Longevity & Aging

MS Brains Harbor Senescent Radial Glia Cells That Drive Smoldering Inflammation

Researchers used direct reprogramming to convert skin fibroblasts from progressive multiple sclerosis (PMS) patients into induced neural stem cells (iNSCs), preserving the epigenetic memory of the donor cells. Whole-genome bisulfite sequencing revealed PMS-specific hypomethylation at lipid metabolism and interferon signaling genes. Single-cell multi-omics uncovered a novel disease-associated radial glia-like cell (DARG) subpopulation marked by senescence and heightened interferon responsiveness. PMS iNSCs also induced paracrine senescence in healthy control cells, an effect reversed by the senolytic drug ABT-263 (navitoclax). Post-mortem brain analysis confirmed DARGs in chronic active MS lesions, spatially co-localizing with inflammatory glia, suggesting they sustain smoldering neuroinflammation and represent a previously unrecognized therapeutic target.