“ 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. ”
BUFFALO, NY — November 5, 2026 — A new research paper was published in Volume 18 of Aging on October 14, 2026, titled “ Ferroptosis-related hub genes and immune infiltration characteristics in Duchenne muscular dystrophy: a molecular framework with implications for aging-related muscle degeneration .”
The study identified three genes associated with ferroptosis, an iron-dependent form of cell death, and changes in immune-related signals in Duchenne muscular dystrophy (DMD). By analyzing human muscle gene-expression data and conducting experiments in mice, the researchers identified molecular characteristics that may also be relevant to age-related muscle degeneration. The findings offer new insights into potential connections between iron metabolism, inflammation and muscle health.
The research was led by equal-contributing first authors Juanjuan Peng, affiliated with Nanjing University of Chinese Medicine , and Jing Hu, affiliated with Nanjing Jiangning Hospital of Chinese Medicine . Corresponding author Houxi Xu is affiliated with the Nanjing University of Chinese Medicine .
Age-related muscle loss, known as sarcopenia, is a major contributor to frailty, disability and declining independence in older adults. Although its causes are complex, growing evidence suggests that iron accumulation, oxidative stress, inflammation and impaired muscle regeneration may contribute to progressive muscle deterioration.
One emerging mechanism is ferroptosis, a form of regulated cell death caused by iron-dependent oxidative damage to cellular membranes. Researchers are increasingly investigating whether this process contributes to muscle degeneration and whether understanding its regulation could reveal new approaches to preserving muscle function.
Duchenne muscular dystrophy, a genetic disorder that causes progressive muscle weakness, shares certain pathological features with aging-related muscle degeneration. These include oxidative stress, chronic inflammation and reduced regenerative capacity. Although DMD is distinct from normal aging, these similarities provide an opportunity to investigate potentially shared molecular pathways.
To explore these connections, the researchers analyzed two publicly available human DMD datasets containing 33 muscle samples from patients with DMD and 12 healthy controls. They identified 35 ferroptosis-related genes showing altered expression, with three emerging as particularly important: HIF1A , CDKN1A and CD44 .
These genes participate in biological processes relevant to muscle health. HIF1A helps regulate cellular responses to low oxygen levels and metabolic stress. CDKN1A is involved in cell-cycle regulation and cellular senescence, a process associated with aging and reduced regenerative capacity. Meanwhile, CD44 contributes to tissue repair, inflammatory signaling and iron metabolism.
Computational analysis also suggested increased proportions of certain immune cells, including gamma-delta T cells and M2 macrophages, alongside reduced regulatory T cells in DMD muscle. Experiments in mice confirmed increased mRNA expression of all three genes, while protein analysis showed significant increases in HIF-1α and CD44.
“ These findings suggest a ferroptosis-related and immune-associated molecular signature in dystrophic muscle that may be relevant to aging-related muscle degeneration. ”
The findings suggest that ferroptosis-related signaling, cellular senescence and immune responses may represent interconnected features of muscle degeneration. Identifying these relationships could help guide future research into molecular biomarkers and potential therapeutic strategies for muscle disorders.
However, the study did not directly demonstrate ferroptotic cell death or establish that the identified genes cause muscle degeneration. The immune-cell findings were computationally estimated, and the animal experiments involved dystrophic mice rather than models of normal aging.
Further research will be needed to determine whether these molecular changes contribute directly to muscle damage and whether similar patterns occur in older adults with sarcopenia. Studies involving direct ferroptosis measurements, independent patient samples and experimental interventions will be essential.
Overall, the study highlights HIF1A , CDKN1A and CD44 as promising targets for further investigation into the molecular processes associated with muscle degeneration. By identifying potential connections between iron-dependent cell death, inflammation and impaired muscle function, the findings provide a foundation for exploring biological mechanisms that may be shared by muscular dystrophy and age-related muscle decline.
Paper DOI : https://doi.org/10.18632/aging.206429
Corresponding author: Houxi Xu - xuhouxi@njucm.edu.cn
Keywords: aging, sarcopenia, ferroptosis, inflammaging, muscle degeneration
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Ferroptosis-related hub genes and immune infiltration characteristics in Duchenne muscular dystrophy: a molecular framework with implications for aging-related muscle degeneration
14-Oct-2026
The authors declare that they have no conflicts of interest.