An integrated multi-omics approach to investigate molecular signature of the skeletal muscle in patients with sarcopenia

Background
Sarcopenia is an age-related, multifactorial skeletal muscle disorder, and reliance on a single omics layer may be insufficient to fully elucidate its pathophysiology. This study aimed to investigate the molecular signatures of skeletal muscle in individuals with sarcopenia using integrated transcriptomic and proteomic analyses.

Methods
Postmenopausal females with distal radius fractures were enrolled and classified into Control and Sarcopenia groups based on the 2019 Asian Sarcopenia Working Group criteria. Pronator quadratus muscle samples were obtained during surgery. Total RNA and proteins were extracted for RNA sequencing and proximity extension assay proteomics analysis. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were identified in each omics layer and integrated for multi-omics analysis. External validation of the findings from multi-omics analyses was conducted using publicly available datasets.

Results
A total of 702 nominal DEGs and 712 nominal DEPs were identified, with 50 overlapping molecules between the two omics layers. Gene ontology annotation and network analysis revealed the involvement of protein glycosylation, extracellular matrix organization, collagen fiber formation, and integrin signaling. Multi-omics integration identified 10 transcripts and 15 proteins as discriminative markers for sarcopenia. Among them, seven key molecules, including TP53I3, AGBL1, DNM3OS, FAP, and WIPF1 transcripts, and MPST, and BCLAF1 proteins were identified, with AGBL1 serving as a hub molecule.

Conclusions
These findings emphasize the molecular landscape of sarcopenia and suggest candidate biomarkers and potential therapeutic targets.