Exploring the role of mitochondria in the changes seen in overall skeletal muscle health associated with ageing and cancer

Purpose: Pathological and age-related declines in both physical fitness and muscle function are well established; however, the role mitochondrial function plays in these changes is less understood. With low skeletal muscle mass and function associated with poorer surgical outcomes, treatments and interventions that can limit the decrease in muscle mass and function seen in the elderly, known as sarcopenia, and in those with cancer, known as cancer cachexia, is vital. Methods: A systematic review and meta-analysis was conducted to determine the impact of sarcopenia on overall and disease-free survival in patients with locally advanced rectal cancer. In addition, young and older healthy volunteers were recruited to determine links between advancing age and declines in global physical fitness and muscle function, as well as investigate if similar declines in mitochondrial function occur. Results: Our systematic review and meta-analysis established that pre-existing sarcopenia was associated with shorter overall and disease-free survival in patients with locally advanced rectal cancer. Within our healthy volunteer cohort, age significantly impacted global physical function (HGS, 1-RM and VO2max) and measures of muscle architecture, with reduced status in older adults. Conversely, mitochondrial function was not different between the age-groups. Conclusions: There is clearly an age-related decline in global physical fitness and muscle function, however it remains unknown to what degree mitochondrial function is implicated in these changes. With sarcopenia and cachexia both having a negative impact on various prognostic outcomes, interventions such as exercise training regimes show promising results in improving cardiovascular fitness and muscle mass/ function in both elderly and cancer patients undergoing surgery. Despite this, if or how these interventions may modify any mitochondrial dysfunction that may exist, especially in cancer patients undergoing neoadjuvant treatment prior to surgery is wholly unknown. More ...