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Effects of Ferrostatin-1 on Vocal Folds in Aging Rats
Yong-Il Cheon1, Soo-Young Bang2, Ji Min Kim2
1Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
The Laryngoscope
|June 30, 2026
Summary
Ferroptosis, a cell death process, contributes to vocal fold aging. Treatment with ferrostatin-1 (Fer-1) mitigated these aging effects by reducing oxidative stress and preserving vocal fold tissue structure.
Area of Science:
- Otolaryngology
- Aging Research
- Cell Biology
Background:
- Vocal fold aging (presbyphonia) involves lamina propria changes, extracellular matrix (ECM) remodeling, and reduced tissue elasticity.
- Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation, is increasingly linked to aging processes in various tissues.
Purpose of the Study:
- To investigate the role of ferroptosis in vocal fold aging.
- To evaluate the therapeutic potential of ferrostatin-1 (Fer-1) in mitigating age-related vocal fold degeneration in a rat model.
Main Methods:
- Thirty-six male Sprague-Dawley rats were divided into Young, Old, and Old-Fer (treated with Fer-1) groups.
- Fer-1 was administered to the vocal folds of the Old-Fer group.
- Vocal folds were analyzed for ferroptosis markers, ECM components (collagen, hyaluronic acid), lamina propria thickness, and inflammatory cytokines.
Main Results:
- Aging rats exhibited increased markers of ferroptosis, including lipid peroxidation, reactive oxygen species, and iron accumulation, alongside reduced glutathione peroxidase 4 activity.
- The Old group showed increased lamina propria thickness, collagen deposition, and decreased hyaluronic acid distribution compared to Young rats.
- Fer-1 treatment in the Old-Fer group attenuated ferroptosis markers, reduced collagen accumulation, preserved hyaluronic acid distribution, and decreased levels of TGF-β and IL-1β.
Conclusions:
- Ferroptosis plays a significant role in the aging process of vocal folds.
- Fer-1 effectively inhibits ferroptotic pathways and ameliorates age-related changes in vocal fold ECM structure and composition.
