The role of adenine nucleotide metabolism is central to the electro-mechanical processes in muscular contraction. Interventions which alter the cellular micro-environment can impact on the fatigue response during exercise possibly mediated by the balance between ATP and ADP. This thesis examined the response of biochemical and physiological markers of muscle fatigue in dietary interventions aimed to alter the cellular environment. Contractile measures included force and relaxation times from contractions of the knee extensors, whilst biochemical markers included anunonia and lactate after voluntary isometric and incremental cycle exercise. Evoked contractile measurements afforded experimental objectivity independent of voluntary intervention whilst the voluntary measures afforded greater transferability. In Chapter 3 the relaxation time response to a train of evoked fatiguing contractions varied depending on the choice of relaxation method (upper exponential, lower exponential, 60-40 exponential, 100-75,95-45,75-37.5,75-25%). Methods describing the earlier portions of the relaxation curve slowed less during fatigue than those comprising the latter portions. Intra-session variability ranged from 1.3 to 5.02% and inter-session variation ranged from 2.85 to 6.97% dependent upon the adopted relaxation method. Such variability was comparable with other laboratories demonstrating significant intervention-induced changes. This has implications for future studies in the choice of relaxation method and magnitude of change necessary for identification of intervention-induced changes. In chapter 4 the magnitudes of change in MVC and time to fatigue in a voluntary isometric contraction between creatine and placebo supplementation were -3% and 2% respectively. The fatigue-induced slowing of evoked relaxation times was greater by -4% and these changes were not significant. The differences in markers of adenine nucleotide degradation after creatine and placebo supplementation were also insignificant. In chapter 5 the creatine supplementation-induced change in the decline in evoked force during a fatiguing train was -1 % but was insignificant. For the voluntary and evoked relaxation times, in chapter 5, the magnitude of changes between placebo and creatine supplementation were <1 %, and insignificant. The ingestion of NaHCO, accelerated the loss of evoked force during a fatiguing train, with a trend towards shorter relaxation times that was only evident in the 100-75% method. Bicarbonate ingestion resulted in higher plasma lactate but had minimal effect on markers of adenine nucleotide degradation. The rate of evoked force loss was greater when muscle glycogen stores were reduced by exercise and low CHO diet and this trend was reversed by additionally supplementing with creatine, but this was not associated with similar trends in markers of nucleotide degradation during incremental cycling. A novel finding of this study was that reducing muscle glycogen resulted in a more severe slowing of relaxation times that was reversed when combined with creatine supplementation. In this thesis the changes in the biochemical markers of ADP homeostasis (NH,) by dietary interventions were insignificant. However, the force and relaxation time responses may highlight the functional importance of maintaining ADP homeostasis. The fatigue-induced slowing of evoked relaxation times was different depending on the chosen method. Despite a smaller relative slowing during fatigue the 100-75% method appeared to be most sensitive to dietary interventions.

Established models of endurance performance (Costill et al. (1973) Med Sci Sports 5(4): 248-252 and Coyle (1995) Ex. Sport Sci. Rev. 23:25-63) are based on the athlete's ability to maintain a fixed %V02peak, normally within the severe intensity domain, e.g. 88 %V02peak (exercise intensity domains being defined as; rest-moderate-heavy-severe-V02peak; Whipp (1994) Med. Sci. Sports Exerc. 26(11): 1319-13-26). The V02 slow component (V02SC) concept (Gaesser and Poole, 1996, Ex. Sport Sci. Rev. 24:35-70), which is based on observations from a healthy/sedentary populations', states that V02 continually increases within the severe intensity domain, and therefore undermines the validity of the performance models. This thesis examined the V02SC in an endurance trained cyclist population. Within the models, V02peak sets the ceiling for endurance performance. Current V02SC theory suggests that V02p"k assessment is protocol independent, as V02 continually increases within the severe intensity domain. This thesis demonstrated that V02peak was protocol dependent for 3 ramp protocols (35, 20 and 5 W.min-'), the V02SC being unable to generate a V02peak response from the 5 W.min-' protocol even though the subjects worked within the severe intensity domain. The V02SC definition states that V02 is elevated above values predicted from moderate intensity exercise at heavy, and increases continually, at severe exercise intensities. The endurance trained subjects demonstrated elevated steady state V02 responses at exercise intensities up to their endurance performance V02. This was within the severe intensity domain, thus validating the performance models for this subject population. The V02SC response in endurance trained cyclists differed from that previously observed for a sedentary/healthy population, therefore the currently accepted cause, increased fast twitch (FT) muscle fibre recruitment, may be questioned. Evidence from EMG studies suggest that muscle recruitment patterns differ between muscles, with increasing intensity (Green and Patla (1992) Med. Sci. Sports Ex. 24(1): 38-46). The recruitment patterns of three muscles were examined during incremental exercise to establish changes in both the magnitude of activation, and potential changes in fibre type recruitment (via the median frequency response). The pattern of muscle recruitment varied between both subjects and muscles. Changes in the recruitment patterns of a number of individual muscles were coincidental with the initiation of the V02SC. No coincidence between muscle fibre type recruitment (assessed via the EMG median frequency response) and the V02SC in endurance trained cyclists was observed. Therefore the V02SC may be due to changes in muscle recruitment patterns as well as FT fibre recruitment. The results of this thesis suggest that current models of endurance performance are valid for the endurance trained cyclist population studied, and that the V02SC concept should be redefined for this population. The V02SC response observed may be due to changes in muscle recruitment patterns and an increase in the number of motor units recruited, as median frequency EMG measures did not support the hypothesis that the V02SC is principally caused by an increased recruitment of FT muscle fibres.

