Cancer cachexia prevention via physical exercise: molecular mechanisms

Abstract

Cancer cachexia is a debilitating consequence of disease progression, characterised by the significant weight loss through the catabolism of both skeletal muscle and adipose tissue, leading to a reduced mobility and muscle function, fatigue, impaired quality of life and ultimately death occurring with 25–30 % total body weight loss. Degradation of proteins and decreased protein synthesis contributes to catabolism of skeletal muscle, while the loss of adipose tissue results mainly from enhanced lipolysis. These mechanisms appear to be at least, in part, mediated by systemic inflammation. Exercise, by virtue of its anti-inflammatory effect, is shown to be effective at counteracting the muscle catabolism by increasing protein synthesis and reducing protein degradation, thus successfully improving muscle strength, physical function and quality of life in patients with non-cancer-related cachexia. Therefore, by implementing appropriate exercise interventions upon diagnosis and at various stages of treatment, it may be possible to reverse protein degradation, while increasing protein synthesis and lean body mass, thus counteracting the wasting seen in cachexia.

Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment

“…102,103 Evidence of positive effects on fraility and sarcopenia through exercising are emerging. 102,[104][105][106][107][108] Recently, an exercise investigation focused on muscle quality in men and women aged 50 years and older suggested that long-term exercise, especially resistance exercise, is beneficial for muscle quality. 109 Interestingly, people over 60 years, who perform aerobic exercise once a week, also show positive association to muscle quality.…”

The wasting continuum in heart failure: from sarcopenia to cachexia

“…Exercise training is also being advocated for patients with cancer in order to improve their exercise capacity and quality of life (78,79) . The present guidelines for HF management by the European Society of Cardiology state that 'it is recommended that regular aerobic exercise is encouraged in patients with HF to improve functional capacity and symptoms (80) .…”

Clinical Implementation of Exercise Guidelines for Cancer Patients: Adaptation of ACSM’s Guidelines to the Italian Model

“…It is well documented that tumorgenesis and cancer treatment is associated with adverse physical and physiological changes leading to metabolic and functional modifications, inducing pathologies of the cardiac, pulmonary, neural, bone and skeletomuscular systems [2]. These alterations effect cardiorespiratory capacity (fitness), strength, body composition, and physical function including immune system integrity, peripheral neuropathy, and quality of life [3][4][5][6][7][8]. However, it is increasingly clear that prescribing exercise during and post-cancer treatment may mitigate many of these adverse changes (Table 1) by decreasing tissue inflammation contributing to tumorgenesis [9][10][11][12][13][14].…”