ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
HSF1 Modulates Lipid Metabolism and Ferroptosis in Sarcopenia: A Novel Diagnostic Biomarker and Therapeutic Target
Provisionally accepted
- 1Department of Clinical Medicine, Fujian Medical University Union Hospital, fujian, China
- 2Department of orthopedics, Fujian Medical University Union Hospital, fujian, China
- 3Department of Respiratory and Critical Care Medicine, Fujian Medical University Union, fujian, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: As an age-correlated decline in skeletal muscle mass and function, sarcopenia is increasingly linked to ferroptosis, which is an iron-dependent form of regulated cell death driven by lipid peroxidation. Nevertheless, it remains poorly understood with regard to the diagnostic potential and mechanistic role of ferroptosis-relevant genes (FRGs) in sarcopenia. Methods: We integrated bioinformatics analyses and experimental validation to identify and characterize key FRGs in sarcopenia. By employing RNA-seq data from public datasets (GSE25941 and GSE9103), we identified differentially expressed FRGs and applied weighted gene co-expression network analysis (WGCNA) and multiple machine learning algorithms (comprising LASSO, SVM, KNN, XGBoost, and NNET) to screen for diagnostic biomarkers. Results: Six hub FRGs (ACSL6, CDKN1A, ATG4D, DECR1, HSF1 and MIB1 ) were identified with AUC>0.8 as robust diagnostic biomarkers, among which HSF1 exhibited the highest diagnostic value (AUC = 0.9247). Molecular docking suggested quercetin and cycloheximide as potential therapeutic agents targeting HSF1. As evidently demonstrated by functional experiments in C2C12 myoblasts, HSF1 silencing facilitated lipid metabolism, elevated ferroptosis markers, and induced muscle atrophy, while its over-expression attenuated these effects. Conclusion: Our findings not only underscore the significance of FRGs in sarcopenia pathogenesis but also highlight their potential as diagnostic markers and therapeutic targets.
Keywords: Diagnostic Markers, ferroptosis-relevant genes, Lipid Metabolism, machine learning algorithms, Sarcopenia
Received: 18 Oct 2025; Accepted: 06 Feb 2026.
Copyright: © 2026 Cheng, Shangguan, Ye, Chen, Lin and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiandong Li
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.