Heat therapy may be an alternative or adjunct intervention to exercise training for improving cardiovascular function and health. However, its prescription must be refined in order to overcome the feasibility and tolerability issues associated with current whole-body heating modes. There is substantial evidence to support the beneficial effects of high doses (e.g., frequency, duration, and intensity) of heating typically achieved using whole-body modes, but there is limited knowledge on whether lower doses of heating administered through local hot water immersion of the limbs can still have an impact on vascular function. All studies were conducted in heathy young men and women. In the first study, we found that regardless of whether local heating was applied to the lower limbs up to the ankles or knees, upper limb endothelial function and lower limb arterial stiffness improved acutely. In the second study, we proceeded to prescribe ankle-level heating in a chronic intervention and compared its effects to that of moderate-intensity cycling exercise training. We observed no changes in endothelial function, but decreases in central arterial stiffness and increases in cardiorespiratory fitness in those who performed heat therapy and exercise training combined with heat therapy. In the third study, we evaluated the ability of acute vascular function responses to predict chronic vascular function responses with heating and exercise interventions, and found significant positive associations between the acute and chronic responses for absolute and relative brachial artery flow-mediated dilation and femoral-foot pulse wave velocity. These findings suggest that, in healthy young men and women, local heating through ankle-level hot water immersion can improve indices of cardiovascular function both acutely and chronically, alone or combined with exercise training. Further, acute responses may be used to determine an individual’s chronic responsiveness to a heat therapy and/or exercise training intervention. More research in larger, more diverse samples and with a longer duration of therapy and/or training should be conducted to determine if the results are replicable. / Dissertation / Doctor of Philosophy (PhD) / Regular participation in whole-body heat therapy can extend health and life span, but it is used infrequently because of a lack of feasibility from a cost, accessibility, and tolerability standpoint. This thesis explored whether local heat therapy in young healthy men and women would be effective for improving blood vessel health defined as endothelial function and arterial stiffness, both of which are linked to the risk of developing many chronic diseases. Furthermore, the effects of local heat therapy were compared to that of exercise training. We found that there were beneficial short- and long-term effects of lower limb hot water immersion that manifested in different areas of the body. Local heat therapy improved upper limb endothelial function and lower limb arterial stiffness immediately after a session, whereas with repeated exposure, it may have improved central arterial stiffness and cardiorespiratory fitness. Exercise training only had beneficial effects on the blood vessels when combined with heat therapy. Finally, short-term vascular responses can predict long-term vascular responses to both heat therapy and/or exercise training. Overall, our findings suggest that there may be some utility for local heat therapy to promote healthy blood vessels, but more work must be done to replicate our findings and explore its effects on other populations.

Yes / Maintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use.

On average, starting an exercise training program decreases one’s risk for chronic disease. However, there is remarkable individual variability in physiologic responses to exercise training. The activity and inactivity during the remaining 95% of the day (when the individual is not training) is rarely considered. The overall objective of this dissertation was to apply validated sedentary behavior (SB) and physical activity (PA) measurement techniques during an exercise training study to determine if time spent in SB and PA outside of training influences the physiological response to training. Twenty subjects participated in a pilot study to determine the feasibility of reducing SB and the validity of PA monitors for measuring SB compared to direct observation (DO). Participants completed a 1-week baseline period and a 1-week intervention period, where they were instructed to decrease SB. The correlation between the AP and DO was R2=0.94 and the AG100 and DO sedentary minutes was R2=0.39. SB significantly decreased from 67% of wear time (baseline period) to 62.7% of wear time (intervention period) according to AP. Only the AP was able to detect reductions in SB and was more precise than the AG. Study Two was a 12-week randomized controlled study. There were 4-groups that were instructed to: 1) CON: maintain habitual PA and SB 2) rST: reduce and break-up SB and increase daily steps 3) EX: exercise 5-days per week for 40-minutes per session at moderate intensity 4) EX-rST: combination of EX and rST. Cardiovascular disease risk factors were assessed pre-and post-intervention. The AP was used to verify AP between-group differences in activity at four time-points. EX-rST had improvements in insulin action variables that EX did not. All other physiologic responses to training were similar between EX groups and rST has less robust changes than either EX group. These data provide validation of activity monitors for measuring SB and present preliminary evidence that activity outside of exercise training may influence the metabolic response to training. This dissertation shows that what is done outside of exercise training can and should be quantified using objective monitors that assess daily exposure to activity and inactivity behavior.

