Circulating MicroRNAs in Plasma Decrease in Response to Sarcopenia in the Elderly

Abstract

sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is a major cause of morbidity and mortality in elders. Current diagnostic criteria of sarcopenia have not been agreed internationally, and the clinical diagnostic biomarkers for sarcopenia have not been identified. Circulating miRNAs (miRNAs, miRs) have recently been characterized as novel biomarkers for sarcopenia. However, the change of circulating miRNAs in response to sarcopenia are still not fully understood. Here, we enrolled a total of 93 elderly patients clinically diagnosed with sarcopenia and matching 93 non-sarcopenia elderly in this study. Specifically, levels of candidate circulating miRNAs which were involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were detected in these two groups. In small-sample screening experiments, plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels were significantly downregulated in sarcopenia compared to those who non-sarcopenia. In contrast, miR-1, mir-133a, miR-133b, miR-21, miR-146a, miR-126, miR-221, and miR-20a were not changed significantly. Subsequently, we expanded the sample size to further detection and verification, and found that plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels in the sarcopenia group were significantly reduced compared to the non-sarcoma group, which is consistent with the results of the small-sample screening experiment. In addition, we showed that ASM/Height2, handgrip strength, knee extension and 4-meter velocity in sarcopenia group were significantly lower than those in non-sarcopenia group. Here we correlated the decrease of miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 in sarcopenia group and non-sarcopenia group with diagnostic indexes of sarcopenia (ASM/Height2, Handgrip strength and 4meter velocity) after adjusting sex. The results showed that miR-208b and miR-155 changes were significantly correlated with handgrip strength in woman, miR-208b, miR-499, and miR-222 changes were significantly correlated with ASM/Height2 in man, while other miRNAs changes did not show a strong correlation with these diagnostic indexes. In conclusion, plasma miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210

Sarcopenia associates with SNAP-25 SNPs and a miRNAs profile which is modulated by structured rehabilitation treatment

“…Intriguingly, the concentration of six of these miRNAs in sarcopenic patients before treatment was similar to that observed in healthy controls, suggesting that their modulation is due to rehabilitation and not to pathology, an unexpected result that will need to be further analyzed. To note, miR-155-5p was found to be up-regulated in muscles of elderly people [ 55 ] whereas, in accordance with our results, its circulatory expression was seen to be down-regulated in sarcopenic patients compared to controls [ 53 ].…”

Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

“…Bulge-Loop TM miRNA qPCR Primer Sets (RiboBio) were used to detect selected miRs expressions by qRT-PCRs with iTaqTM Universal SYBR Green Supermix (BIO-RAD) as described elsewhere [ 28 ]. Reverse transcription of the miRs into cDNA was achieved with the TaqMan microRNA reverse transcription kit (Thermo Fisher, Dubai, UAE) [ 29 ] and TaqMan microRNA assays specific for selected miRs (Applied Biosystems, Thermo Fisher, Dubai, UAE) according to the manufacturer’s recommendations.…”

Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing

“…Most miRNAs are first transcribed into primary miRNAs (pri-miRNAs), processed by the RNase III enzymes Drosha, forming precursor miRNAs (pre-miRNAs), and Dicer, yielding mature miRNAs [269][270][271]. Recent reviews and systematic analyses of microarrays and next-generation sequencing have highlighted a plethora of miRNAs that are differentially expressed in skeletal muscle and/or plasma with ageing and muscle wasting, though the functional roles of many of these novel miRNAs remain to be elucidated [89,[272][273][274][275]. Similarly, within metabolic tissues and the circulation, numerous miRNAs have been implicated in the pathological development of obesity and may serve important functions in metabolic organ cross talk [276][277][278][279][280][281].…”