against muscle atrophy under low glucose conditions. SIRT1 activation increased Myogenic regulatory factor 4 (MRF4) gene expression under LOW glucose conditions which was associated with the observed improvements in myotube size at 24 h. Whereas, SIRT1 activation via resveratrol treatment in normal glucose conditions modulated increased gene expression of Myosin heavy chain 7 (MYHC7) coding for the slow isoform while inhibition of SIRT1 (EX-527) lead to reductions in gene expression of MYHC 1, 2 and 4, coding for faster IIx, IIa, IIb isoforms respectively. Perhaps suggesting that elevated SIRT1 was important in the activation of genes coding for slower myosin heavy chain isoforms. Furthermore, while SIRT activation via resveratrol did modulate increases in IGF-I gene expression, it did not appear to modulate energy sensing AMP activated protein kinase (AMPK) vs. growth related Protein 70 S6 Kinase (p70S6K) signalling pathways. However, SIRT1 inhibition increased AMPK activity in both low and normal glucose with corresponding mean reductions in p70S6K in normal glucose conditions. This indicates that perhaps normal SIRT1 activity was required for appropriate AMPK activation, which may therefore prevent the suppression of p70S6K and the corresponding reductions in myotube size observed in SIRT1 inhibitor conditions. Furthermore, during low glucose induced myotube atrophy resveratrol reduced gene expression of the negative regulator of muscle mass, myostatin and protein degradative ubiquitin ligase enzyme, MUSA1. Overall, SIRT1 activation via a single dose of resveratrol appears to have a role in acutely negating the effect of low glucose induced myotube atrophy and promoting myotube hypertrophy when glucose is readily available.

Understanding the ways in which practitioners can identify and manage undernutrition is important within developing world countries. There is still much uncertainty when it comes to understanding which measures of undernutrition are the most effective predictors of adverse outcomes. This thesis explores how children grow and applies statistical methodology to three longitudinal growth datasets with frequent measurements in the first two years, seeking new insights into how measures of undernutrition can be used to predict future adverse outcomes. The three datasets are diverse - from Malawi, South Africa and Pakistan, the latter of which contains 4 subsets of different socioeconomic groups. The large number of children within the sets made it possible to test several different hypotheses. Growth charts (or reference charts) are charts which allow practitioners to compare a given infant’s anthropometric measurements with a reference population. We developed growth charts from the available datasets using Generalised Additive Models for Location Scale and Shape (GAMLSS), a method which allows users to flexibly model distributions of measurements over time. The reference charts we developed describe the growth of samples of children, many of whom will not have grown at a healthy rate. It is preferable to compare children with healthy infants from a composite external standard. The World Health Organization (WHO) growth standard was developed from a variety of populations from across the globe which describes the growth of a ‘healthy’ population. This suggests an aspirational model, as opposed to a reference, which describes how a sample of children actually grow. In this thesis GAMLSS was used to determine whether real populations of pre-school children from the developing world fit this international standard. We found that relatively affluent populations fit the standard well, or even outperform it, while more deprived populations fall away to varying degrees, then mainly track parallel to the WHO mean beyond 6 months. This suggests that after the first 6 months children from the developing world have rates of weight gain roughly on par with the standard, although the children are much lighter. Plotting measurements on growth charts identifies those whose weight Z score or centile is falling relative to the reference. However, children initially at the extremes tend to regress toward the mean. Conditional weight gain (CWG) takes this expected movement into account, but can only be used within the population in which the child originates, due to certain statistical assumptions. We developed a generalised measure of CWG for use with the WHO external standard. This measure requires the correlation between pairs of groups of measurements at different time points, as the amount of regression to the mean is synonymous with this correlation. If data are not available at these time points, they can be interpolated by firstly computing correlations between all available data, then modelling the resulting matrix. We found that these correlation matrices are heterogeneous within the developing world. Therefore, constructing a generalised correlation model was not possible. This makes the use of the new generalised measure of CWG impractical without access to correlation models computed from local data. However, the measure may be useful within the developed world, where correlation matrices may be less variable. The analysis then explored the ways that children move between different nutritional states, defined as healthy, thin (wasted) and/or short (stunted), over 3-6 month (m), 6-9m and 9-12m timeframes, and the probability these states will lead to death. We used stochastic models to explore the probability of moving state conditional on previous state, exploring the pathways children take through different states over time. Within all timeframes, children who were wasted as well as stunted were more likely to die than wasted children, who were in turn more likely to die than stunted children. Furthermore, as children age, the conditional risk of death in the next time period decreases. However, relative to healthy children, all children