Longevity & AgingIFN-γ Drives Muscle Stem Cell Senescence in Inflammatory Myopathies
Researchers studying idiopathic immune myopathies found that interferon-γ (IFN-γ) is a key driver of muscle atrophy in inclusion body myositis (IBM) and anti-synthetase syndrome. IFN-γ levels correlated with myofibre atrophy, and muscle stem cells (MuSCs) showed abnormal MHC-II expression in IBM biopsies. In mouse models and human cell cultures, IFN-γ impaired MuSC proliferation and fusion while triggering cellular senescence. Crucially, ruxolitinib — an approved JAK1/2 inhibitor — blocked these harmful effects, restoring normal MuSC function and improving muscle fibre size in vivo. This positions JAK inhibitors as a promising repurposed therapy for IBM, a disease notoriously resistant to conventional immunosuppressants.
