Plasma biomarkers in patients with age-related sarcopenia: a proteomic exploration and experimental validation

Abstract Background Various biomarkers associated with sarcopenia have been identified. However, there is a scarcity of studies exploring and validating biomarkers in individuals with age-related sarcopenia. Aims This study aimed to investigate the proteome and identify potential biomarkers for age-related sarcopenia. Methods Proteomic analysis and experimental validation were conducted using plasma from hospitalized older adults. Sarcopenia diagnosis was based on the Asian Working Group for Sarcopenia 2019 criteria. Data-independent acquisition-based proteomics was performed on plasma from 60 participants, with 30 diagnosed with sarcopenia and 30 without sarcopenia. Differentially expressed proteins (DEPs) were selected and evaluated by Receiver Operating Characteristic (ROC) analysis. Biomarker candidates were further quantitatively validated by enzyme-linked immunosorbent assay (ELISA) utilizing plasma from 6 participants with sarcopenia and 6 without sarcopenia. Results A total of 39 DEPs were identified and 12 DEPs were selected for ROC analysis. 8 DEPs were included for ELISA validation based on their predictive performance. Paraoxonase-3 (PON3) consistently showed down-regulation in the sarcopenic group across both methodologies. Insulin-like growth factor-binding protein-2 (IGFBP2) showed inconsistency in the sarcopenic group, with up-regulation observed in proteomic analysis but down-regulation in ELISA. Discussion Decline in PON3 may result in an overload of oxidative stress in skeletal muscles and contribute to sarcopenia. Protein modifications of IGFBP2 might exhibit during sarcopenia pathogenesis. Conclusions Plasma proteins are implicated in sarcopenia pathogenesis. PON3 is highlighted as a potential biomarker for patients with age-related sarcopenia. Further studies are imperative to gain an in-depth understanding of PON3 and IGFBP2.