were less vulnerable within the middle period (6-9m) regardless of state. Children who were wasted were at significantly higher risk than healthy children of later wasting, or becoming stunted as well as wasted, over all timeframes. However, wasting alone significantly increased the risk of later stunting only in the 3-6m timeframe. Across the 3-6-9m timeframes children were much more likely to move from either healthy to healthy to stunted, or healthy to stunted to stunted, than from healthy to wasted to stunted. This indicates children are more likely to move directly into a stunted state than from healthy to stunted via wasted. Change in weight (growth) has been shown to be a predictor of mortality in populations of children, but it is not clear if this measure is more predictive than the latest weight (size). Using weighted Cox proportional hazards models, we determined which of these measures is the most valuable predictor of mortality for the majority of children within each individual dataset, conducting analyses using variable levels of weightings for children at the extremes. We included weight-for-age and height-for-age as predictors within our models to determine what combination of predictors best predict mortality. In all unweighted analyses, size was the best predictor of time until death. However, as the weighting increased, growth entered as the best predictor in populations with low rates of undernutrition. In contrast, size always remained the strongest predictor within populations with high rates of undernutrition, since in these populations, such a high proportion of children fall away from within the centre of the normal range, making growth pattern non-discriminating. This programme of work applied statistical techniques to three diverse longitudinal datasets, gaining insights into how children grow between different socio-economic backgrounds. We investigated measures of size and measures of growth, utilising methods that control for the inevitable fact that healthy children at the centre of the population distribution tend to dominate analyses. Furthermore, these methods were both multidimensional and time dependant, providing us with a useful framework to assess child growth while controlling for influential factors. The results should improve understanding of both the aetiology of undernutrition and its clinical management.

Ramadan requires individuals to abstain from food and fluid intake between sunrise and sunset; physiological considerations predict that poorer mood, physical performance and mental performance will result. In addition, any difficulties will be worsened because preparations for fasting and recovery from it often mean that nocturnal sleep is decreased in length, and this independently affects mood and performance. Previous field studies have indicated that some of these predictions are borne out in practice; in the first study of the present thesis, a field study performed in Libya, these predictions were tested further by adding more physiological measurements and tests of performance. Findings indicated that Ramadan was associated with negative effects upon a wide range of variables, including rising urine daytime osmolality (indicative of progressive dehydration), subjective estimates of amounts of activities actually performed and those wished to be done (indicating less activity in the daytime), and metabolic and subjective responses to a short bout of exercise (increased effort required and metabolism tending towards fat rather than glucose catabolism). Because of the difficulties of performing a battery of tasks in a field study, two laboratory-based experiments were then performed, the second differing from the first in studying a greater range of variables and more time-points during the daytime. These two studies also differed from the situation in Ramadan in that non-Muslim students were volunteers and fasting was performed for only one day. Many of the changes previously found in Ramadan were duplicated in this work, so justifying the use of laboratory experiments lasting one day and using non-Muslim subjects as a model for some of the problems present in Ramadan. However, it was also found that preparations before the fast were often less marked than was the case with Muslims in Ramadan, a difference that can be attributed to subjects' lack of experience of fasting as well as the amount of time spent fasting. A difficulty of interpretation in all these studies was that changes could be due to fasting and/or the length of sleep, which tends to decrease. These two factors were separated in the final experiment, an intervention study performed in the laboratory. This study compared effects of different durations of fasting (4, 8 or 16 h) upon a wide variety of measures (including subjective and objective assessments of performance, dehydration and responses to a short bout of exercise) - but with an unchanged amount of nocturnal sleep and daytime naps not allowed. Many of the negative effects observed in previous studies were present in this experiment also. These findings indicate that fasting was responsible for much of the change previously observed, though some effect of sleep loss, particularly if occurring on successive days (as would occur in Ramadan) cannot be excluded. One finding common to all studies was that tests of performance that had shown variations due to the combination of circadian influences, time awake and sleep loss in other experiments (including grip strength, the Stroop test and accuracy at throwing darts) seemed little affected. Possible reasons for these negative findings are discussed, together with further experiments to separate out effects of sleep loss and fasting, and the role of subjects' experience in studies of fasting. In addition, more detailed studies to investigate changes in sleep and the type and level of physical activities when fasting are proposed.

