Bone Marrow Skeletal Stem Cell Dysfunction: Adipocytes during skeletal aging and senescence

The cell fate regulation of skeletal stem cells (SSCs) into bone marrow adipocytes (BMAd) during physiological and pathological conditions has been a subject of study. Identification, isolation, and characterization of progenitors that give rise to BMAd, is an extensive field of research. The skewing of the cell fate of SSCs to BMAd also alters the fate of the bone accrual process due to increased bone resorption. Among the several molecular pathways that alter cell fate of SSCs is accumulation of reactive oxygen species, DNA damage, and cellular senescence. The current short review will discuss the direct and indirect effects of cellular senescence in the marrow environment, that leads to SSC differentiation to BMAd. Preclinical studies using pharmacological and genetic clearance of senescent cells and suppression of the senescence associated proinflammatory signature lays the foundation for exploring these strategies as therapeutic interventions that could mitigate BMAd and associated bone loss.