Investigation of osteo-lineage cells as primary mediators of senescence in the bone microenvironment
The mammalian skeleton undergoes structural deterioration with aging, diagnosed clinically as osteoporosis, and results in increased fracture risk, frailty, and morbidity. It has been uncovered that cellular senescence contributes to age-related bone loss, as clearance of senescent cells improves bone mass in old mice. However, the specific identity of these deleterious bone cells remains largely unclear. Therefore, the objective of Dr. Doolittle’s research is to define the cells in the bone microenvironment that are most susceptible to developing age-related cellular senescence. Utilizing single-cell proteomics, Dr. Doolittle will deeply characterize the heterogeneous bone cell populations in old mice. Pairing this approach with therapies that target senescent cells will test the hypothesis that osteoblast-lineage cells are primary mediators of senescence in the bone milieu. Identification of these causal senescent cells will uncover mechanisms of bone loss and may allow for cell-specific therapies for the modulation of aging and osteoporosis.