This thesis summarises a series of academic publications that make a contribution to the field of sports nutrition over a period of 30 years. It begins with research in the field of carbohydrate and endurance sport reflecting the early era of research into carbohydrate and endurance performance, and evolves into studies investigating the impact of sports nutrition and hydration on team sports. It presents papers and other peer reviewed outputs that focus on the application of scientific knowledge to enhance human performance, whilst demonstrating the increasing awareness of the relative importance of carbohydrate and hydration in a range of both female and male team and individual sports. The thesis also highlights the challenge faced by the manufacturers of sports nutrition products in making use of advances in science to develop new and innovative products. The thematic nature of this thesis shows how sports nutrition continues to evolve. As science identifies new and legal means of enhancing human performance, so sport, athletes and coaches will demand more advanced and specialised approaches to refuelling and hydration. This thesis draws together findings from a series of publications which demonstrate how scientists, coaches, athletes and sports nutrition manufacturers need to work closely together to research, identify and interpret the next stages in an exciting and demanding area of research. It also reflects the scientific advancement in the field of sports nutrition over a thirty year period, identifies possible areas for future research, and the continued application of hydration and nutrition strategies to enhance male and female endurance and team sports.

At present, the process of parental modelling of eating behaviours and attitudes has received limited research interest. While often mentioned as a possible factor in relation to child feeding and the development of eating behaviours, only a few studies have explicitly researched parental modelling. The main aims of this thesis were to develop a new measure to assess modelling multidimensionally and to explore the relationships between parental modelling of eating behaviours with a variety of parent and child factors. Initially, a parental self-report measure (the Parental Modelling of Eating Behaviours Scale; PARM) was developed, validated and piloted as part of a series of studies exploring the associations between modelling and a range of self-reported parental and child factors. To provide further validation for the PARM, an observational coding scheme was developed, based on the newly developed modelling measure, and this was utilised in two further studies which looked at self-reported and observed parent and child factors. The key findings from this thesis suggest a number of beneficial relationships. For example, maternal modelling was positively correlated with healthy food intake in both mothers and their children. In addition, both maternal and paternal modelling were associated with children s increased enjoyment of food and lower levels of food fussiness. Observations of maternal modelling were also found to be positively related to other observed adaptive, non-directive feeding practices, such as encouragement to eat. However, less positive relationships were also identified, with modelling being related to parents mental health symptoms and to unhealthy food intake in both mothers and their children. In conclusion, this thesis has identified three distinct facets of modelling and highlighted factors which might be linked to parental role modelling around eating behaviours. While much of the research within this thesis is exploratory, and the findings require replication, they would suggest that parental modelling has the potential to positively influence children s eating behaviours. However, parents should also be made aware of the potential detrimental effect that modelling less adaptive eating behaviours may have on their children s food intake, particularly those eating behaviours that parents may be unaware of modelling.