One of the most popular sports globally, soccer has seen a rise in the demands of the game over recent years. An increase in intensity and playing demands, coupled with growing social and economic pressures on soccer players means that optimal preparation is of paramount importance. Recent research has found the modern game, depending on positional role, to consist of approximately 60% more sprint distance in the English Premier League, which was also found to be the case for frequency and success of discrete technical actions (Bush et al., 2015). As a result, the focus on soccer training and player preparedness is becoming more prevalent in scientific research. By designing the appropriate training load, and thus periodization strategies, the aim is to achieve peak fitness in the most efficient way, whilst minimising the risk of injury and illness. Traditionally, training intensity has been based on heart rate responses, however, the emergence of tracking microtechnology such as global positioning system (GPS) and inertial sensors are now able to further quantify biomechanical load as well as physiological stress. Detailed pictures of internal and external loading indices such as these then combine to produce a more holistic view of training load experience by the player during typical drills and phases of training in soccer. The premise of this research is to gain greater understanding of the physical demands of common training methodologies in elite soccer to support optimal match performance. The coaching process may then benefit from being able to prescribe the most effective training to support these. The first experimental chapter in this thesis began by quantify gross training loads of the pre-season and in-season phases in soccer. A broader picture of the training loads inherent in these distinct phases brought more detail as to the type and extent of external loading experienced by soccer players at these times, and how the inclusion of match play influences weekly training rhythms. Training volume (total distance) was found to be high at the start compared to the end of pre-season (37 kilometres and 28 kilometres), where high cardiovascular loads were attained as part of the conditioning focus. This progressed transiently, however, to involve higher-speed, acceleration and change-of-direction stimuli at the end of pre-season compared to the start and to that in-season (1.18 kilometres, 0.70 kilometres and 0.42 kilometres high-intensity running; with 37, 25 and 23 accelerations >3m/s2 respectively) . The decrease in volume and increase in maximal anaerobic activity was evident in the training focus as friendly matches were introduced before the competitive season. The influence of match-play as being a large physical dose in the training week may then determine the change in weekly periodisation and how resulting training loads applied and tapered, if necessary. The focus of research was then directed more specifically to the most common mode of training in soccer, that also featured regularly in the pre-season period in the present study, small-sided games (SSG). The subsequent studies examined numerous manipulations of this specific form of soccer conditioning, such as player numbers as well as absolute and relative playing space available. In contrast to some previous literature, changing the number of players did not seem to influence training responses significantly, although playing format in the possession style brought about larger effects for heart rate (89.9%HRmax) and average velocity (7.6km/h-1). However, the following studies (Chapters 5, 6 and 7) revealed a greater influence of relative playing space available to players in SSG. The larger area at their disposal brought about greater aerobic responses (~90%HRmax), by allowing higher average and peak velocities (>25km/h-1), as well as greater distance acceleration behaviour at greater thresholds (>2.8m/s2). Furthermore, the data points towards space as being a large determinant in strategy of the player in small-sided games (SSG), subsequently shaping their movement behaviour and resulting physical responses. For example, higher average velocities in a possession format (8km/h-1) reflects higher work rate and heart rate load but makes achieving significant neuromuscular accelerations at a high level difficult given higher starting velocities prior to the most intense accelerations (4.2km/h-1). By altering space available and even through intentional numerical imbalances in team numbers, it may be easier for coaches to achieve the desired stimulus for the session or individual player, whether that is for aerobic and neuromuscular conditioning. Large effects were found for heart rate being higher in the underloaded team (85-90%HRmax) compared to the team with more players (80-85%HRmax) as well as for RPE (5AU versus 7AU). This was also apparent for meterage and therefore average velocity. It would also seem neuromuscular load through high acceleration and deceleration efforts were more pronounced with less numbers (given the need to press and close down opponents) and in a larger area relative to the number of players on the underloaded team. The peak accelerations and deceleration achieved was also higher when playing with less players (3-6.2m/s2 and 3-6.1m/s2) Having