Longevity & AgingLab-Grown Muscle Organoids Model Sarcopenia and Test Testosterone as a Fix
Researchers developed human pluripotent stem cell-derived skeletal muscle organoids (hSkMOs) that contain mature muscle fibers, satellite cells, motor neurons, and interneurons. By repeatedly exposing these organoids to TNF-α—a chronic inflammation marker elevated in aging—they recreated the hallmarks of sarcopenia: muscle fiber atrophy, impaired satellite cell activation, and NF-κB pathway hyperactivation. Testosterone treatment significantly reversed these effects, increasing satellite cell proliferation and restoring muscle fiber cross-sectional area. Single-nucleus RNA sequencing and immunohistochemistry confirmed the organoids replicate the full myogenic and neural lineage diversity found in native muscle, offering a powerful human-specific platform for studying age-related muscle loss and screening therapies.