Abstract: Objective：The aim of this study was to investigate the expression of nuclear matrix proteins special AT-rich sequence-binding protein 2 (SATB2) and associated molecules in female mandible-derived bone marrow stromal cells (BMSCs) taken from subjects at different ages, and their relationship with senescence phenotypes of BMSCs. Methods：Trabecular bones of female mandible were isolated from volunteers who sought treatment of impacted tooth or tooth implantation and divided into Y group, M group and O group. MTT and β-Gal staining were performed for analysis of cell proliferation and senescence, Western blot was used to examine the expression of SATB2, stemness factors and senescence-associated proteins. The effects of SATB2 on BMSCs stemness and senescence phenotypes were analyzed by overexpressed SATB2. Results：The proliferation ability, SATB2 and stemness factors expressions of BMSCs decreased with aging, meanwhile, showing increasing senescence phenotypes. SATB2 and stemness factors were closely associated with replicative senescence of BMSCs and mammalian target of rapamycin (mTOR) signaling. After overexpression SATB2 in older BMSCs, the number of senescence positive cells and expression of stemness factors increased, but expression of mTOR, P-mTOR and senescence associated proteins decreased. Conclusions： Senescence of female mandible-derived BMSCs increased with aging. SATB2 may improve anti-senescence ability of BMSCs by regulating stemness factors and inhibiting mTOR signaling.