detailed ways in which to reach desired physical loading responses in common small training formats, Chapter 8 compared SSG to larger 9v9 formats with full-size 11v11 friendly matches. This enabled absolute and relative comparisons to be made and to understand the extent to which smaller training formats are able to replicate the required movements to be successful in competition. In relative terms, it was revealed that relative acceleration distance and Player Load were higher in smaller 4v4 games than match-play (1.1m.min-1 and 0.3m.min-1 >3m/s2; 16.9AU versus 12AU). Although the smallest format did not replicate the high-velocity demands of matches, the results confirmed their efficacy in providing significant neuromuscular load during the training week, which may then be supplemented by high-intensity interval running in order to gain exposure to more maximal speed work. In summary, the data presented provide valuable information from GPS and inertial sensor microtechnology which may then be used to understand training better to manipulate types of load according to physical conditioning objectives. For example, a library of resources to direct planning of drills of varying cardiovascular, neuromuscular and perceptual load can be created to give more confidence in session outcomes. Combining external and internal load data of common soccer training drills, and their application across different phases and training objectives may give coaches a powerful tool to plan and periodize training.

Critical Power (CP) provides a useful indicator of training status in continuous activities lasting between approximately 2 and 30 minutes. To date, determination of CP has been mostly constrained to the laboratory. The conventional laboratory protocol commonly requires multi-day time-to-exhaustion tests. The thesis below addresses whether CP can a) be determined without multi-day exhaustive trials and b) be determined in the field. Studies compared the findings of conventional laboratory determination methods with novel protocols in which either the testing mode, the recovery period between exhaustive trials, or the environment were manipulated. Study 1 demonstrates that the recently developed 3-min all-out protocol does not result in valid CP values, when using the isokinetic ergometer mode. Results indicated low levels of agreement (mean of 23-45 W) between conventionally determined CP and values derived through the 3-min all-out protocol. The average prediction error associated with the relationship between CP and the 3-min all-out End Power was 7%. In Study 2, values of CP derived through a conventional laboratory CP protocol were compared with those determined outdoors on a cycling track. High levels of agreement (mean of 2 -14 W) were observed between the laboratory and field values of CP. The average prediction error associated with the relationship between laboratory and field CP was 2.2%. Based in the laboratory, Study 3 compares a 24 h recovery protocol with a 3 h and a 30 min recovery protocols. High levels of agreement (mean of -2 - 11 W and -2 - 8 W respectively) were observed across protocols. The average prediction error associated with the relationship between the 24 h and 3 h and the 24 h and 30 min protocols was 2.4% and 3.3% respectively, suggesting that determination of CP could be made more ‘athlete-friendly’ by shortening the conventional 3-day protocol to one day. Study 4 uses three protocols to evaluate the shortened 30 min protocol in ecological valid open road conditions. Values of CP derived from laboratory protocols were compared to a) those derived from pre-planned and ‘grouped’ maximal efforts of 3 min, 7 min and 12 min with a 30 min recovery period between efforts (protocol 1), b) those of discrete and randomly performed, yet still pre-planned maximal efforts of the same durations (protocol 2), and c) to those extracted from self-directed training and racing of these same durations (protocol 3). The average prediction error associated with the relationship between the laboratory and the field values of CP was 3.1% (protocol 1), 4.9% (protocol 2) and 4.1% (protocol 3). Results, whilst providing high levels of agreement, also suggested that in particular protocols 1 and 3 potentially provide a practical and arguably ecologically valid alternative to the conventional laboratory protocol. Study 5 further investigates the overall CP determination procedure by comparing collected values of CP derived through 3 data points with both, CP laboratory and field values derived through 2 data points. High levels of agreement and low prediction errors (average 3.2%) associated with the relationship between 3 data points and 2 data points-derived CP were observed. Studies collectively provide support for the acceptance of field performance testing using CP, with either a 30 min inter-maximal effort recovery period or alternatively the extraction of non-planned specified maximal efforts from training and racing data. Overall the investigations described in the thesis suggest that CP determination is feasible beyond the laboratory and that consumer-level technology provides satisfactory ease and reliability of measurement in this context. Moreover, these novel CP determination methods allow coaches to continuously monitor their athletes.