Bakgrund: Generaliserat ångestsyndrom (GAD) är en vanlig diagnos med negativa konsekvenser såväl på individ- som samhällsnivå. För att som fysioterapeuter kunna fånga upp den här typen av patienter och då ha god kunskap om olika träningsformer som tillförlitlig behandling ansågs det fördelaktigt att undersöka det vetenskapliga underlaget för styrketräning som behandlingsmetod. Syfte: Syftet med denna litteraturstudie var att undersöka det vetenskapliga underlaget för effekten av styrketräning, i jämförelse med annan eller ingen intervention, som behandlingsmetod för att minska oros- och ångestsymtom hos vuxna mellan 18-64 år med GAD. Metod: En litteraturstudie av randomiserade kontrollerade studier där populationen var vuxna mellan 18-64 år med GAD. Sökningar genomfördes i databaserna PubMed, Cochrane, PEDro och Psycinfo. Fyra studier inkluderades och granskades sedan med PEDro. Den sammanvägda tillförlitligheten av resultatet av tre studier bedömdes med hjälp av GRADEstud. Resultat: Det vetenskapliga underlaget för styrketräning som behandling för personer med GAD är för begränsat för att kunna dra några starka slutsatser. Alla inkluderade studier visade dock på reducering av oros- och ångestsymtom, som båda är kännetecknande symtom för GAD. Konklusion: Det sammanvägda resultatet indikerar på att styrketräning skulle kunna vara en alternativ behandlingsmetod för denna patientgrupp. Mer forskning behövs dock för att kunna utvärdera effekten av styrketräning som behandling för personer med GAD. / Background: Generalized anxiety disorder (GAD) is a common diagnosis with negative consequences both on an individual and societal level. In order for physiotherapists to be able to catch these patients and then have good knowledge of different forms of exercise as reliable treatment, it was considered beneficial to investigate the scientific basis for resistance exercise training as a treatment method. Objective: The aim of this literature review was to investigate the scientific basis for the effect of resistance exercise training, in comparison with other or no intervention, as a treatment method to reduce worry and anxiety symptoms in adults aged 18-64 with GAD. Method: A literature review of randomized controlled trials where the population was adults between 18-64 years old with GAD. Searches were conducted in the databases PubMed, Cochrane, PEDro and Psycinfo. Four studies were included and reviewed with PEDro. The combined reliability of the results of three studies was assessed using GRADEstud. Results: The scientific basis for resistance exercise training as a treatment for people with GAD is too limited to be able to draw any strong conclusions. However, all included studies showed a reduction in worry and anxiety symptoms, both of which are characteristic symptoms of GAD. Conclusion: The combined results indicate that strength training could be an alternative treatment method for this patient group. However, more research is needed to be able to evaluate the effect of strength training as a treatment for people with GAD.

The carotid artery wall moves longitudinally along the length of the vessel, although little is known about what causes this motion, or what health information it represents. The overarching purpose of this dissertation was to investigate the regulation of carotid artery longitudinal wall motion (CALM) in humans, as well as how CALM can be used to infer information about arterial health. Through observational and experimental designs, we tested evidence for a structural ventricular-vascular coupling effect, which postulates that systolic anterograde CALM is influenced by the forward blood shear rate while systolic retrograde CALM is influenced by left ventricular rotation, although the data suggests a moderate influence of left ventricular rotation, and minimal influence of shear rate. In cross-sectional analyses, we demonstrated that diastolic CALM variables are better related to age and health status compared to systolic CALM displacement and that this relationship was independent of traditional measures of arterial stiffness. These experimental and observational results directed the use of diastolic CALM as a potential indicator of arterial health in subsequent studies, due to the relative independence from systolic events. While there was no effect of 12-weeks of exercise training in healthy men on diastolic CALM variables, we observed increased systolic retrograde CALM and diastolic CALM acceleration in men with a history of resistance exercise training compared to sedentary men, suggesting an effect of habitual exercise training. Our novel findings suggest that CALM is regulated by a complex system, in part related to both arterial wall structure and ventricular-vascular coupling, and may have clinical value in complimenting measures of traditional arterial stiffness in humans. Future studies should examine whether local changes to arterial wall structure or indirect changes in regulatory control dictate differences in CALM with aging and with chronic exercise training, before integrating CALM into routine measurement of arterial health. / Thesis / Doctor of Philosophy (PhD) / We have known for a long time that arteries expand in order to absorb pressure; however, only recently have we identified that arteries also move longitudinally along the length of the arterial wall. The overarching purpose of this dissertation was to study what causes carotid artery longitudinal wall motion (CALM), and how we can use this information to understand arterial health. We demonstrated that CALM is partly controlled through the forward blood velocity wave and left ventricular rotation of the heart, and that diastolic CALM is uniquely related to aging and health status, but is not impacted by exercise training in healthy men. There are many aspects of CALM that need to be examined before wide-spread use, though our results indicate that CALM represents a new way of studying arterial health, which has the potential to complement traditional measures of cardiovascular disease risk in humans.

