Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases.

Abstract

Simple SummaryAs we grow older, our muscles become smaller and weaker, a condition called sarcopenia. Several lung diseases can further worsen sarcopenia. Among them, COPD, asthma and tuberculosis are well-recognized causes of muscle loss. However, it is difficult and time-consuming to assess muscle health in elderly people with lung diseases. Here, we aimed to overcome this problem by measuring the blood levels of specific molecules that are related to muscle size and strength. We first show that elderly people with lung diseases have a greater degree of sarcopenia than healthy people. We then show that the blood levels of certain molecules (Dkk-3, CAF22, microRNAs) have varying degrees of associations with muscle size and strength in these patients. Thus, we propose that these molecules can be useful in assessing muscle health and the physical capacity of the elderly with lung diseases. Our findings have clinical applications since the quality and/or quantity of muscle tissues decide everyday lifestyle in the elderly, such as walking, lifting from chair and going to the bathroom etc. 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.