Senescence of bone marrow mesenchymal stromal cells: a narrative review of mechanisms, functional consequences, and rejuvenation strategies for age-related disorders.

With the intensification of global population aging, research on aging-related diseases has become increasingly critical. Bone marrow mesenchymal stromal cells (BMSCs), residing in bone marrow microvironment, serve as precursors for osteoblasts and adipocytes while playing unique roles in regulating hematopoietic and immune systems. However, BMSCs undergo progressive senescence during aging, characterized by diminished proliferative capacity, skewed differentiation potential, compromised immunomodulatory functions, and the development of a senescence-associated secretory phenotype (SASP). These age-related alterations exacerbate inflammatory responses within the bone marrow microenvironment, contributing to the pathogenesis of degenerative diseases such as osteoporosis and osteoarthritis, while potentially inducing hematopoietic dysfunction and oncogenic transformation. Notably, senescent BMSCs secrete pro-inflammatory cytokines that establish a chronic inflammatory milieu, which not only impairs hematopoietic stem cells (HSCs) functionality but also promotes bone marrow adipogenesis. Despite these insights, the intricate interplay between BMSC senescence and microenvironmental alterations remains incompletely understood. This narrative review Comprehensively synthesizes current knowledge on the molecular mechanisms underlying BMSCs senescence, with particular emphasis on telomere attrition, DNA damage accumulation, oxidative stress, epigenetic dysregulation, and bidirectional microenvironmental crosstalk. Furthermore, we critically evaluate emerging therapeutic strategies aimed at mitigating BMSCs senescence and optimizing their clinical applications in age-related disorders.