Longevity & AgingChemotherapy Destroys Bones by Triggering Senescence in Marrow Fat Cells
Chemotherapy causes bone loss in nearly all cancer patients, but the mechanism has been unclear. Researchers at Washington University found that after chemotherapy, cellular senescence is selectively triggered in two bone marrow cell types: Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). These senescent cells secrete RANKL, a key driver of osteoclast formation, while simultaneously suppressing osteoblast activity — uncoupling bone resorption from formation and causing rapid bone loss. Treating mice with the senolytic drug combination dasatinib and quercetin, or genetically eliminating senescent cells, prevented bone loss without compromising chemotherapy's anti-tumor effects. Inhibiting the p38MAPK-MK2 pathway, which controls SASP factor production, also protected bone integrity.
