Circulating Cell-Free Mitochondrial DNA: A Potential Blood-Based Biomarker for Sarcopenia in Patients Undergoing Maintenance Hemodialysis

BACKGROUND: Mitochondrial impairment and exaggerated inflammation are hallmarks of sarcopenia. Recently, cell-free mitochondrial DNA (cf-mtDNA) has been in the spotlight as an endogenous danger molecule that can potentially elicit inflammation. Yet, its actual impact on sarcopenia, especially in patients with maintenance hemodialysis (MHD), is still at an early stage of investigation. MATERIAL/METHODS: A total of 105 MHD patients were enrolled in this study. The subjects were classified into sarcopenia group (SP) and non-sarcopenia group (NSP) according to the DXA scan and grip strength. Plasma and peripheral blood mononuclear cells (PBMCs) were separated from whole blood. Circulating cf-mtDNA (ccf-mtDNA) was detected using Taq Man RT-qPCR. Cytosolic mtDNA and inflammation- and mitophagy-related genes in PBMCs were quantitated using SYBR Green RT-qPCR. ΔΨm was analyzed using the fluorescent probe JC-1. RESULTS: ccf-mtDNA content was significantly higher in SP group than in NSP group. Multivariate regression analysis showed a significant correlation of ccf-mtDNA with sarcopenia after adjusting for potential confounders. A similar trend of increased mtDNA was also observed in the mitochondria-free cytoplasm of PBMCs from SP patients, together with higher expression of TLR9 and IL-6 in this group. Next, using PBMCs as surrogates for mitochondria-rich cells, we found that ΔΨm was dramatically decreased in the SP group. In parallel, the mRNA levels of mitophagy-related genes Parkin and LAMP2 were increased in the SP group. CONCLUSIONS: The results obtained demonstrated that ccf-mtDNA, as a potential driver of inflammatory component, may be involved in the pathogenesis of the MHD-related sarcopenia.