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Circulatory microRNAs are not effective biomarkers of muscle size and function in middle-aged men
Randall F D'Souza1, Nina Zeng1, Sally D Poppitt2,3
1Liggins Institute, The University of Auckland , Auckland, New Zealand.
Abstract:
Loss of muscle size and strength with aging is a major cause of morbidity. Although muscle size and strength are measured by imaging or fiber cross-sectional staining and exercise testing, respectively, the development of circulatory biomarkers for these phenotypes would greatly simplify identification of muscle function deficits. MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene translation and, thereby, contribute to muscle phenotype. To assess circulatory miRNAs (c-miRNAs) applicability as potential biomarkers of muscular phenotypes, fasting plasma and muscle samples were obtained from 50 middle-aged healthy men [mean (SD); age: 48.8 yr (SD 4.5); BMI: 26.6 kg/m2 (SD 3.3)]. RT-PCR of 38 miRNAs with known regulatory function within skeletal muscle identified four c-miRNAs (miR-221, miR-451a, miR-361, and miR-146a) related to either total body lean mass, leg lean mass, and 50% thigh cross-sectional area (CSA), but not strength. There was no relationship with the expression of these miRNAs in muscle. Six miRNAs within muscle were correlated with whole body lean mass, leg lean mass, and isometric knee extension torque (miR-133a and miR-146a), and 50% thigh CSA (miR-486, miR-208b, miR-133b, and miR-208a). Only miR-23b demonstrated a relationship between tissue and circulatory expression; however, only 10% of the variance was explained. miR-146a in both plasma and muscle was related to phenotype; however, no relationship between plasma and muscle expression was evident. A different subset of miRNAs correlated to muscle phenotype in muscle compared with plasma samples, suggesting that c-miRNA biomarkers of muscle phenotype are likely unrelated to muscle expression in healthy individuals.
Insights
Circulating microRNAs (miRNAs) were assessed as biomarkers for muscle mass and strength in healthy men. While some plasma miRNAs correlated with muscle size, they did not reflect muscle expression levels, suggesting limited utility as direct biomarkers.
Area of Science:
- Biochemistry
- Molecular Biology
- Gerontology
Background:
- Muscle aging leads to morbidity, with current assessments relying on imaging and exercise tests.
- Developing circulatory biomarkers for muscle phenotypes could simplify deficit identification.
- MicroRNAs (miRNAs) regulate gene translation and influence muscle characteristics.
Purpose of the Study:
- To evaluate the potential of circulating miRNAs (c-miRNAs) as biomarkers for muscular phenotypes.
- To investigate the relationship between plasma miRNA expression and muscle mass/strength in middle-aged men.
Main Methods:
- Fasting plasma and muscle samples were collected from 50 healthy middle-aged men.
- RT-PCR was used to analyze the expression of 38 miRNAs in both plasma and muscle tissue.
- Correlations were examined between miRNA levels and measures of total body lean mass, leg lean mass, thigh cross-sectional area (CSA), and knee extension torque.
Main Results:
- Four c-miRNAs (miR-221, miR-451a, miR-361, miR-146a) correlated with muscle size parameters (lean mass, thigh CSA) but not strength.
- No correlation was found between the expression of these c-miRNAs and their levels within muscle tissue.
- Six muscle-specific miRNAs correlated with muscle mass, strength, or CSA.
- Only miR-23b showed a weak link between tissue and circulatory expression, explaining only 10% of variance.
- miR-146a showed relationships with phenotype in both plasma and muscle, but plasma and muscle expression levels were not correlated.
Conclusions:
- Circulating miRNA biomarkers for muscle phenotypes appear largely unrelated to their expression within muscle tissue in healthy individuals.
- The identified c-miRNAs may not be suitable direct biomarkers for muscle size or strength due to a lack of correlation with muscle expression.
- Further research is needed to understand the complex relationship between circulating and tissue-specific miRNAs in muscle health and aging.
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