Skeletal muscle dysfunction in COPD: miRNAs, myokines and exercise

COPD is a multifactorial and heterogeneous disorder, a leading cause of morbidity and mortality worldwide. Not only does its progression compromise lung function, but it is also associated to systemic complications, including skeletal muscle dysfunction. Skeletal muscle dysfunction affects up to 35% of individuals diagnosed with COPD and is marked by muscle atrophy and altered fibre composition, thus resulting in reduced strength, endurance and physical capacity with an increased mortality risk. Multiple factors, including physical inactivity, oxidative stress, chronic inflammation, mitochondrial dysfunction and impaired autophagy, contribute to the development of skeletal muscle dysfunction. Pulmonary rehabilitation, including exercise training, is a key nonpharmacological intervention that mitigates muscle dysfunction by enhancing protein synthesis and promoting beneficial systemic adaptations. These adaptations are mediated by molecular signals such as myokines and microRNAs (miRNAs), regulating inter-organ communication and gene expression relevant to muscle metabolism and homeostasis. Myokines act as messengers between skeletal muscle and other organs, while miRNAs play pivotal roles in muscle remodelling and exercise adaptation. Therefore, the modulation of specific miRNAs may be a promising therapeutic avenue for addressing skeletal muscle dysfunction in COPD. This review explores the interplay between myokines, miRNAs and skeletal muscle dysfunction in COPD and highlights the potential of miRNAs as biomarkers and therapeutic targets in pulmonary rehabilitation.