Die chronische Herzinsuffizienz gehört zu den häufigsten internistischen Krankheitsbildern in Europa. Eine wichtige Rolle in der Therapie der chronischen Herzinsuffizienz spielt das moderate körperliche Ausdauertraining. HDL ist als Vasoprotektor bekannt und ist in der Lage, über die Regulation der endothelialen Stickstoffmonoxidsynthase (eNOS) die Dilatationsfähigkeit von Gefäßen zu regulieren. Da eine gestörte Endothelfunktion verbunden mit einer geringeren eNOS-Expression einen wichtigen Aspekt in der Pathophysiologie der Herzinsuffizienz darstellt, war das Ziel dieser Arbeit zunächst, die HDL-induzierte eNOS-Aktivierung und NO-Produktion in Endothelzellen bei chronisch Herzinsuffizienten mit der von Gesunden zu vergleichen. Des Weiteren wurde der Einfluss körperlichen Ausdauertrainings auf die HDL-Funktion bei chronischer Herzinsuffizienz untersucht. Dafür wurde HDL jeweils aus Blutserum von herzgesunden Probanden und Herzinsuffizienten vor und nach körperlichem Ausdauertraining isoliert. Damit wurden humane aortale Endothelzellen inkubiert und anschließend mittels Western Blot die HDL-induzierte Phosphorylierung der endothelialen Stickstoffmonoxidsynthase (Regulation der eNOS-Aktivierung), der Proteinkinase C-βII sowie der p70S6K ermittelt. Des Weiteren wurde ESR-spektroskopisch die HDL-induzierte NO-Produktion in Endothelzellen gemessen. Letztendlich bestand die Frage, worin der Unterschied zwischen HDL von Gesunden und HDL von Herzinsuffizienten besteht, der die funktionalen Differenzen erklären kann. Dazu wurde die Menge des HDL-gebundenen Malondialdehyds ermittelt. Die Endothelfunktion wurde sonographisch als Fluss-vermittelte Vasodilatation bestimmt. Die Ergebnisse der Untersuchungen belegen, dass die HDL-induzierte eNOS-Aktivierung bei Patienten mit chronischer Herzinsuffizienz im Vergleich zu Gesunden vermindert ist. Des Weiteren kann der Einfluss von HDL auf die eNOS-Aktivierung durch körperliches Ausdauertraining bei Patienten mit chronischer Herzinsuffizienz verbessert werden. Die Verbesserung der HDL-induzierten NO-Produktion korreliert dabei mit der verbesserten Fluss-vermittelten Vasodilatation. Als Unterschied zwischen HDL von Gesunden und dem von chronisch Herzinsuffizienten konnte bei den Letztgenannten eine höhere Menge von gebundenem Malondialdehyd nachgewiesen werden.

