Extended Immunosupressive Therapy in a Non- Myeloablative Conditioning Regimen: Achieving Tolerance inVascularizedCompositeAllotransplantation(VCA)while

RESULTS: Aging is associated with cell intrinsic changes in the skeletal stem cell population and a decline in their regenerative potential. Heterochronic parabiosis rejuvenates aged bones by altering osteoclastogenesis. Transcriptional and metabolomic changes are associated with the age-related functional decline of skeletal stem cells. Manipulation of BMP and Wnt signaling pathways can rejuvenate aged bone by stimulating their innate regenerative capacity. CONCLUSIONS: Skeletal aging is a complex process, associated with cell intrinsic and cell extrinsic changes in the skeletal stem cell and the stem cell niche. We identified multiple differentially regulated transcriptional and metabolomic differences in aged skeletal stem cells and found that through the manipulation of BMP and Wnt signaling pathways, we were able to improve bone healing parameters in aged mice.