Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

Abstract

Skeletal muscle dysfunction is a critical finding in many respiratory diseases. However, a definitive biomarker to assess muscle decline in respiratory diseases is not known. We analyzed the association of plasma levels of glycoprotein Dickkopf-3 (Dkk-3), c-terminal agrin fragment-22 (CAF22) and microRNAs miR-21, miR-134a, miR-133 and miR-206 with hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in male, 54–73-year-old patients with chronic obstructive pulmonary diseases (COPD), asthma or pulmonary TB (n = 83–101/group). Patients with respiratory diseases showed a reduction in HGS and gait speed, while a reduction in ASMI was only found in patients with pulmonary TB. Among the sarcopenia indexes, HGS showed the strongest correlation with plasma CAF22, miR-21 and miR-206 levels while ASMI showed the strongest correlation with Dkk-3 and miR-133 in respiratory diseases. We found a modest-to-significant increase in the plasma markers of inflammation, oxidative stress and muscle damage, which had varying degrees of correlations with Dkk-3, CAF22 and selected micro RNAs (miRs) in respiratory diseases. Taken together, our data show that plasma levels of Dkk-3, CAF22 and selected miRs can be useful tools to assess accelerated sarcopenia phenotype in the elderly with respiratory diseases.

Prediction of sarcopenia using a battery of circulating biomarkers

“…Sarcopenia and other catabolic conditions disrupt NMJ integrity via proteolytic cleavage of agrin into CAF22 that can be detected in circulation. We have previously shown that plasma CAF22 levels are increased in sarcopenia with pulmonary diseases 9 , 16 . Here, we confirm and extend these findings to sarcopenia with CHF.…”

“…Candidate biomarkers for sarcopenia were selected based on the relevant literature and our previous investigations in patients with normal and advanced phases of sarcopenia 9 , 10 , 16 . Among various candidates investigated, circulating levels of P3NP, CAF22, osteonectin, irisin, FABP3 and MIF were significantly different in the COPF and CHF subjects with advanced sarcopenia, when compared to age-matched healthy controls.…”

“…Among them, chronic obstructive pulmonary diseases (COPD) and congestive heart failure (CHF) are common drivers of sarcopenia in the elderly 10 , 14 . We have previously shown that patients with respiratory diseases have accelerated loss of muscle mass and strength than the age-matched healthy elderly 9 .…”

Intercellular Communication by Vascular Endothelial Cell-Derived Extracellular Vesicles and Their MicroRNAs in Respiratory Diseases

“…Although further studies will be needed to elucidate the pathogenic EC-EV functions in linking COPD to the comorbidities, circulating EC-EVs in patients with COPD might exacerbate systemic endothelial injury, potentially leading to the development of cardiovascular disease. As another example, several miRNAs, such as miR-21, miR-134a, miR-133, and miR-206, have been proposed as potential biomarkers of sarcopenia in patients with COPD, and the levels of miR-21 and miR-206 in particular are strongly correlated with hand-grip strength ( Qaisar et al, 2020 ). This suggests that EC-EVs may be involved in COPD-related sarcopenia pathogenesis, since miR-21 is enriched in EVs derived from senescent ECs as mentioned previously.…”

Molecular Regulation of Skeletal Muscle Growth and Organelle Biosynthesis: Practical Recommendations for Exercise Training

“…Skeletal muscles are essential for the maintenance of body’s integrity and health. Failure in muscle homeostasis leads to physiological integrity impairment, which contributes to chronic pathologies such as cachexia, metabolic and respiratory diseases, chronic inflammation, liver cirrhosis, and sarcopenia [ 1 , 2 , 3 , 4 , 5 , 6 ]. Muscle deficiency involves detrimental changes including deteriorations of cell metabolism and loss of muscle volume and strength, resulting in poor physical performance and quality of life [ 7 , 8 , 9 , 10 ].…”