Unstable shoes are a unique category of footwear that provide a training stimulus during casual wear. Reported therapeutic benefits have led to their commercial success, although enhancing muscle activations and balance, normally associated with instability training devices like wobble boards, are not as effective. Therefore, the aim of this thesis was to develop and evaluate an unstable shoe that provides continually unpredictable perturbations. The notion was that a more challenging, and varied instability, alike uneven terrain, would provide an enhanced training stimulus. The first study investigated if the developed shoe with irregular midsole deformations (IM) was more demanding, alike uneven terrain, it was compared to an irregular surface (IS) and a stable shoe-surface during treadmill walking and running. Generally, IM increased instability compared to the control, demonstrated by a more cautious gait pattern and posture at initial contact, and subjectively perceived as less stable whilst walking and running. Certain responses in IM were similar to IS, such as the increased variability of frontal ankle motion and maximum sagittal knee angle in stance phase. This is proposed to benefit IM wearers by improving the level of functional joint variability. The second study assessed if the varied instability of IM would be more de-stabilising than an unstable shoe (US) by comparing joint stability strategies during walking and running. Results revealed joint stiffness reorganisations between the ankle and knee in IM and US during loading. Further joint stiffness re-distributions and increased ankle co-contraction were found in IM compared to US, indicating additional adaptations are required for stability. The third study revealed IM may similarly be beneficial in gym training, as adaptations were also triggered in forward and lateral lunge movements to maintain stability. Increased gastrocnemius medialis and peroneus longus activations were required for the push-off phase in lunges, which related to ankle position. Investigating short-term training effects after regular IM wear was not feasible with the prototype developed, so instead a 6-week IS walking intervention was undertaken, as similar responses were found to IM during locomotion in the first study. Results showed no significant improvements to ankle muscle strength and postural balance compared to a control group, who did not undertake a training intervention. This research revealed IM provided an innovative stimulus that increased instability compared to an US and simulated certain responses to an IS. Unpredictable instability provided by footwear may have potential use for injury prevention and rehabilitation interventions, but future work needs to assess which populations it benefits.

The foot forms the dynamic base upon which a sprinter functions. The actions that occur within the foot are of critical importance to the task of sprint running, since they influence the functional mechanisms of the entire body and especially the lower extremity. The aim of this research was to evaluate how foot function may contribute to sprinting performance and the interaction between the mechanical properties of sprinting footwear and performance, with a focus on the role of the metatarsophalangeal joint (MPJ). Currently, little is known about the effect of footwear upon the normal biomechanical function of the MPJ during sprinting, as this joint has often been neglected in previous biomechanical studies of lower limb energetics. A series of empirical and theoretical investigations were therefore undertaken to advance the understanding in this area. The initial study revealed the importance of two important methodological issues on the analysis of MPJ function during sprinting. Appropriate MPJ axes representation and appropriate data processing procedures are vital to ensure the accurate assessment of joint kinetics. Empirical investigations on eight trained sprinters performing maximal sprint trials, both in barefoot and sprint spike conditions determined normal patterns of foot behaviour and the role of the MPJ during sprinting. Several aspects of foot function, including kinematic, kinetic and pressure characteristics, were determined. Sprint spikes reduced MPJ range of motion and dorsiflexion velocity but increased total energy generated during the push-off phase, biomechanical measures which may be linked to sprinting performance. To investigate whether manipulations in the mechanical properties of sprinting footwear may influence sprinting performance and MPJ function, sprint spikes with insoles of varying stiffness's were manufactured and mechanically tested. For a group of sprinters increasing the sprint spike stiffness did not elicit an improved sprinting performance. Due to the high variability between athletes and highly individualised responses to perturbations in footwear a single- subject analyses was undertaken. This study demonstrated that individual sprinting performance may be improved by implementation of relevant shoe mechanical characteristics. Whilst varying the mechanical characteristics of sprint spikes clearly showed controlling influences over the natural motion of the MPJ, the relatively minimal effect on the resultant MPJ energetics, potentially suggests that sprint spikes do not minimise energy loss during sprinting. The combined empirical and theoretical understanding therefore highlighted several aspects of MPJ function which could be altered by footwear in an attempt to improve sprint running performance.

