This $520,831 Project Grant awarded by the National Institute on Aging (CFDA 93.866 Aging Research) to Mayo Clinic aims to characterize the role of different senescent cell populations in driving age-related bone loss and other aging co-morbidities. The research will leverage the institution's novel mouse models and single-cell analysis techniques to better define the heterogeneity of p16+ senescent cells in the bone microenvironment, as well as characterize a previously identified inflammatory p16+/ki67+ cell population and its potential contribution to skeletal aging. Additionally, the project will evaluate the impact of selectively clearing senescent osteocytes versus other p16+ osteolineage cells on age-related bone pathologies. This 5-year grant, awarded on Aug 1, 2024, will support Mayo Clinic's efforts to develop new approaches for targeting detrimental senescent cell populations and preventing or ameliorating bone loss and other geriatric conditions associated with cellular senescence.