Pre-clinical studies show that senescent bone marrow-derived mesenchymal stromal (a.k.a. stem) cells (MSCs) and osteolineage cells contribute to age-dependent bone loss and bone marrow failure. Therefore, the identification of novel mechanisms that accelerate MSC dysfunction could enable mechanistic approaches to degenerative processes that impact the skeleton. While a handful of in vitro studies previously demonstrated MSCs’ ability to phagocytose apoptotic cells (also known as efferocytosis), matrix, pathogens and metal particles, whether efferocytosis by MSCs impacts their function and bone maintenance is not known. We found that bone marrow MSCs indeed efferocytose apoptotic neutrophils in vivo. In aged mice, where bone marrow macrophages are defective, efferocytosis by MSCs is significantly increased. Transcriptional and functional data in vitro show that excessive efferocytosis by MSCs decreases osteoblastic differentiation and promotes senescence. We hypothesized that phagocytosis by MSCs, when pathologically increased in aging or in the setting of macrophage dysfunction, causes MSC oxidative stress, mitochondrial dysfunction and senescence, thus contributing to bone loss. We are using aging and genetic models to determine the mechanism of MSC efferocytosis, define the pathogenic mechanisms induced by efferocytosis in MSCs, and establish the role of efferocytosis by MSCs in normal osteoimmunology and in aged bone. Adult mice lacking the critical receptor for efferocytosis in MSCs (Axl) demonstrate increased bone. In contrast, mice with transgenic overexpression of the direct phosphatidyl serine receptor BAI1 in MSCs demonstrate bone loss. Since efferocytosis is accompanied by oxidative stress and mitochondrial changes, which we previously found to modulate osteoblastic differentiation, we tested metabolic function in efferocytic MSCs. We found that mitochondrial disruption mediates functional changes in MSCs that clear high numbers of apoptotic cells. In summary, efferocytosis induces metabolic changes and senescence in MSCs, and may therefore represent a novel, targetable mechanism of accelerated skeletal aging.