Aerobic power (VOzma) and cardiac output decrease in both sexes with age. Endurance exercise is known to affect cardiac structures and function, and could therefore attenuate the effects of ageing. However, recent studies have suggested that men and women of similar ages adapt differently to exercise training, including adaptations in cardiac function. In younger men and women, training modality is also an important determinant of improvements in cardiac function, but the full effects of exercise training need to be determined both centrally and peripherally. Cardiac power output (CPO) incorporates measurements of both blood flow (Q) and mean blood pressure (MAP), and is the most comprehensive .method of measuring overall cardiac function. In preliminary studies we elucidated the reliability and reproducibility of the C02 rebreathing technique used to determine Q, and the potential effects of caffeine ingestion on CPO. Then older men and women participated in 30 weeks of training, with step-wise increments in exercise intensity. This programme increased aerobic p~wer and increased the extraction of oxygen in the peripheries, but with no discernable effects on the heart's maximum pumping or reserve capacities. Six week endurance training (interval and continuous) of young men produced similar results. However using proteomics, interval training induced greater expressions of some contractile proteins, creatine kinase-M and heat shock protein 70 kDa, in the vastus lateralis muscle, suggesting possible conversion towards a faster muscle phenotype, but only in men. We conclude that endurance training with exercise intensities < 75 % HRR induces increases in VOZmax and peripheral adaptations in older people, but intensities >75 % HRR are needed to induce changes in cardiac function. We also found no discemable cardiovascular sex-specific differences in either young or older people after either interval or continuous exercise training. However, skeletal muscle exhibited contractile and metabolic adaptations to these training regimes, and these were sex-specific.

It is well documented that regular endurance exercise induces skeletal muscle mitochondrial biogenesis. However, the optimal training stimulus and nutritional intervention for which to maximize mitochondrial adaptations to endurance exercise is not well known. Developments in molecular techniques now permit the examination of the cell signalling responses to acute exercise therefore increasing our understanding of how manipulation of the training protocol and nutrient availability may enhance the training stimulus to a given bout of exercise. The primary aim of this thesis is to therefore characterise the skeletal muscle cell signalling responses thought to regulate mitochondrial biogenesis following an acute bout of high-intensity interval exercise and moderate- intensity continuous exercise. A secondary aim is to subsequently examine how manipulation of carbohydrate (CHa) availability may enhance the activation of key regulatory cell signalling pathways. The aim of the first study (Chapter 4) was to develop two exercise protocols of varied activity profile, which induced comparable total oxygen consumption and energy expenditure after being matched for average intensity, duration and distance ran. In a repeated measures and randomised design, eight active males performed an acute bout of high-intensity interval (HIT) running (6 x 3 min at 90 % V02max interspersed with 6 x 3 min at 50 % V02max also performed with a 7-min warm up and cool down at 70 % V02max) and an acute bout of moderate-intensity continuous (CaNT) running (50-m in continuous running at 70 % V02max). As a result of average intensity (70 % V02max) duration (50-min) and distance ran (9843 ± 176) being equal between protocols, total oxygen consumption (HIT; 162 ± 6, CaNT; 166 ± 10 L) and energy expenditure (HIT; 811 ± 30, CaNT; 832 ± 48 kcal) were matched between protocols (P > 0.05). Despite higher ratings of perceived exertion in HIT compared with CaNT (HIT; 14 ± 0.5, caNT; 13 ± 0.4 AU, P < 0.05), subjects reported greater ratings of perceived enjoyment in the HIT protocol (HIT; 87 ± 2, CaNT; 61 ± 4 AU, P < 0.05) according to the Physical Activity Enjoyment scale. By matching these two protocols for work done, these data therefore provided an appropriate framework for which to examine the molecular signalling responses of human skeletal muscle to acute HIT and CaNT. The aim of the second study (Chapter 5) was to characterise the skeletal muscle cell signalling responses associated with the regulation