Candidate mechanisms underlying effects of contractile activity on muscle morphology and energetics in cancer...

Skeletal muscle wasting is a prominent pathophysiological feature of cancer cachexia. Recent evidence suggests the manifestation of mitochondrial dysfunction along with a diminished oxidative capacity. These abnormalities have been concurrently observed with impaired muscle force production and the accelerated onset of fatigue in both tumour-bearing animals and cancer patients exhibiting wasting. To address the burden imposed by cachexia, nutritional and pharmacological interventions have been investigated extensively; in contrast, contractile activity-based countermeasures (i.e. exercise training) have been less frequently explored. Although limited, several preclinical studies that implemented contractile activity have reported favourable outcomes such as the retention of muscle mass and the restoration of energetic homeostasis. Even fewer investigations have examined the mechanisms accounting for these protective effects. An experimental approach addressing contractile activity-dependent expression of muscle mass and energy metabolism regulators may yield information that provides mechanistic support for exercise countermeasures. In this review, we present several candidate mechanisms underlying the protective effects of contractile activity as support for exercise countermeasure strategies. Given the limited quantity of data in this area, insights will be derived from studies on contractile activity-dependent modulation of common cellular and molecular events regulating muscle morphology and energetics during other muscle wasting conditions (e.g. sarcopenia).