What this means
Sarcopenia, the age-related loss of skeletal muscle mass and function, is a major driver of frailty in older adults, yet its molecular basis remains incompletely defined. Ferroptosis, an iron-dependent regulated cell death, has emerged as a link between iron dysregulation and muscle wasting in aging.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Not stated
- Kind of research
- A study
The science
- Original title
- Ferroptosis-related hub genes and immune infiltration characteristics in Duchenne muscular dystrophy: a molecular framework with implications for aging-related muscle degeneration.
- Authors
- Peng J, Hu J, Wu M et al.
- Journal
- Aging
- Published
- Oct 16, 2026
- Study type
- Study
- PMID
- 42886052 ↗
Abstract
Sarcopenia, the age-related loss of skeletal muscle mass and function, is a major driver of frailty in older adults, yet its molecular basis remains incompletely defined. Ferroptosis, an iron-dependent regulated cell death, has emerged as a link between iron dysregulation and muscle wasting in aging. However, ferroptosis-related signatures and their interplay with immune remodeling in degenerating muscle remain uncharacterized. DMD shares selected molecular and pathological features with aging-related muscle degeneration, including iron overload, oxidative stress, and impaired regenerative capacity, and may provide a disease-accelerated context for exploring ferroptosis-associated muscle pathology. We integrated two DMD transcriptomic datasets from GEO to identify 35 ferroptosis-related differentially expressed genes. Protein-protein interaction analysis identified three hub genes (HIF1A, CDKN1A, and CD44), which are related to hypoxic responses, cellular senescence, and iron-associated cellular processes, respectively. ROC analysis showed high internal discriminatory performance within the integrated dataset. CIBERSORT-based analysis suggested altered immune cell composition, including increased estimated proportions of γδ T cells and M2 macrophages and decreased regulatory T cells. Correlations between hub gene expression and estimated immune cell populations suggested a potential association between ferroptosis-related transcriptional changes and immune remodeling. Reverse transcription-quantitative PCR (RT-qPCR) validated the upregulation of HIF1A, CDKN1A, and CD44 mRNA, whereas western blotting (WB) confirmed significantly increased protein levels of HIF-1α and CD44 in mdx mice. These findings suggest a ferroptosis-related and immune-associated transcriptional and expression-level signature in dystrophic muscle that may be relevant to aging-related muscle degeneration and warrants further validation using direct ferroptosis assays, aged muscle models, and clinical sarcopenia cohorts.
Peng J, Hu J, Wu M et al. Ferroptosis-related hub genes and immune infiltration characteristics in Duchenne muscular dystrophy: a molecular framework with implications for aging-related muscle degeneration. Aging. 2026. doi:10.18632/aging.206429. PMID: 42886052. https://pubmed.ncbi.nlm.nih.gov/42886052/