The Severity of Muscle Performance Deterioration in Sarcopenia Correlates With Circulating Muscle Tissue-Specific miRNAs

Abstract

Sarcopenia is defined as an age-associated loss of skeletal muscle function and muscle mass and is common in older adults. Sarcopenia as a disease is currently of interest not only to orthopedists and surgeons but also to internists, endocrinologists, rheumatologists, cardiologists, diabetologists, gynaecologists, geriatricians and paediatricians. In cooperation with the 5th Internal Medicine Clinic, we, as a unit of clinical research, aimed to describe a sarcopenic specific miRNA expression profile for disease diagnostics and classification of the severity of muscle performance deterioration. This study included a total of 80 patients (age 55-86 years) hospitalized at the V. Internal medicine clinic of LFUK and UNB with different severity of muscle performance deterioration. The study participants were evaluated and classified according to short physical performance battery score (SPPB). In this study, we investigated the role of circulating miRNAs in sarcopenia in the elderly. We hypothesized that sarcopenia effects the expression of muscle tissue-specific miRNAs (MyomiRNAs), which could be potentially reflected in the blood plasma miRNA expression profile. The expression of specific circulating miRNAs in patients with different muscle performances was analyzed. Patients’ blood plasma was evaluated for the expression of myomiRNAs: miRNA-29a, miRNA-29b, miRNA-1, miRNA-133a, miRNA-133b, miRNA-206, miRNA-208b and miRNA-499, and the data were correlated with diagnostic indicators of the disease. We showed a specific sarcopenia miRNA profile that could be considered a possible biomarker for the disease. Patients with low muscle performance showed increased miRNA-1, miRNA-29a and miRNA-29b expression and decreased for the miRNA-206, miRNA-133a, miRNA-133b, miRNA-208b and miRNA-499 expression. We show that the severity of muscle performance deterioration in sarcopenia correlates with specific miRNA expression. We also propose the profile of miRNAs expression in blood plasma as a specific biomarker for sarcopenia diagnostics. Future clinical studies will be necessary to eventually naturally have to elucidate the underlined molecular mechanism responsible for specific miRNAs expression in sarcopenia pathology and progression of the disease.

Sharing Circulating Micro-RNAs between Osteoporosis and Sarcopenia: A Systematic Review

“…Chen et al [ 32 ], examining miR-1-3p, -21-5p, -23a-3p, -24-3p, -100-5p, -125b-5p, -133a-3p, and -206 in the serum of 65 patients, did not find a specific alteration of circulating miRs. In contrast to the study of Chen et al [ 32 ], other studies found that patients with low muscle performance (sarcopenic) showed increased expression of miR-1, miR-29a, and miR-29b, but also a decreased expression of miR-486, miR-146a, miR-206, miR-133a, miR-133b, miR-208b, and miR-499 [ 82 , 83 ]. Alteration in circulating miRs was also demonstrated by He et al: examining plasma from sarcopenic and non-sarcopenic patients showed that miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 were significantly down-regulated in sarcopenic compared to non-sarcopenic patients [ 80 ].…”

“…All the studies on sarcopenia [ 32 , 81 , 82 , 83 ] satisfied all the items in the QUADAS2, which suggests that the overall quality of the included studies was high.…”

“…Osteoporosis was diagnosed by DXA in ~65% of the studies (37/54 studies), which was sometimes also associated to pQCT, X-ray, physical examination, and FRAX tool [ 28 , 36 , 59 , 67 ]. Concerning sarcopenia, it was diagnosed by SPPB score, appendicular skeletal muscle mass (ASM) analysis, relative skeletal muscle mass index, and by grip strength, gait speed, and countermovement jumps tests [ 32 , 80 , 81 , 82 , 83 ]. The most common age group for osteoporosis, sarcopenia, and healthy controls was 60–75 years.…”

“…Some studies (17%) recruited younger participants in healthy control groups [ 38 , 41 , 42 , 44 , 47 , 59 , 60 , 71 , 78 ] and did not match for age, causing potential selection bias. Almost all the studies considered female osteoporotic and sarcopenic patients (76%), but 14/59 studies also included male patients [ 34 , 38 , 50 , 52 , 53 , 58 , 59 , 60 , 61 , 62 , 66 , 73 , 77 , 82 , 83 ]. Twelve studies on osteoporosis and two on sarcopenia did not state sex.…”

Shared and Divergent Epigenetic Mechanisms in Cachexia and Sarcopenia

“…In another study, Valášková et al analyzed the expression of myomiRs in blood samples of patients with low muscle performance [ 132 ]. Among many, they observed a decrease in the expression of miR-208b and miR-499.…”