Proximal stability, or the ability to stabilize and actively control the spine, pelvis and trunk, has been reported to influence sport performance. Traditional training practices for the proximal segments have had little success improving sport performance. The purpose of this dissertation was to investigate the effects a sport specific proximal stability training program can have on throwing velocity and measures of muscular endurance and power which target the proximal segments of the pelvis, spine and trunk. A stratified randomized clinical trial was implemented with a pre- to post-intervention design. Forty-six healthy, Division III collegiate female softball (n=17) and male baseball (n=29) players were randomly assigned to one of two training groups for 7 weeks; a traditional endurance training group (ET) (n=21) or a power stability training group (PS) (n=25). The primary outcome measures were the change in peak throwing velocity/Kg of body weight in mph. Mean throwing velocity, power outputs from a one-repetition maximum chop test and lift test (watts/Kg body weight), and muscular endurance plank tests. Student’s independent t-tests were used to compare differences between change scores of all dependent variables. Peak throwing velocity change scores were significantly faster (ET= .21 ±.55 mph, PS= 3.4 ±1.1 mph, p< .001) in the PS at post-intervention when compared to the ET group. Change scores were significantly greater in the PS group for mean throwing velocity, (ET= 1.1 ±1.6 mph vs. PS= 3.7 ±1.8 mph, p< .001), chop (watts), (ET= 20 ±78 watts vs. PS= 105 ±68 watts, p< .001), and lift, (ET= 49 ±62 watts vs. PS= 114 ±73 watts, p= .003). There were no change score differences for the side and prone plank endurance measures in seconds (p≥ .60). The PS group increased primary outcome measures over the ET program, indicating a more sport specific training regimen targeting the proximal segments is beneficial to both the power measures and throwing performance.

The hyperbolic relationship between power output and endurance time can be measured using all-out exercise. The aims of this thesis were to (i) assess whether the all-out test could be used under novel testing protocols to provide valid power-duration (P-D) parameter estimates; and (ii) attempt to elucidate the likely physiological composition of the P-D curvature constant. All-out tests were initiated from moderate-(M), heavy-(H) and severe-(S2 & S4) intensity ‘baselines’ (chapter 4). The work performed above end power (WEP) was not different to control under M or H conditions but was significantly, predictably reduced under the S2 & S4 conditions (control: 16.3 ± 2.2; M: 17.2 ± 2.4; H: 15.6 ± 2.3 kJ, P > 0.05; S2: 11.5 ± 2.5; S4: 8.9 ± 2.2 kJ, P < 0.05). The 3-min all-out test end power (EP) parameter was unaffected. Muscle glycogen may form part of the WEP. Type I (T1) and type II (T2) muscle fibres were depleted of their glycogen content prior to the all-out test (chapter 5). EP and WEP were unaffected by either T1 or T2 glycogen depletion. The all-out tests was conducted under hypoxic conditions alongside the criterion assessment of the P-D relationship (chapter 6). Normobaric moderate hypoxia caused a reduction in CP (control: 175 ± 25; hypoxia: 132 ± 17 W, P < 0.001) without affecting W′ (control: 13.2 ± 2.2; hypoxia: 12.3 ± 2.7 kJ, P > 0.05). The 3-min all-out test provided EP and WEP estimates, which did not differ to CP and W′ (control: EP 172 ± 30 W, WEP 12.0 ± 2.6 kJ; hypoxia EP 134 ± 23 W, WEP 12.5 ± 1.4 kJ, P > 0.05) providing the ergometer resistance was adjusted for the hypoxic conditions. Furthermore, a significant negative relationship was observed between %∆ ( O2peak – CP) and %∆W′ (r = -0.83, P < 0.001); thus, W′ may represent the relative ‘size’ of the severe-intensity domain. The all-out test was used to track training-induced changes in P-D parameters in response to 6-weeks of sprint or endurance training (chapter 7). EP & WEP were differently altered compared to CP and W′ following sprint training (CP 12 ± 9; EP -0 ± 9 % change; W′ -5 ± 25; WEP 11 ± 15 % change). The all-out test reliably tracked changes in CP and W′ following endurance training. In conclusion, the all-out test provides reliable EP and WEP values. Its validity is acceptable, but is perhaps affected by exercise training that is specific to the execution of the test. The W′ appears to be determined, to a large extent, by the relative size of the severe-intensity domain.

