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Published on: February 16, 2017
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Deciphering the miRNA-mRNA Interaction Network Regulating Aging Skeletal Muscle in Various Exercise Regimens through
Zhi Yu1, Pin-Shi Ni1, Zhuang-Zhi Wang1
1Nanjing Normal University, Nanjing, Jiangsu, China.
Cell Biochemistry and Biophysics
|August 1, 2025
Summary
Resistance exercise and endurance exercise uniquely combat muscle atrophy in older adults by regulating specific microRNAs (miRNAs). Both exercise types converge on key pathways, offering a basis for personalized sarcopenia prevention strategies.
Area of Science:
- Molecular Biology
- Exercise Physiology
- Gerontology
Background:
- Skeletal muscle atrophy, or sarcopenia, is a significant concern in aging populations, impacting mobility and health.
- Understanding the molecular underpinnings of how different exercise modalities counteract muscle loss is critical for effective interventions.
- MicroRNAs (miRNAs) are key regulators of gene expression implicated in muscle health and disease.
Purpose of the Study:
- To investigate the distinct and overlapping molecular mechanisms, particularly miRNA expression profiles, by which resistance exercise (RES) and endurance exercise (END) mitigate skeletal muscle atrophy in older adults.
- To identify exercise-specific miRNA signatures and their associated regulatory pathways involved in combating age-related muscle loss.
Main Methods:
- Analysis of microRNA (miRNA) expression profiles from aging skeletal muscle datasets (GSE165632) using the Gene Expression Omnibus (GEO) database and GEO2R.
- Identification of differentially expressed miRNAs (DEmiRNAs) and prediction of their target genes using databases like miRTarBase, micro-T, and TargetScan.
- Functional enrichment analyses (Gene Ontology, KEGG pathways) and network analyses (transcription factors, protein-protein interactions) were performed using DAVID, ChEA3, and STRING databases.
Main Results:
- Resistance exercise (RES) revealed 30 differentially expressed miRNAs regulating pathways like FoxO signaling, insulin resistance, and AMPK, promoting protein synthesis and reducing apoptosis.
- Endurance exercise (END) identified 21 differentially expressed miRNAs linked to FoxO, TGF-β, MAPK, and cGMP-PKG signaling, enhancing mitochondrial function and metabolic regulation.
- Both RES and END converged on common pathways (MAPK, TGF-β, PI3K-Akt) involving genes like SMAD4 and TRAF6, crucial for myocyte survival and fibrosis suppression.
Conclusions:
- Resistance exercise primarily enhances protein synthesis and inhibits apoptosis, while endurance exercise boosts mitochondrial function and energy metabolism, through distinct miRNA-driven pathways.
- Both exercise types share convergent molecular pathways essential for maintaining skeletal muscle health in aging.
- These findings provide a molecular basis for developing personalized exercise programs to effectively counteract sarcopenia in older adults.
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