Background: Skeletal muscle aging leads to a progressive decline in muscle mass, strength, and overall function, significantly affecting health and quality of life. Although numerous transcriptomics studies of muscle aging have been performed, most rely heavily on Western populations, limiting the understanding of potential population-specific aging signatures. Thus, the extent of universal versus population-specific molecular signatures remains poorly characterized.

Methods: In this study, we compared muscle aging signatures using transcriptomics data from a Korean dataset (n = 6; five subjects in their teens and one in their 40s) against the Genotype-Tissue Expression (GTEx; ages ranging from 20s to 70s) database, which predominantly represents Western populations. Differentially expressed gene (DEG) analysis and gene set enrichment analysis (GSEA) were performed to identify common and population-specific aging signatures.

Results: Despite the limited sample size and narrower age range in the Korean dataset, we identified several consistently altered biological pathways associated with aging, including increased epithelial-mesenchymal transition (EMT) and inflammation, as well as decreased protein secretion and unfolded protein response (UPR). However, the overlap of specific DEGs between Korean and GTEx datasets was notably low (Jaccard similarity = 0.0154), suggesting significant population-specific mechanisms at the gene-expression level. Notably, only a few genes (LMO3, CYP26B1, LEP) were consistently upregulated in both populations, potentially representing universal biomarkers of muscle aging. Further analysis revealed that genes involved in muscle contraction and myosin filament exhibited directionally consistent expression changes between the two populations. In contrast, genes associated with fatty acid metabolism displayed population-specific differences, highlighting that metabolic pathways might be particularly sensitive to population-specific genetic or environmental factors.

Conclusion: Our results suggest the coexistence of universal and population-specific molecular signatures underlying muscle aging, underscoring the importance of including diverse populations in transcriptomics studies. Future research should further validate these universal markers and investigate how environmental and genetic factors shape population-specific aging patterns, ultimately contributing to precision therapeutic strategies tailored to diverse populations.