A caquexia associada ao câncer é uma síndrome multifatorial e multiorgão de etiologia desconhecida caracterizada por profunda perda de massa corporal. Assim, o presente estudo investigou o processo inflamatório sistêmico e no tecido adiposo subcutâneo e testou a hipótese de atenuação da inflamação pelo TF crônico em pacientes com caquexia associada ao câncer e controles. Pacientes foram distribuídos em seis grupos: Controles (Control SED e TR), portadores de tumor gastrintestinal sem caquexia (WSC SED e TR) e portadores de tumor gastrintestinal com caquexia (CC SED e TR). Observamos cessação da perda de massa corporal e ganho cardiorrespiratório (incremento de 209%) entres os pacientes caquéticos treinados e redução de colesterol total no CC TR, de LDL no CC SED e de HDL no CC SED e CC TR. O TF foi capaz de aumentar a concentração de HDL ao longo da intervenção (de 34,83 ± 4,74 mg/dL para 57,0 ± 3,42 mg/dL). Não encontramos diferenças entre as células imunitárias infiltradas no TASC dos pacientes avaliados. Esse é o primeiro estudo, de nosso conhecimento, que demonstra que o exercício físico realizado de forma crônica é capaz de reduzir a inflamação em pacientes com câncer caquéticos, atenuando os sintomas da síndrome. / Cancer cachexia is a multifactorial and multiorgan systemic syndrome with an unknown aetiology and characterized by a profound weight loss. Therefore, this study aimed to investigate the inflammation process in a systemic context and in the subcutaneous adipose tissue (SAT) and to evaluated the possible anti-inflammatory effects of the aerobic exercise in subjects with cancer cachexia. Patients were separated in six groups: Control (sedentary SED and trained TR), weight-stable patients with gastrointestinal cancer (WSC SED and TR) and patients with gastrointestinal cancer and cachexia (CC SED and TR). Cessation of weight loss and cardiorespiratory gain wre observed in the CCTR group and a reduction of total cholesterol in the CCTR group decreased in LDL in the CC SED group and HDL in the CC SED and CC TR groups. Physical exercise was able to increase serum HDL during the intervention. No differences were found in the immune cells infiltrating in the patients sAT (macrophages and MDSC). Inflammatory mediators changed by cachexia were modulated by ET. To our knowledge, this is the first study to demonstrate a reduction of inflammation and cachexia symptoms in cancer patients.

A caquexia do câncer é uma síndrome multifatorial cuja principal característica é a atrofia do músculo esquelético, resultando na progressiva incapacidade funcional do paciente. Essa síndrome está diretamente associada a uma redução da tolerância ao esforço físico e uma menor sobrevida em pacientes com câncer. O tratamento farmacológico para a caquexia ainda é muito limitado, possivelmente devido à característica multifatorial dessa síndrome. Nesse sentido, as evidências indicam que uma abordagem multimodal é necessária para atenuar a caquexia, incluindo estratégias não-farmacológicas como o treinamento físico. Contudo, os mecanismos envolvidos nos efeitos terapêuticos do treinamento físico sobre a caquexia do câncer ainda foram pouco explorados. Portanto, esse estudo teve como objetivo central avaliar os efeitos do treinamento físico aeróbio sobre a disfunção do metabolismo energético e a atrofia muscular em modelos experimentais de caquexia do câncer, além de explorar os mecanismos envolvidos nos possíveis efeitos terapêuticos do treinamento físico. Para isso, inicialmente padronizamos um modelo de caquexia em ratos utilizando injeção de células tumorais Walker 256 na medula óssea. Esse modelo apresentou consistente crescimento tumoral e atrofia muscular. Avaliamos sobre esse modelo os efeitos de dois protocolos diferentes de treinamento físico aeróbio, a saber: treinamento físico aeróbio contínuo em intensidade moderada (MIT, do inglês moderate intensity training) e o treinamento físico intervalado em alta intensidade (HIIT, do inglês high-intensity interval training). Embora não tenham sido observados efeitos sobre o crescimento tumoral, o MIT e o HIIT melhoraram a capacidade aeróbia e aumentaram a sobrevida dos animais, sugerindo que o treinamento físico aeróbio induz efeitos benéficos durante a progressão da caquexia do câncer. De fato, o HIIT normalizou marcadores de estresse oxidativo e reestabeleceu a função do músculo esquelético. Com o intuito de explorar mecanismos responsáveis por esses