Objectives. This study aimed to provide data on water intake from food and beverages of free-living adults in their natural environment, and investigate how this is affected by physiological, psychological, social and environmental factors. A further aim was to monitor the hydration status of free-living adults and relate this data to water intake. Methods The consumption of all food and beverages was recorded in a diary over three consecutive days by 80 healthy adults (40 males, 40 females), aged 18 to 65 years, who were instructed to continue their normal eating and drinking habits and lifestyles throughout the study. The data was analysed to determine total daily water intake and how this was affected by time of day, day of the week, presence of others, location of consumption, age and subjects mood. A further 20 healthy subjects (10 males, 10 females) repeated these procedures but also had blood samples taken for monitoring of blood indices (haemoglobin concentration, haematocrit, sodium concentration, and potassium concentration) and provided urine samples for the measurement of urine indices (volume, colour, specific gravity, osmolality and sodium, potassium, chloride, and creatinine concentrations). Results The total volume of water consumed by the 80 subjects was 2229  882 ml/day (mean  standard deviation). Females tended to consume more water than males (2402  827 ml/day vs 2056  911 ml/day, P = 0.079). Similar volumes were consumed by the additional 20 subjects in the hydration status study. Females appeared euhydrated; males appeared mild dehydrated, having a higher morning and 24-hour urine specific gravity and osmolality than females (P < 0.05, respectively). Conclusions The mean daily total volume of water consumed by females in this study was greater than the adequate intake value set by the European Food Safety Authority; for males it was lower. Females were euhydrated during the study but males tended to be mild dehydrated, reflecting their comparative water intakes.

This thesis used fifty hours of naturally occurring video and audio taped data from the ‘weigh-in' section of four commercial weight management groups in the East Midlands of England. This thesis is a discursive psychological and conversation analytic investigation of the turn-taking organization of the talk, examining what the group leaders and members make relevant in their talk about food and dieting. The data was transcribed using the Jeffersonian method. Group members attend the group weekly, and are weighed - their weight gain, loss or maintenance is recorded on a membership card. The analytic chapters follow the format of the ‘weigh-in' section of the meeting exploring firstly how the group leaders and members manage the practices of getting ready to be weighed; then how the ‘news' of weight gain, loss or maintenance is told and receipted; before exploring how ‘advice-giving' is constructed and the final analytic chapter deals with the issues of morality and accountability in the leaders' and members' talk. Analysis shows that the ‘pre-weigh in practices' involved before the group members are weighed consists of two robust patterns, 1) the practice of getting undressed is not oriented to by either the group members or group leaders and the group leaders avoided direct eye contact and concerned themselves with other business or 2) when no undressing practices took place, the group leaders were much more comfortable with direct eye contact. These sequences show how the body and its practices are constructed in particular ways within, and as part of the practices of getting ready to be weighed. Analysis showed the telling and receipting of weight news gets done differently depending on whether the group members have gained, lost or maintained weight. When the news concerned weight gain, the sequence included a ‘pre-announcement' and the news TCU was punctuated with marked trouble. When the news concerned weight loss, only the group members produced a pre-account and the news TCU contained no marked trouble. Finally, when the group members had maintained weight, the news TCU was delivered bluntly, and there was no evidence of trouble. In relation to advice-giving, analysis showed that group members repeatedly worked to assert their epistemic priority to avoid having to acknowledge the advice and the advice was receipted minimally. Finally, analysis showed that group members produced accounts with reference to a moral evaluation, such as blame or culpability. Sometimes an account was produced to circumvent being held publicly accountable for the event or action. It became apparent that both the group leaders and group members could not orient to themselves, their behaviour or food without it being constructed within a moral or accountable framework. Therefore, the thesis is an exploration of how group leaders and members manage the ‘dieting-practices' involved in getting weighed in a commercial weight management group and how using DP and CA can show the intricate turn by turn organization of such practices.