Background. Chronic aerobic exercise training is associated with improved endothelial function and arterial stiffness and favourable long-term cardiovas

Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but the possibility of heterogeneous responses between muscles and across time remains unclear. Using mice inoculated with Colon-26 cancer, we demonstrate that specific force production was reduced in quadriceps and diaphragm at 2 weeks in the absence of atrophy. At this time, pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H ₂ O ₂ emission was elevated in diaphragm. By 4 weeks, atrophy occurred in both muscles, but specific force production increased to control levels in quadriceps such that reductions in absolute force were due entirely to atrophy. Specific force production remained reduced in diaphragm. Mitochondrial respiration increased and H ₂ O ₂ emission was unchanged in both muscles versus control while mitochondrial creatine sensitivity was reduced in quadriceps. These findings indicate muscle weakness precedes atrophy and is linked to heterogeneous mitochondrial alterations that could involve adaptive responses to metabolic stress. Eventual muscle-specific restorations in specific force and bioenergetics highlight how the effects of cancer on one muscle do not predict the response in another muscle. Exploring heterogeneous responses of muscle to cancer may reveal new mechanisms underlying distinct sensitivities, or resistance, to cancer cachexia.

Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, involves the rapid deterioration of motor neurons resulting in severe muscle atrophy and respiratory insufficiency. It is considered a "multisystemic" disease with many potential mechanisms responsible for its pathology. Currently, there is no cure for ALS. Exercise training is suggested as a potential approach to reduce ALS pathology, but its beneficial role remains controversial. This review provides an overview of the effects of exercise training in ALS-affected mice and patients. It will compare the intensity, duration, and type of exercise on the health of SOD1G93A mice, a mouse model of familial ALS, and review clinical studies involving ALS patients undergoing both endurance and resistance training. In summary, mild-to-moderate swimming-based endurance training appears the most advantageous mode of exercise in SOD1G93A mice, improving animal survival, and delaying the onset and progression of disease. Furthermore, clinical studies show that both endurance and resistance training have an advantageous impact on the quality of life of ALS patients without extending life expectancy. However, small sample sizes, non-representative control populations, heterogeneous disease stage of patients, and the presence of confounders often exist in the exercise studies conducted with ALS patients. This raises concerns about the interpretation of these findings and, therefore, these results should be considered with caution. While promising, more pre-clinical and clinical studies with improved experimental design and fewer limitations are still necessary to confirm the impact of exercise training on the health of ALS patients.

Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND), is a fatal motor neurone disorder. It results in progressive degeneration and death of upper and lower motor neurones, protein aggregation, severe muscle atrophy and respiratory insufficiency. Median survival with ALS is between two to five years from the onset of symptoms. ALS manifests as either familial ALS (FALS) (~10% of cases) or sporadic ALS (SALS), (~90% of cases). Mutations in the copper/zinc (CuZn) superoxide dismutase (SOD1) gene account for ~20% of FALS cases and the mutant SOD1 mouse model has been used extensively to help understand the ALS pathology. As the precise mechanisms causing ALS are not well understood there is presently no cure. Recent evidence suggests that motor neuron degradation may involve a cell non-autonomous phenomenon involving numerous cell types within various tissues. Skeletal muscle is now considered as an important tissue involved in the pathogenesis of ALS by activating a retrograde signalling cascade that degrades motor neurons. Skeletal muscle heath and function are regulated by numerous factors including satellite cells, mitochondria and microRNAs. Studies demonstrate that in ALS these factors show various levels of dysregulation within the skeletal muscle. This review provides an overview of their dysregulation in various ALS models as well as how they may contribute individually and/or synergistically to the ALS pathogenesis.

Cancer cachexia (CC) is a multifactorial syndrome characterised by unintentional loss of body weight and muscle mass in patients with cancer. The major hallmarks associated with CC development and progression include imbalanced protein turnover, inflammatory signalling, mitochondrial dysfunction and satellite cell dysregulation. So far, there is no effective treatment to counteract muscle wasting in patients with CC. Exercise training has been proposed as a potential therapeutic approach for CC. This review provides an overview of the effects of exercise training in CC-related mechanisms as well as how factors such as cancer comorbidities, exercise modality and biological sex can influence exercise effectiveness in CC. Evidence in mice and humans suggests exercise training combats all of the hallmarks of CC. Several exercise modalities induce beneficial adaptations in patients/animals with CC, but concurrent resistance and endurance training is considered the optimal type of exercise. In the case of cancer patients presenting comorbidities, exercise training should be performed only under specific guidelines and precautions to avoid adverse effects. Observational comparison of studies in CC using different biological sex shows exercise-induced adaptations are similar between male and female patients/animals with cancer, but further studies are needed to confirm this.