benefícios, realizamos uma análise proteômica de larga escala no músculo esquelético de ratos controle, do modelo Walker e do modelo Walker submetido ao HIIT. Nessa análise identificamos a COP9 signalosome complex subunit 2/Thyroid receptor interacting protein 15 (COPS2/TRIP15) como uma das principais proteínas alteradas, estando o seu conteúdo reduzido no músculo esquelético de ratos com caquexia e normalizado após a realização do HIIT. Resultados similares foram observados em outro modelo experimental de câncer (B16F10 em camundongos) submetido ou não ao HIIT. Na próxima etapa buscamos avaliar se a COPS2/TRIP15 poderia apresentar um papel terapêutico no músculo esquelético. Para isso, realizamos a superexpressão dessa proteína em miotubos primários de camundongos. Os miotubos foram incubados com meio de cultura previamente condicionado em células tumorais por 48 horas para induzir disfunção do metabolismo e perda de conteúdo proteico. Contudo, a superexpressão da COPS2/TRIP15 nos miotubos não foi suficiente para impedir os efeitos induzidos pelo meio condicionado. Em suma, essa tese de doutorado demonstrou que o HIIT foi capaz de atenuar a intolerância ao esforço físico e normalizar o conteúdo de COPS2/TRIP15 no músculo esquelético em diferentes modelos experimentais de caquexia do câncer. Esses resultados pré-clínicos abrem perspectivas de avaliar os efeitos do HIIT em pacientes com caquexia do câncer. Novos experimentos são necessários para entender a função da COPS2/TRIP15 no músculo esquelético durante a progressão da caquexia / Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle wasting, resulting in a functional impairment. This syndrome is associated with exercise intolerance and early mortality in cancer patients. Pharmacological treatment is still limited, perhaps due to the multifactorial characteristics of this syndrome. In this sense, evidences indicate that a multimodal approach is necessary to counteract cachexia, including non-pharmacological strategies, such as exercise training. However, little is known regarding the mechanisms underlying the potential therapeutic effects of exercise training on cancer cachexia. Therefore, the current study aimed to evaluate the effects of aerobic exercise training on metabolic impairment and skeletal muscle wasting in cancer cachexia experimental models. Additionally, we aimed to explore mechanisms involving the potential therapeutic effects of exercise training. For doing that, we first standardized a cancer cachexia rat model by injecting Walker 256 tumor cells in the bone marrow. This model displayed consistent tumor growth, skeletal muscle wasting and good reproducibility. By using this experimental model, we assessed the effects of two different aerobic exercise training protocols: moderate intensity training (MIT) and high-intensity interval training (HIIT). Even though tumor growth was not affected, both MIT and HIIT improved aerobic capacity and survival. Moreover, HIIT reestablished the skeletal muscle function and normalized oxidative stress markers. To further explore mechanisms underlying such benefits, we applied a proteomics screening in the skeletal muscle of 1) control rats, 2) rats with cancer cachexia and 3) rats with cancer cachexia submitted to HIIT. In this analysis, we identified COP9 signalosome complex subunit 2/Thyroid receptor interacting protein 15 (COPS2/TRIP15) as one of the most regulated proteins, showing lower content in the skeletal muscle during cancer cachexia progression, which was normalized after HIIT. Similar results were observed for B16F10 model in mice submitted or not to HIIT. We further assessed whether COPS2/TRIP15 could present a therapeutic role in the skeletal muscle. For doing that, we overexpressed this protein in primary mouse myotubes using an adenovirus. Cell culture media taken from tumor cells were incubated in the myotubes to induce metabolism impairment and loss of protein content. However, COPS2/TRIP15 overexpression was not sufficient to mitigate deleterious effects induced by the conditioned media. In summary, the current PhD thesis demonstrated that HIIT mitigated exercise intolerance and normalized COPS2/TRIP15 protein content in the skeletal muscle of different cancer cachexia experimental models. These pre-clinical data open perspectives to evaluate HIIT effects in cancer cachexia patients. New experiments are necessary to explore the role of COPS2/TRIP15 during cancer cachexia progression