mitochondrial biogenesis following HIT and CaNT. In a repeated measures and randomised design, muscle biopsies (vastus lateralis) were obtained pre-, post- and 3 h post-exercise from ten active males who performed the HIT and CaNT protocols developed in Chapter 4. Despite the obvious difference in activity profiles between protocols, muscle glycogen (HIT; 116 ± 11, CaNT; 111 ± 17 mmol/kg dry wt) decreased similarly between protocols (P < 0.05), and phosphorylation (P-) of AMPK (HIT; 1.5 ± 0.3, CaNT; 1.5 ± 0.1) and p38MAPK (HIT; 1.9 ± 0.1, CaNT; 1.5 ± 0.2) increased immediately post-exercise before returning to baseline 3 h post exercise. P-p53 (HIT; 2.7 ± 0.8, CaNT; 2.1 ± 0.8) and expression of PGC-1a mRNA (HIT; 4.2 ± 1.7, CaNT; 4.5 ± 0.9) increased 3 h post-exercise in both HIT and CaNT though there were no difference between protocols (P > 0.05). Data therefore demonstrate comparable cell signalling responses between HIT and CaNT when matched for work done, average intensity, duration and distance ran. Furthermore, this is the first time exercise is shown to up-regulate p53 phosphorylation in human skeletal muscle therefore highlighting an additional pathway by which exercise may regulate mitochondrial biogenesis. Progressing from the role of the exercise stimulus in initiating mitochondrial biogenesis, the aim of the third study (Chapter 6) was to examine the effects of reduced CHO availability on modulating the exercise-induced activation of the cell signalling pathways as characterised in Chapter 5. Although HIT and CaNT protocols resulted in comparable signalling in Chapter 5, we chose HIT as our chosen exercise model given that it is perceived as more enjoyable than CaNT, has application for improving both human health and performance and also because of its relevance as a training modality for elite athletes in team and endurance sports. In a repeated measures and randomised design, muscle biopsies (vastus lateralis) were obtained from eight active males pre-, post and 3 h after performing an acute bout of high-intensity interval running with either high (HIGH) or low CHO availability (LOW). In LOW, subjects performed a bout of glycogen depleting exercise the night before and reported to the laboratory on the subsequent morning in a fasted state as well as restricting CHO before, during and after exercise. Subjects in HIGH CHO loaded for 24 h before reporting to the laboratory to perform HIT with CHO consumed before, during and after exercise. Resting muscle glycogen (HIGH, 467 ± 19; LOW, 103 ± 9 rnmol.kq" dw) and utilisation (HIGH, 142 ± 34; LOW, and 30 ± 12) was greater in HIGH compared with LOW (P < 0.05). Phosphorylation (P-) of ACCSer79 (HIGH, 1.4 ± 0.4; LOW, 2.9 ± 0.9), a marker for AMPK activity, and p53ser15 (HIGH, 0.9 ± 0.4; LOW, 2.6 ± 0.8) was higher in LOW immediately post- and 3 h post-exercise, respectively (P < 0.05). Before and 3 h post-exercise, mRNA content of PDK4, Tfam, COXIVand PGC-1a were greater in LOW compared with HIGH (P < 0.05) whereas CPT1 showed trend towards significance (P = 0.09). However, only PGC-1a expression was increased by exercise (P < 0.05) where 3-fold increases occurred independent of CHO availability. Data demonstrate that low CHO availability enhances p53 phosphorylation in a manner that may be related to upstream signalling through AMPK. Given the emergence of p53 as a potential molecular regulator of mitochondrial biogenesis, such nutritional modulation of contraction-induced p53 activation may have implications for both athletic and clinical populations. In summary, the work undertaken from the studies in this thesis provides novel information in relation to the regulation of exercise-induced cell signalling responses associated with mitochondrial biogenesis. Specifically, this is first report to examine cell-signalling responses to running exercise where comparable signalling between HIT and CaNT was observed when protocols are matched for average intensity and duration. Furthermore, these data provide the first report of an exercise-induced increase in p53 phosphorylation in which data demonstrate low CHO availability augments the exercise-induced increase in p53 signalling which may be related to upstream signalling through AMPK. Further studies would now benefit from addressing the nuclear and mitochondrial abundance of p53 in response to an acute exercise challenge as well as comprehensively examining how training status, exercise intensity and CHO availability affects p53 regulation and downstream target genes.

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