MiRNA Profiles On Sarcopenia Components To Explore Biomarkers Of Sarcopenia In Older Adults

MicroRNAs (miRNAs), short, non-coding RNA molecules that regulate gene expression at translational level, are recently emerging as potential biomarkers for sarcopenia. The miRNAs have been extensively studied in etiology of sarcopenia; however, the role of miRNAs on sarcopenia components has not yet been explored. PURPOSE: We aimed to examine the differentially expressed (DE) miRNAs in plasma of older adults in relation to muscle mass, strength, and performance status, and to identify biological pathway associated with DE miRNAs. METHODS: A total of 169 older adults (mean age: 77.5 ± 3.7 years; women: 52.1%) were randomly selected and matched by age and sex from the Korean Frailty and Aging Cohort Study. The participants were categorized into 7 groups based on criteria of Asian Working Group for Sarcopenia 2019: “Control” (n = 25), “Low muscle mass (LMM) only” (n = 23), “Low muscle strength (LMS) only” (n = 25), “Low physical performance (LPP) only” (n = 23), “LMM and LMS” (n = 23), “LMM and LPP” (n = 25), and “LMS and LPP” (n = 25). MiRNA profiles, derived from miRNA sequencing, were established via screening for DE miRNAs in 7 group. The target genes of screened DE miRNAs were examined for identifying biological pathway. RESULTS: MiRNA profiling revealed that 20 miRNAs and 76 miRNAs were differentially expressed in LMM and LMS group and LMM and LPP group compared to Control, respectively (fold change [FC] > 2; FDR p-value <0.05). Of them, 18 DE miRNAs were commonly expressed in two group. To further examine an independent association of DE miRNAs with muscle strength and physical performance, the miRNAs expression in LMM and LMS group and LMM and LPP group were adjusted to that in LMM only. MiR-1227-3p, miRNA-144-3p, miR-142-3p, and miR-101-3p, were upregulated in LMM and LMS group (FC = 2.3; FC = 2.0; FC = 1.5; FC = 1.3; FDR p-value <0.05) and in LMM and LPP group (FC = 4.2; FC = 2.1; FC = 2.7; FC = 2.1; FDR p-value <0.05), compared to LMM only. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses revealed that four miRNAs were mainly related to MAPK, FOXO, autophagy, and longevity regulating pathway (p < 0.05). CONCLUSION: Identification of miRNA profiles for muscle strength and physical performance, independent of muscle mass, can provide a basis for the discovery of biomarkers of sarcopenia in older adults. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIT) (No. 2022R1A2C1012305; RS-2023-00213338)