Circulating MicroRNAs in Plasma Decrease in Response to Sarcopenia in the Elderly
Nana He1,2, Yue Lin Zhang3, Yue Zhang3
1Department of Experimental Medical Science, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
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 down-regulated 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 4-meter 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 decrease in response to sarcopenia in the elderly. Although further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of sarcopenia, present findings set the stage for defining circulating miRNAs as biomarkers and suggesting their physiological roles in elderly with sarcopenia.
Insights
Sarcopenia, an aging-related muscle disease, is associated with decreased levels of specific circulating microRNAs (miRNAs). These miRNAs show potential as novel biomarkers for diagnosing sarcopenia in the elderly.
Area of Science:
- Gerontology
- Molecular Biology
- Biomarkers
Background:
- Sarcopenia is an aging-related disease characterized by loss of muscle mass, strength, and function, contributing to morbidity and mortality in the elderly.
- Current diagnostic criteria for sarcopenia lack international consensus, and reliable clinical biomarkers are yet to be identified.
- Circulating microRNAs (miRNAs) are emerging as potential novel biomarkers for sarcopenia, but their specific changes in response to the condition require further elucidation.
Purpose of the Study:
- To investigate the alterations in circulating miRNA levels in elderly individuals diagnosed with sarcopenia compared to non-sarcopenic controls.
- To identify specific miRNAs that are significantly changed in sarcopenia and correlate these changes with established diagnostic indices of sarcopenia.
- To explore the potential of circulating miRNAs as diagnostic biomarkers for sarcopenia in the elderly population.
Main Methods:
- A case-control study involving 93 elderly patients with sarcopenia and 93 age- and sex-matched controls.
- Quantification of candidate circulating miRNAs involved in angiogenesis, inflammation, and muscle/cardiac enrichment using plasma samples.
- Correlation analysis between identified miRNA levels and sarcopenia diagnostic indicators such as appendicular skeletal muscle mass index (ASM/Height2), handgrip strength, and gait speed.
Main Results:
- Plasma levels of miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 were significantly reduced in the sarcopenia group compared to the non-sarcopenia group.
- Sarcopenia diagnostic indices, including ASM/Height2, handgrip strength, and 4-meter velocity, were significantly lower in the sarcopenia group.
- Specific miRNAs, such as miR-208b and miR-155, showed significant correlations with handgrip strength in women and ASM/Height2 in men, suggesting potential sex-specific associations.
Conclusions:
- Decreased plasma levels of miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 are associated with sarcopenia in the elderly.
- These findings support the potential utility of circulating miRNAs as biomarkers for sarcopenia.
- Further research is warranted to fully establish the role and clinical application of these miRNAs in sarcopenia diagnosis and understanding its pathophysiology.
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