Circulating MicroRNA-486 and MicroRNA-146a serve as potential biomarkers of sarcopenia in the older adults

Huang-Chun Liu, Der-Sheng Han, Chih-Chin Hsu, Jong-Shyan Wang, Huang-Chun Liu, Der-Sheng Han, Chih-Chin Hsu, Jong-Shyan Wang

Abstract

Background: Age-related sarcopenia meaningfully increases the risks of functional limitations and mortality in the older adults. Although circulating microRNAs (c-miRNAs) are associated with aging-related cellular senescence and inflammation, the relationships between c-miRNAs and sarcopenia in the older adults remain unclear. This study investigates whether circulating myo-miRNAs and inflammation-related miRNAs are associated with sarcopenia in the older adults.

Methods: This investigation recruited 77 eligible subjects (41 males and 36 females) from 597 community-dwelling older adults, and then divided them into normal (n = 24), dynapenic (loss of muscular function without mass, n = 35), and sarcopenic groups (loss of muscular function with mass, n = 18). Moreover, myo- (c-miRNA-133a and c-miRNA-486) and inflammation- (c-miRNA-21 and c-miRNA-146a) related miRNAs, as well as, inflammatory-related cytokine and peroxide levels in plasma were determined using quantitative polymerase chain reaction and ELISA, respectively.

Results: Sarcopenic group exhibited lesser skeletal muscle mass index (SMI), handgrip strength, and gait speed, as well as, lower c-miR-486 and c-miR-146a levels, compared to those of normal and dynapenic groups. Moreover, c-miR-486 level was positively related to SMI (r = 0.334, P = 0.003), whereas c-miR-146a level was positively associated with SMI (r = 0.240, P = 0.035) and handgrip strength (r = 0.253, P = 0.027). In the receiver operating characteristic analysis for predicting sarcopenia, the area under the curve in c-miR-486 was 0.708 (95% confidence interval: 0.561-0.855, P = 0.008) and c-miR-146a was 0.676 (95% CI: 0.551-0.801, P = 0.024). However, no significant relationships were observed between SMI/handgrip strength/gait speed and plasma myeloperoxidase/interleukin-1훽/interleukin-6 levels.

Conclusions: Myo-miRNA (c-miR-486) and inflammation-related miRNA (c-miR-146a) are superior to inflammatory peroxide/cytokines in plasma for serving as critical biomarkers of age-related sarcopenia.

Keywords: Aging; Cytokine; Sarcopenia; microRNA.

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1
Fig. 1
Flowchart of enrolled community-dwelling older adults included normal, dynapenic, and sarcopenic subjects during following-up. This study surveyed 597 participants who were recruited community-dwelling older adults. Exclusion criteria listed in the figure were used to recruit eligible candidates. Afterwards, eligible 77 subjects were enrolled into this study, and then divided into three groups: normal (n = 24), dynapenic (n = 35), and sarcopenic groups (n = 18)
Fig. 2
Fig. 2
Comparisons of circulating microRNAs ((A) c-miR-486, (B) c-miR-133a (n = 53, due to Ct number > 35), (C) cmiR-146a, and (D) c-miR 21) among various groups. N, normal group (n = 24); D, dynapenic group (n = 35); S, sarcopenia group (n = 18). *P < 0.05, N vs. D; # P < 0.05, N vs. S. +P < 0.05, D vs. S
Fig. 3
Fig. 3
Different normalization procedures of circulating miRNA levels are no significant changes. N, normal group (n = 24); D, dynapenia group (n = 35); S, sarcopenia group (n = 18). The concentration of c-miR-486 and c-miR-146a in plasma was quantified by normalizing with respect to c-miR-133a (n = 53, due to Ct number > 35) and c-miR-21(A;a), exogenous control cel-miR-39 (B;b), and a combination of both (C;c). P < 0.05
Fig. 4
Fig. 4
Association between: ashows the c-miR-486 and SMI (r = .334, p = .003); bshows the c-miR-146a and handgrip strength (r = .253, p = .027)
Fig. 5
Fig. 5
ROC curves analysis of c-miRNAs for predicting sarcopenia. a c-miR-486 AUC was .708 (95% CI: .561–.855, p = .008). b c-miR-146a AUC was .676 (95% CI: .551–.801, p = .024). ROC, receiver operating characteristic. AUC, areas under the curves. CI, confidence interval

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