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Identification of human skeletal muscle miRNA related to strength by high-throughput sequencing
Cameron J Mitchell1, Randall F D'Souza1, William Schierding1
1Liggins Institute, University of Auckland , Auckland , New Zealand.
Abstract:
The loss of muscle size, strength, and quality with aging is a major determinant of morbidity and mortality in the elderly. The regulatory pathways that impact the muscle phenotype include the translational regulation maintained by microRNAs (miRNA). Yet the miRNAs that are expressed in human skeletal muscle and relationship to muscle size, strength, and quality are unknown. Using next-generation sequencing, we selected the 50 most abundantly expressed miRNAs and then analyzed them in vastus lateralis muscle, obtained by biopsy from middle-aged males ( n = 48; 50.0 ± 4.3 yr). Isokinetic strength testing and midthigh computed tomography was undertaken for muscle phenotype analysis. Muscle attenuation was measured by computerized tomography and is inversely proportional to myofiber lipid content. miR-486-5p accounted for 21% of total miR sequence reads, with miR-10b-5p, miR-133a-3p, and miR-22-3p accounting for a further 15, 12, and 10%, respectively. Isokinetic knee extension strength and muscle cross-sectional area were positively correlated with miR-100-5p, miR-99b-5p, and miR-191-5p expression. Muscle attenuation was negatively correlated to let-7f-5p, miR-30d-5p, and miR-125b-5p expression. In silico analysis implicates miRNAs related to strength and muscle size in the regulation of mammalian target of rapamycin, while miRNAs related to muscle attenuation may have potential roles regulating the transforming growth factor-β/SMAD3 pathway.
Insights
Specific microRNAs (miRNAs) correlate with muscle size and strength in aging men. These findings reveal novel molecular targets for maintaining muscle health and function in older adults.
Area of Science:
- Muscle physiology and aging research.
- Molecular biology and gene regulation.
- Biomarkers for sarcopenia and frailty.
Background:
- Aging is associated with significant loss of muscle mass, strength, and quality, contributing to morbidity and mortality in the elderly.
- MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as critical players in maintaining cellular phenotypes, including in skeletal muscle.
- The specific miRNAs expressed in human skeletal muscle and their direct relationship to age-related changes in muscle size, strength, and quality remain largely uncharacterized.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) expressed in human skeletal muscle.
- To investigate the correlation between the expression of these miRNAs and key indicators of muscle size, strength, and quality in middle-aged men.
- To explore potential regulatory pathways influenced by these miRNAs in skeletal muscle.
Main Methods:
- Next-generation sequencing was employed to profile miRNA expression in vastus lateralis muscle biopsies from 48 middle-aged men.
- Isokinetic strength testing and computed tomography (CT) were used to assess muscle strength, cross-sectional area, and muscle attenuation (an indicator of lipid content).
- In silico analysis was performed to predict the functional roles and regulatory targets of identified miRNAs.
Main Results:
- A subset of miRNAs, including miR-486-5p, miR-10b-5p, miR-133a-3p, and miR-22-3p, were highly abundant in skeletal muscle.
- Expression levels of miR-100-5p, miR-99b-5p, and miR-191-5p were positively correlated with isokinetic knee extension strength and muscle cross-sectional area.
- Expression of let-7f-5p, miR-30d-5p, and miR-125b-5p was negatively correlated with muscle attenuation, suggesting a role in regulating muscle lipid content.
Conclusions:
- Specific miRNAs are significantly associated with muscle size and strength in middle-aged men.
- These miRNAs may play crucial roles in regulating pathways such as mammalian target of rapamycin (mTOR) and transforming growth factor-β/SMAD3, impacting muscle phenotype.
- The findings highlight potential miRNA-based biomarkers and therapeutic targets for mitigating age-related muscle decline.
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