After a traumatic brain injury (TBI), the bone marrow inside the skull ramps up production of inflammatory immune cells that migrate into the brain and sustain chronic damage — a process that worsens dramatically with age. Researchers traced this to a deficiency in PPARα, a lipid-sensing protein, which in older adults causes these immune cells to adopt a hyper-inflammatory state driven by epigenetic changes. When PPARα was reactivated using fenofibrate — a widely available cholesterol drug — the inflammatory cells calmed down and brain infiltration dropped. In a small randomized trial of 40 older adults with chronic TBI, fenofibrate lowered neurofilament light chain (a blood marker of brain damage) and improved cognitive test scores. The findings identify cranial bone marrow as a key driver of age-worsened neurodegeneration after TBI and suggest a repurposable drug may help.
