MSCs as a key modulator of inflammaging. The diagram illustrates how senescence and inflammation regulate MSC fate and lead to inflammaging. Cellular senescence facilitates MSCs to differentiate toward adipogenesis, and biased adipogenesis in the BM niche skews hematopoietic reconstitution, inhibits lymphopoiesis but increased myelopoiesis. Aged MSCs show increased secretion of extracellular vesicles (miR-146a) and SASP that stimulates innate immune cell receptors or macrophage polarization from M2 to M1. Age-related alterations may contribute to increased MDS or AML-related mutations or 2-HG production that possibly further exacerbated hematopoietic niche function or the pathogenesis of myeloid malignancies. BM, bone marrow; EV, extracellular vesicle; MDS, myelodysplastic syndrome; AML, Acute myeloid leukemia; 2-HG, 2-hydroxyglutarate; SASP, Senescence-associated secretory phenotype.